Study of Emicizumab Prophylaxis in Participants With Hemophilia A With or Without Inhibitors Undergoing Minor Surgical Procedures

• Sponsor: Genentech, Inc. (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT03361137
• Collaborator: (none)
• Enrollment: 14
• Locations: 8
• Arms: 5
• Actual Duration (Months): 20.5
• Patients Per Site: 1.8
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This Phase IV, multicenter study will evaluate whether participants with Hemophilia A (PwHA) with or without inhibitors receiving emicizumab prophylaxis can safely undergo minor surgical procedures without additional prophylactic bypassing agents (BPA; for participants with inhibitors) or factor VIII (FVIII; for participants without inhibitors).

Condition or Disease	Intervention/Treatment	Phase
Hemophilia A	Drug: Emicizumab	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 14 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase IV, Multicenter, Single-Arm, Open-Label Study of Emicizumab Prophylaxis in Patients With Hemophilia A With or Without Inhibitors Undergoing Minor Surgical Procedures
• Actual Study Start Date: Jun 28, 2018
• Actual Primary Completion Date: Mar 13, 2020
• Actual Study Completion Date: Mar 13, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: PwHA With Inhibitors, Emicizumab: Surgery Not Performed Cohort This cohort included participants with Hemophilia A (PwHA) with inhibitors that were enrolled but did not have surgery. All participants received emicizumab via subcutaneous (SC) injection at a loading dose of 3 milligrams of medication per kilogram of body weight (mg/kg) once weekly for the first 4 weeks, followed by 1.5 mg/kg once weekly, or by any other approved maintenance regimen, as long as they continued to derive sufficient benefit. Participants must have received all loading doses prior to surgery and planned to continue emicizumab for a minimum of 1 month after surgery.	Drug: Emicizumab; Emicizumab via SC injection at a loading dose 3 mg/kg once weekly for the first 4 weeks, followed by 1.5 mg/kg once weekly, or by any other approved maintenance regimen, as long as the participant continues to derive sufficient benefit. Dosing was to be adjusted if the participant had a significant change in body weight.; Other Names: Hemlibra® ACE910 RG6013
Experimental: PwHA With Inhibitors, Emicizumab: CVAD Removal Cohort This cohort included participants with Hemophilia A (PwHA) with inhibitors that were enrolled and had surgery for central venous access device (CVAD) removal. All participants received emicizumab via subcutaneous (SC) injection at a loading dose of 3 milligrams of medication per kilogram of body weight (mg/kg) once weekly for the first 4 weeks, followed by 1.5 mg/kg once weekly, or by any other approved maintenance regimen, as long as they continued to derive sufficient benefit. Participants must have received all loading doses prior to surgery and planned to continue emicizumab for a minimum of 1 month after surgery.	Drug: Emicizumab; Emicizumab via SC injection at a loading dose 3 mg/kg once weekly for the first 4 weeks, followed by 1.5 mg/kg once weekly, or by any other approved maintenance regimen, as long as the participant continues to derive sufficient benefit. Dosing was to be adjusted if the participant had a significant change in body weight.; Other Names: Hemlibra® ACE910 RG6013
Experimental: PwHA With Inhibitors, Emicizumab: Simple Dental Extraction Cohort This cohort included participants with Hemophilia A (PwHA) with inhibitors that were enrolled and had surgery for simple dental extraction. All participants received emicizumab via subcutaneous (SC) injection at a loading dose of 3 milligrams of medication per kilogram of body weight (mg/kg) once weekly for the first 4 weeks, followed by 1.5 mg/kg once weekly, or by any other approved maintenance regimen, as long as they continued to derive sufficient benefit. Participants must have received all loading doses prior to surgery and planned to continue emicizumab for a minimum of 1 month after surgery.	Drug: Emicizumab; Emicizumab via SC injection at a loading dose 3 mg/kg once weekly for the first 4 weeks, followed by 1.5 mg/kg once weekly, or by any other approved maintenance regimen, as long as the participant continues to derive sufficient benefit. Dosing was to be adjusted if the participant had a significant change in body weight.; Other Names: Hemlibra® ACE910 RG6013
Experimental: PwHA Without Inhibitors, Emicizumab: CVAD Removal Cohort This cohort included participants with Hemophilia A (PwHA) without inhibitors that were enrolled and had surgery for central venous access device (CVAD) removal. All participants received emicizumab via subcutaneous (SC) injection at a loading dose of 3 milligrams of medication per kilogram of body weight (mg/kg) once weekly for the first 4 weeks, followed by 1.5 mg/kg once weekly, or by any other approved maintenance regimen, as long as they continued to derive sufficient benefit. Participants must have received all loading doses prior to surgery and planned to continue emicizumab for a minimum of 1 month after surgery.	Drug: Emicizumab; Emicizumab via SC injection at a loading dose 3 mg/kg once weekly for the first 4 weeks, followed by 1.5 mg/kg once weekly, or by any other approved maintenance regimen, as long as the participant continues to derive sufficient benefit. Dosing was to be adjusted if the participant had a significant change in body weight.; Other Names: Hemlibra® ACE910 RG6013
Experimental: PwHA Without Inhibitors, Emicizumab: Simple Dental Extraction Cohort This cohort included participants with Hemophilia A (PwHA) without inhibitors that were enrolled and had surgery for simple dental extraction. All participants received emicizumab via subcutaneous (SC) injection at a loading dose of 3 milligrams of medication per kilogram of body weight (mg/kg) once weekly for the first 4 weeks, followed by 1.5 mg/kg once weekly, or by any other approved maintenance regimen, as long as they continued to derive sufficient benefit. Participants must have received all loading doses prior to surgery and planned to continue emicizumab for a minimum of 1 month after surgery.	Drug: Emicizumab; Emicizumab via SC injection at a loading dose 3 mg/kg once weekly for the first 4 weeks, followed by 1.5 mg/kg once weekly, or by any other approved maintenance regimen, as long as the participant continues to derive sufficient benefit. Dosing was to be adjusted if the participant had a significant change in body weight.; Other Names: Hemlibra® ACE910 RG6013

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants Without Excessive Bleeding at Surgical Sites and Did Not Require BPA/FVIII Use for Bleeding Related to the Surgery, From the Start of Surgery Until Discharge, as Measured by the ISTH Hemostatic Efficacy Scale [Determined at the time of discharge (within approximately 48 hours after surgery)]

   The International Society on Thrombosis and Haemostasis (ISTH) Assessment of Hemostatic Response for Surgical Procedures scale (see reference PubMed ID:25059285) has four categories, listed here in order of best to worst response: Excellent, Good, Fair, and Poor. The participant's bleeding related to surgery was evaluated by the healthcare professional who performed the procedure using the hemostatic efficacy scale, with an absence of excessive bleeding at the surgical site indicated by a good to excellent rating. The endpoint was met when the response to "Intraoperative and/or postoperative blood loss increased over expectation for the non-hemophilic patient determined at the time of discharge" was "0 to <10%" or "10% to < 25%" AND the response to the question "Did the patient use any bypassing agent (BPA)/factor VIII (FVIII) for the surgery before the discharge?" was "No".

2. Percentage of Participants With Excessive Bleeding at Surgical Sites and Required BPA/FVIII Use for Treating Bleeding Related to the Surgery, From the Start of Surgery Until Discharge, as Measured by the ISTH Hemostatic Efficacy Scale [Determined at the time of discharge (within approximately 48 hours after surgery)]

   The ISTH Assessment of Hemostatic Response for Surgical Procedures scale (see reference PubMed ID:25059285) has four categories, listed here in order of best to worst response: Excellent, Good, Fair, and Poor. The participant's bleeding related to surgery was evaluated by the healthcare professional who performed the procedure using the hemostatic efficacy scale, with excessive bleeding at the surgical site indicated by a fair to poor rating. The endpoint was met when the response to "Intraoperative and/or postoperative blood loss increased over expectation for the non-hemophilic patient determined at the time of discharge" was "25% to <50%" or "≥50%" AND the response to the question "Did the patient use any bypassing agent (BPA)/factor VIII (FVIII) for the surgery before the discharge?" was "Yes". The percentage of participants by type and dose of BPA/FVIII used to treat the bleeding is also reported. rFVIIa = recombinant activated human factor VII (eptacog alfa [activated])

3. Percentage of Participants Who, After Being Discharged From Surgery, Experienced Bleeds That Were Either Related or Unrelated to Surgery and Also Required BPA/FVIII Use [Within 48 hours (if discharged home), and 8 and 28 days after surgery]

   Post-surgical bleeding information was self-reported by participants (or the participant's legally authorized representative) on the "Bleed and Medication Diary". Bypassing agents (BPAs)/factor VIII (FVIII) used to treat excessive bleeding were also self-reported by participants if it was self-administered. BPAs/FVIII administered by the investigators to treat the bleeding were reported on the "Concomitant Medications" case report form page. The percentage of participants by type and dose of BPA/FVIII used to treat the bleeding is also reported. rFVIIa = recombinant activated human factor VII (eptacog alfa [activated])

4. Emicizumab Plasma Concentration on the Day of Surgery [Approximately 24 hours prior to surgery]

   Enrolled participants received a minimum of four loading doses of emicizumab prior to their surgical procedure. Pharmacokinetic blood samples were obtained at study sites 24 hours before the procedures in order to describe emicizumab plasma concentration on the day of surgery for each of the inhibitor and non-inhibitor cohorts.

5. Safety Summary of the Number of Participants With at Least One Adverse Event [From Baseline up to 30 days after surgery]

   All adverse events (AEs) that occurred after informed consent was obtained were coded using the Medical Dictionary for Regulatory Activities (MedDRA) v23.0, summarized by severity according to the World Health Organization (WHO) toxicity grading scale (Grade 1 is mild; Grade 2 is moderate; Grade 3 is severe; Grade 4 is life-threatening; and Grade 5 is death related to AE), and tabulated by body system and preferred term (PT) for individual events within each system organ class (SOC). For each AE, the investigator independently assessed its severity and seriousness, and whether it was considered to be related to the study drug.

6. Percentage of Participants With Surgical Complications Requiring Hospitalization or Return to Surgery [Within 48 hours after surgery, and 8 and 28 days after initial surgery]

   This safety endpoint was a composite endpoint. Surgical complications were entered as adverse events on the case report form page with "Other suspected causes" marked as "Study Surgery or Procedure". This endpoint was met when response to "It required or prolonged inpatient hospitalization" was checked OR response to "Was procedure/surgery performed?" was "Yes".

7. Percentage of Participants Who Needed Blood/Blood Product Transfusions During Surgery [Within 48 hours after surgery, and 8 and 28 days after initial surgery]

   The percentage of participants who needed blood or blood product transfusions (e.g., platelets, plasma, etc.) during surgery was evaluated.

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Any age (newborn and older)

• Ability to comply with the study protocol, in the investigator's judgment

• Diagnosis of hemophilia A and current or history of an inhibitor (Bethesda titer ≥0.6 Bethesda units) and currently using bypassing agents (BPAs) for breakthrough bleeds (for PwHA with inhibitors)

• Diagnosis of hemophilia A and no history of an inhibitor (Bethesda titer <0.6 Bethesda units), or a history of an inhibitor that has been tolerized for >5 years and using FVIII for breakthrough bleeds (for PwHA without inhibitors)

• Plan to receive at least 4 loading doses of emicizumab and been adherent to emicizumab prophylaxis by the time of surgery

• Undergoing minor surgery within 60 days of study enrollment. Other minor surgical procedures could be included upon consultation and approval of Medical Monitor, but examples include central venous catheter insertion/removal/replacement, simple dental extractions, colonoscopy, cystoscopy, or endoscopy with biopsy, excisional skin biopsy

• Must plan to continue emicizumab prophylaxis for at least 1 month after surgery

• For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods that result in a failure rate of <1% per year during the study period

Exclusion Criteria:

• Diagnosis of a bleeding disorder other than hemophilia A

• Participants who have been tolerized to Factor VIII products (for PwHA with inhibitors)

• Tolerized to FVIII products for <5 years (for PwHA without inhibitors)

• Using FVIII products to treat breakthrough bleeds (for PwHA with inhibitors)

• Treatment with BPAs or FVIII within 24 hours prior to surgical procedure

• Undergoing a major surgical procedure

• Previous (in the past 12 months) or current treatment for thromboembolic disease (with the exception of previous catheter-associated thrombosis for which anti-thrombotic treatment is not currently ongoing) or current signs of thromboembolic disease

• Other conditions (e.g., certain autoimmune diseases, including but not limited to diseases such as systemic lupus erythematosus, inflammatory bowel disease, and antiphospholipid syndrome) that may increase the risk of bleeding or thrombosis

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

• Would refuse treatment with blood or blood products, if necessary

• Any serious medical condition or abnormality in clinical laboratory tests that, in the investigator's judgment, precludes the participant's safe participation in and completion of the study

• Pregnant or lactating, or intending to become pregnant during the study; women of childbearing potential must have a negative serum pregnancy test result within 7 days before Study Day 1

• Treatment with any of the following: An investigational drug to treat or reduce the risk of hemophilic bleeds within 5 half-lives of last drug administration before Study Day 1; A non-hemophilia-related investigational drug within the last 30 days or 5 half-lives before Study Day 1 (whichever is longer); An investigational drug concurrently

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

• Known human immunodeficiency virus (HIV) infection with CD4 count < 200 cells/microlitre within 24 weeks prior to enrollment

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Childrens Hospital of LA	Los Angeles	California	United States	90027
2	Stanford University/Lucile Packard Children's Hospital	Palo Alto	California	United States	94304
3	University of Florida	Gainesville	Florida	United States	32607
4	Indiana Hemophilia & Thrombosis center	Indianapolis	Indiana	United States	46260
5	Newark Beth Israel Medical Center	Newark	New Jersey	United States	07112
6	State University of New York at Buffalo; Women's and Children's Hospital of Buffalo	Buffalo	New York	United States	14209
7	Cook Childrens Medical Center	Fort Worth	Texas	United States	76104
8	University of Utah; Division of Gastroenterology/Hepatology	Salt Lake City	Utah	United States	84132

Sponsors and Collaborators

• Genentech, Inc.

Investigators

• Study Director: Clinical Trials, Hoffmann-La Roche

Study Documents (Full-Text)

• Study Protocol - Mar 15, 2019
• Statistical Analysis Plan - May 26, 2020

More Information

Publications

• Blanchette VS, Key NS, Ljung LR, Manco-Johnson MJ, van den Berg HM, Srivastava A; Subcommittee on Factor VIII, Factor IX and Rare Coagulation Disorders of the Scientific and Standardization Committee of the International Society on Thrombosis and Hemostasis. Definitions in hemophilia: communication from the SSC of the ISTH. J Thromb Haemost. 2014 Nov;12(11):1935-9. doi: 10.1111/jth.12672. Epub 2014 Sep 3.

• Responsible Party: Genentech, Inc.
• ClinicalTrials.gov Identifier: NCT03361137
• Other Study ID Numbers: ML39791
• First Posted: Dec 4, 2017
• Last Update Posted: Mar 1, 2021
• Last Verified: Feb 1, 2021

• 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

Arm/Group Title	PwHA With Inhibitors, Emicizumab: Surgery Not Performed Cohort	PwHA With Inhibitors, Emicizumab: CVAD Removal Cohort	PwHA With Inhibitors, Emicizumab: Simple Dental Extraction Cohort	PwHA Without Inhibitors, Emicizumab: CVAD Removal Cohort	PwHA Without Inhibitors, Emicizumab: Simple Dental Extraction Cohort
Arm/Group Description	This cohort included participants with Hemophilia A (PwHA) with inhibitors that were enrolled but did not have surgery. All participants received emicizumab via subcutaneous (SC) injection at a loading dose of 3 milligrams of medication per kilogram of body weight (mg/kg) once weekly for the first 4 weeks, followed by 1.5 mg/kg once weekly, or by any other approved maintenance regimen, as long as they continued to derive sufficient benefit. Participants must have received all loading doses prior to surgery and planned to continue emicizumab for a minimum of 1 month after surgery.	This cohort included participants with Hemophilia A (PwHA) with inhibitors that were enrolled and had surgery for central venous access device (CVAD) removal. All participants received emicizumab via subcutaneous (SC) injection at a loading dose of 3 milligrams of medication per kilogram of body weight (mg/kg) once weekly for the first 4 weeks, followed by 1.5 mg/kg once weekly, or by any other approved maintenance regimen, as long as they continued to derive sufficient benefit. Participants must have received all loading doses prior to surgery and planned to continue emicizumab for a minimum of 1 month after surgery.	This cohort included participants with Hemophilia A (PwHA) with inhibitors that were enrolled and had surgery for simple dental extraction. All participants received emicizumab via subcutaneous (SC) injection at a loading dose of 3 milligrams of medication per kilogram of body weight (mg/kg) once weekly for the first 4 weeks, followed by 1.5 mg/kg once weekly, or by any other approved maintenance regimen, as long as they continued to derive sufficient benefit. Participants must have received all loading doses prior to surgery and planned to continue emicizumab for a minimum of 1 month after surgery.	This cohort included participants with Hemophilia A (PwHA) without inhibitors that were enrolled and had surgery for central venous access device (CVAD) removal. All participants received emicizumab via subcutaneous (SC) injection at a loading dose of 3 milligrams of medication per kilogram of body weight (mg/kg) once weekly for the first 4 weeks, followed by 1.5 mg/kg once weekly, or by any other approved maintenance regimen, as long as they continued to derive sufficient benefit. Participants must have received all loading doses prior to surgery and planned to continue emicizumab for a minimum of 1 month after surgery.	This cohort included participants with Hemophilia A (PwHA) without inhibitors that were enrolled and had surgery for simple dental extraction. All participants received emicizumab via subcutaneous (SC) injection at a loading dose of 3 milligrams of medication per kilogram of body weight (mg/kg) once weekly for the first 4 weeks, followed by 1.5 mg/kg once weekly, or by any other approved maintenance regimen, as long as they continued to derive sufficient benefit. Participants must have received all loading doses prior to surgery and planned to continue emicizumab for a minimum of 1 month after surgery.
Period Title: Overall Study
STARTED	1	9	1	2	1
COMPLETED	0	9	1	2	1
NOT COMPLETED	1	0	0	0	0

Baseline Characteristics

Arm/Group Title	PwHA With Inhibitors, Emicizumab: Surgery Not Performed Cohort	PwHA With Inhibitors, Emicizumab: CVAD Removal Cohort	PwHA With Inhibitors, Emicizumab: Simple Dental Extraction Cohort	PwHA Without Inhibitors, Emicizumab: CVAD Removal Cohort	PwHA Without Inhibitors, Emicizumab: Simple Dental Extraction Cohort	Total
Arm/Group Description	This cohort included participants with Hemophilia A (PwHA) with inhibitors that were enrolled but did not have surgery. All participants received emicizumab via subcutaneous (SC) injection at a loading dose of 3 milligrams of medication per kilogram of body weight (mg/kg) once weekly for the first 4 weeks, followed by 1.5 mg/kg once weekly, or by any other approved maintenance regimen, as long as they continued to derive sufficient benefit. Participants must have received all loading doses prior to surgery and planned to continue emicizumab for a minimum of 1 month after surgery.	This cohort included participants with Hemophilia A (PwHA) with inhibitors that were enrolled and had surgery for central venous access device (CVAD) removal. All participants received emicizumab via subcutaneous (SC) injection at a loading dose of 3 milligrams of medication per kilogram of body weight (mg/kg) once weekly for the first 4 weeks, followed by 1.5 mg/kg once weekly, or by any other approved maintenance regimen, as long as they continued to derive sufficient benefit. Participants must have received all loading doses prior to surgery and planned to continue emicizumab for a minimum of 1 month after surgery.	This cohort included participants with Hemophilia A (PwHA) with inhibitors that were enrolled and had surgery for simple dental extraction. All participants received emicizumab via subcutaneous (SC) injection at a loading dose of 3 milligrams of medication per kilogram of body weight (mg/kg) once weekly for the first 4 weeks, followed by 1.5 mg/kg once weekly, or by any other approved maintenance regimen, as long as they continued to derive sufficient benefit. Participants must have received all loading doses prior to surgery and planned to continue emicizumab for a minimum of 1 month after surgery.	This cohort included participants with Hemophilia A (PwHA) without inhibitors that were enrolled and had surgery for central venous access device (CVAD) removal. All participants received emicizumab via subcutaneous (SC) injection at a loading dose of 3 milligrams of medication per kilogram of body weight (mg/kg) once weekly for the first 4 weeks, followed by 1.5 mg/kg once weekly, or by any other approved maintenance regimen, as long as they continued to derive sufficient benefit. Participants must have received all loading doses prior to surgery and planned to continue emicizumab for a minimum of 1 month after surgery.	This cohort included participants with Hemophilia A (PwHA) without inhibitors that were enrolled and had surgery for simple dental extraction. All participants received emicizumab via subcutaneous (SC) injection at a loading dose of 3 milligrams of medication per kilogram of body weight (mg/kg) once weekly for the first 4 weeks, followed by 1.5 mg/kg once weekly, or by any other approved maintenance regimen, as long as they continued to derive sufficient benefit. Participants must have received all loading doses prior to surgery and planned to continue emicizumab for a minimum of 1 month after surgery.	Total of all reporting groups
Overall Participants	1	9	1	2	1	14
Age, Customized (Count of Participants)
<18 Years Old	1 100%	7 77.8%	1 100%	2 100%	0 0%	11 78.6%
≥18 to <65 Years Old	0 0%	2 22.2%	0 0%	0 0%	1 100%	3 21.4%
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Male	1 100%	9 100%	1 100%	2 100%	1 100%	14 100%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	3 33.3%	1 100%	1 50%	0 0%	5 35.7%
Not Hispanic or Latino	1 100%	6 66.7%	0 0%	1 50%	1 100%	9 64.3%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Race/Ethnicity, Customized (Count of Participants)
Asian	0 0%	1 11.1%	0 0%	0 0%	0 0%	1 7.1%
Black or African American	1 100%	0 0%	0 0%	0 0%	1 100%	2 14.3%
White	0 0%	5 55.6%	1 100%	1 50%	0 0%	7 50%
Multiple	0 0%	2 22.2%	0 0%	0 0%	0 0%	2 14.3%
Unknown	0 0%	1 11.1%	0 0%	1 50%	0 0%	2 14.3%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants Without Excessive Bleeding at Surgical Sites and Did Not Require BPA/FVIII Use for Bleeding Related to the Surgery, From the Start of Surgery Until Discharge, as Measured by the ISTH Hemostatic Efficacy Scale
Description	The International Society on Thrombosis and Haemostasis (ISTH) Assessment of Hemostatic Response for Surgical Procedures scale (see reference PubMed ID:25059285) has four categories, listed here in order of best to worst response: Excellent, Good, Fair, and Poor. The participant's bleeding related to surgery was evaluated by the healthcare professional who performed the procedure using the hemostatic efficacy scale, with an absence of excessive bleeding at the surgical site indicated by a good to excellent rating. The endpoint was met when the response to "Intraoperative and/or postoperative blood loss increased over expectation for the non-hemophilic patient determined at the time of discharge" was "0 to <10%" or "10% to < 25%" AND the response to the question "Did the patient use any bypassing agent (BPA)/factor VIII (FVIII) for the surgery before the discharge?" was "No".
Time Frame	Determined at the time of discharge (within approximately 48 hours after surgery)

Outcome Measure Data

Analysis Population Description

Efficacy Analysis Population: All enrolled participants who received emicizumab and underwent a minor surgery. One participant with hemophilia A with inhibitors did not undergo surgery and was therefore excluded from efficacy analysis.

Arm/Group Title	PwHA With Inhibitors, Emicizumab: Surgery Not Performed Cohort	PwHA With Inhibitors, Emicizumab: CVAD Removal Cohort	PwHA With Inhibitors, Emicizumab: Simple Dental Extraction Cohort	PwHA Without Inhibitors, Emicizumab: CVAD Removal Cohort	PwHA Without Inhibitors, Emicizumab: Simple Dental Extraction Cohort
Arm/Group Description	This cohort included participants with Hemophilia A (PwHA) with inhibitors that were enrolled but did not have surgery. All participants received emicizumab via subcutaneous (SC) injection at a loading dose of 3 milligrams of medication per kilogram of body weight (mg/kg) once weekly for the first 4 weeks, followed by 1.5 mg/kg once weekly, or by any other approved maintenance regimen, as long as they continued to derive sufficient benefit. Participants must have received all loading doses prior to surgery and planned to continue emicizumab for a minimum of 1 month after surgery.	This cohort included participants with Hemophilia A (PwHA) with inhibitors that were enrolled and had surgery for central venous access device (CVAD) removal. All participants received emicizumab via subcutaneous (SC) injection at a loading dose of 3 milligrams of medication per kilogram of body weight (mg/kg) once weekly for the first 4 weeks, followed by 1.5 mg/kg once weekly, or by any other approved maintenance regimen, as long as they continued to derive sufficient benefit. Participants must have received all loading doses prior to surgery and planned to continue emicizumab for a minimum of 1 month after surgery.	This cohort included participants with Hemophilia A (PwHA) with inhibitors that were enrolled and had surgery for simple dental extraction. All participants received emicizumab via subcutaneous (SC) injection at a loading dose of 3 milligrams of medication per kilogram of body weight (mg/kg) once weekly for the first 4 weeks, followed by 1.5 mg/kg once weekly, or by any other approved maintenance regimen, as long as they continued to derive sufficient benefit. Participants must have received all loading doses prior to surgery and planned to continue emicizumab for a minimum of 1 month after surgery.	This cohort included participants with Hemophilia A (PwHA) without inhibitors that were enrolled and had surgery for central venous access device (CVAD) removal. All participants received emicizumab via subcutaneous (SC) injection at a loading dose of 3 milligrams of medication per kilogram of body weight (mg/kg) once weekly for the first 4 weeks, followed by 1.5 mg/kg once weekly, or by any other approved maintenance regimen, as long as they continued to derive sufficient benefit. Participants must have received all loading doses prior to surgery and planned to continue emicizumab for a minimum of 1 month after surgery.	This cohort included participants with Hemophilia A (PwHA) without inhibitors that were enrolled and had surgery for simple dental extraction. All participants received emicizumab via subcutaneous (SC) injection at a loading dose of 3 milligrams of medication per kilogram of body weight (mg/kg) once weekly for the first 4 weeks, followed by 1.5 mg/kg once weekly, or by any other approved maintenance regimen, as long as they continued to derive sufficient benefit. Participants must have received all loading doses prior to surgery and planned to continue emicizumab for a minimum of 1 month after surgery.
Measure Participants	0	9	1	2	1
Number [Percentage of participants]	66.7 6670%	100.0 1111.1%	100.0 10000%	100.0 5000%

2. Primary Outcome

Title	Percentage of Participants With Excessive Bleeding at Surgical Sites and Required BPA/FVIII Use for Treating Bleeding Related to the Surgery, From the Start of Surgery Until Discharge, as Measured by the ISTH Hemostatic Efficacy Scale
Description	The ISTH Assessment of Hemostatic Response for Surgical Procedures scale (see reference PubMed ID:25059285) has four categories, listed here in order of best to worst response: Excellent, Good, Fair, and Poor. The participant's bleeding related to surgery was evaluated by the healthcare professional who performed the procedure using the hemostatic efficacy scale, with excessive bleeding at the surgical site indicated by a fair to poor rating. The endpoint was met when the response to "Intraoperative and/or postoperative blood loss increased over expectation for the non-hemophilic patient determined at the time of discharge" was "25% to <50%" or "≥50%" AND the response to the question "Did the patient use any bypassing agent (BPA)/factor VIII (FVIII) for the surgery before the discharge?" was "Yes". The percentage of participants by type and dose of BPA/FVIII used to treat the bleeding is also reported. rFVIIa = recombinant activated human factor VII (eptacog alfa [activated])
Time Frame	Determined at the time of discharge (within approximately 48 hours after surgery)

Outcome Measure Data

Analysis Population Description

Efficacy Analysis Population: All enrolled participants who received emicizumab and underwent a minor surgery. One participant with hemophilia A with inhibitors did not undergo surgery and was therefore excluded from efficacy analysis.

Arm/Group Title	PwHA With Inhibitors, Emicizumab: Surgery Not Performed Cohort	PwHA With Inhibitors, Emicizumab: CVAD Removal Cohort	PwHA With Inhibitors, Emicizumab: Simple Dental Extraction Cohort	PwHA Without Inhibitors, Emicizumab: CVAD Removal Cohort	PwHA Without Inhibitors, Emicizumab: Simple Dental Extraction Cohort
Arm/Group Description	This cohort included participants with Hemophilia A (PwHA) with inhibitors that were enrolled but did not have surgery. All participants received emicizumab via subcutaneous (SC) injection at a loading dose of 3 milligrams of medication per kilogram of body weight (mg/kg) once weekly for the first 4 weeks, followed by 1.5 mg/kg once weekly, or by any other approved maintenance regimen, as long as they continued to derive sufficient benefit. Participants must have received all loading doses prior to surgery and planned to continue emicizumab for a minimum of 1 month after surgery.	This cohort included participants with Hemophilia A (PwHA) with inhibitors that were enrolled and had surgery for central venous access device (CVAD) removal. All participants received emicizumab via subcutaneous (SC) injection at a loading dose of 3 milligrams of medication per kilogram of body weight (mg/kg) once weekly for the first 4 weeks, followed by 1.5 mg/kg once weekly, or by any other approved maintenance regimen, as long as they continued to derive sufficient benefit. Participants must have received all loading doses prior to surgery and planned to continue emicizumab for a minimum of 1 month after surgery.	This cohort included participants with Hemophilia A (PwHA) with inhibitors that were enrolled and had surgery for simple dental extraction. All participants received emicizumab via subcutaneous (SC) injection at a loading dose of 3 milligrams of medication per kilogram of body weight (mg/kg) once weekly for the first 4 weeks, followed by 1.5 mg/kg once weekly, or by any other approved maintenance regimen, as long as they continued to derive sufficient benefit. Participants must have received all loading doses prior to surgery and planned to continue emicizumab for a minimum of 1 month after surgery.	This cohort included participants with Hemophilia A (PwHA) without inhibitors that were enrolled and had surgery for central venous access device (CVAD) removal. All participants received emicizumab via subcutaneous (SC) injection at a loading dose of 3 milligrams of medication per kilogram of body weight (mg/kg) once weekly for the first 4 weeks, followed by 1.5 mg/kg once weekly, or by any other approved maintenance regimen, as long as they continued to derive sufficient benefit. Participants must have received all loading doses prior to surgery and planned to continue emicizumab for a minimum of 1 month after surgery.	This cohort included participants with Hemophilia A (PwHA) without inhibitors that were enrolled and had surgery for simple dental extraction. All participants received emicizumab via subcutaneous (SC) injection at a loading dose of 3 milligrams of medication per kilogram of body weight (mg/kg) once weekly for the first 4 weeks, followed by 1.5 mg/kg once weekly, or by any other approved maintenance regimen, as long as they continued to derive sufficient benefit. Participants must have received all loading doses prior to surgery and planned to continue emicizumab for a minimum of 1 month after surgery.
Measure Participants	0	9	1	2	1
Total with Excessive Bleeding and Received BPA/FVIII	11.1 1110%	0.0 0%	0.0 0%	0.0 0%
Treated with 2 mg rFVIIa	11.1 1110%	0.0 0%	0.0 0%	0.0 0%

3. Primary Outcome

Title	Percentage of Participants Who, After Being Discharged From Surgery, Experienced Bleeds That Were Either Related or Unrelated to Surgery and Also Required BPA/FVIII Use
Description	Post-surgical bleeding information was self-reported by participants (or the participant's legally authorized representative) on the "Bleed and Medication Diary". Bypassing agents (BPAs)/factor VIII (FVIII) used to treat excessive bleeding were also self-reported by participants if it was self-administered. BPAs/FVIII administered by the investigators to treat the bleeding were reported on the "Concomitant Medications" case report form page. The percentage of participants by type and dose of BPA/FVIII used to treat the bleeding is also reported. rFVIIa = recombinant activated human factor VII (eptacog alfa [activated])
Time Frame	Within 48 hours (if discharged home), and 8 and 28 days after surgery

Outcome Measure Data

Analysis Population Description

Efficacy Analysis Population: All enrolled participants who received emicizumab and underwent a minor surgery. One participant with hemophilia A with inhibitors did not undergo surgery and was therefore excluded from efficacy analysis.

Arm/Group Title	PwHA With Inhibitors, Emicizumab: Surgery Not Performed Cohort	PwHA With Inhibitors, Emicizumab: CVAD Removal Cohort	PwHA With Inhibitors, Emicizumab: Simple Dental Extraction Cohort	PwHA Without Inhibitors, Emicizumab: CVAD Removal Cohort	PwHA Without Inhibitors, Emicizumab: Simple Dental Extraction Cohort
Arm/Group Description	This cohort included participants with Hemophilia A (PwHA) with inhibitors that were enrolled but did not have surgery. All participants received emicizumab via subcutaneous (SC) injection at a loading dose of 3 milligrams of medication per kilogram of body weight (mg/kg) once weekly for the first 4 weeks, followed by 1.5 mg/kg once weekly, or by any other approved maintenance regimen, as long as they continued to derive sufficient benefit. Participants must have received all loading doses prior to surgery and planned to continue emicizumab for a minimum of 1 month after surgery.	This cohort included participants with Hemophilia A (PwHA) with inhibitors that were enrolled and had surgery for central venous access device (CVAD) removal. All participants received emicizumab via subcutaneous (SC) injection at a loading dose of 3 milligrams of medication per kilogram of body weight (mg/kg) once weekly for the first 4 weeks, followed by 1.5 mg/kg once weekly, or by any other approved maintenance regimen, as long as they continued to derive sufficient benefit. Participants must have received all loading doses prior to surgery and planned to continue emicizumab for a minimum of 1 month after surgery.	This cohort included participants with Hemophilia A (PwHA) with inhibitors that were enrolled and had surgery for simple dental extraction. All participants received emicizumab via subcutaneous (SC) injection at a loading dose of 3 milligrams of medication per kilogram of body weight (mg/kg) once weekly for the first 4 weeks, followed by 1.5 mg/kg once weekly, or by any other approved maintenance regimen, as long as they continued to derive sufficient benefit. Participants must have received all loading doses prior to surgery and planned to continue emicizumab for a minimum of 1 month after surgery.	This cohort included participants with Hemophilia A (PwHA) without inhibitors that were enrolled and had surgery for central venous access device (CVAD) removal. All participants received emicizumab via subcutaneous (SC) injection at a loading dose of 3 milligrams of medication per kilogram of body weight (mg/kg) once weekly for the first 4 weeks, followed by 1.5 mg/kg once weekly, or by any other approved maintenance regimen, as long as they continued to derive sufficient benefit. Participants must have received all loading doses prior to surgery and planned to continue emicizumab for a minimum of 1 month after surgery.	This cohort included participants with Hemophilia A (PwHA) without inhibitors that were enrolled and had surgery for simple dental extraction. All participants received emicizumab via subcutaneous (SC) injection at a loading dose of 3 milligrams of medication per kilogram of body weight (mg/kg) once weekly for the first 4 weeks, followed by 1.5 mg/kg once weekly, or by any other approved maintenance regimen, as long as they continued to derive sufficient benefit. Participants must have received all loading doses prior to surgery and planned to continue emicizumab for a minimum of 1 month after surgery.
Measure Participants	0	9	1	2	1
Total with Post-surgical Bleeding and Received BPA/FVIII	22.2 2220%	100.0 1111.1%	0.0 0%	0.0 0%
Treated with 2 mg rFVIIa	11.1 1110%	100.0 1111.1%	0.0 0%	0.0 0%
Treated with 5 mg rFVIIa	11.1 1110%	0.0 0%	0.0 0%	0.0 0%

4. Primary Outcome

Title	Emicizumab Plasma Concentration on the Day of Surgery
Description	Enrolled participants received a minimum of four loading doses of emicizumab prior to their surgical procedure. Pharmacokinetic blood samples were obtained at study sites 24 hours before the procedures in order to describe emicizumab plasma concentration on the day of surgery for each of the inhibitor and non-inhibitor cohorts.
Time Frame	Approximately 24 hours prior to surgery

Outcome Measure Data

Analysis Population Description

Efficacy Analysis Population: All enrolled participants who received emicizumab and underwent a minor surgery. One participant with hemophilia A with inhibitors did not undergo surgery and was therefore excluded from this analysis.

Arm/Group Title	PwHA With Inhibitors, Emicizumab: All Surgery Cohorts	PwHA Without Inhibitors, Emicizumab: All Surgery Cohorts
Arm/Group Description	This analysis set included all participants with Hemophilia A (PwHA) with inhibitors who had undergone surgery. All participants received emicizumab via subcutaneous (SC) injection at a loading dose of 3 milligrams of medication per kilogram of body weight (mg/kg) once weekly for the first 4 weeks, followed by 1.5 mg/kg once weekly, or by any other approved maintenance regimen, as long as they continued to derive sufficient benefit. Participants must have received all loading doses prior to surgery and planned to continue emicizumab for a minimum of 1 month after surgery.	This analysis set included all participants with Hemophilia A (PwHA) without inhibitors who had undergone surgery. All participants received emicizumab via subcutaneous (SC) injection at a loading dose of 3 milligrams of medication per kilogram of body weight (mg/kg) once weekly for the first 4 weeks, followed by 1.5 mg/kg once weekly, or by any other approved maintenance regimen, as long as they continued to derive sufficient benefit. Participants must have received all loading doses prior to surgery and planned to continue emicizumab for a minimum of 1 month after surgery.
Measure Participants	10	3
Mean (Standard Deviation) [micrograms per millilitre (μg/mL)]	53.74 (28.67)	38.40 (8.95)

5. Primary Outcome

Title	Safety Summary of the Number of Participants With at Least One Adverse Event
Description	All adverse events (AEs) that occurred after informed consent was obtained were coded using the Medical Dictionary for Regulatory Activities (MedDRA) v23.0, summarized by severity according to the World Health Organization (WHO) toxicity grading scale (Grade 1 is mild; Grade 2 is moderate; Grade 3 is severe; Grade 4 is life-threatening; and Grade 5 is death related to AE), and tabulated by body system and preferred term (PT) for individual events within each system organ class (SOC). For each AE, the investigator independently assessed its severity and seriousness, and whether it was considered to be related to the study drug.
Time Frame	From Baseline up to 30 days after surgery

Outcome Measure Data

Analysis Population Description

The analysis included all enrolled participants who provided informed consent.

Arm/Group Title	PwHA With Inhibitors, Emicizumab: Surgery Not Performed Cohort	PwHA With Inhibitors, Emicizumab: CVAD Removal Cohort	PwHA With Inhibitors, Emicizumab: Simple Dental Extraction Cohort	PwHA Without Inhibitors, Emicizumab: CVAD Removal Cohort	PwHA Without Inhibitors, Emicizumab: Simple Dental Extraction Cohort
Arm/Group Description	This cohort included participants with Hemophilia A (PwHA) with inhibitors that were enrolled but did not have surgery. All participants received emicizumab via subcutaneous (SC) injection at a loading dose of 3 milligrams of medication per kilogram of body weight (mg/kg) once weekly for the first 4 weeks, followed by 1.5 mg/kg once weekly, or by any other approved maintenance regimen, as long as they continued to derive sufficient benefit. Participants must have received all loading doses prior to surgery and planned to continue emicizumab for a minimum of 1 month after surgery.	This cohort included participants with Hemophilia A (PwHA) with inhibitors that were enrolled and had surgery for central venous access device (CVAD) removal. All participants received emicizumab via subcutaneous (SC) injection at a loading dose of 3 milligrams of medication per kilogram of body weight (mg/kg) once weekly for the first 4 weeks, followed by 1.5 mg/kg once weekly, or by any other approved maintenance regimen, as long as they continued to derive sufficient benefit. Participants must have received all loading doses prior to surgery and planned to continue emicizumab for a minimum of 1 month after surgery.	This cohort included participants with Hemophilia A (PwHA) with inhibitors that were enrolled and had surgery for simple dental extraction. All participants received emicizumab via subcutaneous (SC) injection at a loading dose of 3 milligrams of medication per kilogram of body weight (mg/kg) once weekly for the first 4 weeks, followed by 1.5 mg/kg once weekly, or by any other approved maintenance regimen, as long as they continued to derive sufficient benefit. Participants must have received all loading doses prior to surgery and planned to continue emicizumab for a minimum of 1 month after surgery.	This cohort included participants with Hemophilia A (PwHA) without inhibitors that were enrolled and had surgery for central venous access device (CVAD) removal. All participants received emicizumab via subcutaneous (SC) injection at a loading dose of 3 milligrams of medication per kilogram of body weight (mg/kg) once weekly for the first 4 weeks, followed by 1.5 mg/kg once weekly, or by any other approved maintenance regimen, as long as they continued to derive sufficient benefit. Participants must have received all loading doses prior to surgery and planned to continue emicizumab for a minimum of 1 month after surgery.	This cohort included participants with Hemophilia A (PwHA) without inhibitors that were enrolled and had surgery for simple dental extraction. All participants received emicizumab via subcutaneous (SC) injection at a loading dose of 3 milligrams of medication per kilogram of body weight (mg/kg) once weekly for the first 4 weeks, followed by 1.5 mg/kg once weekly, or by any other approved maintenance regimen, as long as they continued to derive sufficient benefit. Participants must have received all loading doses prior to surgery and planned to continue emicizumab for a minimum of 1 month after surgery.
Measure Participants	1	9	1	2	1
Any Adverse Event (AE)	1 100%	4 44.4%	0 0%	0 0%	0 0%
AE with Fatal Outcome	0 0%	0 0%	0 0%	0 0%	0 0%
Serious Adverse Event (SAE)	0 0%	0 0%	0 0%	0 0%	0 0%
SAE Leading to Withdrawal from Treatment	0 0%	0 0%	0 0%	0 0%	0 0%
SAE Leading to Dose Modification/Interruption	0 0%	0 0%	0 0%	0 0%	0 0%
Related SAE	0 0%	0 0%	0 0%	0 0%	0 0%
AE Leading to Withdrawal from Treatment	0 0%	0 0%	0 0%	0 0%	0 0%
AE Leading to Dose Modification/Interruption	0 0%	0 0%	0 0%	0 0%	0 0%
Related AE	0 0%	0 0%	0 0%	0 0%	0 0%
Related AE Leading to Withdrawal from Treatment	0 0%	0 0%	0 0%	0 0%	0 0%
Related AE Leading to Dose Modification/Interruption	0 0%	0 0%	0 0%	0 0%	0 0%
Grade 3-5 AE	0 0%	0 0%	0 0%	0 0%	0 0%

6. Primary Outcome

Title	Percentage of Participants With Surgical Complications Requiring Hospitalization or Return to Surgery
Description	This safety endpoint was a composite endpoint. Surgical complications were entered as adverse events on the case report form page with "Other suspected causes" marked as "Study Surgery or Procedure". This endpoint was met when response to "It required or prolonged inpatient hospitalization" was checked OR response to "Was procedure/surgery performed?" was "Yes".
Time Frame	Within 48 hours after surgery, and 8 and 28 days after initial surgery

Outcome Measure Data

Analysis Population Description

The analysis included all enrolled participants who received emicizumab and underwent a minor surgery. One participant with hemophilia A with inhibitors did not undergo surgery and was therefore excluded from analysis.

Arm/Group Title	PwHA With Inhibitors, Emicizumab: Surgery Not Performed Cohort	PwHA With Inhibitors, Emicizumab: CVAD Removal Cohort	PwHA With Inhibitors, Emicizumab: Simple Dental Extraction Cohort	PwHA Without Inhibitors, Emicizumab: CVAD Removal Cohort	PwHA Without Inhibitors, Emicizumab: Simple Dental Extraction Cohort
Arm/Group Description	This cohort included participants with Hemophilia A (PwHA) with inhibitors that were enrolled but did not have surgery. All participants received emicizumab via subcutaneous (SC) injection at a loading dose of 3 milligrams of medication per kilogram of body weight (mg/kg) once weekly for the first 4 weeks, followed by 1.5 mg/kg once weekly, or by any other approved maintenance regimen, as long as they continued to derive sufficient benefit. Participants must have received all loading doses prior to surgery and planned to continue emicizumab for a minimum of 1 month after surgery.	This cohort included participants with Hemophilia A (PwHA) with inhibitors that were enrolled and had surgery for central venous access device (CVAD) removal. All participants received emicizumab via subcutaneous (SC) injection at a loading dose of 3 milligrams of medication per kilogram of body weight (mg/kg) once weekly for the first 4 weeks, followed by 1.5 mg/kg once weekly, or by any other approved maintenance regimen, as long as they continued to derive sufficient benefit. Participants must have received all loading doses prior to surgery and planned to continue emicizumab for a minimum of 1 month after surgery.	This cohort included participants with Hemophilia A (PwHA) with inhibitors that were enrolled and had surgery for simple dental extraction. All participants received emicizumab via subcutaneous (SC) injection at a loading dose of 3 milligrams of medication per kilogram of body weight (mg/kg) once weekly for the first 4 weeks, followed by 1.5 mg/kg once weekly, or by any other approved maintenance regimen, as long as they continued to derive sufficient benefit. Participants must have received all loading doses prior to surgery and planned to continue emicizumab for a minimum of 1 month after surgery.	This cohort included participants with Hemophilia A (PwHA) without inhibitors that were enrolled and had surgery for central venous access device (CVAD) removal. All participants received emicizumab via subcutaneous (SC) injection at a loading dose of 3 milligrams of medication per kilogram of body weight (mg/kg) once weekly for the first 4 weeks, followed by 1.5 mg/kg once weekly, or by any other approved maintenance regimen, as long as they continued to derive sufficient benefit. Participants must have received all loading doses prior to surgery and planned to continue emicizumab for a minimum of 1 month after surgery.	This cohort included participants with Hemophilia A (PwHA) without inhibitors that were enrolled and had surgery for simple dental extraction. All participants received emicizumab via subcutaneous (SC) injection at a loading dose of 3 milligrams of medication per kilogram of body weight (mg/kg) once weekly for the first 4 weeks, followed by 1.5 mg/kg once weekly, or by any other approved maintenance regimen, as long as they continued to derive sufficient benefit. Participants must have received all loading doses prior to surgery and planned to continue emicizumab for a minimum of 1 month after surgery.
Measure Participants	0	9	1	2	1
Number [Percentage of participants]	0.0 0%	0.0 0%	0.0 0%	0.0 0%

7. Primary Outcome

Title	Percentage of Participants Who Needed Blood/Blood Product Transfusions During Surgery
Description	The percentage of participants who needed blood or blood product transfusions (e.g., platelets, plasma, etc.) during surgery was evaluated.
Time Frame	Within 48 hours after surgery, and 8 and 28 days after initial surgery

Outcome Measure Data

Analysis Population Description

The analysis included all enrolled participants who received emicizumab and underwent a minor surgery. One participant with hemophilia A with inhibitors did not undergo surgery and was therefore excluded from analysis.

Arm/Group Title	PwHA With Inhibitors, Emicizumab: Surgery Not Performed Cohort	PwHA With Inhibitors, Emicizumab: CVAD Removal Cohort	PwHA With Inhibitors, Emicizumab: Simple Dental Extraction Cohort	PwHA Without Inhibitors, Emicizumab: CVAD Removal Cohort	PwHA Without Inhibitors, Emicizumab: Simple Dental Extraction Cohort
Arm/Group Description	This cohort included participants with Hemophilia A (PwHA) with inhibitors that were enrolled but did not have surgery. All participants received emicizumab via subcutaneous (SC) injection at a loading dose of 3 milligrams of medication per kilogram of body weight (mg/kg) once weekly for the first 4 weeks, followed by 1.5 mg/kg once weekly, or by any other approved maintenance regimen, as long as they continued to derive sufficient benefit. Participants must have received all loading doses prior to surgery and planned to continue emicizumab for a minimum of 1 month after surgery.	This cohort included participants with Hemophilia A (PwHA) with inhibitors that were enrolled and had surgery for central venous access device (CVAD) removal. All participants received emicizumab via subcutaneous (SC) injection at a loading dose of 3 milligrams of medication per kilogram of body weight (mg/kg) once weekly for the first 4 weeks, followed by 1.5 mg/kg once weekly, or by any other approved maintenance regimen, as long as they continued to derive sufficient benefit. Participants must have received all loading doses prior to surgery and planned to continue emicizumab for a minimum of 1 month after surgery.	This cohort included participants with Hemophilia A (PwHA) with inhibitors that were enrolled and had surgery for simple dental extraction. All participants received emicizumab via subcutaneous (SC) injection at a loading dose of 3 milligrams of medication per kilogram of body weight (mg/kg) once weekly for the first 4 weeks, followed by 1.5 mg/kg once weekly, or by any other approved maintenance regimen, as long as they continued to derive sufficient benefit. Participants must have received all loading doses prior to surgery and planned to continue emicizumab for a minimum of 1 month after surgery.	This cohort included participants with Hemophilia A (PwHA) without inhibitors that were enrolled and had surgery for central venous access device (CVAD) removal. All participants received emicizumab via subcutaneous (SC) injection at a loading dose of 3 milligrams of medication per kilogram of body weight (mg/kg) once weekly for the first 4 weeks, followed by 1.5 mg/kg once weekly, or by any other approved maintenance regimen, as long as they continued to derive sufficient benefit. Participants must have received all loading doses prior to surgery and planned to continue emicizumab for a minimum of 1 month after surgery.	This cohort included participants with Hemophilia A (PwHA) without inhibitors that were enrolled and had surgery for simple dental extraction. All participants received emicizumab via subcutaneous (SC) injection at a loading dose of 3 milligrams of medication per kilogram of body weight (mg/kg) once weekly for the first 4 weeks, followed by 1.5 mg/kg once weekly, or by any other approved maintenance regimen, as long as they continued to derive sufficient benefit. Participants must have received all loading doses prior to surgery and planned to continue emicizumab for a minimum of 1 month after surgery.
Measure Participants	0	9	1	2	1
Number [Percentage of participants]	0.0 0%	0.0 0%	0.0 0%	0.0 0%

Adverse Events

Time Frame	From Baseline up to 30 days after surgery
Arm/Group Title	PwHA With Inhibitors, Emicizumab: Surgery Not Performed Cohort		PwHA With Inhibitors, Emicizumab: CVAD Removal Cohort		PwHA With Inhibitors, Emicizumab: Simple Dental Extraction Cohort		PwHA Without Inhibitors, Emicizumab: CVAD Removal Cohort		PwHA Without Inhibitors, Emicizumab: Simple Dental Extraction Cohort
Arm/Group Description	This cohort included participants with Hemophilia A (PwHA) with inhibitors that were enrolled but did not have surgery. All participants received emicizumab via subcutaneous (SC) injection at a loading dose of 3 milligrams of medication per kilogram of body weight (mg/kg) once weekly for the first 4 weeks, followed by 1.5 mg/kg once weekly, or by any other approved maintenance regimen, as long as they continued to derive sufficient benefit. Participants must have received all loading doses prior to surgery and planned to continue emicizumab for a minimum of 1 month after surgery.		This cohort included participants with Hemophilia A (PwHA) with inhibitors that were enrolled and had surgery for central venous access device (CVAD) removal. All participants received emicizumab via subcutaneous (SC) injection at a loading dose of 3 milligrams of medication per kilogram of body weight (mg/kg) once weekly for the first 4 weeks, followed by 1.5 mg/kg once weekly, or by any other approved maintenance regimen, as long as they continued to derive sufficient benefit. Participants must have received all loading doses prior to surgery and planned to continue emicizumab for a minimum of 1 month after surgery.		This cohort included participants with Hemophilia A (PwHA) with inhibitors that were enrolled and had surgery for simple dental extraction. All participants received emicizumab via subcutaneous (SC) injection at a loading dose of 3 milligrams of medication per kilogram of body weight (mg/kg) once weekly for the first 4 weeks, followed by 1.5 mg/kg once weekly, or by any other approved maintenance regimen, as long as they continued to derive sufficient benefit. Participants must have received all loading doses prior to surgery and planned to continue emicizumab for a minimum of 1 month after surgery.		This cohort included participants with Hemophilia A (PwHA) without inhibitors that were enrolled and had surgery for central venous access device (CVAD) removal. All participants received emicizumab via subcutaneous (SC) injection at a loading dose of 3 milligrams of medication per kilogram of body weight (mg/kg) once weekly for the first 4 weeks, followed by 1.5 mg/kg once weekly, or by any other approved maintenance regimen, as long as they continued to derive sufficient benefit. Participants must have received all loading doses prior to surgery and planned to continue emicizumab for a minimum of 1 month after surgery.		This cohort included participants with Hemophilia A (PwHA) without inhibitors that were enrolled and had surgery for simple dental extraction. All participants received emicizumab via subcutaneous (SC) injection at a loading dose of 3 milligrams of medication per kilogram of body weight (mg/kg) once weekly for the first 4 weeks, followed by 1.5 mg/kg once weekly, or by any other approved maintenance regimen, as long as they continued to derive sufficient benefit. Participants must have received all loading doses prior to surgery and planned to continue emicizumab for a minimum of 1 month after surgery.
All Cause Mortality
	PwHA With Inhibitors, Emicizumab: Surgery Not Performed Cohort		PwHA With Inhibitors, Emicizumab: CVAD Removal Cohort		PwHA With Inhibitors, Emicizumab: Simple Dental Extraction Cohort		PwHA Without Inhibitors, Emicizumab: CVAD Removal Cohort		PwHA Without Inhibitors, Emicizumab: Simple Dental Extraction Cohort
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/1 (0%)		0/9 (0%)		0/1 (0%)		0/2 (0%)		0/1 (0%)
Serious Adverse Events
	PwHA With Inhibitors, Emicizumab: Surgery Not Performed Cohort		PwHA With Inhibitors, Emicizumab: CVAD Removal Cohort		PwHA With Inhibitors, Emicizumab: Simple Dental Extraction Cohort		PwHA Without Inhibitors, Emicizumab: CVAD Removal Cohort		PwHA Without Inhibitors, Emicizumab: Simple Dental Extraction Cohort
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/1 (0%)		0/9 (0%)		0/1 (0%)		0/2 (0%)		0/1 (0%)
Other (Not Including Serious) Adverse Events
	PwHA With Inhibitors, Emicizumab: Surgery Not Performed Cohort		PwHA With Inhibitors, Emicizumab: CVAD Removal Cohort		PwHA With Inhibitors, Emicizumab: Simple Dental Extraction Cohort		PwHA Without Inhibitors, Emicizumab: CVAD Removal Cohort		PwHA Without Inhibitors, Emicizumab: Simple Dental Extraction Cohort
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/1 (100%)		4/9 (44.4%)		0/1 (0%)		0/2 (0%)		0/1 (0%)
Gastrointestinal disorders
Constipation	0/1 (0%)	0	1/9 (11.1%)	1	0/1 (0%)	0	0/2 (0%)	0	0/1 (0%)	0
General disorders
Pyrexia	1/1 (100%)	1	0/9 (0%)	0	0/1 (0%)	0	0/2 (0%)	0	0/1 (0%)	0
Injury, poisoning and procedural complications
Limb injury	1/1 (100%)	1	0/9 (0%)	0	0/1 (0%)	0	0/2 (0%)	0	0/1 (0%)	0
Procedural pain	0/1 (0%)	0	1/9 (11.1%)	1	0/1 (0%)	0	0/2 (0%)	0	0/1 (0%)	0
Nervous system disorders
Headache	1/1 (100%)	1	2/9 (22.2%)	2	0/1 (0%)	0	0/2 (0%)	0	0/1 (0%)	0
Product Issues
Device occlusion	1/1 (100%)	1	0/9 (0%)	0	0/1 (0%)	0	0/2 (0%)	0	0/1 (0%)	0
Surgical and medical procedures
Adhesiolysis	0/1 (0%)	0	1/9 (11.1%)	1	0/1 (0%)	0	0/2 (0%)	0	0/1 (0%)	0
Vascular disorders
Haematoma	0/1 (0%)	0	1/9 (11.1%)	1	0/1 (0%)	0	0/2 (0%)	0	0/1 (0%)	0

Limitations/Caveats

No definitive efficacy conclusions were drawn due to study limitations that included early enrollment termination, limited number of participants enrolled, and evaluation in only 2 minor surgical procedure types.

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.