HAVEN 2: A Study of Emicizumab Administered Subcutaneously (SC) in Pediatric Participants With Hemophilia A and Factor VIII (FVIII) Inhibitors

• Sponsor: Hoffmann-La Roche (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02795767
• Collaborator: Chugai Pharmaceutical (Industry)
• Enrollment: 88
• Locations: 28
• Arms: 3
• Actual Duration (Months): 51.7
• Patients Per Site: 3.1
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This non-randomized, multicenter, open-label, Phase III clinical study will evaluate the efficacy, safety, and pharmacokinetics of emicizumab administered subcutaneously initially once weekly (QW) in pediatric participants with hemophilia A with FVIII inhibitors. This study will open two additional non-randomized cohorts to investigate once every 2 weeks (Q2W) and once every 4 weeks (Q4W) regimens in pediatric participants.

Condition or Disease	Intervention/Treatment	Phase
Hemophilia A	Drug: Emicizumab	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 88 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Multicenter, Open-Label, Phase III Clinical Trial to Evaluate the Efficacy, Safety, and Pharmacokinetics of Subcutaneous Administration of Emicizumab in Hemophilia A Pediatric Patients With Inhibitors
• Actual Study Start Date: Jul 22, 2016
• Actual Primary Completion Date: Apr 30, 2018
• Actual Study Completion Date: Nov 11, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cohort A: 1.5 mg/kg Emicizumab QW Participants will receive emicizumab at a loading dose of 3 milligrams per kilogram (mg/kg) QW SC for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg QW SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurs first.	Drug: Emicizumab; Emicizumab will be administered as per the schedule specified in the respective arm.; Other Names: Hemlibra RO5534262 RG6013 ACE910
Experimental: Cohort B: 3 mg/kg Emicizumab Q2W Participants will receive emicizumab at a loading dose of 3 mg/kg QW SC for the first 4 weeks followed by a maintenance dose of 3 mg/kg every 2 weeks (Q2W) SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurs first.	Drug: Emicizumab; Emicizumab will be administered as per the schedule specified in the respective arm.; Other Names: Hemlibra RO5534262 RG6013 ACE910
Experimental: Cohort C: 6 mg/kg Emicizumab Q4W Participants will receive emicizumab at a loading dose of 3 mg/kg QW SC for the first 4 weeks followed by a maintenance dose of 6 mg/kg every 4 weeks (Q4W) SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurs first.	Drug: Emicizumab; Emicizumab will be administered as per the schedule specified in the respective arm.; Other Names: Hemlibra RO5534262 RG6013 ACE910

Outcome Measures

Primary Outcome Measures

1. Cohort A: Model-Based Annualized Bleed Rate (ABR) for Treated Bleeds in Treated Participants <12 Years of Age [From Baseline to 52 weeks; At the primary completion date, the median (min-max) duration of the efficacy period in Cohort A was 57.57 (17.9-92.6) weeks.]

   The number of treated bleeds over the efficacy period is presented here as a model-based ABR that was analyzed using a negative binomial regression model with efficacy period as an offset to account for the difference in follow-up times. A bleed is considered a "treated bleed" if it is directly followed (i.e., no intervening bleed) by a hemophilia medication reported to be a "treatment for bleed", irrespective of time between treatment and the preceding bleed. A bleed and the first treatment thereafter and before a new bleed starts, are considered to be pairs, with the following exception: if multiple bleeds occur on the same calendar day, the subsequent treatment is considered to apply for each of these multiple bleeds. The 72-hour rule was implemented: two bleeds of the same type and at the same anatomical location are counted as one bleed if the second bleed occurs within 72 hours from the last treatment for the first bleed. Bleeds due to surgery/procedure are excluded.

2. Cohort A: Model-Based Annualized Bleed Rate (ABR) for All Bleeds in Treated Participants <12 Years of Age [From Baseline to 52 weeks; At the primary completion date, the median (min-max) duration of the efficacy period in Cohort A was 57.57 (17.9-92.6) weeks.]

   The number of all bleeds over the efficacy period is presented here as a model-based ABR that was analyzed using a negative binomial regression model with efficacy period as an offset to account for the difference in followup times (i.e., the time that each participant stays in the study). In this outcome measure, all bleeds are included, irrespective of treatment with coagulation factors, with the following exception: bleeds due to surgery/procedure are excluded. As "all bleeds" comprises both treated and non-treated bleeds, the 72-hour rule was implemented separately for treated and non-treated bleeds. For treated bleeds, the 72-hour rule was implemented exactly as defined for the "treated bleeds" outcome measure. For non-treated bleeds, the 72-hour rule was implemented by calculating a treatment-free period of 72 hours from the bleed itself.

3. Cohort A: Model-Based Annualized Bleed Rate (ABR) for Treated Spontaneous Bleeds in Treated Participants <12 Years of Age [From Baseline to 52 weeks; At the primary completion date, the median (min-max) duration of the efficacy period in Cohort A was 57.57 (17.9-92.6) weeks.]

   The number of treated spontaneous bleeds over the efficacy period is presented here as a model-based ABR that was analyzed using a negative binomial regression model with efficacy period as an offset to account for the difference in follow-up times (i.e., the time that each participant stays in the study). A bleed is classified as "spontaneous" if there is no other known contributing factor such as trauma or procedure/surgery. A "treated spontaneous bleed" is a spontaneous bleed that also fulfills the conditions of a treated bleed (see ABR for Treated Bleeds for the definition). Treated bleeds that fulfilled the 72-hour rule were included in the analysis of spontaneous bleeds. Bleeds due to surgery/procedure are excluded.

4. Cohort A: Model-Based Annualized Bleed Rate (ABR) for Treated Joint Bleeds in Treated Participants <12 Years of Age [From Baseline to 52 weeks; At the primary completion date, the median (min-max) duration of the efficacy period in Cohort A was 57.57 (17.9-92.6) weeks.]

   The number of treated joint bleeds over the efficacy period is presented here as a model-based ABR that was analyzed using a negative binomial regression model with efficacy period as an offset to account for the difference in follow-up times (i.e., the time that each participant stays in the study). A "joint bleed" is defined as a bleed with type reported as "joint" and with at least one of the following symptoms: increasing swelling or warmth of the skin over the joint and/or increasing pain, decreased range of motion, or difficulty using the joint compared with baseline. A "treated joint bleed" is a joint bleed that also fulfills the conditions of a treated bleed (see ABR for Treated Bleeds for the definition). Only treated bleeds that fulfilled the 72-hour rule were included in the analysis of treated joint bleeds, excluding bleeds due to surgery/procedure.

5. Cohort A: Model-Based Annualized Bleed Rate (ABR) for Treated Target Joint Bleeds in Treated Participants <12 Years of Age [From Baseline to 52 weeks; At the primary completion date, the median (min-max) duration of the efficacy period in Cohort A was 57.57 (17.9-92.6) weeks.]

   The number of treated target joint bleeds over the efficacy period is presented here as a model-based ABR that was analyzed using a negative binomial regression model with efficacy period as an offset to account for the difference in follow-up times (i.e., the time that each participant stays in the study). A "target joint bleed" is defined as a joint bleed in a target joint, which is a joint location where at least 3 bleeds have occurred over the last 24 weeks prior to study entry. A "treated target joint bleed" is a target joint bleed that also fulfills the conditions of a treated bleed (see ABR for Treated Bleeds for the definition). Bleeds due to surgery/procedure are excluded.

6. Cohort A: Mean Calculated Annualized Bleed Rate (ABR) for Treated Bleeds in Treated Participants <12 Years of Age [From Baseline to 52 weeks; At the primary completion date, the median (min-max) duration of the efficacy period in Cohort A was 57.57 (17.9-92.6) weeks.]

   The number of treated bleeds over the efficacy period is presented here as a calculated ABR that was annualized for each participant using the following formula: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. A bleed is considered a "treated bleed" if it is directly followed (i.e., no intervening bleed) by a hemophilia medication reported to be a "treatment for bleed", irrespective of time between treatment and the preceding bleed. A bleed and the first treatment thereafter and before a new bleed starts, are considered to be pairs, with the following exception: if multiple bleeds occur on the same calendar day, the subsequent treatment is considered to apply for each of these multiple bleeds. The 72-hour rule was implemented: two bleeds of the same type and at the same anatomical location are counted as one bleed if the second bleed occurs within 72 hours from the last treatment for the first bleed. Bleeds due to surgery/procedure are excluded.

7. Cohort A: Mean Calculated Annualized Bleed Rate (ABR) for All Bleeds in Treated Participants <12 Years of Age [From Baseline to 52 weeks; At the primary completion date, the median (min-max) duration of the efficacy period in Cohort A was 57.57 (17.9-92.6) weeks.]

   The number of all bleeds over the efficacy period is presented here as a calculated ABR that was annualized for each participant using the following formula: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. In this outcome measure, all bleeds are included, irrespective of treatment with coagulation factors, with the following exception: bleeds due to surgery/procedure are excluded. As "all bleeds" comprises both treated and non-treated bleeds, the 72-hour rule was implemented separately for treated and non-treated bleeds. For treated bleeds, the 72-hour rule was implemented exactly as defined for the "treated bleeds" outcome measure. For non-treated bleeds, the 72-hour rule was implemented by calculating a treatment-free period of 72 hours from the bleed itself.

8. Cohort A: Mean Calculated Annualized Bleed Rate (ABR) for Treated Spontaneous Bleeds in Treated Participants <12 Years of Age [From Baseline to 52 weeks; At the primary completion date, the median (min-max) duration of the efficacy period in Cohort A was 57.57 (17.9-92.6) weeks.]

   The number of treated spontaneous bleeds over the efficacy period is presented here as a calculated ABR that was annualized for each participant using the following formula: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. A bleed is classified as "spontaneous" if there is no other known contributing factor such as trauma or procedure/surgery. A "treated spontaneous bleed" is a spontaneous bleed that also fulfills the conditions of a treated bleed (see ABR for Treated Bleeds for the definition). Treated bleeds that fulfilled the 72-hour rule were included in the analysis of spontaneous bleeds. Bleeds due to surgery/procedure are excluded.

9. Cohort A: Mean Calculated Annualized Bleed Rate (ABR) for Treated Joint Bleeds in Treated Participants <12 Years of Age [From Baseline to 52 weeks; At the primary completion date, the median (min-max) duration of the efficacy period in Cohort A was 57.57 (17.9-92.6) weeks.]

   The number of treated joint bleeds over the efficacy period is presented here as a calculated ABR that was annualized for each participant using the following formula: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. A "joint bleed" is defined as a bleed with type reported as "joint" and with at least one of the following symptoms: increasing swelling or warmth of the skin over the joint and/or increasing pain, decreased range of motion, or difficulty using the joint compared with baseline. A "treated joint bleed" is a joint bleed that also fulfills the conditions of a treated bleed (see ABR for Treated Bleeds for the definition). Only treated bleeds that fulfilled the 72-hour rule were included in the analysis of treated joint bleeds, excluding bleeds due to surgery/procedure.

10. Cohort A: Mean Calculated Annualized Bleed Rate (ABR) for Treated Target Joint Bleeds in Treated Participants <12 Years of Age [From Baseline to 52 weeks; At the primary completion date, the median (min-max) duration of the efficacy period in Cohort A was 57.57 (17.9-92.6) weeks.]

    The number of treated target joint bleeds over the efficacy period is presented here as a calculated ABR that was annualized for each participant using the following formula: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. A "target joint bleed" is defined as a joint bleed in a target joint, which is a joint location where at least 3 bleeds have occurred over the last 24 weeks prior to study entry. A "treated target joint bleed" is a target joint bleed that also fulfills the conditions of a treated bleed (see ABR for Treated Bleeds for the definition). Bleeds due to surgery/procedure are excluded.

11. Cohort A: Median Calculated Annualized Bleed Rate (ABR) for Treated Bleeds in Treated Participants <12 Years of Age [From Baseline to 52 weeks; At the primary completion date, the median (min-max) duration of the efficacy period in Cohort A was 57.57 (17.9-92.6) weeks.]

    The number of treated bleeds over the efficacy period is presented here as a calculated ABR that was annualized for each participant using the following formula: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. A bleed is considered a "treated bleed" if it is directly followed (i.e., no intervening bleed) by a hemophilia medication reported to be a "treatment for bleed", irrespective of time between treatment and the preceding bleed. A bleed and the first treatment thereafter and before a new bleed starts, are considered to be pairs, with the following exception: if multiple bleeds occur on the same calendar day, the subsequent treatment is considered to apply for each of these multiple bleeds. The 72-hour rule was implemented: two bleeds of the same type and at the same anatomical location are counted as one bleed if the second bleed occurs within 72 hours from the last treatment for the first bleed. Bleeds due to surgery/procedure are excluded.

12. Cohort A: Median Calculated Annualized Bleed Rate (ABR) for All Bleeds in Treated Participants <12 Years of Age [From Baseline to 52 weeks; At the primary completion date, the median (min-max) duration of the efficacy period in Cohort A was 57.57 (17.9-92.6) weeks.]

    The number of all bleeds over the efficacy period is presented here as a calculated ABR that was annualized for each participant using the following formula: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. In this outcome measure, all bleeds are included, irrespective of treatment with coagulation factors, with the following exception: bleeds due to surgery/procedure are excluded. As "all bleeds" comprises both treated and non-treated bleeds, the 72-hour rule was implemented separately for treated and non-treated bleeds. For treated bleeds, the 72-hour rule was implemented exactly as defined for the "treated bleeds" outcome measure. For non-treated bleeds, the 72-hour rule was implemented by calculating a treatment-free period of 72 hours from the bleed itself.

13. Cohort A: Median Calculated Annualized Bleed Rate (ABR) for Treated Spontaneous Bleeds in Treated Participants <12 Years of Age [From Baseline to 52 weeks; At the primary completion date, the median (min-max) duration of the efficacy period in Cohort A was 57.57 (17.9-92.6) weeks.]

    The number of treated spontaneous bleeds over the efficacy period is presented here as a calculated ABR that was annualized for each participant using the following formula: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. A bleed is classified as "spontaneous" if there is no other known contributing factor such as trauma or procedure/surgery. A "treated spontaneous bleed" is a spontaneous bleed that also fulfills the conditions of a treated bleed (see ABR for Treated Bleeds for the definition). Treated bleeds that fulfilled the 72-hour rule were included in the analysis of spontaneous bleeds. Bleeds due to surgery/procedure are excluded.

14. Cohort A: Median Calculated Annualized Bleed Rate (ABR) for Treated Joint Bleeds in Treated Participants <12 Years of Age [From Baseline to 52 weeks; At the primary completion date, the median (min-max) duration of the efficacy period in Cohort A was 57.57 (17.9-92.6) weeks.]

    The number of treated joint bleeds over the efficacy period is presented here as a calculated ABR that was annualized for each participant using the following formula: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. A "joint bleed" is defined as a bleed with type reported as "joint" and with at least one of the following symptoms: increasing swelling or warmth of the skin over the joint and/or increasing pain, decreased range of motion, or difficulty using the joint compared with baseline. A "treated joint bleed" is a joint bleed that also fulfills the conditions of a treated bleed (see ABR for Treated Bleeds for the definition). Only treated bleeds that fulfilled the 72-hour rule were included in the analysis of treated joint bleeds, excluding bleeds due to surgery/procedure.

15. Cohort A: Median Calculated Annualized Bleed Rate (ABR) for Treated Target Joint Bleeds in Treated Participants <12 Years of Age [From Baseline to 52 weeks; At the primary completion date, the median (min-max) duration of the efficacy period in Cohort A was 57.57 (17.9-92.6) weeks.]

    The number of treated target joint bleeds over the efficacy period is presented here as a calculated ABR that was annualized for each participant using the following formula: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. A "target joint bleed" is defined as a joint bleed in a target joint, which is a joint location where at least 3 bleeds have occurred over the last 24 weeks prior to study entry. A "treated target joint bleed" is a target joint bleed that also fulfills the conditions of a treated bleed (see ABR for Treated Bleeds for the definition). Bleeds due to surgery/procedure are excluded.

16. Cohort A: Percentage of Participants by Categorized Number of Treated Bleeds Over the Efficacy Period in Treated Participants <12 Years of Age [From Baseline to 52 weeks; At the primary completion date, the median (min-max) duration of the efficacy period in Cohort A was 57.57 (17.9-92.6) weeks.]

    The percentage of participants by categorized number of treated bleeds over the efficacy period is presented here. A bleed is considered a "treated bleed" if it is directly followed (i.e., no intervening bleed) by a hemophilia medication reported to be a "treatment for bleed", irrespective of time between treatment and the preceding bleed. A bleed and the first treatment thereafter and before a new bleed starts, are considered to be pairs, with the following exception: if multiple bleeds occur on the same calendar day, the subsequent treatment is considered to apply for each of these multiple bleeds. The 72-hour rule was implemented: two bleeds of the same type and at the same anatomical location are counted as one bleed if the second bleed occurs within 72 hours from the last treatment for the first bleed. Bleeds due to surgery/procedure are excluded.

17. Cohort A: Percentage of Participants by Categorized Number of All Bleeds Over the Efficacy Period in Treated Participants <12 Years of Age [From Baseline to 52 weeks; At the primary completion date, the median (min-max) duration of the efficacy period in Cohort A was 57.57 (17.9-92.6) weeks.]

    The percentage of participants by categorized number of all bleeds over the efficacy period is presented here. In this outcome measure, all bleeds are included, irrespective of treatment with coagulation factors, with the following exception: bleeds due to surgery/procedure are excluded. As "all bleeds" comprises both treated and non-treated bleeds, the 72-hour rule was implemented separately for treated and non-treated bleeds. For treated bleeds, the 72-hour rule was implemented exactly as defined for the "treated bleeds" outcome measure. For non-treated bleeds, the 72-hour rule was implemented by calculating a treatment-free period of 72 hours from the bleed itself.

18. Cohort A: Percentage of Participants by Categorized Number of Treated Spontaneous Bleeds Over the Efficacy Period in Treated Participants <12 Years of Age [From Baseline to 52 weeks; At the primary completion date, the median (min-max) duration of the efficacy period in Cohort A was 57.57 (17.9-92.6) weeks.]

    The percentage of participants by categorized number of treated spontaneous bleeds over the efficacy period is presented here. A bleed is classified as "spontaneous" if there is no other known contributing factor such as trauma or procedure/surgery. A "treated spontaneous bleed" is a spontaneous bleed that also fulfills the conditions of a treated bleed (see ABR for Treated Bleeds for the definition). Treated bleeds that fulfilled the 72-hour rule were included in the analysis of spontaneous bleeds. Bleeds due to surgery/procedure are excluded.

19. Cohort A: Percentage of Participants by Categorized Number of Treated Joint Bleeds Over the Efficacy Period in Treated Participants <12 Years of Age [From Baseline to 52 weeks; At the primary completion date, the median (min-max) duration of the efficacy period in Cohort A was 57.57 (17.9-92.6) weeks.]

    The percentage of participants by categorized number of treated joint bleeds over the efficacy period is presented here. A "joint bleed" is defined as a bleed with type reported as "joint" and with at least one of the following symptoms: increasing swelling or warmth of the skin over the joint and/or increasing pain, decreased range of motion, or difficulty using the joint compared with baseline. A "treated joint bleed" is a joint bleed that also fulfills the conditions of a treated bleed (see ABR for Treated Bleeds for the definition). Only treated bleeds that fulfilled the 72-hour rule were included in the analysis of treated joint bleeds, excluding bleeds due to surgery/procedure.

20. Cohort A: Percentage of Participants by Categorized Number of Treated Target Joint Bleeds Over the Efficacy Period in Treated Participants <12 Years of Age [From Baseline to 52 weeks; At the primary completion date, the median (min-max) duration of the efficacy period in Cohort A was 57.57 (17.9-92.6) weeks.]

    The percentage of participants by categorized number of treated target joint bleeds over the efficacy period is presented here. A "target joint bleed" is defined as a joint bleed in a target joint, which is a joint location where at least 3 bleeds have occurred over the last 24 weeks prior to study entry. A "treated target joint bleed" is a target joint bleed that also fulfills the conditions of a treated bleed (see ABR for Treated Bleeds for the definition). Bleeds due to surgery/procedure are excluded.

Secondary Outcome Measures

1. Cohorts B and C: Model-Based Annualized Bleed Rate (ABR) for Treated Bleeds in Treated Participants <12 Years of Age [From Baseline to 24 weeks; At the primary completion date, the median (min-max) duration of the efficacy periods in Cohorts B and C were 21.29 (18.6-24.1) weeks and 19.86 (8.9-24.1) weeks, respectively.]

   The number of treated bleeds over the efficacy period is presented as a model-based ABR that was analyzed using a negative binomial regression model with efficacy period as an offset to account for the difference in follow-up times. A bleed is considered a "treated bleed" if it is directly followed (i.e., no intervening bleed) by a hemophilia medication reported to be a "treatment for bleed", irrespective of time between treatment and the preceding bleed. A bleed and the first treatment thereafter and before a new bleed starts, are considered to be pairs, with the following exception: if multiple bleeds occur on the same calendar day, the subsequent treatment is considered to apply for each of these multiple bleeds. The 72-hour rule was implemented: two bleeds of the same type and at the same anatomical location are counted as one bleed if the second bleed occurs within 72 hours from the last treatment for the first bleed. Bleeds due to surgery/procedure are excluded.

2. Cohorts B and C: Model-Based Annualized Bleed Rate (ABR) for All Bleeds in Treated Participants <12 Years of Age [From Baseline to 24 weeks; At the primary completion date, the median (min-max) duration of the efficacy periods in Cohorts B and C were 21.29 (18.6-24.1) weeks and 19.86 (8.9-24.1) weeks, respectively.]

   The number of all bleeds over the efficacy period is presented as a model-based ABR that was analyzed using a negative binomial regression model with efficacy period as an offset to account for the difference in follow-up times (i.e., the time that each participant stays in the study). In this outcome measure, all bleeds are included, irrespective of treatment with coagulation factors, with the following exception: bleeds due to surgery/procedure are excluded. As "all bleeds" comprises both treated and non-treated bleeds, the 72-hour rule was implemented separately for treated and non-treated bleeds. For treated bleeds, the 72-hour rule was implemented exactly as defined for the "treated bleeds" outcome measure. For non-treated bleeds, the 72-hour rule was implemented by calculating a treatment-free period of 72 hours from the bleed itself.

3. Cohorts B and C: Model-Based Annualized Bleed Rate (ABR) for Treated Spontaneous Bleeds in Treated Participants <12 Years of Age [From Baseline to 24 weeks; At the primary completion date, the median (min-max) duration of the efficacy periods in Cohorts B and C were 21.29 (18.6-24.1) weeks and 19.86 (8.9-24.1) weeks, respectively.]

   The number of treated spontaneous bleeds over the efficacy period is presented as a model-based ABR that was analyzed using a negative binomial regression model with efficacy period as an offset to account for the difference in follow-up times (i.e., the time that each participant stays in the study). A bleed is classified as "spontaneous" if there is no other known contributing factor such as trauma or procedure/surgery. A "treated spontaneous bleed" is a spontaneous bleed that also fulfills the conditions of a treated bleed (see ABR for Treated Bleeds for the definition). Treated bleeds that fulfilled the 72-hour rule were included in the analysis of spontaneous bleeds. Bleeds due to surgery/procedure are excluded.

4. Cohorts B and C: Model-Based Annualized Bleed Rate (ABR) for Treated Joint Bleeds in Treated Participants <12 Years of Age [From Baseline to 24 weeks; At the primary completion date, the median (min-max) duration of the efficacy periods in Cohorts B and C were 21.29 (18.6-24.1) weeks and 19.86 (8.9-24.1) weeks, respectively.]

   The number of treated joint bleeds over the efficacy period is presented as a model-based ABR that was analyzed using a negative binomial regression model with efficacy period as an offset to account for the difference in follow-up times (i.e., the time that each participant stays in the study). A "joint bleed" is defined as a bleed with type reported as "joint" and with at least one of the following symptoms: increasing swelling or warmth of the skin over the joint and/or increasing pain, decreased range of motion, or difficulty using the joint compared with baseline. A "treated joint bleed" is a joint bleed that also fulfills the conditions of a treated bleed (see ABR for Treated Bleeds for the definition). Only treated bleeds that fulfilled the 72-hour rule were included in the analysis of treated joint bleeds, excluding bleeds due to surgery/procedure.

5. Cohorts B and C: Model-Based Annualized Bleed Rate (ABR) for Treated Target Joint Bleeds in Treated Participants <12 Years of Age [From Baseline to 24 weeks; At the primary completion date, the median (min-max) duration of the efficacy periods in Cohorts B and C were 21.29 (18.6-24.1) weeks and 19.86 (8.9-24.1) weeks, respectively.]

   The number of treated target joint bleeds over the efficacy period is presented as a model-based ABR that was analyzed using a negative binomial regression model with efficacy period as an offset to account for the difference in follow-up times (i.e., the time that each participant stays in the study). A "target joint bleed" is defined as a joint bleed in a target joint, which is a joint location where at least 3 bleeds have occurred over the last 24 weeks prior to study entry. A "treated target joint bleed" is a target joint bleed that also fulfills the conditions of a treated bleed (see ABR for Treated Bleeds for the definition). Bleeds due to surgery/procedure are excluded.

6. Cohorts B and C: Mean Calculated Annualized Bleed Rate (ABR) for Treated Bleeds in Treated Participants <12 Years of Age [From Baseline to 24 weeks; At the primary completion date, the median (min-max) duration of the efficacy periods in Cohorts B and C were 21.29 (18.6-24.1) weeks and 19.86 (8.9-24.1) weeks, respectively.]

   The number of treated bleeds over the efficacy period is presented here as a calculated ABR that was annualized for each participant using the following formula: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. A bleed is considered a "treated bleed" if it is directly followed (i.e., no intervening bleed) by a hemophilia medication reported to be a "treatment for bleed", irrespective of time between treatment and the preceding bleed. A bleed and the first treatment thereafter and before a new bleed starts, are considered to be pairs, with the following exception: if multiple bleeds occur on the same calendar day, the subsequent treatment is considered to apply for each of these multiple bleeds. The 72-hour rule was implemented: two bleeds of the same type and at the same anatomical location are counted as one bleed if the second bleed occurs within 72 hours from the last treatment for the first bleed. Bleeds due to surgery/procedure are excluded.

7. Cohorts B and C: Mean Calculated Annualized Bleed Rate (ABR) for All Bleeds in Treated Participants <12 Years of Age [From Baseline to 24 weeks; At the primary completion date, the median (min-max) duration of the efficacy periods in Cohorts B and C were 21.29 (18.6-24.1) weeks and 19.86 (8.9-24.1) weeks, respectively.]

   The number of all bleeds over the efficacy period is presented here as a calculated ABR that was annualized for each participant using the following formula: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. In this outcome measure, all bleeds are included, irrespective of treatment with coagulation factors, with the following exception: bleeds due to surgery/procedure are excluded. As "all bleeds" comprises both treated and non-treated bleeds, the 72-hour rule was implemented separately for treated and non-treated bleeds. For treated bleeds, the 72-hour rule was implemented exactly as defined for the "treated bleeds" outcome measure. For non-treated bleeds, the 72-hour rule was implemented by calculating a treatment-free period of 72 hours from the bleed itself.

8. Cohorts B and C: Mean Calculated Annualized Bleed Rate (ABR) for Treated Spontaneous Bleeds in Treated Participants <12 Years of Age [From Baseline to 24 weeks; At the primary completion date, the median (min-max) duration of the efficacy periods in Cohorts B and C were 21.29 (18.6-24.1) weeks and 19.86 (8.9-24.1) weeks, respectively.]

   The number of treated spontaneous bleeds over the efficacy period is presented here as a calculated ABR that was annualized for each participant using the following formula: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. A bleed is classified as "spontaneous" if there is no other known contributing factor such as trauma or procedure/surgery. A "treated spontaneous bleed" is a spontaneous bleed that also fulfills the conditions of a treated bleed (see ABR for Treated Bleeds for the definition). Treated bleeds that fulfilled the 72-hour rule were included in the analysis of spontaneous bleeds. Bleeds due to surgery/procedure are excluded.

9. Cohorts B and C: Mean Calculated Annualized Bleed Rate (ABR) for Treated Joint Bleeds in Treated Participants <12 Years of Age [From Baseline to 24 weeks; At the primary completion date, the median (min-max) duration of the efficacy periods in Cohorts B and C were 21.29 (18.6-24.1) weeks and 19.86 (8.9-24.1) weeks, respectively.]

   The number of treated joint bleeds over the efficacy period is presented here as a calculated ABR that was annualized for each participant using the following formula: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. A "joint bleed" is defined as a bleed with type reported as "joint" and with at least one of the following symptoms: increasing swelling or warmth of the skin over the joint and/or increasing pain, decreased range of motion, or difficulty using the joint compared with baseline. A "treated joint bleed" is a joint bleed that also fulfills the conditions of a treated bleed (see ABR for Treated Bleeds for the definition). Only treated bleeds that fulfilled the 72-hour rule were included in the analysis of treated joint bleeds, excluding bleeds due to surgery/procedure.

10. Cohorts B and C: Mean Calculated Annualized Bleed Rate (ABR) for Treated Target Joint Bleeds in Treated Participants <12 Years of Age [From Baseline to 24 weeks; At the primary completion date, the median (min-max) duration of the efficacy periods in Cohorts B and C were 21.29 (18.6-24.1) weeks and 19.86 (8.9-24.1) weeks, respectively.]

    The number of treated target joint bleeds over the efficacy period is presented here as a calculated ABR that was annualized for each participant using the following formula: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. A "target joint bleed" is defined as a joint bleed in a target joint, which is a joint location where at least 3 bleeds have occurred over the last 24 weeks prior to study entry. A "treated target joint bleed" is a target joint bleed that also fulfills the conditions of a treated bleed (see ABR for Treated Bleeds for the definition). Bleeds due to surgery/procedure are excluded.

11. Cohorts B and C: Median Calculated Annualized Bleed Rate (ABR) for Treated Bleeds in Treated Participants <12 Years of Age [From Baseline to 24 weeks; At the primary completion date, the median (min-max) duration of the efficacy periods in Cohorts B and C were 21.29 (18.6-24.1) weeks and 19.86 (8.9-24.1) weeks, respectively.]

    The number of treated bleeds over the efficacy period is presented here as a calculated ABR that was annualized for each participant using the following formula: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. A bleed is considered a "treated bleed" if it is directly followed (i.e., no intervening bleed) by a hemophilia medication reported to be a "treatment for bleed", irrespective of time between treatment and the preceding bleed. A bleed and the first treatment thereafter and before a new bleed starts, are considered to be pairs, with the following exception: if multiple bleeds occur on the same calendar day, the subsequent treatment is considered to apply for each of these multiple bleeds. The 72-hour rule was implemented: two bleeds of the same type and at the same anatomical location are counted as one bleed if the second bleed occurs within 72 hours from the last treatment for the first bleed. Bleeds due to surgery/procedure are excluded.

12. Cohorts B and C: Median Calculated Annualized Bleed Rate (ABR) for All Bleeds in Treated Participants <12 Years of Age [From Baseline to 24 weeks; At the primary completion date, the median (min-max) duration of the efficacy periods in Cohorts B and C were 21.29 (18.6-24.1) weeks and 19.86 (8.9-24.1) weeks, respectively.]

    The number of all bleeds over the efficacy period is presented here as a calculated ABR that was annualized for each participant using the following formula: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. In this outcome measure, all bleeds are included, irrespective of treatment with coagulation factors, with the following exception: bleeds due to surgery/procedure are excluded. As "all bleeds" comprises both treated and non-treated bleeds, the 72-hour rule was implemented separately for treated and non-treated bleeds. For treated bleeds, the 72-hour rule was implemented exactly as defined for the "treated bleeds" outcome measure. For non-treated bleeds, the 72-hour rule was implemented by calculating a treatment-free period of 72 hours from the bleed itself.

13. Cohorts B and C: Median Calculated Annualized Bleed Rate (ABR) for Treated Spontaneous Bleeds in Treated Participants <12 Years of Age [From Baseline to 24 weeks; At the primary completion date, the median (min-max) duration of the efficacy periods in Cohorts B and C were 21.29 (18.6-24.1) weeks and 19.86 (8.9-24.1) weeks, respectively.]

    The number of treated spontaneous bleeds over the efficacy period is presented here as a calculated ABR that was annualized for each participant using the following formula: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. A bleed is classified as "spontaneous" if there is no other known contributing factor such as trauma or procedure/surgery. A "treated spontaneous bleed" is a spontaneous bleed that also fulfills the conditions of a treated bleed (see ABR for Treated Bleeds for the definition). Treated bleeds that fulfilled the 72-hour rule were included in the analysis of spontaneous bleeds. Bleeds due to surgery/procedure are excluded.

14. Cohorts B and C: Median Calculated Annualized Bleed Rate (ABR) for Treated Joint Bleeds in Treated Participants <12 Years of Age [From Baseline to 24 weeks; At the primary completion date, the median (min-max) duration of the efficacy periods in Cohorts B and C were 21.29 (18.6-24.1) weeks and 19.86 (8.9-24.1) weeks, respectively.]

    The number of treated joint bleeds over the efficacy period is presented here as a calculated ABR that was annualized for each participant using the following formula: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. A "joint bleed" is defined as a bleed with type reported as "joint" and with at least one of the following symptoms: increasing swelling or warmth of the skin over the joint and/or increasing pain, decreased range of motion, or difficulty using the joint compared with baseline. A "treated joint bleed" is a joint bleed that also fulfills the conditions of a treated bleed (see ABR for Treated Bleeds for the definition). Only treated bleeds that fulfilled the 72-hour rule were included in the analysis of treated joint bleeds, excluding bleeds due to surgery/procedure.

15. Cohorts B and C: Median Calculated Annualized Bleed Rate (ABR) for Treated Target Joint Bleeds in Treated Participants <12 Years of Age [From Baseline to 24 weeks; At the primary completion date, the median (min-max) duration of the efficacy periods in Cohorts B and C were 21.29 (18.6-24.1) weeks and 19.86 (8.9-24.1) weeks, respectively.]

    The number of treated target joint bleeds over the efficacy period is presented here as a calculated ABR that was annualized for each participant using the following formula: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. A "target joint bleed" is defined as a joint bleed in a target joint, which is a joint location where at least 3 bleeds have occurred over the last 24 weeks prior to study entry. A "treated target joint bleed" is a target joint bleed that also fulfills the conditions of a treated bleed (see ABR for Treated Bleeds for the definition). Bleeds due to surgery/procedure are excluded.

16. Cohorts B and C: Percentage of Participants by Categorized Number of Treated Bleeds Over the Efficacy Period in Treated Participants <12 Years of Age [From Baseline to 24 weeks; At the primary completion date, the median (min-max) duration of the efficacy periods in Cohorts B and C were 21.29 (18.6-24.1) weeks and 19.86 (8.9-24.1) weeks, respectively.]

    The percentage of participants by categorized number of treated bleeds over the efficacy period is presented here. A bleed is considered a "treated bleed" if it is directly followed (i.e., no intervening bleed) by a hemophilia medication reported to be a "treatment for bleed", irrespective of time between treatment and the preceding bleed. A bleed and the first treatment thereafter and before a new bleed starts, are considered to be pairs, with the following exception: if multiple bleeds occur on the same calendar day, the subsequent treatment is considered to apply for each of these multiple bleeds. The 72-hour rule was implemented: two bleeds of the same type and at the same anatomical location are counted as one bleed if the second bleed occurs within 72 hours from the last treatment for the first bleed. Bleeds due to surgery/procedure are excluded.

17. Cohorts B and C: Percentage of Participants by Categorized Number of All Bleeds Over the Efficacy Period in Treated Participants <12 Years of Age [From Baseline to 24 weeks; At the primary completion date, the median (min-max) duration of the efficacy periods in Cohorts B and C were 21.29 (18.6-24.1) weeks and 19.86 (8.9-24.1) weeks, respectively.]

    The percentage of participants by categorized number of all bleeds over the efficacy period is presented here. In this outcome measure, all bleeds are included, irrespective of treatment with coagulation factors, with the following exception: bleeds due to surgery/procedure are excluded. As "all bleeds" comprises both treated and non-treated bleeds, the 72-hour rule was implemented separately for treated and non-treated bleeds. For treated bleeds, the 72-hour rule was implemented exactly as defined for the "treated bleeds" outcome measure. For non-treated bleeds, the 72-hour rule was implemented by calculating a treatment-free period of 72 hours from the bleed itself.

18. Cohorts B and C: Percentage of Participants by Categorized Number of Treated Spontaneous Bleeds Over the Efficacy Period in Treated Participants <12 Years of Age [From Baseline to 24 weeks; At the primary completion date, the median (min-max) duration of the efficacy periods in Cohorts B and C were 21.29 (18.6-24.1) weeks and 19.86 (8.9-24.1) weeks, respectively.]

    The percentage of participants by categorized number of treated spontaneous bleeds over the efficacy period is presented here. A bleed is classified as "spontaneous" if there is no other known contributing factor such as trauma or procedure/surgery. A "treated spontaneous bleed" is a spontaneous bleed that also fulfills the conditions of a treated bleed (see ABR for Treated Bleeds for the definition). Treated bleeds that fulfilled the 72-hour rule were included in the analysis of spontaneous bleeds. Bleeds due to surgery/procedure are excluded.

19. Cohorts B and C: Percentage of Participants by Categorized Number of Treated Joint Bleeds Over the Efficacy Period in Treated Participants <12 Years of Age [From Baseline to 24 weeks; At the primary completion date, the median (min-max) duration of the efficacy periods in Cohorts B and C were 21.29 (18.6-24.1) weeks and 19.86 (8.9-24.1) weeks, respectively.]

    The percentage of participants by categorized number of treated joint bleeds over the efficacy period is presented here. A "joint bleed" is defined as a bleed with type reported as "joint" and with at least one of the following symptoms: increasing swelling or warmth of the skin over the joint and/or increasing pain, decreased range of motion, or difficulty using the joint compared with baseline. A "treated joint bleed" is a joint bleed that also fulfills the conditions of a treated bleed (see ABR for Treated Bleeds for the definition). Only treated bleeds that fulfilled the 72-hour rule were included in the analysis of treated joint bleeds, excluding bleeds due to surgery/procedure.

20. Cohorts B and C: Percentage of Participants by Categorized Number of Treated Target Joint Bleeds Over the Efficacy Period in Treated Participants <12 Years of Age [From Baseline to 24 weeks; At the primary completion date, the median (min-max) duration of the efficacy periods in Cohorts B and C were 21.29 (18.6-24.1) weeks and 19.86 (8.9-24.1) weeks, respectively.]

    The percentage of participants by categorized number of treated target joint bleeds over the efficacy period is presented here. A "target joint bleed" is defined as a joint bleed in a target joint, which is a joint location where at least 3 bleeds have occurred over the last 24 weeks prior to study entry. A "treated target joint bleed" is a target joint bleed that also fulfills the conditions of a treated bleed (see ABR for Treated Bleeds for the definition). Bleeds due to surgery/procedure are excluded.

21. Cohort A: Intra-Participant Comparison of the Model-Based ABR for Treated Bleeds on Study Versus Pre-Study in Treated Participants <12 Years of Age From the Non-Interventional Study (NIS) Population [Up to 24 weeks in NIS BH29768 (NCT02476942) prior to study entry and from Baseline to 52 weeks on this study; At primary completion date, the median (min-max) duration of the efficacy period in the NIS population was 88.57 (55.9-92.6) weeks.]

    This is an intra-participant comparison of the model-based annualized bleeding rate (ABR) for treated bleeds (i.e., number of treated bleeds over efficacy period using negative binomial regression model) on study versus pre-study in the NIS population who had previously participated in study BH29768 (NCT02476942). A "treated bleed" is a bleed directly followed by a hemophilia medication reported to be a "treatment for bleed", irrespective of time between treatment and the preceding bleed. A bleed and first treatment thereafter are considered to be pairs, with the following exception: if multiple bleeds occur on the same calendar day, the subsequent treatment is considered to apply for each of these multiple bleeds. The 72-hour rule was implemented: two bleeds of the same type and at the same anatomical location are counted as one bleed if the second bleed occurs within 72 hours from the last treatment for the first bleed. Bleeds due to surgery/procedure are excluded.

22. Cohort A: Intra-Participant Comparison of the Model-Based ABR for All Bleeds on Study Versus Pre-Study in Treated Participants <12 Years of Age From the NIS Population [Up to 24 weeks in NIS BH29768 (NCT02476942) prior to study entry and from Baseline to 52 weeks on this study; At primary completion date, the median (min-max) duration of the efficacy period in the NIS population was 88.57 (55.9-92.6) weeks.]

    This is an intra-participant comparison of the model-based annualized bleeding rate (ABR) for all bleeds (i.e., number of all bleeds over efficacy period using negative binomial regression model) on study versus pre-study in the NIS population who had previously participated in study BH29768 (NCT02476942). In this outcome measure, all bleeds are included, irrespective of treatment with coagulation factors, with the following exception: bleeds due to surgery/procedure are excluded. As "all bleeds" comprises both treated and non-treated bleeds, the 72-hour rule was implemented separately for treated and non-treated bleeds. For treated bleeds, the 72-hour rule was implemented exactly as defined for the "treated bleeds" outcome measure. For non-treated bleeds, the 72-hour rule was implemented by calculating a treatment-free period of 72 hours from the bleed itself.

23. Cohort A: Intra-Participant Comparison of the Median Calculated ABR for Treated Bleeds on Study Versus Pre-Study in Treated Participants <12 Years of Age From the NIS Population [Up to 24 weeks in NIS BH29768 (NCT02476942) prior to study entry and from Baseline to 52 weeks on this study; At primary completion date, the median (min-max) duration of the efficacy period in the NIS population was 88.57 (55.9-92.6) weeks.]

    This is an intra-participant comparison of the calculated ABR for treated bleeds (annualized per participant using the following formula: ABR = [number of bleeds/number of days during the efficacy period] x 365.25) on study versus pre-study in the NIS population who had previously participated in study BH29768 (NCT02476942). A "treated bleed" is a bleed directly followed by a hemophilia medication reported to be a "treatment for bleed", irrespective of time between treatment and the preceding bleed. A bleed and first treatment thereafter are considered to be pairs, with the following exception: if multiple bleeds occur on the same calendar day, the subsequent treatment is considered to apply for each of these multiple bleeds. The 72-hour rule was implemented: two bleeds of the same type and at the same anatomical location are counted as one bleed if the second bleed occurs within 72 hours from the last treatment for the first bleed. Bleeds due to surgery/procedure are excluded.

24. Cohort A: Intra-Participant Comparison of the Median Calculated ABR for All Bleeds on Study Versus Pre-Study in Treated Participants <12 Years of Age From the NIS Population [Up to 24 weeks in NIS BH29768 (NCT02476942) prior to study entry and from Baseline to 52 weeks on this study; At primary completion date, the median (min-max) duration of the efficacy period in the NIS population was 88.57 (55.9-92.6) weeks.]

    This is an intra-participant comparison of the calculated annualized bleeding rate (ABR) for all bleeds (annualized for each participant using the following formula: ABR = [number of bleeds/number of days during the efficacy period] x 365.25) on study versus pre-study in the NIS population who had previously participated in study BH29768 (NCT02476942). In this outcome measure, all bleeds are included, irrespective of treatment with coagulation factors, with the following exception: bleeds due to surgery/procedure are excluded. As "all bleeds" comprises both treated and non-treated bleeds, the 72-hour rule was implemented separately for treated and non-treated bleeds. For treated bleeds, the 72-hour rule was implemented exactly as defined for the "treated bleeds" outcome measure. For non-treated bleeds, the 72-hour rule was implemented by calculating a treatment-free period of 72 hours from the bleed itself.

25. Cohort A: Intra-Participant Comparison of Percentage of Participants by Categorized Number of Treated Bleeds on Study Versus Pre-Study in Treated Participants <12 Years of Age From the NIS Population [Up to 24 weeks in NIS BH29768 (NCT02476942) prior to study entry and from Baseline to 52 weeks on this study; At primary completion date, the median (min-max) duration of the efficacy period in the NIS population was 88.57 (55.9-92.6) weeks.]

    This is an intra-participant comparison of the percentage of participants by categorized number of treated bleeds over the efficacy period on study versus pre-study in the NIS population who had previously participated in study BH29768 (NCT02476942). A "treated bleed" is a bleed directly followed by a hemophilia medication reported to be a "treatment for bleed", irrespective of time between treatment and the preceding bleed. A bleed and first treatment thereafter are considered to be pairs, with the following exception: if multiple bleeds occur on the same calendar day, the subsequent treatment is considered to apply for each of these multiple bleeds. The 72-hour rule was implemented: two bleeds of the same type and at the same anatomical location are counted as one bleed if the second bleed occurs within 72 hours from the last treatment for the first bleed. Bleeds due to surgery/procedure are excluded.

26. Cohort A: Intra-Participant Comparison of Percentage of Participants by Categorized Number of All Bleeds on Study Versus Pre-Study in Treated Participants <12 Years of Age From the NIS Population [Up to 24 weeks in NIS BH29768 (NCT02476942) prior to study entry and from Baseline to 52 weeks on this study; At primary completion date, the median (min-max) duration of the efficacy period in the NIS population was 88.57 (55.9-92.6) weeks.]

    This is an intra-participant comparison of the percentage of participants by categorized number of all bleeds over the efficacy period on study versus pre-study in the NIS population who had previously participated in study BH29768 (NCT02476942). In this outcome measure, all bleeds are included, irrespective of treatment with coagulation factors, with the following exception: bleeds due to surgery/procedure are excluded. As "all bleeds" comprises both treated and non-treated bleeds, the 72-hour rule was implemented separately for treated and non-treated bleeds. For treated bleeds, the 72-hour rule was implemented exactly as defined for the "treated bleeds" outcome measure. For non-treated bleeds, the 72-hour rule was implemented by calculating a treatment-free period of 72 hours from the bleed itself.

27. Model-Based Annualized Bleed Rate (ABR) for Treated Bleeds in Treated Participants ≥12 Years of Age and <40 kg Body Weight [From Baseline to 52 weeks]

    The number of treated bleeds over the efficacy period is presented here as a model-based ABR that was analyzed using a negative binomial regression model with efficacy period as an offset to account for the difference in follow-up times. A bleed is considered a "treated bleed" if it is directly followed (i.e., no intervening bleed) by a hemophilia medication reported to be a "treatment for bleed", irrespective of time between treatment and the preceding bleed. A bleed and the first treatment thereafter and before a new bleed starts, are considered to be pairs, with the following exception: if multiple bleeds occur on the same calendar day, the subsequent treatment is considered to apply for each of these multiple bleeds. The 72-hour rule was implemented: two bleeds of the same type and at the same anatomical location are counted as one bleed if the second bleed occurs within 72 hours from the last treatment for the first bleed. Bleeds due to surgery/procedure are excluded.

28. Model-Based Annualized Bleed Rate (ABR) for All Bleeds in Treated Participants ≥12 Years of Age and <40 kg Body Weight [From Baseline to 52 weeks]

    The number of all bleeds over the efficacy period is presented as a model-based ABR that was analyzed using a negative binomial regression model with efficacy period as an offset to account for the difference in followup times (i.e., the time that each participant stays in the study). In this outcome measure, all bleeds are included, irrespective of treatment with coagulation factors, with the following exception: bleeds due to surgery/procedure are excluded. As "all bleeds" comprises both treated and non-treated bleeds, the 72-hour rule was implemented separately for treated and non-treated bleeds. For treated bleeds, the 72-hour rule was implemented exactly as defined for the "treated bleeds" outcome measure. For non-treated bleeds, the 72-hour rule was implemented by calculating a treatment-free period of 72 hours from the bleed itself.

29. Median Calculated Annualized Bleed Rate (ABR) for Treated Bleeds in Treated Participants ≥12 Years of Age and <40 kg Body Weight [From Baseline to 52 weeks]

    The number of treated bleeds over the efficacy period is presented here as a calculated ABR that was annualized for each participant using the following formula: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. A bleed is considered a "treated bleed" if it is directly followed (i.e., no intervening bleed) by a hemophilia medication reported to be a "treatment for bleed", irrespective of time between treatment and the preceding bleed. A bleed and the first treatment thereafter and before a new bleed starts, are considered to be pairs, with the following exception: if multiple bleeds occur on the same calendar day, the subsequent treatment is considered to apply for each of these multiple bleeds. The 72-hour rule was implemented: two bleeds of the same type and at the same anatomical location are counted as one bleed if the second bleed occurs within 72 hours from the last treatment for the first bleed. Bleeds due to surgery/procedure are excluded.

30. Median Calculated Annualized Bleed Rate (ABR) for All Bleeds in Treated Participants ≥12 Years of Age and <40 kg Body Weight [From Baseline to 52 weeks]

    The number of all bleeds over the efficacy period is presented here as a calculated ABR that was annualized for each participant using the following formula: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. In this outcome measure, all bleeds are included, irrespective of treatment with coagulation factors, with the following exception: bleeds due to surgery/procedure are excluded. As "all bleeds" comprises both treated and non-treated bleeds, the 72-hour rule was implemented separately for treated and non-treated bleeds. For treated bleeds, the 72-hour rule was implemented exactly as defined for the "treated bleeds" outcome measure. For non-treated bleeds, the 72-hour rule was implemented by calculating a treatment-free period of 72 hours from the bleed itself.

31. Number of Treated Bleeds Over Time in Participants With Dose Up-Titration [From Baseline to study completion (up to at least 52 weeks)]

    The number of treated bleeds over time was to be analyzed in participants whose emicizumab maintenance dose was up-titrated to 3 mg/kg QW if they had experienced suboptimal bleeding control on emicizumab at steady-state, per protocol criteria. A bleed is considered a "treated bleed" if it is directly followed (i.e., no intervening bleed) by a hemophilia medication reported to be a "treatment for bleed", irrespective of time between treatment and the preceding bleed. A bleed and the first treatment thereafter and before a new bleed starts, are considered to be pairs, with the following exception: if multiple bleeds occur on the same calendar day, the subsequent treatment is considered to apply for each of these multiple bleeds. The 72-hour rule was implemented: two bleeds of the same type and at the same anatomical location are counted as one bleed if the second bleed occurs within 72 hours from the last treatment for the first bleed. Bleeds due to surgery/procedure are excluded.

32. Number of All Bleeds Over Time in Participants With Dose Up-Titration [From Baseline to study completion (up to at least 52 weeks)]

    The number of all bleeds over time was to be analyzed in participants whose emicizumab maintenance dose was up-titrated to 3 mg/kg QW if they had experienced suboptimal bleeding control on emicizumab at steady-state, per protocol criteria. In this outcome measure, all bleeds are included, irrespective of treatment with coagulation factors, with the following exception: bleeds due to surgery/procedure are excluded. As "all bleeds" comprises both treated and non-treated bleeds, the 72-hour rule was implemented separately for treated and non-treated bleeds. For treated bleeds, the 72-hour rule was implemented exactly as defined for the "treated bleeds" outcome measure. For non-treated bleeds, the 72-hour rule was implemented by calculating a treatment-free period of 72 hours from the bleed itself.

33. Long-Term Efficacy of Emicizumab in All Cohorts: Model-Based Annualized Bleed Rate (ABR) for Treated Bleeds, All Bleeds, Treated Spontaneous Bleeds, Treated Joint Bleeds, and Treated Target Joint Bleeds in Treated Participants <12 Years of Age [From Baseline to study completion (median [min-max] duration of the efficacy periods in Cohorts A, B, and C were 92.29 [36.1-187.7] weeks, 68.21 [56.7-129.4] weeks, and 69.43 [8.9-144.3] weeks, respectively)]

    The number of bleeds over the efficacy period was shown as a model-based ABR that used a negative binomial regression model with efficacy period as an offset to account for the difference in follow-up times. A bleed is considered a "treated bleed" if it is directly followed (i.e., no intervening bleed) by a hemophilia medication reported to be a "treatment for bleed", irrespective of time between treatment and the preceding bleed. "All bleeds" included bleeds irrespective of treatment with coagulation factors, with the following exception: bleeds due to surgery/procedure are excluded. Bleeds are classified as "spontaneous" if there is no other known contributing factor such as trauma or procedure/surgery. A "joint bleed" is defined as a bleed occurring in a joint. A "target joint bleed" is defined as a joint bleed in a target joint (≥3 bleeds have occurred over the last 24 weeks prior to study entry).

34. Long-Term Efficacy of Emicizumab in All Cohorts: Mean Calculated Annualized Bleed Rate (ABR) for Treated Bleeds, All Bleeds, Treated Spontaneous Bleeds, Treated Joint Bleeds, and Treated Target Joint Bleeds in Treated Participants <12 Years of Age [From Baseline to study completion (median [min-max] duration of the efficacy periods in Cohorts A, B, and C were 92.29 [36.1-187.7] weeks, 68.21 [56.7-129.4] weeks, and 69.43 [8.9-144.3] weeks, respectively)]

    The number of treated bleeds over the efficacy period is presented here as a calculated ABR that was annualized for each participant using the following formula: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. A bleed is considered a "treated bleed" if it is directly followed (i.e., no intervening bleed) by a hemophilia medication reported to be a "treatment for bleed", irrespective of time between treatment and the preceding bleed. "All bleeds" included bleeds irrespective of treatment with coagulation factors, with the following exception: bleeds due to surgery/procedure are excluded. Bleeds are classified as "spontaneous" if there is no other known contributing factor such as trauma or procedure/surgery. A "joint bleed" is defined as a bleed with type reported as "joint". A "target joint bleed" is defined as a joint bleed in a target joint, which is a joint location where at least 3 bleeds have occurred over the last 24 weeks prior to study entry.

35. Long-Term Efficacy of Emicizumab in All Cohorts: Median Calculated Annualized Bleed Rate (ABR) for Treated Bleeds, All Bleeds, Treated Spontaneous Bleeds, Treated Joint Bleeds, and Treated Target Joint Bleeds in Treated Participants <12 Years of Age [From Baseline to study completion (median [min-max] duration of the efficacy periods in Cohorts A, B, and C were 92.29 [36.1-187.7] weeks, 68.21 [56.7-129.4] weeks, and 69.43 [8.9-144.3] weeks, respectively)]

    The number of treated bleeds over the efficacy period is presented here as a calculated ABR that was annualized for each participant using the following formula: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. A bleed is considered a "treated bleed" if it is directly followed (i.e., no intervening bleed) by a hemophilia medication reported to be a "treatment for bleed", irrespective of time between treatment and the preceding bleed. "All bleeds" included bleeds irrespective of treatment with coagulation factors, with the following exception: bleeds due to surgery/procedure are excluded. Bleeds are classified as "spontaneous" if there is no other known contributing factor such as trauma or procedure/surgery. A "joint bleed" is defined as a bleed with type reported as "joint". A "target joint bleed" is defined as a joint bleed in a target joint, which is a joint location where at least 3 bleeds have occurred over the last 24 weeks prior to study entry.

36. Change From Baseline Over Time in the Hemophilia-Specific Quality of Life Short Form (Haemo-QoL-SF) Questionnaire Total Score, as Completed by Treated Participants ≥8 to <12 Years of Age [Baseline (Week 1), Weeks 13, 25, 37, 49, 57, 81, 105, 129, 153, and 177, and at study completion [SC] or early discontinuation [ED] (up to 188 weeks)]

    The Haemo-QoL-SF is a self-reported questionnaire for children ≥8 years of age. It contains 35 items, which cover nine domains considered relevant for the children's health-related quality of life: Physical Health, Feelings, View of Yourself, Family, Friends, Other People, Sports and School, Dealing with Hemophilia, and Treatment. Items are rated with five respective response options: never, seldom, sometimes, often, and always. The Total Score is derived from the scores for all domains and ranges from 0 to 100, with a lower score reflective of better health-related quality of life.

37. Change From Baseline Over Time in the Haemo-QoL-SF Questionnaire Physical Health Domain Score, as Completed by Treated Participants ≥8 to <12 Years of Age [Baseline (Week 1), Weeks 13, 25, 37, 49, 57, 81, 105, 129, 153, and 177, and at study completion [SC] or early discontinuation [ED] (up to 188 weeks)]

    The Haemo-QoL-SF is a self-reported questionnaire for children ≥8 years of age. It contains 35 items, which cover nine domains considered relevant for the children's health-related quality of life: Physical Health, Feelings, View of Yourself, Family, Friends, Other People, Sports and School, Dealing with Hemophilia, and Treatment. The Physical Health domain assesses hemophilia-related symptoms (painful swellings and presence of joint pain) and physical functioning (pain with movement). Items are rated with five respective response options: never, seldom, sometimes, often, and always. The Physical Health domain score ranges from 0 to 100, with a lower score reflective of better physical health.

38. Change From Baseline Over Time in Caregiver-Reported Adapted Health-Related Quality of Life for Hemophilia Patients With Inhibitors Including Aspects of Caregiver Burden (Adapted Inhib-QoL) Questionnaire Total Score, Treated Participants <12 Years of Age [Baseline (Week 1), Weeks 13, 25, 37, 49, 57, 81, 105, 129, 153, and 177, and at study completion [SC] or early discontinuation [ED] (up to 188 weeks)]

    Proxy assessment of health-related quality of life (HRQoL) and aspects of caregiver burden were assessed using the Adapted Inhib-QoL questionnaire, which comprises two parts with a total of 30 questions. The first part asks the caregiver for his/her opinion on the child's HRQoL and consists of two scales: Physical Health and Treatment. The second part asks the caregiver to rate how the child's situation is for them (i.e., the impact of the child's disease and treatment on the caregiver) and consists of 6 scales (5 if the child does not have siblings): General Condition, Dealing with the Inhibitor, Perceive Treatment, Family life, Siblings, Contact with Others. Items are rated with five respective response options: never, seldom, sometimes, often, and all the time. The Total Score is derived from the individual scores of all of the domains and it ranges from 0 to 100, with lower scores reflective of better HRQoL.

39. Change From Baseline Over Time in the Caregiver-Reported Adapted Inhib-QoL Questionnaire Physical Health Domain Score, Treated Participants <12 Years of Age [Baseline (Week 1), Weeks 13, 25, 37, 49, 57, 81, 105, 129, 153, and 177, and at study completion [SC] or early discontinuation [ED] (up to 188 weeks)]

    Proxy assessment of health-related quality of life (HRQoL) and aspects of caregiver burden were assessed using the Adapted Inhib-QoL questionnaire, which comprises two parts with a total of 30 questions. The first part asks the caregiver for his/her opinion on the child's HRQoL (proxy HRQoL) and consists of two scales: Physical Health and Treatment. The second part asks the caregiver to rate how the child's situation is for them (i.e., the impact of the child's disease and treatment on the caregiver) and consists of 6 scales (5 if the child does not have siblings): General Condition, Dealing with the Inhibitor, Perceive Treatment, Family Life, Siblings, Contact with Others. Items are rated with five respective response options: never, seldom, sometimes, often, and all the time. A total score is calculated as the sum of all of the items in the scale. The Physical Health domain score ranges from 0 to 100, with lower scores reflective of better physical health.

40. Number of Participants With at Least One Adverse Event [From Baseline up to 24 weeks after study drug discontinuation; the median (min-max) observation periods in Cohorts A, B, and C were 96.93 (36.1-188.1) weeks, 68.21 (56.7-129.4) weeks, and 69.43 (38.9-144.3) weeks, respectively.]

    The number of participants experiencing at least one adverse event, including all non-serious and serious adverse events, are reported.

41. Number of Participants With at Least One Grade ≥3 Adverse Event [From Baseline up to 24 weeks after study drug discontinuation; the median (min-max) observation periods in Cohorts A, B, and C were 96.93 (36.1-188.1) weeks, 68.21 (56.7-129.4) weeks, and 69.43 (38.9-144.3) weeks, respectively.]

    The World Health Organization (WHO) toxicity grading scale was used for assessing adverse event severity. For adverse events that are not specifically listed in the WHO toxicity grading scale, a grade 3 adverse event is defined as: severe, marked limitation in activity, some assistance usually required, medical intervention or therapy required, hospitalization possible; and a grade 4 adverse event is defined as: life-threatening, extreme limitation in activity, significant assistance required, significant medical intervention or therapy required, hospitalization or hospice care probable.

42. Number of Participants With at Least One Adverse Event Leading to Withdrawal From Treatment [From Baseline up to 24 weeks after study drug discontinuation; the median (min-max) observation periods in Cohorts A, B, and C were 96.93 (36.1-188.1) weeks, 68.21 (56.7-129.4) weeks, and 69.43 (38.9-144.3) weeks, respectively.]

43. Number of Participants With at Least One Adverse Event of Local Injection Site Reaction [From Baseline up to 24 weeks after study drug discontinuation; the median (min-max) observation periods in Cohorts A, B, and C were 96.93 (36.1-188.1) weeks, 68.21 (56.7-129.4) weeks, and 69.43 (38.9-144.3) weeks, respectively.]

    Local adverse events that occurred within 24 hours after study drug administration and, in the investigator's opinion, were judged to be related to study drug injection, were captured as an "injection-site reaction" on the Adverse Event electronic Case Report Form (eCRF). An injection-related reaction that was localized was marked as a "local injection-site reaction."

44. Number of Participants With at Least One Adverse Event of Systemic Hypersensitivity, Anaphylaxis, or Anaphylactoid Reaction [From Baseline up to 24 weeks after study drug discontinuation; the median (min-max) observation periods in Cohorts A, B, and C were 96.93 (36.1-188.1) weeks, 68.21 (56.7-129.4) weeks, and 69.43 (38.9-144.3) weeks, respectively.]

    Systemic hypersensitivity, anaphylaxis, or anaphylactoid reactions were identified by the investigator using Sampson's criteria, as defined in the protocol. At the primary completion date, one participant had reported two non-serious adverse events (cough and abdominal pain) that were identified as a potential case based on a Standardised MedDRA Queries (SMQ) search for Sampson's criteria. However, after medical review of the case, it was confirmed that this case was not indicative of a systemic hypersensitivity, anaphylaxis, or anaphylactoid reaction.

45. Number of Participants With at Least One Adverse Event of Thromboembolic Event [From Baseline up to 24 weeks after study drug discontinuation; the median (min-max) observation periods in Cohorts A, B, and C were 96.93 (36.1-188.1) weeks, 68.21 (56.7-129.4) weeks, and 69.43 (38.9-144.3) weeks, respectively.]

46. Number of Participants With at Least One Adverse Event of Thrombotic Microangiopathy [From Baseline up to 24 weeks after study drug discontinuation; the median (min-max) observation periods in Cohorts A, B, and C were 96.93 (36.1-188.1) weeks, 68.21 (56.7-129.4) weeks, and 69.43 (38.9-144.3) weeks, respectively.]

47. Number of Participants Testing Negative or Positive for the Presence of Anti-Drug Antibodies (ADAs), Including Neutralizing ADAs, During the Study [Predose (0 hour) at Weeks 1, 5, 17, 33, 49, 57; then every 12 weeks until study completion (up to 188 weeks)]

    'Total ADA Negative' is the sum of all subjects who tested negative for ADA in the 2 following categories: 'ADA Negative', those who are pre-dose ADA negative or are missing pre-dose ADA data and who have all negative post-dose ADA results; and 'ADA Negative (Treatment Unaffected)', a subset who are pre-dose ADA positive but do not have a ≥4-fold increase in post-dose ADA levels compared to baseline measurement. 'Total ADA Positive' is the sum of all subjects who tested positive for ADA in the 2 following categories: 'ADA Positive (Treatment Boosted)', those who are pre-dose ADA positive and have a ≥4-fold increase in post-dose ADA levels compared to baseline measurement; and 'ADA Positive (Treatment Induced)', those who are pre-dose ADA negative or missing data and who have at least one post-dose ADA positive sample. ADA-positive samples were further analyzed for neutralizing capacity using a modified FVIII chromogenic assay; if also positive, they were considered neutralizing ADAs.

48. Number of Participants by Hematology Parameter Laboratory Test Results as a Shift From Baseline to Highest WHO Grade Post-Baseline [From Baseline until study completion (up to 188 weeks)]

    The World Health Organization (WHO) toxicity grading scale was used for determining the severity of laboratory abnormalities (i.e., test results outside of the reference range) for hematology parameters; Grade 0 is normal and Grades 1 to 4 represent worsening levels of the parameter outside of the normal range in the specified direction of the abnormality (high and low are above and below the range, respectively). Not every laboratory abnormality qualified as an adverse event (AE). A laboratory test result was reported as an AE if it met any of the following criteria: was accompanied by clinical symptoms; resulted in a change in study treatment; resulted in a medical intervention or a change in concomitant therapy; or was clinically significant in the investigator's judgment. Baseline was defined as the last available assessment prior to first receipt of study drug. Abs = absolute count

49. Number of Participants by Chemistry Parameter Laboratory Test Results as a Shift From Baseline to Highest WHO Grade Post-Baseline [From Baseline until study completion (up to 188 weeks)]

    The World Health Organization (WHO) toxicity grading scale was used for determining the severity of laboratory abnormalities (i.e., test results outside of the reference range) for chemistry parameters; Grade 0 is normal and Grades 1 to 4 represent worsening levels of the parameter outside of the normal range in the specified direction of the abnormality (high and low are above and below the range, respectively). Not every laboratory abnormality qualified as an adverse event (AE). A laboratory test result was reported as an AE if it met any of the following criteria: was accompanied by clinical symptoms; resulted in a change in study treatment; resulted in a medical intervention or a change in concomitant therapy; or was clinically significant in the investigator's judgment. Baseline was defined as the last available assessment prior to first receipt of study drug. SGOT/AST = aspartate aminotransferase; SGPT/ALT = alanine aminotransferase

50. Plasma Trough Concentration (Ctrough) of Emicizumab [Predose (0 hour) at Weeks 1, 2, 3, 4, 5, 7, 9, 13, 17, 21, 25, 29, 33, 37, 41, 49, 57, 69, 81, 93, 105, 117, 129, 141, 153, 165, and 177]

    Pre-dose (trough) plasma concentrations of emicizumab were analyzed using a validated enzyme-linked immunosorbent assay (ELISA). The lower limit of quantitation was 0.1 micrograms per milliliter (μg/mL).

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A to 17 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Children less than (<) 12 years of age, with allowance for participants 12 to 17 years of age who weigh <40 kilograms (kg) (Cohort A only); and participants <2 years of age will be allowed to participate only after the protocol-defined interim data review criteria are met (Cohort A only)

• Diagnosis of congenital hemophilia A of any severity and documented history of high-titer inhibitor (that is [i.e.], greater than or equal to [>/=] 5 bethesda units [BU])

• Requires treatment with bypassing agents

• Adequate hematologic, hepatic, and renal function

Exclusion Criteria:

• Inherited or acquired bleeding disorder other than hemophilia A

• Ongoing (or planning to receive during the study) immune tolerance induction (ITI) therapy or prophylaxis treatment with FVIII

• Previous (in the past 12 months) or current treatment for thromboembolic disease or signs of thromboembolic disease

• Other disease that may increase risk of bleeding or thrombosis

• History of clinically significant hypersensitivity associated with monoclonal antibody therapy or components of the emicizumab injection

• Known infection with human immunodeficiency virus (HIV) or hepatitis B or C virus

• Use of systemic immunomodulators at enrollment or planned use during the study period

• Planned surgery (excluding minor procedures such as tooth extraction or incision and drainage) during the study

• Inability (or unwillingness by caregiver) to receive (allow receipt of) blood or blood products (or any standard-of-care treatment for a life-threatening condition)

• Participants who are at high risk for thrombotic microangiopathy (TMA) (e.g., have a previous medical or family history of TMA), in the investigator's judgement

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Children's Hospital Los Angeles	Los Angeles	California	United States	90010
2	University of Colorado Denver, Children's Hospital	Aurora	Colorado	United States	80045
3	Children'S Healthcare of Atlanta	Atlanta	Georgia	United States	30322
4	Rush Medical Center	Chicago	Illinois	United States	60612
5	Children's Hospital of Michigan; Pediatrics	Detroit	Michigan	United States	48201
6	North Shore/Long Island Jewish PRIME; Pediatric Hematology/Oncology & Stem Cell Transplantation	New Hyde Park	New York	United States	11040
7	Oregon Health & Science Uni ; Dept of Pediatrics	Portland	Oregon	United States	97201
8	Bloodworks Northwest (formerly Puget Sound Blood Center); Hemophilia	Seattle	Washington	United States	98104
9	ICIC	San Jose		Costa Rica	1000
10	Hopital Cardio-vasculaire Louis Pradel; Hemostase clinique	Bron		France	69677
11	CH de Bicetre; Centre de Traitement d' Hemophilie	Le Kremlin Bicetre		France	94275
12	Groupe Hospitalier Necker Enfants Malades	Paris		France	75015
13	Universitätsklinikum Bonn; Institut für Experimentelle Hämatologie und Transfusionsmedizin	Bonn		Germany	53127
14	IRCCS Ca' Granda Ospedale Maggiore Policlinico; Centro Emofilia e Trombosi "Angelo Bianchi e Bonomi"	Milano	Lombardia	Italy	20122
15	Nagoya University Hospital	Aichi		Japan	466-8560
16	Hospital of the University of Occupational and Environmental Health,Japan	Kitakyushu-shi		Japan	807-8556
17	Nara Medical University Hospital	Nara		Japan	634-8522
18	Shizuoka Children's Hospital	Shizuoka		Japan	420-8660
19	Ogikubo Hospital	Tokyo		Japan	167-0035
20	Charlotte Maxeke Johannesburg Hospital; Haemophilia Comprehensive Care Center	Johannesburg		South Africa	2193
21	Hospital Universitario la Paz; Servicio de Hematologia	Madrid		Spain	28046
22	Hospital Universitario Virgen del Rocio; Servicio de Hematologia	Sevilla		Spain	41013
23	Hospital Universitario la Fe; Servicio de Hematologia	Valencia		Spain	46026
24	Adana Acibadem Hospital; Pediatric Hematology	Adana		Turkey	01130
25	Istanbul Uni Istanbul Medical Faculty	Istanbul		Turkey	34093
26	Istanbul University, Cerrahpasa Medical Faculty; Pediatrics Department	Istanbul		Turkey	34098
27	Ege University, School of Medicine; Pediatrics Department	Izmir		Turkey	35100
28	Great Ormond street Hospital for Children NHS Foundation Trust; Haemophilia Centre	London		United Kingdom	WC1N 3HR

Sponsors and Collaborators

• Hoffmann-La Roche
• Chugai Pharmaceutical

Investigators

• Study Director: Clinical Trials, Hoffmann-La Roche

Study Documents (Full-Text)

• Study Protocol - Sep 1, 2017
• Statistical Analysis Plan - Mar 14, 2018

More Information

Publications

None provided.

• Responsible Party: Hoffmann-La Roche
• ClinicalTrials.gov Identifier: NCT02795767
• Other Study ID Numbers: BH29992; 2016-000073-21
• First Posted: Jun 10, 2016
• Last Update Posted: Jun 2, 2021
• Last Verified: May 1, 2021

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Hemophilia A

Study Results

Participant Flow

Recruitment Details	Following completion of accrual to Cohort A: 1.5 mg/kg Emicizumab QW, enrollment was opened to Cohort B: 3 mg/kg Emicizumab Q2W and Cohort C: 6 mg/kg Emicizumab Q4W. Of note, enrollment remained open to Cohort A only for participants who were <2 years old, and enrollment to Cohorts B and C was limited to participants who were 2-11 years old.

Arm/Group Title	Cohort A: 1.5 mg/kg Emicizumab QW	Cohort B: 3 mg/kg Emicizumab Q2W	Cohort C: 6 mg/kg Emicizumab Q4W
Arm/Group Description	Participants received emicizumab at a loading dose of 3 milligrams per kilogram (mg/kg) once every week (QW) subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg QW SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.	Participants received emicizumab at a loading dose of 3 mg/kg QW subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 3 mg/kg once every 2 weeks (Q2W) SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.	Participants received emicizumab at a loading dose of 3 mg/kg QW subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 6 mg/kg once every 4 weeks (Q4W) SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Period Title: Overall Study
STARTED	68	10	10
Received at Least One Dose of Emicizumab	68	10	10
Dose Up-Titrated to 3 mg/kg QW	0	0	3
Completed 52 Weeks in Study	67	10	9
COMPLETED	67	10	10
NOT COMPLETED	1	0	0

Baseline Characteristics

Arm/Group Title	Cohort A: 1.5 mg/kg Emicizumab QW	Cohort B: 3 mg/kg Emicizumab Q2W	Cohort C: 6 mg/kg Emicizumab Q4W	Total
Arm/Group Description	Participants received emicizumab at a loading dose of 3 milligrams per kilogram (mg/kg) once every week (QW) subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg QW SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.	Participants received emicizumab at a loading dose of 3 mg/kg QW subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 3 mg/kg once every 2 weeks (Q2W) SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.	Participants received emicizumab at a loading dose of 3 mg/kg QW subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 6 mg/kg once every 4 weeks (Q4W) SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.	Total of all reporting groups
Overall Participants	68	10	10	88
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	6.2 (3.6)	6.9 (3.2)	7.9 (3.0)	6.5 (3.5)
Age, Customized (Count of Participants)
0 to <2 Years Old	8 11.8%	0 0%	0 0%	8 9.1%
2 to <6 Years Old	19 27.9%	3 30%	2 20%	24 27.3%
6 to <12 Years Old	38 55.9%	7 70%	8 80%	53 60.2%
≥12 Years Old	3 4.4%	0 0%	0 0%	3 3.4%
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%	0 0%
Male	68 100%	10 100%	10 100%	88 100%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	5 7.4%	1 10%	1 10%	7 8%
Not Hispanic or Latino	61 89.7%	9 90%	9 90%	79 89.8%
Unknown or Not Reported	2 2.9%	0 0%	0 0%	2 2.3%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%
Asian	10 14.7%	1 10%	2 20%	13 14.8%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%
Black or African American	11 16.2%	1 10%	0 0%	12 13.6%
White	39 57.4%	7 70%	8 80%	54 61.4%
More than one race	2 2.9%	0 0%	0 0%	2 2.3%
Unknown or Not Reported	6 8.8%	1 10%	0 0%	7 8%
Number of Participants with 0, 1, or >1 Target Joint in the Last 24 Weeks Prior to Study Entry (Count of Participants)
0 Target Joints	44 64.7%	3 30%	7 70%	54 61.4%
1 Target Joint	9 13.2%	6 60%	1 10%	16 18.2%
>1 Target Joint	15 22.1%	1 10%	2 20%	18 20.5%

Outcome Measures

1. Primary Outcome

Title	Cohort A: Model-Based Annualized Bleed Rate (ABR) for Treated Bleeds in Treated Participants <12 Years of Age
Description	The number of treated bleeds over the efficacy period is presented here as a model-based ABR that was analyzed using a negative binomial regression model with efficacy period as an offset to account for the difference in follow-up times. A bleed is considered a "treated bleed" if it is directly followed (i.e., no intervening bleed) by a hemophilia medication reported to be a "treatment for bleed", irrespective of time between treatment and the preceding bleed. A bleed and the first treatment thereafter and before a new bleed starts, are considered to be pairs, with the following exception: if multiple bleeds occur on the same calendar day, the subsequent treatment is considered to apply for each of these multiple bleeds. The 72-hour rule was implemented: two bleeds of the same type and at the same anatomical location are counted as one bleed if the second bleed occurs within 72 hours from the last treatment for the first bleed. Bleeds due to surgery/procedure are excluded.
Time Frame	From Baseline to 52 weeks; At the primary completion date, the median (min-max) duration of the efficacy period in Cohort A was 57.57 (17.9-92.6) weeks.

Outcome Measure Data

Analysis Population Description

All treated participants in Cohort A who were on the same dose of emicizumab for at least 12 weeks and were <12 years of age

Arm/Group Title	Cohort A: 1.5 mg/kg Emicizumab QW
Arm/Group Description	Participants received emicizumab at a loading dose of 3 milligrams per kilogram (mg/kg) once every week (QW) subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg QW SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Measure Participants	65
Number (95% Confidence Interval) [treated bleed rate per year]	0.3

2. Primary Outcome

Title	Cohort A: Model-Based Annualized Bleed Rate (ABR) for All Bleeds in Treated Participants <12 Years of Age
Description	The number of all bleeds over the efficacy period is presented here as a model-based ABR that was analyzed using a negative binomial regression model with efficacy period as an offset to account for the difference in followup times (i.e., the time that each participant stays in the study). In this outcome measure, all bleeds are included, irrespective of treatment with coagulation factors, with the following exception: bleeds due to surgery/procedure are excluded. As "all bleeds" comprises both treated and non-treated bleeds, the 72-hour rule was implemented separately for treated and non-treated bleeds. For treated bleeds, the 72-hour rule was implemented exactly as defined for the "treated bleeds" outcome measure. For non-treated bleeds, the 72-hour rule was implemented by calculating a treatment-free period of 72 hours from the bleed itself.
Time Frame	From Baseline to 52 weeks; At the primary completion date, the median (min-max) duration of the efficacy period in Cohort A was 57.57 (17.9-92.6) weeks.

Outcome Measure Data

Analysis Population Description

All treated participants in Cohort A who were on the same dose of emicizumab for at least 12 weeks and were <12 years of age

Arm/Group Title	Cohort A: 1.5 mg/kg Emicizumab QW
Arm/Group Description	Participants received emicizumab at a loading dose of 3 milligrams per kilogram (mg/kg) once every week (QW) subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg QW SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Measure Participants	65
Number (95% Confidence Interval) [all bleed rate per year]	3.2

3. Primary Outcome

Title	Cohort A: Model-Based Annualized Bleed Rate (ABR) for Treated Spontaneous Bleeds in Treated Participants <12 Years of Age
Description	The number of treated spontaneous bleeds over the efficacy period is presented here as a model-based ABR that was analyzed using a negative binomial regression model with efficacy period as an offset to account for the difference in follow-up times (i.e., the time that each participant stays in the study). A bleed is classified as "spontaneous" if there is no other known contributing factor such as trauma or procedure/surgery. A "treated spontaneous bleed" is a spontaneous bleed that also fulfills the conditions of a treated bleed (see ABR for Treated Bleeds for the definition). Treated bleeds that fulfilled the 72-hour rule were included in the analysis of spontaneous bleeds. Bleeds due to surgery/procedure are excluded.
Time Frame	From Baseline to 52 weeks; At the primary completion date, the median (min-max) duration of the efficacy period in Cohort A was 57.57 (17.9-92.6) weeks.

Outcome Measure Data

Analysis Population Description

All treated participants in Cohort A who were on the same dose of emicizumab for at least 12 weeks and were <12 years of age

Arm/Group Title	Cohort A: 1.5 mg/kg Emicizumab QW
Arm/Group Description	Participants received emicizumab at a loading dose of 3 milligrams per kilogram (mg/kg) once every week (QW) subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg QW SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Measure Participants	65
Number (95% Confidence Interval) [treated spontaneous bleed rate per year]	0.0

4. Primary Outcome

Title	Cohort A: Model-Based Annualized Bleed Rate (ABR) for Treated Joint Bleeds in Treated Participants <12 Years of Age
Description	The number of treated joint bleeds over the efficacy period is presented here as a model-based ABR that was analyzed using a negative binomial regression model with efficacy period as an offset to account for the difference in follow-up times (i.e., the time that each participant stays in the study). A "joint bleed" is defined as a bleed with type reported as "joint" and with at least one of the following symptoms: increasing swelling or warmth of the skin over the joint and/or increasing pain, decreased range of motion, or difficulty using the joint compared with baseline. A "treated joint bleed" is a joint bleed that also fulfills the conditions of a treated bleed (see ABR for Treated Bleeds for the definition). Only treated bleeds that fulfilled the 72-hour rule were included in the analysis of treated joint bleeds, excluding bleeds due to surgery/procedure.
Time Frame	From Baseline to 52 weeks; At the primary completion date, the median (min-max) duration of the efficacy period in Cohort A was 57.57 (17.9-92.6) weeks.

Outcome Measure Data

Analysis Population Description

All treated participants in Cohort A who were on the same dose of emicizumab for at least 12 weeks and were <12 years of age

Arm/Group Title	Cohort A: 1.5 mg/kg Emicizumab QW
Arm/Group Description	Participants received emicizumab at a loading dose of 3 milligrams per kilogram (mg/kg) once every week (QW) subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg QW SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Measure Participants	65
Number (95% Confidence Interval) [treated joint bleed rate per year]	0.2

5. Primary Outcome

Title	Cohort A: Model-Based Annualized Bleed Rate (ABR) for Treated Target Joint Bleeds in Treated Participants <12 Years of Age
Description	The number of treated target joint bleeds over the efficacy period is presented here as a model-based ABR that was analyzed using a negative binomial regression model with efficacy period as an offset to account for the difference in follow-up times (i.e., the time that each participant stays in the study). A "target joint bleed" is defined as a joint bleed in a target joint, which is a joint location where at least 3 bleeds have occurred over the last 24 weeks prior to study entry. A "treated target joint bleed" is a target joint bleed that also fulfills the conditions of a treated bleed (see ABR for Treated Bleeds for the definition). Bleeds due to surgery/procedure are excluded.
Time Frame	From Baseline to 52 weeks; At the primary completion date, the median (min-max) duration of the efficacy period in Cohort A was 57.57 (17.9-92.6) weeks.

Outcome Measure Data

Analysis Population Description

All treated participants in Cohort A who were on the same dose of emicizumab for at least 12 weeks and were <12 years of age

Arm/Group Title	Cohort A: 1.5 mg/kg Emicizumab QW
Arm/Group Description	Participants received emicizumab at a loading dose of 3 milligrams per kilogram (mg/kg) once every week (QW) subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg QW SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Measure Participants	65
Number (95% Confidence Interval) [treated target joint bleed rate per year]	NA

6. Primary Outcome

Title	Cohort A: Mean Calculated Annualized Bleed Rate (ABR) for Treated Bleeds in Treated Participants <12 Years of Age
Description	The number of treated bleeds over the efficacy period is presented here as a calculated ABR that was annualized for each participant using the following formula: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. A bleed is considered a "treated bleed" if it is directly followed (i.e., no intervening bleed) by a hemophilia medication reported to be a "treatment for bleed", irrespective of time between treatment and the preceding bleed. A bleed and the first treatment thereafter and before a new bleed starts, are considered to be pairs, with the following exception: if multiple bleeds occur on the same calendar day, the subsequent treatment is considered to apply for each of these multiple bleeds. The 72-hour rule was implemented: two bleeds of the same type and at the same anatomical location are counted as one bleed if the second bleed occurs within 72 hours from the last treatment for the first bleed. Bleeds due to surgery/procedure are excluded.
Time Frame	From Baseline to 52 weeks; At the primary completion date, the median (min-max) duration of the efficacy period in Cohort A was 57.57 (17.9-92.6) weeks.

Outcome Measure Data

Analysis Population Description

All treated participants in Cohort A who were on the same dose of emicizumab for at least 12 weeks and were <12 years of age

Arm/Group Title	Cohort A: 1.5 mg/kg Emicizumab QW
Arm/Group Description	Participants received emicizumab at a loading dose of 3 milligrams per kilogram (mg/kg) once every week (QW) subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg QW SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Measure Participants	65
Mean (95% Confidence Interval) [treated bleed rate per year]	0.3

7. Primary Outcome

Title	Cohort A: Mean Calculated Annualized Bleed Rate (ABR) for All Bleeds in Treated Participants <12 Years of Age
Description	The number of all bleeds over the efficacy period is presented here as a calculated ABR that was annualized for each participant using the following formula: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. In this outcome measure, all bleeds are included, irrespective of treatment with coagulation factors, with the following exception: bleeds due to surgery/procedure are excluded. As "all bleeds" comprises both treated and non-treated bleeds, the 72-hour rule was implemented separately for treated and non-treated bleeds. For treated bleeds, the 72-hour rule was implemented exactly as defined for the "treated bleeds" outcome measure. For non-treated bleeds, the 72-hour rule was implemented by calculating a treatment-free period of 72 hours from the bleed itself.
Time Frame	From Baseline to 52 weeks; At the primary completion date, the median (min-max) duration of the efficacy period in Cohort A was 57.57 (17.9-92.6) weeks.

Outcome Measure Data

Analysis Population Description

All treated participants in Cohort A who were on the same dose of emicizumab for at least 12 weeks and were <12 years of age

Arm/Group Title	Cohort A: 1.5 mg/kg Emicizumab QW
Arm/Group Description	Participants received emicizumab at a loading dose of 3 milligrams per kilogram (mg/kg) once every week (QW) subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg QW SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Measure Participants	65
Mean (95% Confidence Interval) [all bleed rate per year]	3.2

8. Primary Outcome

Title	Cohort A: Mean Calculated Annualized Bleed Rate (ABR) for Treated Spontaneous Bleeds in Treated Participants <12 Years of Age
Description	The number of treated spontaneous bleeds over the efficacy period is presented here as a calculated ABR that was annualized for each participant using the following formula: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. A bleed is classified as "spontaneous" if there is no other known contributing factor such as trauma or procedure/surgery. A "treated spontaneous bleed" is a spontaneous bleed that also fulfills the conditions of a treated bleed (see ABR for Treated Bleeds for the definition). Treated bleeds that fulfilled the 72-hour rule were included in the analysis of spontaneous bleeds. Bleeds due to surgery/procedure are excluded.
Time Frame	From Baseline to 52 weeks; At the primary completion date, the median (min-max) duration of the efficacy period in Cohort A was 57.57 (17.9-92.6) weeks.

Outcome Measure Data

Analysis Population Description

All treated participants in Cohort A who were on the same dose of emicizumab for at least 12 weeks and were <12 years of age

Arm/Group Title	Cohort A: 1.5 mg/kg Emicizumab QW
Arm/Group Description	Participants received emicizumab at a loading dose of 3 milligrams per kilogram (mg/kg) once every week (QW) subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg QW SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Measure Participants	65
Mean (95% Confidence Interval) [treated spontaneous bleed rate per year]	0.0

9. Primary Outcome

Title	Cohort A: Mean Calculated Annualized Bleed Rate (ABR) for Treated Joint Bleeds in Treated Participants <12 Years of Age
Description	The number of treated joint bleeds over the efficacy period is presented here as a calculated ABR that was annualized for each participant using the following formula: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. A "joint bleed" is defined as a bleed with type reported as "joint" and with at least one of the following symptoms: increasing swelling or warmth of the skin over the joint and/or increasing pain, decreased range of motion, or difficulty using the joint compared with baseline. A "treated joint bleed" is a joint bleed that also fulfills the conditions of a treated bleed (see ABR for Treated Bleeds for the definition). Only treated bleeds that fulfilled the 72-hour rule were included in the analysis of treated joint bleeds, excluding bleeds due to surgery/procedure.
Time Frame	From Baseline to 52 weeks; At the primary completion date, the median (min-max) duration of the efficacy period in Cohort A was 57.57 (17.9-92.6) weeks.

Outcome Measure Data

Analysis Population Description

All treated participants in Cohort A who were on the same dose of emicizumab for at least 12 weeks and were <12 years of age

Arm/Group Title	Cohort A: 1.5 mg/kg Emicizumab QW
Arm/Group Description	Participants received emicizumab at a loading dose of 3 milligrams per kilogram (mg/kg) once every week (QW) subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg QW SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Measure Participants	65
Mean (95% Confidence Interval) [treated joint bleed rate per year]	0.2

10. Primary Outcome

Title	Cohort A: Mean Calculated Annualized Bleed Rate (ABR) for Treated Target Joint Bleeds in Treated Participants <12 Years of Age
Description	The number of treated target joint bleeds over the efficacy period is presented here as a calculated ABR that was annualized for each participant using the following formula: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. A "target joint bleed" is defined as a joint bleed in a target joint, which is a joint location where at least 3 bleeds have occurred over the last 24 weeks prior to study entry. A "treated target joint bleed" is a target joint bleed that also fulfills the conditions of a treated bleed (see ABR for Treated Bleeds for the definition). Bleeds due to surgery/procedure are excluded.
Time Frame	From Baseline to 52 weeks; At the primary completion date, the median (min-max) duration of the efficacy period in Cohort A was 57.57 (17.9-92.6) weeks.

Outcome Measure Data

Analysis Population Description

All treated participants in Cohort A who were on the same dose of emicizumab for at least 12 weeks and were <12 years of age

Arm/Group Title	Cohort A: 1.5 mg/kg Emicizumab QW
Arm/Group Description	Participants received emicizumab at a loading dose of 3 milligrams per kilogram (mg/kg) once every week (QW) subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg QW SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Measure Participants	65
Mean (95% Confidence Interval) [treated target joint bleed rate per year]	0.1

11. Primary Outcome

Title	Cohort A: Median Calculated Annualized Bleed Rate (ABR) for Treated Bleeds in Treated Participants <12 Years of Age
Description	The number of treated bleeds over the efficacy period is presented here as a calculated ABR that was annualized for each participant using the following formula: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. A bleed is considered a "treated bleed" if it is directly followed (i.e., no intervening bleed) by a hemophilia medication reported to be a "treatment for bleed", irrespective of time between treatment and the preceding bleed. A bleed and the first treatment thereafter and before a new bleed starts, are considered to be pairs, with the following exception: if multiple bleeds occur on the same calendar day, the subsequent treatment is considered to apply for each of these multiple bleeds. The 72-hour rule was implemented: two bleeds of the same type and at the same anatomical location are counted as one bleed if the second bleed occurs within 72 hours from the last treatment for the first bleed. Bleeds due to surgery/procedure are excluded.
Time Frame	From Baseline to 52 weeks; At the primary completion date, the median (min-max) duration of the efficacy period in Cohort A was 57.57 (17.9-92.6) weeks.

Outcome Measure Data

Analysis Population Description

All treated participants in Cohort A who were on the same dose of emicizumab for at least 12 weeks and were <12 years of age

Arm/Group Title	Cohort A: 1.5 mg/kg Emicizumab QW
Arm/Group Description	Participants received emicizumab at a loading dose of 3 milligrams per kilogram (mg/kg) once every week (QW) subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg QW SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Measure Participants	65
Median (Inter-Quartile Range) [treated bleed rate per year]	0.0

12. Primary Outcome

Title	Cohort A: Median Calculated Annualized Bleed Rate (ABR) for All Bleeds in Treated Participants <12 Years of Age
Description	The number of all bleeds over the efficacy period is presented here as a calculated ABR that was annualized for each participant using the following formula: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. In this outcome measure, all bleeds are included, irrespective of treatment with coagulation factors, with the following exception: bleeds due to surgery/procedure are excluded. As "all bleeds" comprises both treated and non-treated bleeds, the 72-hour rule was implemented separately for treated and non-treated bleeds. For treated bleeds, the 72-hour rule was implemented exactly as defined for the "treated bleeds" outcome measure. For non-treated bleeds, the 72-hour rule was implemented by calculating a treatment-free period of 72 hours from the bleed itself.
Time Frame	From Baseline to 52 weeks; At the primary completion date, the median (min-max) duration of the efficacy period in Cohort A was 57.57 (17.9-92.6) weeks.

Outcome Measure Data

Analysis Population Description

All treated participants in Cohort A who were on the same dose of emicizumab for at least 12 weeks and were <12 years of age

Arm/Group Title	Cohort A: 1.5 mg/kg Emicizumab QW
Arm/Group Description	Participants received emicizumab at a loading dose of 3 milligrams per kilogram (mg/kg) once every week (QW) subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg QW SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Measure Participants	65
Median (Inter-Quartile Range) [all bleed rate per year]	0.6

13. Primary Outcome

Title	Cohort A: Median Calculated Annualized Bleed Rate (ABR) for Treated Spontaneous Bleeds in Treated Participants <12 Years of Age
Description	The number of treated spontaneous bleeds over the efficacy period is presented here as a calculated ABR that was annualized for each participant using the following formula: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. A bleed is classified as "spontaneous" if there is no other known contributing factor such as trauma or procedure/surgery. A "treated spontaneous bleed" is a spontaneous bleed that also fulfills the conditions of a treated bleed (see ABR for Treated Bleeds for the definition). Treated bleeds that fulfilled the 72-hour rule were included in the analysis of spontaneous bleeds. Bleeds due to surgery/procedure are excluded.
Time Frame	From Baseline to 52 weeks; At the primary completion date, the median (min-max) duration of the efficacy period in Cohort A was 57.57 (17.9-92.6) weeks.

Outcome Measure Data

Analysis Population Description

All treated participants in Cohort A who were on the same dose of emicizumab for at least 12 weeks and were <12 years of age

Arm/Group Title	Cohort A: 1.5 mg/kg Emicizumab QW
Arm/Group Description	Participants received emicizumab at a loading dose of 3 milligrams per kilogram (mg/kg) once every week (QW) subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg QW SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Measure Participants	65
Median (Inter-Quartile Range) [treated spontaneous bleed rate per year]	0.0

14. Primary Outcome

Title	Cohort A: Median Calculated Annualized Bleed Rate (ABR) for Treated Joint Bleeds in Treated Participants <12 Years of Age
Description	The number of treated joint bleeds over the efficacy period is presented here as a calculated ABR that was annualized for each participant using the following formula: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. A "joint bleed" is defined as a bleed with type reported as "joint" and with at least one of the following symptoms: increasing swelling or warmth of the skin over the joint and/or increasing pain, decreased range of motion, or difficulty using the joint compared with baseline. A "treated joint bleed" is a joint bleed that also fulfills the conditions of a treated bleed (see ABR for Treated Bleeds for the definition). Only treated bleeds that fulfilled the 72-hour rule were included in the analysis of treated joint bleeds, excluding bleeds due to surgery/procedure.
Time Frame	From Baseline to 52 weeks; At the primary completion date, the median (min-max) duration of the efficacy period in Cohort A was 57.57 (17.9-92.6) weeks.

Outcome Measure Data

Analysis Population Description

All treated participants in Cohort A who were on the same dose of emicizumab for at least 12 weeks and were <12 years of age

Arm/Group Title	Cohort A: 1.5 mg/kg Emicizumab QW
Arm/Group Description	Participants received emicizumab at a loading dose of 3 milligrams per kilogram (mg/kg) once every week (QW) subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg QW SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Measure Participants	65
Median (Inter-Quartile Range) [treated joint bleed rate per year]	0.0

15. Primary Outcome

Title	Cohort A: Median Calculated Annualized Bleed Rate (ABR) for Treated Target Joint Bleeds in Treated Participants <12 Years of Age
Description	The number of treated target joint bleeds over the efficacy period is presented here as a calculated ABR that was annualized for each participant using the following formula: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. A "target joint bleed" is defined as a joint bleed in a target joint, which is a joint location where at least 3 bleeds have occurred over the last 24 weeks prior to study entry. A "treated target joint bleed" is a target joint bleed that also fulfills the conditions of a treated bleed (see ABR for Treated Bleeds for the definition). Bleeds due to surgery/procedure are excluded.
Time Frame	From Baseline to 52 weeks; At the primary completion date, the median (min-max) duration of the efficacy period in Cohort A was 57.57 (17.9-92.6) weeks.

Outcome Measure Data

Analysis Population Description

All treated participants in Cohort A who were on the same dose of emicizumab for at least 12 weeks and were <12 years of age

Arm/Group Title	Cohort A: 1.5 mg/kg Emicizumab QW
Arm/Group Description	Participants received emicizumab at a loading dose of 3 milligrams per kilogram (mg/kg) once every week (QW) subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg QW SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Measure Participants	65
Median (Inter-Quartile Range) [treated target joint bleed rate per year]	0.0

16. Primary Outcome

Title	Cohort A: Percentage of Participants by Categorized Number of Treated Bleeds Over the Efficacy Period in Treated Participants <12 Years of Age
Description	The percentage of participants by categorized number of treated bleeds over the efficacy period is presented here. A bleed is considered a "treated bleed" if it is directly followed (i.e., no intervening bleed) by a hemophilia medication reported to be a "treatment for bleed", irrespective of time between treatment and the preceding bleed. A bleed and the first treatment thereafter and before a new bleed starts, are considered to be pairs, with the following exception: if multiple bleeds occur on the same calendar day, the subsequent treatment is considered to apply for each of these multiple bleeds. The 72-hour rule was implemented: two bleeds of the same type and at the same anatomical location are counted as one bleed if the second bleed occurs within 72 hours from the last treatment for the first bleed. Bleeds due to surgery/procedure are excluded.
Time Frame	From Baseline to 52 weeks; At the primary completion date, the median (min-max) duration of the efficacy period in Cohort A was 57.57 (17.9-92.6) weeks.

Outcome Measure Data

Analysis Population Description

All treated participants in Cohort A who were on the same dose of emicizumab for at least 12 weeks and were <12 years of age

Arm/Group Title	Cohort A: 1.5 mg/kg Emicizumab QW
Arm/Group Description	Participants received emicizumab at a loading dose of 3 milligrams per kilogram (mg/kg) once every week (QW) subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg QW SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Measure Participants	65
0 Bleeds	76.9 113.1%
0-3 Bleeds	100.0 147.1%
0-10 Bleeds	100.0 147.1%
>10 Bleeds	0.0 0%

17. Primary Outcome

Title	Cohort A: Percentage of Participants by Categorized Number of All Bleeds Over the Efficacy Period in Treated Participants <12 Years of Age
Description	The percentage of participants by categorized number of all bleeds over the efficacy period is presented here. In this outcome measure, all bleeds are included, irrespective of treatment with coagulation factors, with the following exception: bleeds due to surgery/procedure are excluded. As "all bleeds" comprises both treated and non-treated bleeds, the 72-hour rule was implemented separately for treated and non-treated bleeds. For treated bleeds, the 72-hour rule was implemented exactly as defined for the "treated bleeds" outcome measure. For non-treated bleeds, the 72-hour rule was implemented by calculating a treatment-free period of 72 hours from the bleed itself.
Time Frame	From Baseline to 52 weeks; At the primary completion date, the median (min-max) duration of the efficacy period in Cohort A was 57.57 (17.9-92.6) weeks.

Outcome Measure Data

Analysis Population Description

All treated participants in Cohort A who were on the same dose of emicizumab for at least 12 weeks and were <12 years of age

Arm/Group Title	Cohort A: 1.5 mg/kg Emicizumab QW
Arm/Group Description	Participants received emicizumab at a loading dose of 3 milligrams per kilogram (mg/kg) once every week (QW) subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg QW SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Measure Participants	65
0 Bleeds	49.2 72.4%
0-3 Bleeds	72.3 106.3%
0-10 Bleeds	92.3 135.7%
>10 Bleeds	7.7 11.3%

18. Primary Outcome

Title	Cohort A: Percentage of Participants by Categorized Number of Treated Spontaneous Bleeds Over the Efficacy Period in Treated Participants <12 Years of Age
Description	The percentage of participants by categorized number of treated spontaneous bleeds over the efficacy period is presented here. A bleed is classified as "spontaneous" if there is no other known contributing factor such as trauma or procedure/surgery. A "treated spontaneous bleed" is a spontaneous bleed that also fulfills the conditions of a treated bleed (see ABR for Treated Bleeds for the definition). Treated bleeds that fulfilled the 72-hour rule were included in the analysis of spontaneous bleeds. Bleeds due to surgery/procedure are excluded.
Time Frame	From Baseline to 52 weeks; At the primary completion date, the median (min-max) duration of the efficacy period in Cohort A was 57.57 (17.9-92.6) weeks.

Outcome Measure Data

Analysis Population Description

All treated participants in Cohort A who were on the same dose of emicizumab for at least 12 weeks and were <12 years of age

Arm/Group Title	Cohort A: 1.5 mg/kg Emicizumab QW
Arm/Group Description	Participants received emicizumab at a loading dose of 3 milligrams per kilogram (mg/kg) once every week (QW) subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg QW SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Measure Participants	65
0 Bleeds	96.9 142.5%
0-3 Bleeds	100.0 147.1%
0-10 Bleeds	100.0 147.1%
>10 Bleeds	0.0 0%

19. Primary Outcome

Title	Cohort A: Percentage of Participants by Categorized Number of Treated Joint Bleeds Over the Efficacy Period in Treated Participants <12 Years of Age
Description	The percentage of participants by categorized number of treated joint bleeds over the efficacy period is presented here. A "joint bleed" is defined as a bleed with type reported as "joint" and with at least one of the following symptoms: increasing swelling or warmth of the skin over the joint and/or increasing pain, decreased range of motion, or difficulty using the joint compared with baseline. A "treated joint bleed" is a joint bleed that also fulfills the conditions of a treated bleed (see ABR for Treated Bleeds for the definition). Only treated bleeds that fulfilled the 72-hour rule were included in the analysis of treated joint bleeds, excluding bleeds due to surgery/procedure.
Time Frame	From Baseline to 52 weeks; At the primary completion date, the median (min-max) duration of the efficacy period in Cohort A was 57.57 (17.9-92.6) weeks.

Outcome Measure Data

Analysis Population Description

All treated participants in Cohort A who were on the same dose of emicizumab for at least 12 weeks and were <12 years of age

Arm/Group Title	Cohort A: 1.5 mg/kg Emicizumab QW
Arm/Group Description	Participants received emicizumab at a loading dose of 3 milligrams per kilogram (mg/kg) once every week (QW) subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg QW SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Measure Participants	65
0 Bleeds	84.6 124.4%
0-3 Bleeds	100.0 147.1%
0-10 Bleeds	100.0 147.1%
>10 Bleeds	0.0 0%

20. Primary Outcome

Title	Cohort A: Percentage of Participants by Categorized Number of Treated Target Joint Bleeds Over the Efficacy Period in Treated Participants <12 Years of Age
Description	The percentage of participants by categorized number of treated target joint bleeds over the efficacy period is presented here. A "target joint bleed" is defined as a joint bleed in a target joint, which is a joint location where at least 3 bleeds have occurred over the last 24 weeks prior to study entry. A "treated target joint bleed" is a target joint bleed that also fulfills the conditions of a treated bleed (see ABR for Treated Bleeds for the definition). Bleeds due to surgery/procedure are excluded.
Time Frame	From Baseline to 52 weeks; At the primary completion date, the median (min-max) duration of the efficacy period in Cohort A was 57.57 (17.9-92.6) weeks.

Outcome Measure Data

Analysis Population Description

All treated participants in Cohort A who were on the same dose of emicizumab for at least 12 weeks and were <12 years of age

Arm/Group Title	Cohort A: 1.5 mg/kg Emicizumab QW
Arm/Group Description	Participants received emicizumab at a loading dose of 3 milligrams per kilogram (mg/kg) once every week (QW) subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg QW SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Measure Participants	65
0 Bleeds	95.4 140.3%
0-3 Bleeds	100.0 147.1%
0-10 Bleeds	100.0 147.1%
>10 Bleeds	0.0 0%

21. Secondary Outcome

Title	Cohorts B and C: Model-Based Annualized Bleed Rate (ABR) for Treated Bleeds in Treated Participants <12 Years of Age
Description	The number of treated bleeds over the efficacy period is presented as a model-based ABR that was analyzed using a negative binomial regression model with efficacy period as an offset to account for the difference in follow-up times. A bleed is considered a "treated bleed" if it is directly followed (i.e., no intervening bleed) by a hemophilia medication reported to be a "treatment for bleed", irrespective of time between treatment and the preceding bleed. A bleed and the first treatment thereafter and before a new bleed starts, are considered to be pairs, with the following exception: if multiple bleeds occur on the same calendar day, the subsequent treatment is considered to apply for each of these multiple bleeds. The 72-hour rule was implemented: two bleeds of the same type and at the same anatomical location are counted as one bleed if the second bleed occurs within 72 hours from the last treatment for the first bleed. Bleeds due to surgery/procedure are excluded.
Time Frame	From Baseline to 24 weeks; At the primary completion date, the median (min-max) duration of the efficacy periods in Cohorts B and C were 21.29 (18.6-24.1) weeks and 19.86 (8.9-24.1) weeks, respectively.

Outcome Measure Data

Analysis Population Description

All treated participants in Cohorts B and C who were on the same dose of emicizumab for at least 12 weeks and were <12 years of age

Arm/Group Title	Cohort B: 3 mg/kg Emicizumab Q2W	Cohort C: 6 mg/kg Emicizumab Q4W
Arm/Group Description	Participants received emicizumab at a loading dose of 3 mg/kg QW subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 3 mg/kg once every 2 weeks (Q2W) SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.	Participants received emicizumab at a loading dose of 3 mg/kg QW subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 6 mg/kg once every 4 weeks (Q4W) SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Measure Participants	10	10
Number (95% Confidence Interval) [treated bleed rate per year]	0.2	2.2

22. Secondary Outcome

Title	Cohorts B and C: Model-Based Annualized Bleed Rate (ABR) for All Bleeds in Treated Participants <12 Years of Age
Description	The number of all bleeds over the efficacy period is presented as a model-based ABR that was analyzed using a negative binomial regression model with efficacy period as an offset to account for the difference in follow-up times (i.e., the time that each participant stays in the study). In this outcome measure, all bleeds are included, irrespective of treatment with coagulation factors, with the following exception: bleeds due to surgery/procedure are excluded. As "all bleeds" comprises both treated and non-treated bleeds, the 72-hour rule was implemented separately for treated and non-treated bleeds. For treated bleeds, the 72-hour rule was implemented exactly as defined for the "treated bleeds" outcome measure. For non-treated bleeds, the 72-hour rule was implemented by calculating a treatment-free period of 72 hours from the bleed itself.
Time Frame	From Baseline to 24 weeks; At the primary completion date, the median (min-max) duration of the efficacy periods in Cohorts B and C were 21.29 (18.6-24.1) weeks and 19.86 (8.9-24.1) weeks, respectively.

Outcome Measure Data

Analysis Population Description

All treated participants in Cohorts B and C who were on the same dose of emicizumab for at least 12 weeks and were <12 years of age

Arm/Group Title	Cohort B: 3 mg/kg Emicizumab Q2W	Cohort C: 6 mg/kg Emicizumab Q4W
Arm/Group Description	Participants received emicizumab at a loading dose of 3 mg/kg QW subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 3 mg/kg once every 2 weeks (Q2W) SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.	Participants received emicizumab at a loading dose of 3 mg/kg QW subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 6 mg/kg once every 4 weeks (Q4W) SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Measure Participants	10	10
Number (95% Confidence Interval) [all bleed rate per year]	1.5	3.8

23. Secondary Outcome

Title	Cohorts B and C: Model-Based Annualized Bleed Rate (ABR) for Treated Spontaneous Bleeds in Treated Participants <12 Years of Age
Description	The number of treated spontaneous bleeds over the efficacy period is presented as a model-based ABR that was analyzed using a negative binomial regression model with efficacy period as an offset to account for the difference in follow-up times (i.e., the time that each participant stays in the study). A bleed is classified as "spontaneous" if there is no other known contributing factor such as trauma or procedure/surgery. A "treated spontaneous bleed" is a spontaneous bleed that also fulfills the conditions of a treated bleed (see ABR for Treated Bleeds for the definition). Treated bleeds that fulfilled the 72-hour rule were included in the analysis of spontaneous bleeds. Bleeds due to surgery/procedure are excluded.
Time Frame	From Baseline to 24 weeks; At the primary completion date, the median (min-max) duration of the efficacy periods in Cohorts B and C were 21.29 (18.6-24.1) weeks and 19.86 (8.9-24.1) weeks, respectively.

Outcome Measure Data

Analysis Population Description

All treated participants in Cohorts B and C who were on the same dose of emicizumab for at least 12 weeks and were <12 years of age

Arm/Group Title	Cohort B: 3 mg/kg Emicizumab Q2W	Cohort C: 6 mg/kg Emicizumab Q4W
Arm/Group Description	Participants received emicizumab at a loading dose of 3 mg/kg QW subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 3 mg/kg once every 2 weeks (Q2W) SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.	Participants received emicizumab at a loading dose of 3 mg/kg QW subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 6 mg/kg once every 4 weeks (Q4W) SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Measure Participants	10	10
Number (95% Confidence Interval) [treated spontaneous bleed rate per year]	NA	0.8

24. Secondary Outcome

Title	Cohorts B and C: Model-Based Annualized Bleed Rate (ABR) for Treated Joint Bleeds in Treated Participants <12 Years of Age
Description	The number of treated joint bleeds over the efficacy period is presented as a model-based ABR that was analyzed using a negative binomial regression model with efficacy period as an offset to account for the difference in follow-up times (i.e., the time that each participant stays in the study). A "joint bleed" is defined as a bleed with type reported as "joint" and with at least one of the following symptoms: increasing swelling or warmth of the skin over the joint and/or increasing pain, decreased range of motion, or difficulty using the joint compared with baseline. A "treated joint bleed" is a joint bleed that also fulfills the conditions of a treated bleed (see ABR for Treated Bleeds for the definition). Only treated bleeds that fulfilled the 72-hour rule were included in the analysis of treated joint bleeds, excluding bleeds due to surgery/procedure.
Time Frame	From Baseline to 24 weeks; At the primary completion date, the median (min-max) duration of the efficacy periods in Cohorts B and C were 21.29 (18.6-24.1) weeks and 19.86 (8.9-24.1) weeks, respectively.

Outcome Measure Data

Analysis Population Description

All treated participants in Cohorts B and C who were on the same dose of emicizumab for at least 12 weeks and were <12 years of age

Arm/Group Title	Cohort B: 3 mg/kg Emicizumab Q2W	Cohort C: 6 mg/kg Emicizumab Q4W
Arm/Group Description	Participants received emicizumab at a loading dose of 3 mg/kg QW subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 3 mg/kg once every 2 weeks (Q2W) SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.	Participants received emicizumab at a loading dose of 3 mg/kg QW subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 6 mg/kg once every 4 weeks (Q4W) SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Measure Participants	10	10
Number (95% Confidence Interval) [treated joint bleed rate per year]	0.2	1.7

25. Secondary Outcome

Title	Cohorts B and C: Model-Based Annualized Bleed Rate (ABR) for Treated Target Joint Bleeds in Treated Participants <12 Years of Age
Description	The number of treated target joint bleeds over the efficacy period is presented as a model-based ABR that was analyzed using a negative binomial regression model with efficacy period as an offset to account for the difference in follow-up times (i.e., the time that each participant stays in the study). A "target joint bleed" is defined as a joint bleed in a target joint, which is a joint location where at least 3 bleeds have occurred over the last 24 weeks prior to study entry. A "treated target joint bleed" is a target joint bleed that also fulfills the conditions of a treated bleed (see ABR for Treated Bleeds for the definition). Bleeds due to surgery/procedure are excluded.
Time Frame	From Baseline to 24 weeks; At the primary completion date, the median (min-max) duration of the efficacy periods in Cohorts B and C were 21.29 (18.6-24.1) weeks and 19.86 (8.9-24.1) weeks, respectively.

Outcome Measure Data

Analysis Population Description

All treated participants in Cohorts B and C who were on the same dose of emicizumab for at least 12 weeks and were <12 years of age

Arm/Group Title	Cohort B: 3 mg/kg Emicizumab Q2W	Cohort C: 6 mg/kg Emicizumab Q4W
Arm/Group Description	Participants received emicizumab at a loading dose of 3 mg/kg QW subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 3 mg/kg once every 2 weeks (Q2W) SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.	Participants received emicizumab at a loading dose of 3 mg/kg QW subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 6 mg/kg once every 4 weeks (Q4W) SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Measure Participants	10	10
Number (95% Confidence Interval) [treated target joint bleed rate per year]	0.2	0.5

26. Secondary Outcome

Title	Cohorts B and C: Mean Calculated Annualized Bleed Rate (ABR) for Treated Bleeds in Treated Participants <12 Years of Age
Description	The number of treated bleeds over the efficacy period is presented here as a calculated ABR that was annualized for each participant using the following formula: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. A bleed is considered a "treated bleed" if it is directly followed (i.e., no intervening bleed) by a hemophilia medication reported to be a "treatment for bleed", irrespective of time between treatment and the preceding bleed. A bleed and the first treatment thereafter and before a new bleed starts, are considered to be pairs, with the following exception: if multiple bleeds occur on the same calendar day, the subsequent treatment is considered to apply for each of these multiple bleeds. The 72-hour rule was implemented: two bleeds of the same type and at the same anatomical location are counted as one bleed if the second bleed occurs within 72 hours from the last treatment for the first bleed. Bleeds due to surgery/procedure are excluded.
Time Frame	From Baseline to 24 weeks; At the primary completion date, the median (min-max) duration of the efficacy periods in Cohorts B and C were 21.29 (18.6-24.1) weeks and 19.86 (8.9-24.1) weeks, respectively.

Outcome Measure Data

Analysis Population Description

All treated participants in Cohorts B and C who were on the same dose of emicizumab for at least 12 weeks and were <12 years of age

Arm/Group Title	Cohort B: 3 mg/kg Emicizumab Q2W	Cohort C: 6 mg/kg Emicizumab Q4W
Arm/Group Description	Participants received emicizumab at a loading dose of 3 mg/kg QW subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 3 mg/kg once every 2 weeks (Q2W) SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.	Participants received emicizumab at a loading dose of 3 mg/kg QW subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 6 mg/kg once every 4 weeks (Q4W) SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Measure Participants	10	10
Mean (95% Confidence Interval) [treated bleed rate per year]	0.2	2.5

27. Secondary Outcome

Title	Cohorts B and C: Mean Calculated Annualized Bleed Rate (ABR) for All Bleeds in Treated Participants <12 Years of Age
Description	The number of all bleeds over the efficacy period is presented here as a calculated ABR that was annualized for each participant using the following formula: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. In this outcome measure, all bleeds are included, irrespective of treatment with coagulation factors, with the following exception: bleeds due to surgery/procedure are excluded. As "all bleeds" comprises both treated and non-treated bleeds, the 72-hour rule was implemented separately for treated and non-treated bleeds. For treated bleeds, the 72-hour rule was implemented exactly as defined for the "treated bleeds" outcome measure. For non-treated bleeds, the 72-hour rule was implemented by calculating a treatment-free period of 72 hours from the bleed itself.
Time Frame	From Baseline to 24 weeks; At the primary completion date, the median (min-max) duration of the efficacy periods in Cohorts B and C were 21.29 (18.6-24.1) weeks and 19.86 (8.9-24.1) weeks, respectively.

Outcome Measure Data

Analysis Population Description

All treated participants in Cohorts B and C who were on the same dose of emicizumab for at least 12 weeks and were <12 years of age

Arm/Group Title	Cohort B: 3 mg/kg Emicizumab Q2W	Cohort C: 6 mg/kg Emicizumab Q4W
Arm/Group Description	Participants received emicizumab at a loading dose of 3 mg/kg QW subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 3 mg/kg once every 2 weeks (Q2W) SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.	Participants received emicizumab at a loading dose of 3 mg/kg QW subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 6 mg/kg once every 4 weeks (Q4W) SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Measure Participants	10	10
Mean (95% Confidence Interval) [all bleed rate per year]	1.5	4.0

28. Secondary Outcome

Title	Cohorts B and C: Mean Calculated Annualized Bleed Rate (ABR) for Treated Spontaneous Bleeds in Treated Participants <12 Years of Age
Description	The number of treated spontaneous bleeds over the efficacy period is presented here as a calculated ABR that was annualized for each participant using the following formula: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. A bleed is classified as "spontaneous" if there is no other known contributing factor such as trauma or procedure/surgery. A "treated spontaneous bleed" is a spontaneous bleed that also fulfills the conditions of a treated bleed (see ABR for Treated Bleeds for the definition). Treated bleeds that fulfilled the 72-hour rule were included in the analysis of spontaneous bleeds. Bleeds due to surgery/procedure are excluded.
Time Frame	From Baseline to 24 weeks; At the primary completion date, the median (min-max) duration of the efficacy periods in Cohorts B and C were 21.29 (18.6-24.1) weeks and 19.86 (8.9-24.1) weeks, respectively.

Outcome Measure Data

Analysis Population Description

All treated participants in Cohorts B and C who were on the same dose of emicizumab for at least 12 weeks and were <12 years of age

Arm/Group Title	Cohort B: 3 mg/kg Emicizumab Q2W	Cohort C: 6 mg/kg Emicizumab Q4W
Arm/Group Description	Participants received emicizumab at a loading dose of 3 mg/kg QW subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 3 mg/kg once every 2 weeks (Q2W) SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.	Participants received emicizumab at a loading dose of 3 mg/kg QW subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 6 mg/kg once every 4 weeks (Q4W) SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Measure Participants	10	10
Mean (95% Confidence Interval) [treated spontaneous bleed rate per year]	0.0	0.8

29. Secondary Outcome

Title	Cohorts B and C: Mean Calculated Annualized Bleed Rate (ABR) for Treated Joint Bleeds in Treated Participants <12 Years of Age
Description	The number of treated joint bleeds over the efficacy period is presented here as a calculated ABR that was annualized for each participant using the following formula: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. A "joint bleed" is defined as a bleed with type reported as "joint" and with at least one of the following symptoms: increasing swelling or warmth of the skin over the joint and/or increasing pain, decreased range of motion, or difficulty using the joint compared with baseline. A "treated joint bleed" is a joint bleed that also fulfills the conditions of a treated bleed (see ABR for Treated Bleeds for the definition). Only treated bleeds that fulfilled the 72-hour rule were included in the analysis of treated joint bleeds, excluding bleeds due to surgery/procedure.
Time Frame	From Baseline to 24 weeks; At the primary completion date, the median (min-max) duration of the efficacy periods in Cohorts B and C were 21.29 (18.6-24.1) weeks and 19.86 (8.9-24.1) weeks, respectively.

Outcome Measure Data

Analysis Population Description

All treated participants in Cohorts B and C who were on the same dose of emicizumab for at least 12 weeks and were <12 years of age

Arm/Group Title	Cohort B: 3 mg/kg Emicizumab Q2W	Cohort C: 6 mg/kg Emicizumab Q4W
Arm/Group Description	Participants received emicizumab at a loading dose of 3 mg/kg QW subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 3 mg/kg once every 2 weeks (Q2W) SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.	Participants received emicizumab at a loading dose of 3 mg/kg QW subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 6 mg/kg once every 4 weeks (Q4W) SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Measure Participants	10	10
Mean (95% Confidence Interval) [treated joint bleed rate per year]	0.2	1.9

30. Secondary Outcome

Title	Cohorts B and C: Mean Calculated Annualized Bleed Rate (ABR) for Treated Target Joint Bleeds in Treated Participants <12 Years of Age
Description	The number of treated target joint bleeds over the efficacy period is presented here as a calculated ABR that was annualized for each participant using the following formula: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. A "target joint bleed" is defined as a joint bleed in a target joint, which is a joint location where at least 3 bleeds have occurred over the last 24 weeks prior to study entry. A "treated target joint bleed" is a target joint bleed that also fulfills the conditions of a treated bleed (see ABR for Treated Bleeds for the definition). Bleeds due to surgery/procedure are excluded.
Time Frame	From Baseline to 24 weeks; At the primary completion date, the median (min-max) duration of the efficacy periods in Cohorts B and C were 21.29 (18.6-24.1) weeks and 19.86 (8.9-24.1) weeks, respectively.

Outcome Measure Data

Analysis Population Description

All treated participants in Cohorts B and C who were on the same dose of emicizumab for at least 12 weeks and were <12 years of age

Arm/Group Title	Cohort B: 3 mg/kg Emicizumab Q2W	Cohort C: 6 mg/kg Emicizumab Q4W
Arm/Group Description	Participants received emicizumab at a loading dose of 3 mg/kg QW subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 3 mg/kg once every 2 weeks (Q2W) SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.	Participants received emicizumab at a loading dose of 3 mg/kg QW subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 6 mg/kg once every 4 weeks (Q4W) SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Measure Participants	10	10
Mean (95% Confidence Interval) [treated target joint bleed rate per year]	0.2	0.5

31. Secondary Outcome

Title	Cohorts B and C: Median Calculated Annualized Bleed Rate (ABR) for Treated Bleeds in Treated Participants <12 Years of Age
Description	The number of treated bleeds over the efficacy period is presented here as a calculated ABR that was annualized for each participant using the following formula: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. A bleed is considered a "treated bleed" if it is directly followed (i.e., no intervening bleed) by a hemophilia medication reported to be a "treatment for bleed", irrespective of time between treatment and the preceding bleed. A bleed and the first treatment thereafter and before a new bleed starts, are considered to be pairs, with the following exception: if multiple bleeds occur on the same calendar day, the subsequent treatment is considered to apply for each of these multiple bleeds. The 72-hour rule was implemented: two bleeds of the same type and at the same anatomical location are counted as one bleed if the second bleed occurs within 72 hours from the last treatment for the first bleed. Bleeds due to surgery/procedure are excluded.
Time Frame	From Baseline to 24 weeks; At the primary completion date, the median (min-max) duration of the efficacy periods in Cohorts B and C were 21.29 (18.6-24.1) weeks and 19.86 (8.9-24.1) weeks, respectively.

Outcome Measure Data

Analysis Population Description

All treated participants in Cohorts B and C who were on the same dose of emicizumab for at least 12 weeks and were <12 years of age

Arm/Group Title	Cohort B: 3 mg/kg Emicizumab Q2W	Cohort C: 6 mg/kg Emicizumab Q4W
Arm/Group Description	Participants received emicizumab at a loading dose of 3 mg/kg QW subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 3 mg/kg once every 2 weeks (Q2W) SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.	Participants received emicizumab at a loading dose of 3 mg/kg QW subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 6 mg/kg once every 4 weeks (Q4W) SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Measure Participants	10	10
Median (Inter-Quartile Range) [treated bleed rate per year]	0.0	0.0

32. Secondary Outcome

Title	Cohorts B and C: Median Calculated Annualized Bleed Rate (ABR) for All Bleeds in Treated Participants <12 Years of Age
Description	The number of all bleeds over the efficacy period is presented here as a calculated ABR that was annualized for each participant using the following formula: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. In this outcome measure, all bleeds are included, irrespective of treatment with coagulation factors, with the following exception: bleeds due to surgery/procedure are excluded. As "all bleeds" comprises both treated and non-treated bleeds, the 72-hour rule was implemented separately for treated and non-treated bleeds. For treated bleeds, the 72-hour rule was implemented exactly as defined for the "treated bleeds" outcome measure. For non-treated bleeds, the 72-hour rule was implemented by calculating a treatment-free period of 72 hours from the bleed itself.
Time Frame	From Baseline to 24 weeks; At the primary completion date, the median (min-max) duration of the efficacy periods in Cohorts B and C were 21.29 (18.6-24.1) weeks and 19.86 (8.9-24.1) weeks, respectively.

Outcome Measure Data

Analysis Population Description

All treated participants in Cohorts B and C who were on the same dose of emicizumab for at least 12 weeks and were <12 years of age

Arm/Group Title	Cohort B: 3 mg/kg Emicizumab Q2W	Cohort C: 6 mg/kg Emicizumab Q4W
Arm/Group Description	Participants received emicizumab at a loading dose of 3 mg/kg QW subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 3 mg/kg once every 2 weeks (Q2W) SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.	Participants received emicizumab at a loading dose of 3 mg/kg QW subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 6 mg/kg once every 4 weeks (Q4W) SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Measure Participants	10	10
Median (Inter-Quartile Range) [all bleed rate per year]	0.0	1.6

33. Secondary Outcome

Title	Cohorts B and C: Median Calculated Annualized Bleed Rate (ABR) for Treated Spontaneous Bleeds in Treated Participants <12 Years of Age
Description	The number of treated spontaneous bleeds over the efficacy period is presented here as a calculated ABR that was annualized for each participant using the following formula: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. A bleed is classified as "spontaneous" if there is no other known contributing factor such as trauma or procedure/surgery. A "treated spontaneous bleed" is a spontaneous bleed that also fulfills the conditions of a treated bleed (see ABR for Treated Bleeds for the definition). Treated bleeds that fulfilled the 72-hour rule were included in the analysis of spontaneous bleeds. Bleeds due to surgery/procedure are excluded.
Time Frame	From Baseline to 24 weeks; At the primary completion date, the median (min-max) duration of the efficacy periods in Cohorts B and C were 21.29 (18.6-24.1) weeks and 19.86 (8.9-24.1) weeks, respectively.

Outcome Measure Data

Analysis Population Description

All treated participants in Cohorts B and C who were on the same dose of emicizumab for at least 12 weeks and were <12 years of age

Arm/Group Title	Cohort B: 3 mg/kg Emicizumab Q2W	Cohort C: 6 mg/kg Emicizumab Q4W
Arm/Group Description	Participants received emicizumab at a loading dose of 3 mg/kg QW subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 3 mg/kg once every 2 weeks (Q2W) SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.	Participants received emicizumab at a loading dose of 3 mg/kg QW subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 6 mg/kg once every 4 weeks (Q4W) SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Measure Participants	10	10
Median (Inter-Quartile Range) [treated spontaneous bleed rate per year]	0.0	0.0

34. Secondary Outcome

Title	Cohorts B and C: Median Calculated Annualized Bleed Rate (ABR) for Treated Joint Bleeds in Treated Participants <12 Years of Age
Description	The number of treated joint bleeds over the efficacy period is presented here as a calculated ABR that was annualized for each participant using the following formula: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. A "joint bleed" is defined as a bleed with type reported as "joint" and with at least one of the following symptoms: increasing swelling or warmth of the skin over the joint and/or increasing pain, decreased range of motion, or difficulty using the joint compared with baseline. A "treated joint bleed" is a joint bleed that also fulfills the conditions of a treated bleed (see ABR for Treated Bleeds for the definition). Only treated bleeds that fulfilled the 72-hour rule were included in the analysis of treated joint bleeds, excluding bleeds due to surgery/procedure.
Time Frame	From Baseline to 24 weeks; At the primary completion date, the median (min-max) duration of the efficacy periods in Cohorts B and C were 21.29 (18.6-24.1) weeks and 19.86 (8.9-24.1) weeks, respectively.

Outcome Measure Data

Analysis Population Description

All treated participants in Cohorts B and C who were on the same dose of emicizumab for at least 12 weeks and were <12 years of age

Arm/Group Title	Cohort B: 3 mg/kg Emicizumab Q2W	Cohort C: 6 mg/kg Emicizumab Q4W
Arm/Group Description	Participants received emicizumab at a loading dose of 3 mg/kg QW subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 3 mg/kg once every 2 weeks (Q2W) SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.	Participants received emicizumab at a loading dose of 3 mg/kg QW subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 6 mg/kg once every 4 weeks (Q4W) SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Measure Participants	10	10
Median (Inter-Quartile Range) [treated joint bleed rate per year]	0.0	0.0

35. Secondary Outcome

Title	Cohorts B and C: Median Calculated Annualized Bleed Rate (ABR) for Treated Target Joint Bleeds in Treated Participants <12 Years of Age
Description	The number of treated target joint bleeds over the efficacy period is presented here as a calculated ABR that was annualized for each participant using the following formula: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. A "target joint bleed" is defined as a joint bleed in a target joint, which is a joint location where at least 3 bleeds have occurred over the last 24 weeks prior to study entry. A "treated target joint bleed" is a target joint bleed that also fulfills the conditions of a treated bleed (see ABR for Treated Bleeds for the definition). Bleeds due to surgery/procedure are excluded.
Time Frame	From Baseline to 24 weeks; At the primary completion date, the median (min-max) duration of the efficacy periods in Cohorts B and C were 21.29 (18.6-24.1) weeks and 19.86 (8.9-24.1) weeks, respectively.

Outcome Measure Data

Analysis Population Description

All treated participants in Cohorts B and C who were on the same dose of emicizumab for at least 12 weeks and were <12 years of age

Arm/Group Title	Cohort B: 3 mg/kg Emicizumab Q2W	Cohort C: 6 mg/kg Emicizumab Q4W
Arm/Group Description	Participants received emicizumab at a loading dose of 3 mg/kg QW subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 3 mg/kg once every 2 weeks (Q2W) SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.	Participants received emicizumab at a loading dose of 3 mg/kg QW subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 6 mg/kg once every 4 weeks (Q4W) SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Measure Participants	10	10
Median (Inter-Quartile Range) [treated target joint bleed rate per year]	0.0	0.0

36. Secondary Outcome

Title	Cohorts B and C: Percentage of Participants by Categorized Number of Treated Bleeds Over the Efficacy Period in Treated Participants <12 Years of Age
Description	The percentage of participants by categorized number of treated bleeds over the efficacy period is presented here. A bleed is considered a "treated bleed" if it is directly followed (i.e., no intervening bleed) by a hemophilia medication reported to be a "treatment for bleed", irrespective of time between treatment and the preceding bleed. A bleed and the first treatment thereafter and before a new bleed starts, are considered to be pairs, with the following exception: if multiple bleeds occur on the same calendar day, the subsequent treatment is considered to apply for each of these multiple bleeds. The 72-hour rule was implemented: two bleeds of the same type and at the same anatomical location are counted as one bleed if the second bleed occurs within 72 hours from the last treatment for the first bleed. Bleeds due to surgery/procedure are excluded.
Time Frame	From Baseline to 24 weeks; At the primary completion date, the median (min-max) duration of the efficacy periods in Cohorts B and C were 21.29 (18.6-24.1) weeks and 19.86 (8.9-24.1) weeks, respectively.

Outcome Measure Data

Analysis Population Description

All treated participants in Cohorts B and C who were on the same dose of emicizumab for at least 12 weeks and were <12 years of age

Arm/Group Title	Cohort B: 3 mg/kg Emicizumab Q2W	Cohort C: 6 mg/kg Emicizumab Q4W
Arm/Group Description	Participants received emicizumab at a loading dose of 3 mg/kg QW subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 3 mg/kg once every 2 weeks (Q2W) SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.	Participants received emicizumab at a loading dose of 3 mg/kg QW subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 6 mg/kg once every 4 weeks (Q4W) SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Measure Participants	10	10
0 Bleeds	90.0 132.4%	60.0 600%
0-3 Bleeds	100.0 147.1%	100.0 1000%
0-10 Bleeds	100.0 147.1%	100.0 1000%
>10 Bleeds	0.0 0%	0.0 0%

37. Secondary Outcome

Title	Cohorts B and C: Percentage of Participants by Categorized Number of All Bleeds Over the Efficacy Period in Treated Participants <12 Years of Age
Description	The percentage of participants by categorized number of all bleeds over the efficacy period is presented here. In this outcome measure, all bleeds are included, irrespective of treatment with coagulation factors, with the following exception: bleeds due to surgery/procedure are excluded. As "all bleeds" comprises both treated and non-treated bleeds, the 72-hour rule was implemented separately for treated and non-treated bleeds. For treated bleeds, the 72-hour rule was implemented exactly as defined for the "treated bleeds" outcome measure. For non-treated bleeds, the 72-hour rule was implemented by calculating a treatment-free period of 72 hours from the bleed itself.
Time Frame	From Baseline to 24 weeks; At the primary completion date, the median (min-max) duration of the efficacy periods in Cohorts B and C were 21.29 (18.6-24.1) weeks and 19.86 (8.9-24.1) weeks, respectively.

Outcome Measure Data

Analysis Population Description

All treated participants in Cohorts B and C who were on the same dose of emicizumab for at least 12 weeks and were <12 years of age

Arm/Group Title	Cohort B: 3 mg/kg Emicizumab Q2W	Cohort C: 6 mg/kg Emicizumab Q4W
Arm/Group Description	Participants received emicizumab at a loading dose of 3 mg/kg QW subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 3 mg/kg once every 2 weeks (Q2W) SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.	Participants received emicizumab at a loading dose of 3 mg/kg QW subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 6 mg/kg once every 4 weeks (Q4W) SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Measure Participants	10	10
0 Bleeds	60.0 88.2%	50.0 500%
0-3 Bleeds	100.0 147.1%	90.0 900%
0-10 Bleeds	100.0 147.1%	100.0 1000%
>10 Bleeds	0.0 0%	0.0 0%

38. Secondary Outcome

Title	Cohorts B and C: Percentage of Participants by Categorized Number of Treated Spontaneous Bleeds Over the Efficacy Period in Treated Participants <12 Years of Age
Description	The percentage of participants by categorized number of treated spontaneous bleeds over the efficacy period is presented here. A bleed is classified as "spontaneous" if there is no other known contributing factor such as trauma or procedure/surgery. A "treated spontaneous bleed" is a spontaneous bleed that also fulfills the conditions of a treated bleed (see ABR for Treated Bleeds for the definition). Treated bleeds that fulfilled the 72-hour rule were included in the analysis of spontaneous bleeds. Bleeds due to surgery/procedure are excluded.
Time Frame	From Baseline to 24 weeks; At the primary completion date, the median (min-max) duration of the efficacy periods in Cohorts B and C were 21.29 (18.6-24.1) weeks and 19.86 (8.9-24.1) weeks, respectively.

Outcome Measure Data

Analysis Population Description

All treated participants in Cohorts B and C who were on the same dose of emicizumab for at least 12 weeks and were <12 years of age

Arm/Group Title	Cohort B: 3 mg/kg Emicizumab Q2W	Cohort C: 6 mg/kg Emicizumab Q4W
Arm/Group Description	Participants received emicizumab at a loading dose of 3 mg/kg QW subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 3 mg/kg once every 2 weeks (Q2W) SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.	Participants received emicizumab at a loading dose of 3 mg/kg QW subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 6 mg/kg once every 4 weeks (Q4W) SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Measure Participants	10	10
0 Bleeds	100.0 147.1%	90.0 900%
0-3 Bleeds	100.0 147.1%	100.0 1000%
0-10 Bleeds	100.0 147.1%	100.0 1000%
>10 Bleeds	0.0 0%	0.0 0%

39. Secondary Outcome

Title	Cohorts B and C: Percentage of Participants by Categorized Number of Treated Joint Bleeds Over the Efficacy Period in Treated Participants <12 Years of Age
Description	The percentage of participants by categorized number of treated joint bleeds over the efficacy period is presented here. A "joint bleed" is defined as a bleed with type reported as "joint" and with at least one of the following symptoms: increasing swelling or warmth of the skin over the joint and/or increasing pain, decreased range of motion, or difficulty using the joint compared with baseline. A "treated joint bleed" is a joint bleed that also fulfills the conditions of a treated bleed (see ABR for Treated Bleeds for the definition). Only treated bleeds that fulfilled the 72-hour rule were included in the analysis of treated joint bleeds, excluding bleeds due to surgery/procedure.
Time Frame	From Baseline to 24 weeks; At the primary completion date, the median (min-max) duration of the efficacy periods in Cohorts B and C were 21.29 (18.6-24.1) weeks and 19.86 (8.9-24.1) weeks, respectively.

Outcome Measure Data

Analysis Population Description

All treated participants in Cohorts B and C who were on the same dose of emicizumab for at least 12 weeks and were <12 years of age

Arm/Group Title	Cohort B: 3 mg/kg Emicizumab Q2W	Cohort C: 6 mg/kg Emicizumab Q4W
Arm/Group Description	Participants received emicizumab at a loading dose of 3 mg/kg QW subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 3 mg/kg once every 2 weeks (Q2W) SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.	Participants received emicizumab at a loading dose of 3 mg/kg QW subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 6 mg/kg once every 4 weeks (Q4W) SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Measure Participants	10	10
0 Bleeds	90.0 132.4%	60.0 600%
0-3 Bleeds	100.0 147.1%	100.0 1000%
0-10 Bleeds	100.0 147.1%	100.0 1000%
>10 Bleeds	0.0 0%	0.0 0%

40. Secondary Outcome

Title	Cohorts B and C: Percentage of Participants by Categorized Number of Treated Target Joint Bleeds Over the Efficacy Period in Treated Participants <12 Years of Age
Description	The percentage of participants by categorized number of treated target joint bleeds over the efficacy period is presented here. A "target joint bleed" is defined as a joint bleed in a target joint, which is a joint location where at least 3 bleeds have occurred over the last 24 weeks prior to study entry. A "treated target joint bleed" is a target joint bleed that also fulfills the conditions of a treated bleed (see ABR for Treated Bleeds for the definition). Bleeds due to surgery/procedure are excluded.
Time Frame	From Baseline to 24 weeks; At the primary completion date, the median (min-max) duration of the efficacy periods in Cohorts B and C were 21.29 (18.6-24.1) weeks and 19.86 (8.9-24.1) weeks, respectively.

Outcome Measure Data

Analysis Population Description

All treated participants in Cohorts B and C who were on the same dose of emicizumab for at least 12 weeks and were <12 years of age

Arm/Group Title	Cohort B: 3 mg/kg Emicizumab Q2W	Cohort C: 6 mg/kg Emicizumab Q4W
Arm/Group Description	Participants received emicizumab at a loading dose of 3 mg/kg QW subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 3 mg/kg once every 2 weeks (Q2W) SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.	Participants received emicizumab at a loading dose of 3 mg/kg QW subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 6 mg/kg once every 4 weeks (Q4W) SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Measure Participants	10	10
0 Bleeds	90.0 132.4%	90.0 900%
0-3 Bleeds	100.0 147.1%	100.0 1000%
0-10 Bleeds	100.0 147.1%	100.0 1000%
>10 Bleeds	0.0 0%	0.0 0%

41. Secondary Outcome

Title	Cohort A: Intra-Participant Comparison of the Model-Based ABR for Treated Bleeds on Study Versus Pre-Study in Treated Participants <12 Years of Age From the Non-Interventional Study (NIS) Population
Description	This is an intra-participant comparison of the model-based annualized bleeding rate (ABR) for treated bleeds (i.e., number of treated bleeds over efficacy period using negative binomial regression model) on study versus pre-study in the NIS population who had previously participated in study BH29768 (NCT02476942). A "treated bleed" is a bleed directly followed by a hemophilia medication reported to be a "treatment for bleed", irrespective of time between treatment and the preceding bleed. A bleed and first treatment thereafter are considered to be pairs, with the following exception: if multiple bleeds occur on the same calendar day, the subsequent treatment is considered to apply for each of these multiple bleeds. The 72-hour rule was implemented: two bleeds of the same type and at the same anatomical location are counted as one bleed if the second bleed occurs within 72 hours from the last treatment for the first bleed. Bleeds due to surgery/procedure are excluded.
Time Frame	Up to 24 weeks in NIS BH29768 (NCT02476942) prior to study entry and from Baseline to 52 weeks on this study; At primary completion date, the median (min-max) duration of the efficacy period in the NIS population was 88.57 (55.9-92.6) weeks.

Outcome Measure Data

Analysis Population Description

Treated participants <12 years of age who had participated in NIS BH29768 (NCT02476942) prior to enrollment in this study and were on the same dose of emicizumab for at least 12 weeks in this study

Arm/Group Title	Cohort A NIS Population (<12 Years): Bypassing Agents	Cohort A NIS Population (<12 Years): 1.5 mg/kg Emicizumab QW
Arm/Group Description	This group includes historical data from participants <12 years old who had participated in the non-interventional study (NIS) BH29768 (NCT02476942) in which they had received prophylactic or episodic treatment with bypassing agents and had been followed for a minimum of 24 weeks on the NIS prior to enrollment in Cohort A of this study (BH29992).	Participants <12 years old who had previously received prophylactic or episodic treatment with bypassing agents in NIS BH29768 (NCT02476942) and were enrolled in Cohort A of this study (BH29992) received emicizumab at a loading dose of 3 milligrams per kilogram (mg/kg) once every week (QW) subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg emicizumab QW SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Measure Participants	18	18
Number (95% Confidence Interval) [treated bleed rate per year]	19.9	0.2

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Cohort A: 1.5 mg/kg Emicizumab QW, Cohort C: 6 mg/kg Emicizumab Q4W
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	ABR Ratio
	Estimated Value	0.01
	Confidence Interval	(2-Sided) 95%; 0.006 to 0.023
	Parameter Dispersion	Type: Value:
	Estimation Comments	Emicizumab QW is the numerator and Prophylactic/Episodic Bypassing Agent is the denominator.

42. Secondary Outcome

Title	Cohort A: Intra-Participant Comparison of the Model-Based ABR for All Bleeds on Study Versus Pre-Study in Treated Participants <12 Years of Age From the NIS Population
Description	This is an intra-participant comparison of the model-based annualized bleeding rate (ABR) for all bleeds (i.e., number of all bleeds over efficacy period using negative binomial regression model) on study versus pre-study in the NIS population who had previously participated in study BH29768 (NCT02476942). In this outcome measure, all bleeds are included, irrespective of treatment with coagulation factors, with the following exception: bleeds due to surgery/procedure are excluded. As "all bleeds" comprises both treated and non-treated bleeds, the 72-hour rule was implemented separately for treated and non-treated bleeds. For treated bleeds, the 72-hour rule was implemented exactly as defined for the "treated bleeds" outcome measure. For non-treated bleeds, the 72-hour rule was implemented by calculating a treatment-free period of 72 hours from the bleed itself.
Time Frame	Up to 24 weeks in NIS BH29768 (NCT02476942) prior to study entry and from Baseline to 52 weeks on this study; At primary completion date, the median (min-max) duration of the efficacy period in the NIS population was 88.57 (55.9-92.6) weeks.

Outcome Measure Data

Analysis Population Description

Treated participants <12 years of age who had participated in NIS BH29768 (NCT02476942) prior to enrollment in this study and were on the same dose of emicizumab for at least 12 weeks in this study

Arm/Group Title	Cohort A NIS Population (<12 Years): Bypassing Agents	Cohort A NIS Population (<12 Years): 1.5 mg/kg Emicizumab QW
Arm/Group Description	This group includes historical data from participants <12 years old who had participated in the non-interventional study (NIS) BH29768 (NCT02476942) in which they had received prophylactic or episodic treatment with bypassing agents and had been followed for a minimum of 24 weeks on the NIS prior to enrollment in Cohort A of this study (BH29992).	Participants <12 years old who had previously received prophylactic or episodic treatment with bypassing agents in NIS BH29768 (NCT02476942) and were enrolled in Cohort A of this study (BH29992) received emicizumab at a loading dose of 3 milligrams per kilogram (mg/kg) once every week (QW) subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg emicizumab QW SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Measure Participants	18	18
Number (95% Confidence Interval) [all bleed rate per year]	31.9	3.3

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Cohort A: 1.5 mg/kg Emicizumab QW, Cohort C: 6 mg/kg Emicizumab Q4W
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	ABR Ratio
	Estimated Value	0.10
	Confidence Interval	(2-Sided) 95%; 0.051 to 0.210
	Parameter Dispersion	Type: Value:
	Estimation Comments	Emicizumab QW is the numerator and Prophylactic/Episodic Bypassing Agent is the denominator.

43. Secondary Outcome

Title	Cohort A: Intra-Participant Comparison of the Median Calculated ABR for Treated Bleeds on Study Versus Pre-Study in Treated Participants <12 Years of Age From the NIS Population
Description	This is an intra-participant comparison of the calculated ABR for treated bleeds (annualized per participant using the following formula: ABR = [number of bleeds/number of days during the efficacy period] x 365.25) on study versus pre-study in the NIS population who had previously participated in study BH29768 (NCT02476942). A "treated bleed" is a bleed directly followed by a hemophilia medication reported to be a "treatment for bleed", irrespective of time between treatment and the preceding bleed. A bleed and first treatment thereafter are considered to be pairs, with the following exception: if multiple bleeds occur on the same calendar day, the subsequent treatment is considered to apply for each of these multiple bleeds. The 72-hour rule was implemented: two bleeds of the same type and at the same anatomical location are counted as one bleed if the second bleed occurs within 72 hours from the last treatment for the first bleed. Bleeds due to surgery/procedure are excluded.
Time Frame	Up to 24 weeks in NIS BH29768 (NCT02476942) prior to study entry and from Baseline to 52 weeks on this study; At primary completion date, the median (min-max) duration of the efficacy period in the NIS population was 88.57 (55.9-92.6) weeks.

Outcome Measure Data

Analysis Population Description

Treated participants <12 years of age who had participated in NIS BH29768 (NCT02476942) prior to enrollment in this study and were on the same dose of emicizumab for at least 12 weeks in this study

Arm/Group Title	Cohort A NIS Population (<12 Years): Bypassing Agents	Cohort A NIS Population (<12 Years): 1.5 mg/kg Emicizumab QW
Arm/Group Description	This group includes historical data from participants <12 years old who had participated in the non-interventional study (NIS) BH29768 (NCT02476942) in which they had received prophylactic or episodic treatment with bypassing agents and had been followed for a minimum of 24 weeks on the NIS prior to enrollment in Cohort A of this study (BH29992).	Participants <12 years old who had previously received prophylactic or episodic treatment with bypassing agents in NIS BH29768 (NCT02476942) and were enrolled in Cohort A of this study (BH29992) received emicizumab at a loading dose of 3 milligrams per kilogram (mg/kg) once every week (QW) subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg emicizumab QW SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Measure Participants	18	18
Median (Inter-Quartile Range) [treated bleed rate per year]	16.2	0.0

44. Secondary Outcome

Title	Cohort A: Intra-Participant Comparison of the Median Calculated ABR for All Bleeds on Study Versus Pre-Study in Treated Participants <12 Years of Age From the NIS Population
Description	This is an intra-participant comparison of the calculated annualized bleeding rate (ABR) for all bleeds (annualized for each participant using the following formula: ABR = [number of bleeds/number of days during the efficacy period] x 365.25) on study versus pre-study in the NIS population who had previously participated in study BH29768 (NCT02476942). In this outcome measure, all bleeds are included, irrespective of treatment with coagulation factors, with the following exception: bleeds due to surgery/procedure are excluded. As "all bleeds" comprises both treated and non-treated bleeds, the 72-hour rule was implemented separately for treated and non-treated bleeds. For treated bleeds, the 72-hour rule was implemented exactly as defined for the "treated bleeds" outcome measure. For non-treated bleeds, the 72-hour rule was implemented by calculating a treatment-free period of 72 hours from the bleed itself.
Time Frame	Up to 24 weeks in NIS BH29768 (NCT02476942) prior to study entry and from Baseline to 52 weeks on this study; At primary completion date, the median (min-max) duration of the efficacy period in the NIS population was 88.57 (55.9-92.6) weeks.

Outcome Measure Data

Analysis Population Description

Treated participants <12 years of age who had participated in NIS BH29768 (NCT02476942) prior to enrollment in this study and were on the same dose of emicizumab for at least 12 weeks in this study

Arm/Group Title	Cohort A NIS Population (<12 Years): Bypassing Agents	Cohort A NIS Population (<12 Years): 1.5 mg/kg Emicizumab QW
Arm/Group Description	This group includes historical data from participants <12 years old who had participated in the non-interventional study (NIS) BH29768 (NCT02476942) in which they had received prophylactic or episodic treatment with bypassing agents and had been followed for a minimum of 24 weeks on the NIS prior to enrollment in Cohort A of this study (BH29992).	Participants <12 years old who had previously received prophylactic or episodic treatment with bypassing agents in NIS BH29768 (NCT02476942) and were enrolled in Cohort A of this study (BH29992) received emicizumab at a loading dose of 3 milligrams per kilogram (mg/kg) once every week (QW) subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg emicizumab QW SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Measure Participants	18	18
Median (Inter-Quartile Range) [all bleed rate per year]	21.3	1.1

45. Secondary Outcome

Title	Cohort A: Intra-Participant Comparison of Percentage of Participants by Categorized Number of Treated Bleeds on Study Versus Pre-Study in Treated Participants <12 Years of Age From the NIS Population
Description	This is an intra-participant comparison of the percentage of participants by categorized number of treated bleeds over the efficacy period on study versus pre-study in the NIS population who had previously participated in study BH29768 (NCT02476942). A "treated bleed" is a bleed directly followed by a hemophilia medication reported to be a "treatment for bleed", irrespective of time between treatment and the preceding bleed. A bleed and first treatment thereafter are considered to be pairs, with the following exception: if multiple bleeds occur on the same calendar day, the subsequent treatment is considered to apply for each of these multiple bleeds. The 72-hour rule was implemented: two bleeds of the same type and at the same anatomical location are counted as one bleed if the second bleed occurs within 72 hours from the last treatment for the first bleed. Bleeds due to surgery/procedure are excluded.
Time Frame	Up to 24 weeks in NIS BH29768 (NCT02476942) prior to study entry and from Baseline to 52 weeks on this study; At primary completion date, the median (min-max) duration of the efficacy period in the NIS population was 88.57 (55.9-92.6) weeks.

Outcome Measure Data

Analysis Population Description

Treated participants <12 years of age who had participated in NIS BH29768 (NCT02476942) prior to enrollment in this study and were on the same dose of emicizumab for at least 12 weeks in this study

Arm/Group Title	Cohort A NIS Population (<12 Years): Bypassing Agents	Cohort A NIS Population (<12 Years): 1.5 mg/kg Emicizumab QW
Arm/Group Description	This group includes historical data from participants <12 years old who had participated in the non-interventional study (NIS) BH29768 (NCT02476942) in which they had received prophylactic or episodic treatment with bypassing agents and had been followed for a minimum of 24 weeks on the NIS prior to enrollment in Cohort A of this study (BH29992).	Participants <12 years old who had previously received prophylactic or episodic treatment with bypassing agents in NIS BH29768 (NCT02476942) and were enrolled in Cohort A of this study (BH29992) received emicizumab at a loading dose of 3 milligrams per kilogram (mg/kg) once every week (QW) subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg emicizumab QW SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Measure Participants	18	18
0 Bleeds	5.6 8.2%	72.2 722%
0-3 Bleeds	16.7 24.6%	100.0 1000%
0-10 Bleeds	66.7 98.1%	100.0 1000%
>10 Bleeds	33.3 49%	0.0 0%

46. Secondary Outcome

Title	Cohort A: Intra-Participant Comparison of Percentage of Participants by Categorized Number of All Bleeds on Study Versus Pre-Study in Treated Participants <12 Years of Age From the NIS Population
Description	This is an intra-participant comparison of the percentage of participants by categorized number of all bleeds over the efficacy period on study versus pre-study in the NIS population who had previously participated in study BH29768 (NCT02476942). In this outcome measure, all bleeds are included, irrespective of treatment with coagulation factors, with the following exception: bleeds due to surgery/procedure are excluded. As "all bleeds" comprises both treated and non-treated bleeds, the 72-hour rule was implemented separately for treated and non-treated bleeds. For treated bleeds, the 72-hour rule was implemented exactly as defined for the "treated bleeds" outcome measure. For non-treated bleeds, the 72-hour rule was implemented by calculating a treatment-free period of 72 hours from the bleed itself.
Time Frame	Up to 24 weeks in NIS BH29768 (NCT02476942) prior to study entry and from Baseline to 52 weeks on this study; At primary completion date, the median (min-max) duration of the efficacy period in the NIS population was 88.57 (55.9-92.6) weeks.

Outcome Measure Data

Analysis Population Description

Treated participants <12 years of age who had participated in NIS BH29768 (NCT02476942) prior to enrollment in this study and were on the same dose of emicizumab for at least 12 weeks in this study

Arm/Group Title	Cohort A NIS Population (<12 Years): Bypassing Agents	Cohort A NIS Population (<12 Years): 1.5 mg/kg Emicizumab QW
Arm/Group Description	This group includes historical data from participants <12 years old who had participated in the non-interventional study (NIS) BH29768 (NCT02476942) in which they had received prophylactic or episodic treatment with bypassing agents and had been followed for a minimum of 24 weeks on the NIS prior to enrollment in Cohort A of this study (BH29992).	Participants <12 years old who had previously received prophylactic or episodic treatment with bypassing agents in NIS BH29768 (NCT02476942) and were enrolled in Cohort A of this study (BH29992) received emicizumab at a loading dose of 3 milligrams per kilogram (mg/kg) once every week (QW) subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg emicizumab QW SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Measure Participants	18	18
0 Bleeds	0.0 0%	33.3 333%
0-3 Bleeds	11.1 16.3%	72.2 722%
0-10 Bleeds	44.4 65.3%	83.3 833%
>10 Bleeds	55.6 81.8%	16.7 167%

47. Secondary Outcome

Title	Model-Based Annualized Bleed Rate (ABR) for Treated Bleeds in Treated Participants ≥12 Years of Age and <40 kg Body Weight
Description	The number of treated bleeds over the efficacy period is presented here as a model-based ABR that was analyzed using a negative binomial regression model with efficacy period as an offset to account for the difference in follow-up times. A bleed is considered a "treated bleed" if it is directly followed (i.e., no intervening bleed) by a hemophilia medication reported to be a "treatment for bleed", irrespective of time between treatment and the preceding bleed. A bleed and the first treatment thereafter and before a new bleed starts, are considered to be pairs, with the following exception: if multiple bleeds occur on the same calendar day, the subsequent treatment is considered to apply for each of these multiple bleeds. The 72-hour rule was implemented: two bleeds of the same type and at the same anatomical location are counted as one bleed if the second bleed occurs within 72 hours from the last treatment for the first bleed. Bleeds due to surgery/procedure are excluded.
Time Frame	From Baseline to 52 weeks

Outcome Measure Data

Analysis Population Description

All participants who received at least one dose of emicizumab and were ≥12 years old and weighed <40 kg at the time of informed consent; none of the participants enrolled in Cohorts B and C fit these criteria.

Arm/Group Title	Cohort A: 1.5 mg/kg Emicizumab QW	Cohort B: 3 mg/kg Emicizumab Q2W	Cohort C: 6 mg/kg Emicizumab Q4W
Arm/Group Description	Participants received emicizumab at a loading dose of 3 milligrams per kilogram (mg/kg) once every week (QW) subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg QW SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.	Participants received emicizumab at a loading dose of 3 mg/kg QW subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 3 mg/kg once every 2 weeks (Q2W) SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.	Participants received emicizumab at a loading dose of 3 mg/kg QW subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 6 mg/kg once every 4 weeks (Q4W) SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Measure Participants	3	0	0
Number (95% Confidence Interval) [treated bleed rate per year]	0.8

48. Secondary Outcome

Title	Model-Based Annualized Bleed Rate (ABR) for All Bleeds in Treated Participants ≥12 Years of Age and <40 kg Body Weight
Description	The number of all bleeds over the efficacy period is presented as a model-based ABR that was analyzed using a negative binomial regression model with efficacy period as an offset to account for the difference in followup times (i.e., the time that each participant stays in the study). In this outcome measure, all bleeds are included, irrespective of treatment with coagulation factors, with the following exception: bleeds due to surgery/procedure are excluded. As "all bleeds" comprises both treated and non-treated bleeds, the 72-hour rule was implemented separately for treated and non-treated bleeds. For treated bleeds, the 72-hour rule was implemented exactly as defined for the "treated bleeds" outcome measure. For non-treated bleeds, the 72-hour rule was implemented by calculating a treatment-free period of 72 hours from the bleed itself.
Time Frame	From Baseline to 52 weeks

Outcome Measure Data

Analysis Population Description

All participants who received at least one dose of emicizumab and were ≥12 years old and weighed <40 kg at the time of informed consent; none of the participants enrolled in Cohorts B and C fit these criteria.

Arm/Group Title	Cohort A: 1.5 mg/kg Emicizumab QW	Cohort B: 3 mg/kg Emicizumab Q2W	Cohort C: 6 mg/kg Emicizumab Q4W
Arm/Group Description	Participants received emicizumab at a loading dose of 3 milligrams per kilogram (mg/kg) once every week (QW) subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg QW SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.	Participants received emicizumab at a loading dose of 3 mg/kg QW subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 3 mg/kg once every 2 weeks (Q2W) SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.	Participants received emicizumab at a loading dose of 3 mg/kg QW subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 6 mg/kg once every 4 weeks (Q4W) SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Measure Participants	3	0	0
Number (95% Confidence Interval) [all bleed rate per year]	1.4

49. Secondary Outcome

Title	Median Calculated Annualized Bleed Rate (ABR) for Treated Bleeds in Treated Participants ≥12 Years of Age and <40 kg Body Weight
Description	The number of treated bleeds over the efficacy period is presented here as a calculated ABR that was annualized for each participant using the following formula: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. A bleed is considered a "treated bleed" if it is directly followed (i.e., no intervening bleed) by a hemophilia medication reported to be a "treatment for bleed", irrespective of time between treatment and the preceding bleed. A bleed and the first treatment thereafter and before a new bleed starts, are considered to be pairs, with the following exception: if multiple bleeds occur on the same calendar day, the subsequent treatment is considered to apply for each of these multiple bleeds. The 72-hour rule was implemented: two bleeds of the same type and at the same anatomical location are counted as one bleed if the second bleed occurs within 72 hours from the last treatment for the first bleed. Bleeds due to surgery/procedure are excluded.
Time Frame	From Baseline to 52 weeks

Outcome Measure Data

Analysis Population Description

All participants who received at least one dose of emicizumab and were ≥12 years old and weighed <40 kg at the time of informed consent; none of the participants enrolled in Cohorts B and C fit these criteria.

Arm/Group Title	Cohort A: 1.5 mg/kg Emicizumab QW	Cohort B: 3 mg/kg Emicizumab Q2W	Cohort C: 6 mg/kg Emicizumab Q4W
Arm/Group Description	Participants received emicizumab at a loading dose of 3 milligrams per kilogram (mg/kg) once every week (QW) subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg QW SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.	Participants received emicizumab at a loading dose of 3 mg/kg QW subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 3 mg/kg once every 2 weeks (Q2W) SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.	Participants received emicizumab at a loading dose of 3 mg/kg QW subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 6 mg/kg once every 4 weeks (Q4W) SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Measure Participants	3	0	0
Median (Inter-Quartile Range) [treated bleed rate per year]	0.9

50. Secondary Outcome

Title	Median Calculated Annualized Bleed Rate (ABR) for All Bleeds in Treated Participants ≥12 Years of Age and <40 kg Body Weight
Description	The number of all bleeds over the efficacy period is presented here as a calculated ABR that was annualized for each participant using the following formula: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. In this outcome measure, all bleeds are included, irrespective of treatment with coagulation factors, with the following exception: bleeds due to surgery/procedure are excluded. As "all bleeds" comprises both treated and non-treated bleeds, the 72-hour rule was implemented separately for treated and non-treated bleeds. For treated bleeds, the 72-hour rule was implemented exactly as defined for the "treated bleeds" outcome measure. For non-treated bleeds, the 72-hour rule was implemented by calculating a treatment-free period of 72 hours from the bleed itself.
Time Frame	From Baseline to 52 weeks

Outcome Measure Data

Analysis Population Description

All participants who received at least one dose of emicizumab and were ≥12 years old and weighed <40 kg at the time of informed consent; none of the participants enrolled in Cohorts B and C fit these criteria.

Arm/Group Title	Cohort A: 1.5 mg/kg Emicizumab QW	Cohort B: 3 mg/kg Emicizumab Q2W	Cohort C: 6 mg/kg Emicizumab Q4W
Arm/Group Description	Participants received emicizumab at a loading dose of 3 milligrams per kilogram (mg/kg) once every week (QW) subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg QW SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.	Participants received emicizumab at a loading dose of 3 mg/kg QW subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 3 mg/kg once every 2 weeks (Q2W) SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.	Participants received emicizumab at a loading dose of 3 mg/kg QW subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 6 mg/kg once every 4 weeks (Q4W) SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Measure Participants	3	0	0
Median (Inter-Quartile Range) [all bleed rate per year]	0.9

51. Secondary Outcome

Title	Number of Treated Bleeds Over Time in Participants With Dose Up-Titration
Description	The number of treated bleeds over time was to be analyzed in participants whose emicizumab maintenance dose was up-titrated to 3 mg/kg QW if they had experienced suboptimal bleeding control on emicizumab at steady-state, per protocol criteria. A bleed is considered a "treated bleed" if it is directly followed (i.e., no intervening bleed) by a hemophilia medication reported to be a "treatment for bleed", irrespective of time between treatment and the preceding bleed. A bleed and the first treatment thereafter and before a new bleed starts, are considered to be pairs, with the following exception: if multiple bleeds occur on the same calendar day, the subsequent treatment is considered to apply for each of these multiple bleeds. The 72-hour rule was implemented: two bleeds of the same type and at the same anatomical location are counted as one bleed if the second bleed occurs within 72 hours from the last treatment for the first bleed. Bleeds due to surgery/procedure are excluded.
Time Frame	From Baseline to study completion (up to at least 52 weeks)

Outcome Measure Data

Analysis Population Description

All participants with emicizumab dose up-titration; At study completion, 0 participants in Cohorts A and B and 3 participants in Cohort C had their emicizumab dose up-titrated over the course of this clinical trial. Data were not aggregated for this outcome measure because it was not part of the pre-specified analysis plan and because of the limited sample size. The results will not be disclosed on an individual patient level because of data privacy concerns.

Arm/Group Title	Cohort A: 1.5 mg/kg Emicizumab QW	Cohort B: 3 mg/kg Emicizumab Q2W	Cohort C: 6 mg/kg Emicizumab Q4W
Arm/Group Description	Participants received emicizumab at a loading dose of 3 milligrams per kilogram (mg/kg) once every week (QW) subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg QW SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.	Participants received emicizumab at a loading dose of 3 mg/kg QW subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 3 mg/kg once every 2 weeks (Q2W) SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.	Participants received emicizumab at a loading dose of 3 mg/kg QW subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 6 mg/kg once every 4 weeks (Q4W) SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Measure Participants	0	0	0

52. Secondary Outcome

Title	Number of All Bleeds Over Time in Participants With Dose Up-Titration
Description	The number of all bleeds over time was to be analyzed in participants whose emicizumab maintenance dose was up-titrated to 3 mg/kg QW if they had experienced suboptimal bleeding control on emicizumab at steady-state, per protocol criteria. In this outcome measure, all bleeds are included, irrespective of treatment with coagulation factors, with the following exception: bleeds due to surgery/procedure are excluded. As "all bleeds" comprises both treated and non-treated bleeds, the 72-hour rule was implemented separately for treated and non-treated bleeds. For treated bleeds, the 72-hour rule was implemented exactly as defined for the "treated bleeds" outcome measure. For non-treated bleeds, the 72-hour rule was implemented by calculating a treatment-free period of 72 hours from the bleed itself.
Time Frame	From Baseline to study completion (up to at least 52 weeks)

Outcome Measure Data

Analysis Population Description

All participants with emicizumab dose up-titration; At study completion, 0 participants in Cohorts A and B and 3 participants in Cohort C had their emicizumab dose up-titrated over the course of this clinical trial. Data were not aggregated for this outcome measure because it was not part of the pre-specified analysis plan and because of the limited sample size. The results will not be disclosed on an individual patient level because of data privacy concerns.

Arm/Group Title	Cohort A: 1.5 mg/kg Emicizumab QW	Cohort B: 3 mg/kg Emicizumab Q2W	Cohort C: 6 mg/kg Emicizumab Q4W
Arm/Group Description	Participants received emicizumab at a loading dose of 3 milligrams per kilogram (mg/kg) once every week (QW) subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg QW SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.	Participants received emicizumab at a loading dose of 3 mg/kg QW subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 3 mg/kg once every 2 weeks (Q2W) SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.	Participants received emicizumab at a loading dose of 3 mg/kg QW subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 6 mg/kg once every 4 weeks (Q4W) SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Measure Participants	0	0	0

53. Secondary Outcome

Title	Long-Term Efficacy of Emicizumab in All Cohorts: Model-Based Annualized Bleed Rate (ABR) for Treated Bleeds, All Bleeds, Treated Spontaneous Bleeds, Treated Joint Bleeds, and Treated Target Joint Bleeds in Treated Participants <12 Years of Age
Description	The number of bleeds over the efficacy period was shown as a model-based ABR that used a negative binomial regression model with efficacy period as an offset to account for the difference in follow-up times. A bleed is considered a "treated bleed" if it is directly followed (i.e., no intervening bleed) by a hemophilia medication reported to be a "treatment for bleed", irrespective of time between treatment and the preceding bleed. "All bleeds" included bleeds irrespective of treatment with coagulation factors, with the following exception: bleeds due to surgery/procedure are excluded. Bleeds are classified as "spontaneous" if there is no other known contributing factor such as trauma or procedure/surgery. A "joint bleed" is defined as a bleed occurring in a joint. A "target joint bleed" is defined as a joint bleed in a target joint (≥3 bleeds have occurred over the last 24 weeks prior to study entry).
Time Frame	From Baseline to study completion (median [min-max] duration of the efficacy periods in Cohorts A, B, and C were 92.29 [36.1-187.7] weeks, 68.21 [56.7-129.4] weeks, and 69.43 [8.9-144.3] weeks, respectively)

Outcome Measure Data

Analysis Population Description

All treated participants in Cohorts A, B, and C who were on the same dose of emicizumab for at least 12 weeks and were <12 years of age

Arm/Group Title	Cohort A: 1.5 mg/kg Emicizumab QW	Cohort B: 3 mg/kg Emicizumab Q2W	Cohort C: 6 mg/kg Emicizumab Q4W
Arm/Group Description	Participants received emicizumab at a loading dose of 3 milligrams per kilogram (mg/kg) once every week (QW) subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg QW SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.	Participants received emicizumab at a loading dose of 3 mg/kg QW subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 3 mg/kg once every 2 weeks (Q2W) SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.	Participants received emicizumab at a loading dose of 3 mg/kg QW subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 6 mg/kg once every 4 weeks (Q4W) SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Measure Participants	65	10	10
Treated Bleeds	0.3	0.2	1.8
All Bleeds	3.0	0.8	2.4
Treated Spontaneous Bleeds	0.01	NA	0.9
Treated Joint Bleeds	0.2	0.2	1.3
Treated Target Joint Bleeds	0.1	0.1	0.5

54. Secondary Outcome

Title	Long-Term Efficacy of Emicizumab in All Cohorts: Mean Calculated Annualized Bleed Rate (ABR) for Treated Bleeds, All Bleeds, Treated Spontaneous Bleeds, Treated Joint Bleeds, and Treated Target Joint Bleeds in Treated Participants <12 Years of Age
Description	The number of treated bleeds over the efficacy period is presented here as a calculated ABR that was annualized for each participant using the following formula: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. A bleed is considered a "treated bleed" if it is directly followed (i.e., no intervening bleed) by a hemophilia medication reported to be a "treatment for bleed", irrespective of time between treatment and the preceding bleed. "All bleeds" included bleeds irrespective of treatment with coagulation factors, with the following exception: bleeds due to surgery/procedure are excluded. Bleeds are classified as "spontaneous" if there is no other known contributing factor such as trauma or procedure/surgery. A "joint bleed" is defined as a bleed with type reported as "joint". A "target joint bleed" is defined as a joint bleed in a target joint, which is a joint location where at least 3 bleeds have occurred over the last 24 weeks prior to study entry.
Time Frame	From Baseline to study completion (median [min-max] duration of the efficacy periods in Cohorts A, B, and C were 92.29 [36.1-187.7] weeks, 68.21 [56.7-129.4] weeks, and 69.43 [8.9-144.3] weeks, respectively)

Outcome Measure Data

Analysis Population Description

All treated participants in Cohorts A, B, and C who were on the same dose of emicizumab for at least 12 weeks and were <12 years of age

Arm/Group Title	Cohort A: 1.5 mg/kg Emicizumab QW	Cohort B: 3 mg/kg Emicizumab Q2W	Cohort C: 6 mg/kg Emicizumab Q4W
Arm/Group Description	Participants received emicizumab at a loading dose of 3 milligrams per kilogram (mg/kg) once every week (QW) subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg QW SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.	Participants received emicizumab at a loading dose of 3 mg/kg QW subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 3 mg/kg once every 2 weeks (Q2W) SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.	Participants received emicizumab at a loading dose of 3 mg/kg QW subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 6 mg/kg once every 4 weeks (Q4W) SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Measure Participants	65	10	10
Treated Bleeds	0.3	0.2	2.2
All Bleeds	3.0	0.8	3.0
Treated Spontaneous Bleeds	0.0	0.0	1.0
Treated Joint Bleeds	0.1	0.2	1.6
Treated Target Joint Bleeds	0.1	0.1	0.5

55. Secondary Outcome

Title	Long-Term Efficacy of Emicizumab in All Cohorts: Median Calculated Annualized Bleed Rate (ABR) for Treated Bleeds, All Bleeds, Treated Spontaneous Bleeds, Treated Joint Bleeds, and Treated Target Joint Bleeds in Treated Participants <12 Years of Age
Description	The number of treated bleeds over the efficacy period is presented here as a calculated ABR that was annualized for each participant using the following formula: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. A bleed is considered a "treated bleed" if it is directly followed (i.e., no intervening bleed) by a hemophilia medication reported to be a "treatment for bleed", irrespective of time between treatment and the preceding bleed. "All bleeds" included bleeds irrespective of treatment with coagulation factors, with the following exception: bleeds due to surgery/procedure are excluded. Bleeds are classified as "spontaneous" if there is no other known contributing factor such as trauma or procedure/surgery. A "joint bleed" is defined as a bleed with type reported as "joint". A "target joint bleed" is defined as a joint bleed in a target joint, which is a joint location where at least 3 bleeds have occurred over the last 24 weeks prior to study entry.
Time Frame	From Baseline to study completion (median [min-max] duration of the efficacy periods in Cohorts A, B, and C were 92.29 [36.1-187.7] weeks, 68.21 [56.7-129.4] weeks, and 69.43 [8.9-144.3] weeks, respectively)

Outcome Measure Data

Analysis Population Description

All treated participants in Cohorts A, B, and C who were on the same dose of emicizumab for at least 12 weeks and were <12 years of age

Arm/Group Title	Cohort A: 1.5 mg/kg Emicizumab QW	Cohort B: 3 mg/kg Emicizumab Q2W	Cohort C: 6 mg/kg Emicizumab Q4W
Arm/Group Description	Participants received emicizumab at a loading dose of 3 milligrams per kilogram (mg/kg) once every week (QW) subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg QW SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.	Participants received emicizumab at a loading dose of 3 mg/kg QW subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 3 mg/kg once every 2 weeks (Q2W) SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.	Participants received emicizumab at a loading dose of 3 mg/kg QW subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 6 mg/kg once every 4 weeks (Q4W) SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Measure Participants	65	10	10
Treated Bleeds	0.0	0.0	0.0
All Bleeds	0.7	0.8	0.6
Treated Spontaneous Bleeds	0.0	0.0	0.0
Treated Joint Bleeds	0.0	0.0	0.0
Treated Target Joint Bleeds	0.0	0.0	0.0

56. Secondary Outcome

Title	Change From Baseline Over Time in the Hemophilia-Specific Quality of Life Short Form (Haemo-QoL-SF) Questionnaire Total Score, as Completed by Treated Participants ≥8 to <12 Years of Age
Description	The Haemo-QoL-SF is a self-reported questionnaire for children ≥8 years of age. It contains 35 items, which cover nine domains considered relevant for the children's health-related quality of life: Physical Health, Feelings, View of Yourself, Family, Friends, Other People, Sports and School, Dealing with Hemophilia, and Treatment. Items are rated with five respective response options: never, seldom, sometimes, often, and always. The Total Score is derived from the scores for all domains and ranges from 0 to 100, with a lower score reflective of better health-related quality of life.
Time Frame	Baseline (Week 1), Weeks 13, 25, 37, 49, 57, 81, 105, 129, 153, and 177, and at study completion [SC] or early discontinuation [ED] (up to 188 weeks)

Outcome Measure Data

Analysis Population Description

All treated participants ≥8 to <12 years of age; at each timepoint, the number analyzed is the number of participants who completed a sufficient number of questionnaire items.

Arm/Group Title	Cohort A: 1.5 mg/kg Emicizumab QW	Cohort B: 3 mg/kg Emicizumab Q2W	Cohort C: 6 mg/kg Emicizumab Q4W
Arm/Group Description	Participants received emicizumab at a loading dose of 3 milligrams per kilogram (mg/kg) once every week (QW) subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg QW SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.	Participants received emicizumab at a loading dose of 3 mg/kg QW subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 3 mg/kg once every 2 weeks (Q2W) SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.	Participants received emicizumab at a loading dose of 3 mg/kg QW subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 6 mg/kg once every 4 weeks (Q4W) SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Measure Participants	22	6	6
Baseline (value at visit)	33.37	25.60	25.12
Change from Baseline at Week 13	-7.02	-9.17	0.29
Change from Baseline at Week 25	-9.17	-13.21	-14.64
Change from Baseline at Week 37	-11.64	-15.48	-17.86
Change from Baseline at Week 49	-9.62	-15.14	-16.43
Change from Baseline at Week 57	-11.13	-16.43	-25.00
Change from Baseline at Week 81	-11.79	-14.52
Change from Baseline at Week 105	-18.57	-14.76
Change from Baseline at Week 129	-14.90
Change from Baseline at Week 153	-14.46
Change from Baseline at Week 177	-5.36
Change from Baseline at SC or ED	-13.05	-21.43	-28.21

57. Secondary Outcome

Title	Change From Baseline Over Time in the Haemo-QoL-SF Questionnaire Physical Health Domain Score, as Completed by Treated Participants ≥8 to <12 Years of Age
Description	The Haemo-QoL-SF is a self-reported questionnaire for children ≥8 years of age. It contains 35 items, which cover nine domains considered relevant for the children's health-related quality of life: Physical Health, Feelings, View of Yourself, Family, Friends, Other People, Sports and School, Dealing with Hemophilia, and Treatment. The Physical Health domain assesses hemophilia-related symptoms (painful swellings and presence of joint pain) and physical functioning (pain with movement). Items are rated with five respective response options: never, seldom, sometimes, often, and always. The Physical Health domain score ranges from 0 to 100, with a lower score reflective of better physical health.
Time Frame	Baseline (Week 1), Weeks 13, 25, 37, 49, 57, 81, 105, 129, 153, and 177, and at study completion [SC] or early discontinuation [ED] (up to 188 weeks)

Outcome Measure Data

Analysis Population Description

All treated participants ≥8 to <12 years of age; at each timepoint, the number analyzed is the number of participants who completed a sufficient number of questionnaire items.

Arm/Group Title	Cohort A: 1.5 mg/kg Emicizumab QW	Cohort B: 3 mg/kg Emicizumab Q2W	Cohort C: 6 mg/kg Emicizumab Q4W
Arm/Group Description	Participants received emicizumab at a loading dose of 3 milligrams per kilogram (mg/kg) once every week (QW) subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg QW SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.	Participants received emicizumab at a loading dose of 3 mg/kg QW subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 3 mg/kg once every 2 weeks (Q2W) SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.	Participants received emicizumab at a loading dose of 3 mg/kg QW subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 6 mg/kg once every 4 weeks (Q4W) SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Measure Participants	22	6	6
Baseline (value at visit)	29.51	30.21	19.79
Change from Baseline at Week 13	-18.40	-23.96	3.75
Change from Baseline at Week 25	-18.40	-17.71	-17.19
Change from Baseline at Week 37	-21.32	-25.00	-22.92
Change from Baseline at Week 49	-15.44	-23.75	-25.00
Change from Baseline at Week 57	-17.19	-23.44	-25.00
Change from Baseline at Week 81	-14.06	-16.67
Change from Baseline at Week 105	-16.67	-20.83
Change from Baseline at Week 129	-12.50
Change from Baseline at Week 153	-21.88
Change from Baseline at Week 177	6.25
Change from Baseline at SC or ED	-23.30	-29.17	-40.63

58. Secondary Outcome

Title	Change From Baseline Over Time in Caregiver-Reported Adapted Health-Related Quality of Life for Hemophilia Patients With Inhibitors Including Aspects of Caregiver Burden (Adapted Inhib-QoL) Questionnaire Total Score, Treated Participants <12 Years of Age
Description	Proxy assessment of health-related quality of life (HRQoL) and aspects of caregiver burden were assessed using the Adapted Inhib-QoL questionnaire, which comprises two parts with a total of 30 questions. The first part asks the caregiver for his/her opinion on the child's HRQoL and consists of two scales: Physical Health and Treatment. The second part asks the caregiver to rate how the child's situation is for them (i.e., the impact of the child's disease and treatment on the caregiver) and consists of 6 scales (5 if the child does not have siblings): General Condition, Dealing with the Inhibitor, Perceive Treatment, Family life, Siblings, Contact with Others. Items are rated with five respective response options: never, seldom, sometimes, often, and all the time. The Total Score is derived from the individual scores of all of the domains and it ranges from 0 to 100, with lower scores reflective of better HRQoL.
Time Frame	Baseline (Week 1), Weeks 13, 25, 37, 49, 57, 81, 105, 129, 153, and 177, and at study completion [SC] or early discontinuation [ED] (up to 188 weeks)

Outcome Measure Data

Analysis Population Description

All treated participants <12 years of age, as completed by their caregivers; at each timepoint, the number analyzed is the number of participants who completed a sufficient number of questionnaire items.

Arm/Group Title	Cohort A: 1.5 mg/kg Emicizumab QW	Cohort B: 3 mg/kg Emicizumab Q2W	Cohort C: 6 mg/kg Emicizumab Q4W
Arm/Group Description	Participants received emicizumab at a loading dose of 3 milligrams per kilogram (mg/kg) once every week (QW) subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg QW SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.	Participants received emicizumab at a loading dose of 3 mg/kg QW subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 3 mg/kg once every 2 weeks (Q2W) SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.	Participants received emicizumab at a loading dose of 3 mg/kg QW subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 6 mg/kg once every 4 weeks (Q4W) SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Measure Participants	65	10	10
Baseline (value at visit)	43.10	40.56	31.45
Change from Baseline at Week 13	-19.76	-21.46	-9.24
Change from Baseline at Week 25	-21.67	-26.11	-13.93
Change from Baseline at Week 37	-21.79	-24.62	-12.55
Change from Baseline at Week 49	-22.12	-24.57	-18.18
Change from Baseline at Week 57	-20.86	-24.37	-20.28
Change from Baseline at Week 81	-22.29	-24.95	-14.84
Change from Baseline at Week 105	-18.04	-21.82	-15.82
Change from Baseline at Week 129	-15.43
Change from Baseline at Week 153	-11.68
Change from Baseline at Week 177	-22.41
Change from Baseline at SC or ED	-23.59	-25.83	-13.73

59. Secondary Outcome

Title	Change From Baseline Over Time in the Caregiver-Reported Adapted Inhib-QoL Questionnaire Physical Health Domain Score, Treated Participants <12 Years of Age
Description	Proxy assessment of health-related quality of life (HRQoL) and aspects of caregiver burden were assessed using the Adapted Inhib-QoL questionnaire, which comprises two parts with a total of 30 questions. The first part asks the caregiver for his/her opinion on the child's HRQoL (proxy HRQoL) and consists of two scales: Physical Health and Treatment. The second part asks the caregiver to rate how the child's situation is for them (i.e., the impact of the child's disease and treatment on the caregiver) and consists of 6 scales (5 if the child does not have siblings): General Condition, Dealing with the Inhibitor, Perceive Treatment, Family Life, Siblings, Contact with Others. Items are rated with five respective response options: never, seldom, sometimes, often, and all the time. A total score is calculated as the sum of all of the items in the scale. The Physical Health domain score ranges from 0 to 100, with lower scores reflective of better physical health.
Time Frame	Baseline (Week 1), Weeks 13, 25, 37, 49, 57, 81, 105, 129, 153, and 177, and at study completion [SC] or early discontinuation [ED] (up to 188 weeks)

Outcome Measure Data

Analysis Population Description

All treated participants <12 years of age, as completed by their caregivers; at each timepoint, the number analyzed is the number of participants who completed a sufficient number of questionnaire items.

Arm/Group Title	Cohort A: 1.5 mg/kg Emicizumab QW	Cohort B: 3 mg/kg Emicizumab Q2W	Cohort C: 6 mg/kg Emicizumab Q4W
Arm/Group Description	Participants received emicizumab at a loading dose of 3 milligrams per kilogram (mg/kg) once every week (QW) subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg QW SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.	Participants received emicizumab at a loading dose of 3 mg/kg QW subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 3 mg/kg once every 2 weeks (Q2W) SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.	Participants received emicizumab at a loading dose of 3 mg/kg QW subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 6 mg/kg once every 4 weeks (Q4W) SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Measure Participants	65	10	10
Baseline (value at visit)	37.13	34.64	20.00
Change from Baseline at Week 13	-31.10	-30.00	-6.35
Change from Baseline at Week 25	-30.73	-29.64	-17.86
Change from Baseline at Week 37	-31.20	-31.07	-21.94
Change from Baseline at Week 49	-28.76	-29.37	-22.96
Change from Baseline at Week 57	-27.79	-32.65	-26.19
Change from Baseline at Week 81	-31.36	-23.21	-13.39
Change from Baseline at Week 105	-27.86	-18.75	-16.96
Change from Baseline at Week 129	-27.01
Change from Baseline at Week 153	-30.10
Change from Baseline at Week 177	-32.14
Change from Baseline at SC or ED	-30.29	-35.12	-21.43

60. Secondary Outcome

Title	Number of Participants With at Least One Adverse Event
Description	The number of participants experiencing at least one adverse event, including all non-serious and serious adverse events, are reported.
Time Frame	From Baseline up to 24 weeks after study drug discontinuation; the median (min-max) observation periods in Cohorts A, B, and C were 96.93 (36.1-188.1) weeks, 68.21 (56.7-129.4) weeks, and 69.43 (38.9-144.3) weeks, respectively.

Outcome Measure Data

Analysis Population Description

All participants who received at least one dose of emicizumab

Arm/Group Title	Cohort A: 1.5 mg/kg Emicizumab QW	Cohort B: 3 mg/kg Emicizumab Q2W	Cohort C: 6 mg/kg Emicizumab Q4W
Arm/Group Description	Participants received emicizumab at a loading dose of 3 milligrams per kilogram (mg/kg) once every week (QW) subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg QW SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.	Participants received emicizumab at a loading dose of 3 mg/kg QW subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 3 mg/kg once every 2 weeks (Q2W) SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.	Participants received emicizumab at a loading dose of 3 mg/kg QW subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 6 mg/kg once every 4 weeks (Q4W) SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Measure Participants	68	10	10
Count of Participants [Participants]	64 94.1%	9 90%	10 100%

61. Secondary Outcome

Title	Number of Participants With at Least One Grade ≥3 Adverse Event
Description	The World Health Organization (WHO) toxicity grading scale was used for assessing adverse event severity. For adverse events that are not specifically listed in the WHO toxicity grading scale, a grade 3 adverse event is defined as: severe, marked limitation in activity, some assistance usually required, medical intervention or therapy required, hospitalization possible; and a grade 4 adverse event is defined as: life-threatening, extreme limitation in activity, significant assistance required, significant medical intervention or therapy required, hospitalization or hospice care probable.
Time Frame	From Baseline up to 24 weeks after study drug discontinuation; the median (min-max) observation periods in Cohorts A, B, and C were 96.93 (36.1-188.1) weeks, 68.21 (56.7-129.4) weeks, and 69.43 (38.9-144.3) weeks, respectively.

Outcome Measure Data

Analysis Population Description

All participants who received at least one dose of emicizumab

Arm/Group Title	Cohort A: 1.5 mg/kg Emicizumab QW	Cohort B: 3 mg/kg Emicizumab Q2W	Cohort C: 6 mg/kg Emicizumab Q4W
Arm/Group Description	Participants received emicizumab at a loading dose of 3 milligrams per kilogram (mg/kg) once every week (QW) subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg QW SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.	Participants received emicizumab at a loading dose of 3 mg/kg QW subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 3 mg/kg once every 2 weeks (Q2W) SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.	Participants received emicizumab at a loading dose of 3 mg/kg QW subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 6 mg/kg once every 4 weeks (Q4W) SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Measure Participants	68	10	10
Count of Participants [Participants]	15 22.1%	1 10%	3 30%

62. Secondary Outcome

Title	Number of Participants With at Least One Adverse Event Leading to Withdrawal From Treatment
Time Frame	From Baseline up to 24 weeks after study drug discontinuation; the median (min-max) observation periods in Cohorts A, B, and C were 96.93 (36.1-188.1) weeks, 68.21 (56.7-129.4) weeks, and 69.43 (38.9-144.3) weeks, respectively.

Outcome Measure Data

Analysis Population Description

All participants who received at least one dose of emicizumab

Arm/Group Title	Cohort A: 1.5 mg/kg Emicizumab QW	Cohort B: 3 mg/kg Emicizumab Q2W	Cohort C: 6 mg/kg Emicizumab Q4W
Arm/Group Description	Participants received emicizumab at a loading dose of 3 milligrams per kilogram (mg/kg) once every week (QW) subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg QW SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.	Participants received emicizumab at a loading dose of 3 mg/kg QW subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 3 mg/kg once every 2 weeks (Q2W) SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.	Participants received emicizumab at a loading dose of 3 mg/kg QW subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 6 mg/kg once every 4 weeks (Q4W) SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Measure Participants	68	10	10
Count of Participants [Participants]	0 0%	0 0%	1 10%

63. Secondary Outcome

Title	Number of Participants With at Least One Adverse Event of Local Injection Site Reaction
Description	Local adverse events that occurred within 24 hours after study drug administration and, in the investigator's opinion, were judged to be related to study drug injection, were captured as an "injection-site reaction" on the Adverse Event electronic Case Report Form (eCRF). An injection-related reaction that was localized was marked as a "local injection-site reaction."
Time Frame	From Baseline up to 24 weeks after study drug discontinuation; the median (min-max) observation periods in Cohorts A, B, and C were 96.93 (36.1-188.1) weeks, 68.21 (56.7-129.4) weeks, and 69.43 (38.9-144.3) weeks, respectively.

Outcome Measure Data

Analysis Population Description

All participants who received at least one dose of emicizumab

Arm/Group Title	Cohort A: 1.5 mg/kg Emicizumab QW	Cohort B: 3 mg/kg Emicizumab Q2W	Cohort C: 6 mg/kg Emicizumab Q4W
Arm/Group Description	Participants received emicizumab at a loading dose of 3 milligrams per kilogram (mg/kg) once every week (QW) subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg QW SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.	Participants received emicizumab at a loading dose of 3 mg/kg QW subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 3 mg/kg once every 2 weeks (Q2W) SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.	Participants received emicizumab at a loading dose of 3 mg/kg QW subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 6 mg/kg once every 4 weeks (Q4W) SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Measure Participants	68	10	10
Count of Participants [Participants]	23 33.8%	2 20%	6 60%

64. Secondary Outcome

Title	Number of Participants With at Least One Adverse Event of Systemic Hypersensitivity, Anaphylaxis, or Anaphylactoid Reaction
Description	Systemic hypersensitivity, anaphylaxis, or anaphylactoid reactions were identified by the investigator using Sampson's criteria, as defined in the protocol. At the primary completion date, one participant had reported two non-serious adverse events (cough and abdominal pain) that were identified as a potential case based on a Standardised MedDRA Queries (SMQ) search for Sampson's criteria. However, after medical review of the case, it was confirmed that this case was not indicative of a systemic hypersensitivity, anaphylaxis, or anaphylactoid reaction.
Time Frame	From Baseline up to 24 weeks after study drug discontinuation; the median (min-max) observation periods in Cohorts A, B, and C were 96.93 (36.1-188.1) weeks, 68.21 (56.7-129.4) weeks, and 69.43 (38.9-144.3) weeks, respectively.

Outcome Measure Data

Analysis Population Description

All participants who received at least one dose of emicizumab

Arm/Group Title	Cohort A: 1.5 mg/kg Emicizumab QW	Cohort B: 3 mg/kg Emicizumab Q2W	Cohort C: 6 mg/kg Emicizumab Q4W
Arm/Group Description	Participants received emicizumab at a loading dose of 3 milligrams per kilogram (mg/kg) once every week (QW) subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg QW SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.	Participants received emicizumab at a loading dose of 3 mg/kg QW subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 3 mg/kg once every 2 weeks (Q2W) SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.	Participants received emicizumab at a loading dose of 3 mg/kg QW subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 6 mg/kg once every 4 weeks (Q4W) SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Measure Participants	68	10	10
Count of Participants [Participants]	1 1.5%	0 0%	0 0%

65. Secondary Outcome

Title	Number of Participants With at Least One Adverse Event of Thromboembolic Event
Time Frame	From Baseline up to 24 weeks after study drug discontinuation; the median (min-max) observation periods in Cohorts A, B, and C were 96.93 (36.1-188.1) weeks, 68.21 (56.7-129.4) weeks, and 69.43 (38.9-144.3) weeks, respectively.

Outcome Measure Data

Analysis Population Description

All participants who received at least one dose of emicizumab

Arm/Group Title	Cohort A: 1.5 mg/kg Emicizumab QW	Cohort B: 3 mg/kg Emicizumab Q2W	Cohort C: 6 mg/kg Emicizumab Q4W
Arm/Group Description	Participants received emicizumab at a loading dose of 3 milligrams per kilogram (mg/kg) once every week (QW) subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg QW SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.	Participants received emicizumab at a loading dose of 3 mg/kg QW subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 3 mg/kg once every 2 weeks (Q2W) SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.	Participants received emicizumab at a loading dose of 3 mg/kg QW subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 6 mg/kg once every 4 weeks (Q4W) SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Measure Participants	68	10	10
Count of Participants [Participants]	0 0%	0 0%	0 0%

66. Secondary Outcome

Title	Number of Participants With at Least One Adverse Event of Thrombotic Microangiopathy
Time Frame	From Baseline up to 24 weeks after study drug discontinuation; the median (min-max) observation periods in Cohorts A, B, and C were 96.93 (36.1-188.1) weeks, 68.21 (56.7-129.4) weeks, and 69.43 (38.9-144.3) weeks, respectively.

Outcome Measure Data

Analysis Population Description

All participants who received at least one dose of emicizumab

Arm/Group Title	Cohort A: 1.5 mg/kg Emicizumab QW	Cohort B: 3 mg/kg Emicizumab Q2W	Cohort C: 6 mg/kg Emicizumab Q4W
Arm/Group Description	Participants received emicizumab at a loading dose of 3 milligrams per kilogram (mg/kg) once every week (QW) subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg QW SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.	Participants received emicizumab at a loading dose of 3 mg/kg QW subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 3 mg/kg once every 2 weeks (Q2W) SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.	Participants received emicizumab at a loading dose of 3 mg/kg QW subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 6 mg/kg once every 4 weeks (Q4W) SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Measure Participants	68	10	10
Count of Participants [Participants]	0 0%	0 0%	0 0%

67. Secondary Outcome

Title	Number of Participants Testing Negative or Positive for the Presence of Anti-Drug Antibodies (ADAs), Including Neutralizing ADAs, During the Study
Description	'Total ADA Negative' is the sum of all subjects who tested negative for ADA in the 2 following categories: 'ADA Negative', those who are pre-dose ADA negative or are missing pre-dose ADA data and who have all negative post-dose ADA results; and 'ADA Negative (Treatment Unaffected)', a subset who are pre-dose ADA positive but do not have a ≥4-fold increase in post-dose ADA levels compared to baseline measurement. 'Total ADA Positive' is the sum of all subjects who tested positive for ADA in the 2 following categories: 'ADA Positive (Treatment Boosted)', those who are pre-dose ADA positive and have a ≥4-fold increase in post-dose ADA levels compared to baseline measurement; and 'ADA Positive (Treatment Induced)', those who are pre-dose ADA negative or missing data and who have at least one post-dose ADA positive sample. ADA-positive samples were further analyzed for neutralizing capacity using a modified FVIII chromogenic assay; if also positive, they were considered neutralizing ADAs.
Time Frame	Predose (0 hour) at Weeks 1, 5, 17, 33, 49, 57; then every 12 weeks until study completion (up to 188 weeks)

Outcome Measure Data

Analysis Population Description

All participants who received at least one dose of emicizumab

Arm/Group Title	Cohort A: 1.5 mg/kg Emicizumab QW	Cohort B: 3 mg/kg Emicizumab Q2W	Cohort C: 6 mg/kg Emicizumab Q4W
Arm/Group Description	Participants received emicizumab at a loading dose of 3 milligrams per kilogram (mg/kg) once every week (QW) subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg QW SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.	Participants received emicizumab at a loading dose of 3 mg/kg QW subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 3 mg/kg once every 2 weeks (Q2W) SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.	Participants received emicizumab at a loading dose of 3 mg/kg QW subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 6 mg/kg once every 4 weeks (Q4W) SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Measure Participants	68	10	10
Total ADA Negative (Neg + Neg Unaffected)	63 92.6%	10 100%	9 90%
ADA Negative	59 86.8%	10 100%	9 90%
ADA Negative (Treatment Unaffected)	4 5.9%	0 0%	0 0%
Total ADA Positive (Boosted + Induced)	5 7.4%	0 0%	1 10%
ADA Positive (Treatment Boosted)	0 0%	0 0%	0 0%
ADA Positive (Treatment Induced)	5 7.4%	0 0%	1 10%
ADA Positive with Neutralizing ADAs	2 2.9%	0 0%	1 10%

68. Secondary Outcome

Title	Number of Participants by Hematology Parameter Laboratory Test Results as a Shift From Baseline to Highest WHO Grade Post-Baseline
Description	The World Health Organization (WHO) toxicity grading scale was used for determining the severity of laboratory abnormalities (i.e., test results outside of the reference range) for hematology parameters; Grade 0 is normal and Grades 1 to 4 represent worsening levels of the parameter outside of the normal range in the specified direction of the abnormality (high and low are above and below the range, respectively). Not every laboratory abnormality qualified as an adverse event (AE). A laboratory test result was reported as an AE if it met any of the following criteria: was accompanied by clinical symptoms; resulted in a change in study treatment; resulted in a medical intervention or a change in concomitant therapy; or was clinically significant in the investigator's judgment. Baseline was defined as the last available assessment prior to first receipt of study drug. Abs = absolute count
Time Frame	From Baseline until study completion (up to 188 weeks)

Outcome Measure Data

Analysis Population Description

All participants who received at least one dose of emicizumab

Arm/Group Title	Cohort A: 1.5 mg/kg Emicizumab QW	Cohort B: 3 mg/kg Emicizumab Q2W	Cohort C: 6 mg/kg Emicizumab Q4W
Arm/Group Description	Participants received emicizumab at a loading dose of 3 milligrams per kilogram (mg/kg) once every week (QW) subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg QW SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.	Participants received emicizumab at a loading dose of 3 mg/kg QW subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 3 mg/kg once every 2 weeks (Q2W) SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.	Participants received emicizumab at a loading dose of 3 mg/kg QW subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 6 mg/kg once every 4 weeks (Q4W) SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Measure Participants	68	10	10
Hemoglobin, Low - Grade 0 to 0	53 77.9%	10 100%	9 90%
Hemoglobin, Low - Grade 0 to 1	3 4.4%	0 0%	1 10%
Hemoglobin, Low - Grade 0 to 2	4 5.9%	0 0%	0 0%
Hemoglobin, Low - Grade 1 to 0	3 4.4%	0 0%	0 0%
Hemoglobin, Low - Grade 1 to 1	4 5.9%	0 0%	0 0%
Hemoglobin, Low - Grade 2 to 2	1 1.5%	0 0%	0 0%
Neutrophils (Total, Abs), Low - Grade 0 to 0	39 57.4%	7 70%	9 90%
Neutrophils (Total, Abs), Low - Grade 0 to 1	14 20.6%	1 10%	1 10%
Neutrophils (Total, Abs), Low - Grade 0 to 2	5 7.4%	2 20%	0 0%
Neutrophils (Total, Abs), Low - Grade 0 to 3	3 4.4%	0 0%	0 0%
Neutrophils (Total, Abs), Low - Grade 0 to 4	1 1.5%	0 0%	0 0%
Neutrophils (Total, Abs), Low - Grade 1 to 1	4 5.9%	0 0%	0 0%
Neutrophils (Total, Abs), Low - Grade 1 to 2	1 1.5%	0 0%	0 0%
Neutrophils (Total, Abs), Low - Grade 1 to 3	1 1.5%	0 0%	0 0%
Platelets, Low - Grade 0 to 0	68 100%	8 80%	10 100%
Platelets, Low - Grade 0 to 1	0 0%	2 20%	0 0%

69. Secondary Outcome

Title	Number of Participants by Chemistry Parameter Laboratory Test Results as a Shift From Baseline to Highest WHO Grade Post-Baseline
Description	The World Health Organization (WHO) toxicity grading scale was used for determining the severity of laboratory abnormalities (i.e., test results outside of the reference range) for chemistry parameters; Grade 0 is normal and Grades 1 to 4 represent worsening levels of the parameter outside of the normal range in the specified direction of the abnormality (high and low are above and below the range, respectively). Not every laboratory abnormality qualified as an adverse event (AE). A laboratory test result was reported as an AE if it met any of the following criteria: was accompanied by clinical symptoms; resulted in a change in study treatment; resulted in a medical intervention or a change in concomitant therapy; or was clinically significant in the investigator's judgment. Baseline was defined as the last available assessment prior to first receipt of study drug. SGOT/AST = aspartate aminotransferase; SGPT/ALT = alanine aminotransferase
Time Frame	From Baseline until study completion (up to 188 weeks)

Outcome Measure Data

Analysis Population Description

All participants who received at least one dose of emicizumab

Arm/Group Title	Cohort A: 1.5 mg/kg Emicizumab QW	Cohort B: 3 mg/kg Emicizumab Q2W	Cohort C: 6 mg/kg Emicizumab Q4W
Arm/Group Description	Participants received emicizumab at a loading dose of 3 milligrams per kilogram (mg/kg) once every week (QW) subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg QW SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.	Participants received emicizumab at a loading dose of 3 mg/kg QW subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 3 mg/kg once every 2 weeks (Q2W) SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.	Participants received emicizumab at a loading dose of 3 mg/kg QW subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 6 mg/kg once every 4 weeks (Q4W) SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Measure Participants	68	10	10
Alkaline Phosphatase, High - Grade 0 to 0	49 72.1%	8 80%	6 60%
Alkaline Phosphatase, High - Grade 0 to 1	4 5.9%	1 10%	0 0%
Alkaline Phosphatase, High - Grade 0 to 2	2 2.9%	0 0%	0 0%
Alkaline Phosphatase, High - Grade 1 to 1	6 8.8%	1 10%	2 20%
Alkaline Phosphatase, High - Grade 1 to 2	3 4.4%	0 0%	1 10%
Alkaline Phosphatase, High - Grade 2 to 1	1 1.5%	0 0%	0 0%
Alkaline Phosphatase, High - Grade 2 to 2	1 1.5%	0 0%	0 0%
Alkaline Phosphatase, High - Missing to Grade 0	0 0%	0 0%	1 10%
Alkaline Phosphatase, High - Missing to Grade 3	2 2.9%	0 0%	0 0%
Bilirubin, High - Grade 0 to 0	62 91.2%	10 100%	10 100%
Bilirubin, High - Grade 0 to 1	1 1.5%	0 0%	0 0%
Bilirubin, High - Grade 0 to 2	2 2.9%	0 0%	0 0%
Bilirubin, High - Missing to Grade 0	3 4.4%	0 0%	0 0%
Blood Urea Nitrogen, High - Grade 0 to 0	58 85.3%	10 100%	9 90%
Blood Urea Nitrogen, High - Grade 0 to 1	3 4.4%	0 0%	1 10%
Blood Urea Nitrogen, High - Grade 1 to 1	3 4.4%	0 0%	0 0%
Blood Urea Nitrogen, High - Missing to Grade 0	1 1.5%	0 0%	0 0%
Blood Urea Nitrogen, High - Missing to Grade 1	1 1.5%	0 0%	0 0%
Blood Urea Nitrogen, High - Missing to Grade 2	2 2.9%	0 0%	0 0%
Calcium (Corrected), Low - Grade 0 to 0	54 79.4%	7 70%	9 90%
Calcium (Corrected), Low - Grade 0 to 1	5 7.4%	3 30%	0 0%
Calcium (Corrected), Low - Grade 0 to 2	2 2.9%	0 0%	0 0%
Calcium (Corrected), Low - Grade 0 to 4	1 1.5%	0 0%	0 0%
Calcium (Corrected), Low - Missing to Grade 0	5 7.4%	0 0%	1 10%
Calcium (Corrected), Low - Missing to Grade 2	1 1.5%	0 0%	0 0%
Calcium (Corrected), High - Grade 0 to 0	61 89.7%	10 100%	9 90%
Calcium (Corrected), High - Grade 2 to 0	1 1.5%	0 0%	0 0%
Calcium (Corrected), High - Missing to Grade 0	6 8.8%	0 0%	1 10%
Creatinine, High - Grade 0 to 0	62 91.2%	9 90%	9 90%
Creatinine, High - Grade 0 to 1	5 7.4%	1 10%	0 0%
Creatinine, High - Grade 1 to 1	1 1.5%	0 0%	1 10%
Glucose, Low - Grade 0 to 0	57 83.8%	8 80%	8 80%
Glucose, Low - Grade 0 to 1	6 8.8%	2 20%	1 10%
Glucose, Low - Grade 0 to 2	1 1.5%	0 0%	0 0%
Glucose, Low - Grade 0 to 3	1 1.5%	0 0%	0 0%
Glucose, Low - Grade 1 to 0	0 0%	0 0%	1 10%
Glucose, Low - Grade 2 to 0	1 1.5%	0 0%	0 0%
Glucose, Low - Missing to Grade 0	1 1.5%	0 0%	0 0%
Glucose, Low - Missing to Grade 1	1 1.5%	0 0%	0 0%
Glucose, High - Grade 0 to 0	31 45.6%	5 50%	4 40%
Glucose, High - Grade 0 to 1	28 41.2%	3 30%	6 60%
Glucose, High - Grade 0 to 2	4 5.9%	0 0%	0 0%
Glucose, High - Grade 1 to 0	1 1.5%	1 10%	0 0%
Glucose, High - Grade 1 to 1	1 1.5%	0 0%	0 0%
Glucose, High - Grade 2 to 1	1 1.5%	0 0%	0 0%
Glucose, High - Grade 2 to 3	0 0%	1 10%	0 0%
Glucose, High - Missing to Grade 0	1 1.5%	0 0%	0 0%
Glucose, High - Missing to Grade 1	1 1.5%	0 0%	0 0%
Magnesium, Low - Grade 0 to 0	57 83.8%	9 90%	9 90%
Magnesium, Low - Grade 0 to 1	6 8.8%	1 10%	1 10%
Magnesium, Low - Grade 4 to 1	1 1.5%	0 0%	0 0%
Magnesium, Low - Missing to Grade 0	3 4.4%	0 0%	0 0%
Magnesium, Low - Missing to Grade 2	1 1.5%	0 0%	0 0%
Phosphorus, Low - Grade 0 to 0	64 94.1%	10 100%	10 100%
Phosphorus, Low - Missing to Grade 0	4 5.9%	0 0%	0 0%
Potassium, Low - Grade 0 to 0	61 89.7%	9 90%	10 100%
Potassium, Low - Grade 0 to 1	5 7.4%	1 10%	0 0%
Potassium, Low - Grade 0 to 2	1 1.5%	0 0%	0 0%
Potassium, Low - Grade 1 to 0	1 1.5%	0 0%	0 0%
Potassium, High - Grade 0 to 0	66 97.1%	10 100%	10 100%
Potassium, High - Grade 0 to 1	1 1.5%	0 0%	0 0%
Potassium, High - Grade 0 to 4	1 1.5%	0 0%	0 0%
SGOT/AST, High - Grade 0 to 0	54 79.4%	8 80%	9 90%
SGOT/AST, High - Grade 0 to 1	9 13.2%	1 10%	1 10%
SGOT/AST, High - Grade 0 to 2	1 1.5%	0 0%	0 0%
SGOT/AST, High - Grade 1 to 1	3 4.4%	0 0%	0 0%
SGOT/AST, High - Missing to Grade 1	1 1.5%	1 10%	0 0%
SGPT/ALT, High - Grade 0 to 0	52 76.5%	10 100%	9 90%
SGPT/ALT, High - Grade 0 to 1	8 11.8%	0 0%	0 0%
SGPT/ALT, High - Grade 0 to 2	4 5.9%	0 0%	0 0%
SGPT/ALT, High - Grade 0 to 3	1 1.5%	0 0%	0 0%
SGPT/ALT, High - Grade 1 to 1	2 2.9%	0 0%	1 10%
SGPT/ALT, High - Missing to Grade 0	1 1.5%	0 0%	0 0%
Sodium, Low - Grade 0 to 0	45 66.2%	8 80%	8 80%
Sodium, Low - Grade 0 to 1	18 26.5%	1 10%	0 0%
Sodium, Low - Grade 0 to 2	2 2.9%	0 0%	0 0%
Sodium, Low - Grade 1 to 0	0 0%	0 0%	2 20%
Sodium, Low - Grade 1 to 1	2 2.9%	1 10%	0 0%
Sodium, Low - Grade 1 to 2	1 1.5%	0 0%	0 0%
Sodium, High - Grade 0 to 0	58 85.3%	9 90%	10 100%
Sodium, High - Grade 0 to 1	8 11.8%	1 10%	0 0%
Sodium, High - Grade 0 to 2	1 1.5%	0 0%	0 0%
Sodium, High - Grade 0 to 4	1 1.5%	0 0%	0 0%

70. Secondary Outcome

Title	Plasma Trough Concentration (Ctrough) of Emicizumab
Description	Pre-dose (trough) plasma concentrations of emicizumab were analyzed using a validated enzyme-linked immunosorbent assay (ELISA). The lower limit of quantitation was 0.1 micrograms per milliliter (μg/mL).
Time Frame	Predose (0 hour) at Weeks 1, 2, 3, 4, 5, 7, 9, 13, 17, 21, 25, 29, 33, 37, 41, 49, 57, 69, 81, 93, 105, 117, 129, 141, 153, 165, and 177

Outcome Measure Data

Analysis Population Description

Participants who received at least one dose of emicizumab and had at least one post-dose emicizumab plasma concentration result available

Arm/Group Title	Cohort A: 1.5 mg/kg Emicizumab QW	Cohort B: 3 mg/kg Emicizumab Q2W	Cohort C: 6 mg/kg Emicizumab Q4W
Arm/Group Description	Participants received emicizumab at a loading dose of 3 milligrams per kilogram (mg/kg) once every week (QW) subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg QW SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.	Participants received emicizumab at a loading dose of 3 mg/kg QW subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 3 mg/kg once every 2 weeks (Q2W) SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.	Participants received emicizumab at a loading dose of 3 mg/kg QW subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 6 mg/kg once every 4 weeks (Q4W) SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Measure Participants	68	10	10
Week 1	NA (NA)	NA (NA)	NA (NA)
Week 2	18.2 (5.5)	17.0 (3.9)	17.2 (4.1)
Week 3	31.6 (5.6)	31.7 (6.8)	33.9 (5.8)
Week 4	42.9 (8.0)	42.4 (9.5)	44.7 (7.0)
Week 5	53.3 (10.6)	51.8 (10.5)	56.4 (12.3)
Week 7	51.2 (10.5)	51.5 (9.6)	59.9 (24.6)
Week 9	49.9 (9.7)	51.9 (11.2)	39.3 (16.7)
Week 13	48.3 (13.3)	45.3 (10.8)	37.1 (10.6)
Week 17	46.1 (11.2)	48.7 (10.4)	36.3 (6.1)
Week 21	45.2 (11.1)	43.9 (11.0)	36.2 (12.4)
Week 25	46.9 (11.7)	41.9 (8.5)	33.7 (8.9)
Week 29	47.9 (13.0)	46.7 (5.1)	34.4 (9.0)
Week 33	51.3 (13.8)	51.0 (6.8)	34.7 (11.2)
Week 37	51.0 (15.3)	50.4 (6.4)	35.9 (9.1)
Week 41	48.5 (14.2)	55.3 (10.7)	38.1 (9.9)
Week 49	49.4 (12.6)	48.6 (9.2)	32.4 (7.5)
Week 57	46.2 (15.9)	46.4 (9.8)	28.5 (10.7)
Week 69	46.4 (16.0)	54.7 (11.5)	41.1 (5.2)
Week 81	45.6 (14.2)	38.0 (5.3)	35.7 (21.2)
Week 93	44.3 (13.8)	41.2 (6.6)	41.6 (26.8)
Week 105	46.9 (15.9)	43.4 (5.7)	34.2 (14.4)
Week 117	37.8 (12.3)	46.6 (10.2)	37.1 (12.9)
Week 129	39.7 (13.8)
Week 141	46.5 (17.2)
Week 153	39.5 (15.6)
Week 165	39.9 (17.8)
Week 177	38.9 (19.0)

Adverse Events

Time Frame	From Baseline up to 24 weeks after study drug discontinuation; the median (min-max) observation periods in Cohorts A, B, and C were 96.93 (36.1-188.1) weeks, 68.21 (56.7-129.4) weeks, and 69.43 (38.9-144.3) weeks, respectively.
Arm/Group Title	Cohort A: 1.5 mg/kg Emicizumab QW		Cohort B: 3 mg/kg Emicizumab Q2W		Cohort C: 6 mg/kg Emicizumab Q4W
Arm/Group Description	Participants received emicizumab at a loading dose of 3 milligrams per kilogram (mg/kg) once every week (QW) subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg QW SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.		Participants received emicizumab at a loading dose of 3 mg/kg QW subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 3 mg/kg once every 2 weeks (Q2W) SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.		Participants received emicizumab at a loading dose of 3 mg/kg QW subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 6 mg/kg once every 4 weeks (Q4W) SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
All Cause Mortality
	Cohort A: 1.5 mg/kg Emicizumab QW		Cohort B: 3 mg/kg Emicizumab Q2W		Cohort C: 6 mg/kg Emicizumab Q4W
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/68 (0%)		0/10 (0%)		0/10 (0%)
Serious Adverse Events
	Cohort A: 1.5 mg/kg Emicizumab QW		Cohort B: 3 mg/kg Emicizumab Q2W		Cohort C: 6 mg/kg Emicizumab Q4W
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	23/68 (33.8%)		1/10 (10%)		3/10 (30%)
Gastrointestinal disorders
Mouth haemorrhage	1/68 (1.5%)	1	0/10 (0%)	0	0/10 (0%)	0
General disorders
Catheter site haematoma	1/68 (1.5%)	1	0/10 (0%)	0	0/10 (0%)	0
Infections and infestations
Appendicitis	1/68 (1.5%)	1	0/10 (0%)	0	1/10 (10%)	1
Bronchiolitis	1/68 (1.5%)	1	0/10 (0%)	0	0/10 (0%)	0
Epididymitis	1/68 (1.5%)	1	0/10 (0%)	0	0/10 (0%)	0
Acute sinusitis	1/68 (1.5%)	1	0/10 (0%)	0	0/10 (0%)	0
Bronchitis	1/68 (1.5%)	1	0/10 (0%)	0	0/10 (0%)	0
Peritonsillar abscess	1/68 (1.5%)	1	0/10 (0%)	0	0/10 (0%)	0
Tonsillitis	1/68 (1.5%)	1	0/10 (0%)	0	0/10 (0%)	0
Vascular device infection	3/68 (4.4%)	3	0/10 (0%)	0	0/10 (0%)	0
Injury, poisoning and procedural complications
Clavicle fracture	1/68 (1.5%)	1	0/10 (0%)	0	0/10 (0%)	0
Fall	1/68 (1.5%)	1	0/10 (0%)	0	0/10 (0%)	0
Head injury	1/68 (1.5%)	1	0/10 (0%)	0	0/10 (0%)	0
Ligament sprain	1/68 (1.5%)	1	0/10 (0%)	0	0/10 (0%)	0
Mouth injury	1/68 (1.5%)	1	0/10 (0%)	0	0/10 (0%)	0
Traumatic haematoma	1/68 (1.5%)	1	0/10 (0%)	0	0/10 (0%)	0
Investigations
Neutralising antibodies positive	0/68 (0%)	0	0/10 (0%)	0	1/10 (10%)	1
Metabolism and nutrition disorders
Ketoacidosis	0/68 (0%)	0	1/10 (10%)	1	0/10 (0%)	0
Musculoskeletal and connective tissue disorders
Haemarthrosis	2/68 (2.9%)	2	0/10 (0%)	0	0/10 (0%)	0
Haematoma muscle	3/68 (4.4%)	3	0/10 (0%)	0	0/10 (0%)	0
Nervous system disorders
Headache	1/68 (1.5%)	1	0/10 (0%)	0	0/10 (0%)	0
Respiratory, thoracic and mediastinal disorders
Asthma	1/68 (1.5%)	2	0/10 (0%)	0	0/10 (0%)	0
Vascular disorders
Haemorrhage	2/68 (2.9%)	2	0/10 (0%)	0	1/10 (10%)	1
Haematoma	2/68 (2.9%)	2	0/10 (0%)	0	0/10 (0%)	0
Other (Not Including Serious) Adverse Events
	Cohort A: 1.5 mg/kg Emicizumab QW		Cohort B: 3 mg/kg Emicizumab Q2W		Cohort C: 6 mg/kg Emicizumab Q4W
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	64/68 (94.1%)		9/10 (90%)		10/10 (100%)
Blood and lymphatic system disorders
Anaemia	2/68 (2.9%)	2	0/10 (0%)	0	1/10 (10%)	1
Ear and labyrinth disorders
Middle ear effusion	0/68 (0%)	0	0/10 (0%)	0	1/10 (10%)	1
Gastrointestinal disorders
Abdominal pain	4/68 (5.9%)	4	2/10 (20%)	2	0/10 (0%)	0
Abdominal pain upper	4/68 (5.9%)	6	0/10 (0%)	0	1/10 (10%)	1
Constipation	4/68 (5.9%)	4	1/10 (10%)	1	0/10 (0%)	0
Diarrhoea	12/68 (17.6%)	16	3/10 (30%)	5	0/10 (0%)	0
Nausea	3/68 (4.4%)	3	1/10 (10%)	2	1/10 (10%)	1
Vomiting	13/68 (19.1%)	15	2/10 (20%)	2	0/10 (0%)	0
Dental caries	5/68 (7.4%)	7	1/10 (10%)	1	0/10 (0%)	0
General disorders
Injection site reaction	22/68 (32.4%)	44	2/10 (20%)	6	6/10 (60%)	19
Pain	0/68 (0%)	0	1/10 (10%)	1	0/10 (0%)	0
Pyrexia	21/68 (30.9%)	44	6/10 (60%)	8	4/10 (40%)	5
Swelling face	1/68 (1.5%)	1	1/10 (10%)	1	0/10 (0%)	0
Peripheral swelling	2/68 (2.9%)	2	0/10 (0%)	0	1/10 (10%)	1
Vaccination site erythema	3/68 (4.4%)	3	0/10 (0%)	0	1/10 (10%)	1
Immune system disorders
Seasonal allergy	4/68 (5.9%)	4	1/10 (10%)	1	0/10 (0%)	0
Infections and infestations
Bronchitis	7/68 (10.3%)	10	0/10 (0%)	0	0/10 (0%)	0
Conjunctivitis	3/68 (4.4%)	7	0/10 (0%)	0	1/10 (10%)	2
Ear infection	4/68 (5.9%)	4	0/10 (0%)	0	0/10 (0%)	0
Gastroenteritis	8/68 (11.8%)	9	0/10 (0%)	0	0/10 (0%)	0
Influenza	8/68 (11.8%)	13	1/10 (10%)	2	0/10 (0%)	0
Nasopharyngitis	29/68 (42.6%)	53	3/10 (30%)	11	4/10 (40%)	10
Otitis media	7/68 (10.3%)	8	0/10 (0%)	0	0/10 (0%)	0
Rhinitis	3/68 (4.4%)	4	0/10 (0%)	0	1/10 (10%)	1
Sinusitis	2/68 (2.9%)	2	0/10 (0%)	0	1/10 (10%)	2
Tinea versicolour	0/68 (0%)	0	1/10 (10%)	1	0/10 (0%)	0
Tonsilitis	7/68 (10.3%)	13	0/10 (0%)	0	0/10 (0%)	0
Tracheitis	1/68 (1.5%)	1	1/10 (10%)	1	0/10 (0%)	0
Upper respiratory tract infection	23/68 (33.8%)	44	0/10 (0%)	0	2/10 (20%)	2
Varicella	4/68 (5.9%)	4	0/10 (0%)	0	0/10 (0%)	0
Gastrointestinal infection	4/68 (5.9%)	4	0/10 (0%)	0	0/10 (0%)	0
Paronychia	1/68 (1.5%)	2	0/10 (0%)	0	1/10 (10%)	1
Pharyngitis	4/68 (5.9%)	7	0/10 (0%)	0	0/10 (0%)	0
Injury, poisoning and procedural complications
Contusion	11/68 (16.2%)	70	0/10 (0%)	0	1/10 (10%)	2
Fall	10/68 (14.7%)	21	1/10 (10%)	1	1/10 (10%)	1
Head injury	3/68 (4.4%)	3	1/10 (10%)	1	0/10 (0%)	0
Joint injury	3/68 (4.4%)	4	1/10 (10%)	1	0/10 (0%)	0
Skin laceration	5/68 (7.4%)	6	0/10 (0%)	0	0/10 (0%)	0
Ligament sprain	8/68 (11.8%)	11	0/10 (0%)	0	1/10 (10%)	1
Limb injury	6/68 (8.8%)	6	0/10 (0%)	0	0/10 (0%)	0
Skin abrasion	8/68 (11.8%)	15	0/10 (0%)	0	0/10 (0%)	0
Investigations
Indeterminable ABO blood type	1/68 (1.5%)	1	1/10 (10%)	1	1/10 (10%)	1
Metabolism and nutrition disorders
Diabetes mellitus	0/68 (0%)	0	1/10 (10%)	1	0/10 (0%)	0
Iron deficiency	3/68 (4.4%)	3	0/10 (0%)	0	1/10 (10%)	2
Musculoskeletal and connective tissue disorders
Arthralgia	8/68 (11.8%)	19	2/10 (20%)	2	2/10 (20%)	13
Groin pain	0/68 (0%)	0	0/10 (0%)	0	1/10 (10%)	1
Limb discomfort	0/68 (0%)	0	0/10 (0%)	0	1/10 (10%)	1
Neck pain	0/68 (0%)	0	0/10 (0%)	0	1/10 (10%)	1
Pain in extremity	6/68 (8.8%)	6	0/10 (0%)	0	3/10 (30%)	5
Arthropathy	0/68 (0%)	0	1/10 (10%)	1	0/10 (0%)	0
Synovitis	0/68 (0%)	0	1/10 (10%)	1	0/10 (0%)	0
Nervous system disorders
Headache	12/68 (17.6%)	17	1/10 (10%)	10	2/10 (20%)	2
Product Issues
Device breakage	0/68 (0%)	0	1/10 (10%)	1	0/10 (0%)	0
Device malfunction	0/68 (0%)	0	0/10 (0%)	0	1/10 (10%)	1
Psychiatric disorders
Anxiety	0/68 (0%)	0	0/10 (0%)	0	1/10 (10%)	1
Respiratory, thoracic and mediastinal disorders
Cough	21/68 (30.9%)	28	4/10 (40%)	4	0/10 (0%)	0
Oropharyngeal pain	5/68 (7.4%)	8	2/10 (20%)	4	0/10 (0%)	0
Rhinorrhoea	5/68 (7.4%)	5	1/10 (10%)	1	0/10 (0%)	0
Skin and subcutaneous tissue disorders
Erythema	2/68 (2.9%)	3	0/10 (0%)	0	1/10 (10%)	3
Rash	5/68 (7.4%)	6	0/10 (0%)	0	0/10 (0%)	0
Rash pruritic	1/68 (1.5%)	1	1/10 (10%)	1	0/10 (0%)	0
Seborrhoeic dermatitis	0/68 (0%)	0	1/10 (10%)	1	0/10 (0%)	0
Urticaria	4/68 (5.9%)	5	0/10 (0%)	0	0/10 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.