A Study of Ravulizumab (ALXN1210) in Children and Adolescents With Paroxysmal Nocturnal Hemoglobinuria

• Sponsor: Alexion Pharmaceuticals (Industry)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT03406507
• Collaborator: (none)
• Enrollment: 13
• Locations: 9
• Arm: 1
• Anticipated Duration (Months): 88.2
• Patients Per Site: 1.4
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

The purpose of this study was to assess the pharmacokinetics (PK), pharmacodynamics (PD), safety, and efficacy of ravulizumab in pediatric participants with paroxysmal nocturnal hemoglobinuria (PNH).

Condition or Disease	Intervention/Treatment	Phase
Paroxysmal Nocturnal Hemoglobinuria	Biological: Ravulizumab	Phase 3

Detailed Description

The study consists of a 4-week Screening Period, a 26-week Primary Evaluation Period, and an Extension Period of up to 4 years (with the exception of any country-specific mandates), whichever occurs first.

Efficacy and safety data are reported for the 26-week Primary Evaluation Period only. Analyses were conducted separately for complement inhibitor treatment-naïve participants and eculizumab-experienced participants.

Study Design

• Study Type: Interventional
• Actual Enrollment: 13 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 3, Open-Label Study of ALXN1210 in Children and Adolescents With Paroxysmal Nocturnal Hemoglobinuria (PNH)
• Actual Study Start Date: Feb 22, 2018
• Actual Primary Completion Date: Mar 25, 2020
• Anticipated Study Completion Date: Jun 30, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Ravulizumab Complement inhibitor treatment-naïve and eculizumab-experienced participants received ravulizumab.	Biological: Ravulizumab; Single intravenous (IV) loading dose on Day 1, followed by regular IV maintenance dosing beginning on Day 15, based on weight.; Other Names: ALXN1210 Ultomiris

Outcome Measures

Primary Outcome Measures

1. Maximum Observed Serum Concentration (Cmax) Of Ravulizumab [Week 1 (Day 1), Week 2 (Day 15), Week 10 (Day 71), and Week 18 (Day 127)]

   Blood samples for determination of ravulizumab Cmax were collected before and after administration of study drug at designated time points. Results are reported in micrograms/milliliter (μg/mL).

2. Trough Serum Concentration (Ctrough) Of Ravulizumab [Week 2 (Day 15), Week 10 (Day 71), Week 18 (Day 127), Week 26 (Day 183)]

   Blood samples for determination of ravulizumab Ctrough were collected before and after administration of study drug at designated time points. Trough serum concentration was measured at end of dosing interval at steady state. Results are reported in μg/mL.

3. Mean Accumulation Ratio For Cmax Of Ravulizumab Following The Last Maintenance Dose Relative To The First Maintenance Dose [Week 18]

   Blood samples for determination of ravulizumab accumulation ratio for Cmax were collected before and after administration of study drug at designated time points. The accumulation ratio was calculated as Cmax from the last maintenance dose (Week 18) divided by Cmax from the first maintenance dose (Week 2).

4. Change In Free Complement Component C5 (C5) Concentrations Over Time [Baseline, Weeks 2, 10, 18, and 26 (end of infusion)]

   Blood samples for determination of free C5 were collected before and after administration of study drug at designated time points.

5. Change In Chicken Red Blood Cell (cRBC) Hemolytic Activity Over Time [Baseline, Weeks 2, 10, 18, and 26]

   Blood samples for determination of cRBC hemolytic activity were collected before and after administration of study drug at designated time points.

6. Mean Accumulation Ratio For Ctrough Of Ravulizumab Following The Last Maintenance Dose Relative To The First Maintenance Dose [Week 18]

   Blood samples for determination of ravulizumab accumulation ratio for Ctrough were collected before and after administration of study drug at designated time points. The accumulation ratio was calculated as Ctrough from the last maintenance dose (Week 18) divided by Ctrough from the first maintenance dose (Week 2).

Secondary Outcome Measures

1. Percentage Change From Baseline At Week 26 In Lactate Dehydrogenase (LDH) Levels [Baseline, Week 26]

   Blood and urine samples for determination of LDH levels were collected at designated time points. Baseline was defined as the average of all assessments analyzed by the central laboratory prior to first study drug administration.

2. Percentage Of Participants Who Achieved Transfusion Avoidance (TA) [Week 26]

   Transfusion avoidance was defined as the proportion of participants who remained transfusion-free and did not require a transfusion according to protocol-specified guidelines. Point estimates and 2-sided 95% exact confidence intervals (CIs) were computed. Participants who withdrew from the study due to lack of efficacy during the Primary Evaluation Period were considered as non-responders and were counted in the group needing transfusion. For participants who withdrew from the study for any other reason during the Primary Evaluation Period, their data up to the time of withdrawal was used to assess TA.

3. Change In Quality Of Life (QoL) From Baseline To Week 26 [Baseline, Week 26]

   Quality of life was measured by Pediatric Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue Questionnaire (participants ≥ 5 years of age), a 13-item questionnaire that assesses fatigue and its impact upon daily activities and function over the preceding 7 days. Each item is scored on a 5-point scale, and total scores range from 0 to 52, with a higher score indicating better QoL. The scoring guideline for the Pediatric FACIT-Fatigue instrument was used to calculate a FACIT-Fatigue score. Changes from baseline in FACIT-Fatigue scores were summarized at baseline and at the study visits where this assessment was collected up to Day 183 (Week 26). At each study visit, the proportion of participants who showed an improvement of at least 3 points for the Pediatric FACIT-Fatigue scores were summarized by point estimates and 2-sided 95% exact CIs.

4. Percentage Of Participants With Stabilized Hemoglobin At Week 26 [Week 26]

   Stabilized hemoglobin was defined as avoidance of a ≥ 2 g/dL decrease in hemoglobin level from baseline in the absence of transfusion through Week 26. Point estimates and 2-sided 95% exact CIs were computed. Participants who withdrew from the study due to lack of efficacy during the Primary Evaluation Period were considered as non-responders and were counted in the group who did not meet the stabilized hemoglobin definition. For participants who withdrew from the study for any other reason during the Primary Evaluation Period, their data up to the time of withdrawal were used to assess stabilized hemoglobin.

5. Percentage Change In Free Hemoglobin From Baseline To Week 26 [Baseline, Week 26]

   Percentage change from baseline in free hemoglobin was summarized at all study visits up to Day 183 (Week 26). Baseline was defined as the last non-missing assessment value prior to the first study drug infusion.

6. Percentage Of Participants With Breakthrough Hemolysis (BTH) At Week 26 [Week 26]

   Breakthrough hemolysis was defined as at least one new or worsening symptom or sign of intravascular hemolysis (fatigue, hemoglobinuria, abdominal pain, shortness of breath [dyspnea], anemia, major adverse vascular event [including thrombosis], dysphagia, or erectile dysfunction) in the presence of elevated LDH as follows: for participants who entered the study naïve to complement inhibitor treatment, elevated LDH ≥ 2 × the upper limit of normal (ULN) after prior LDH reduction to < 1.5 × ULN on therapy; for participants who entered the study stabilized on eculizumab treatment, elevated LDH ≥ 2 × ULN. Participants who withdrew from the study due to lack of efficacy during the Primary Evaluation Period were considered as non-responders and were counted in the group with BTH. For participants who withdrew from the study for any other reason during the Primary Evaluation Period, their data up to the time of withdrawal were used to assess BTH. No participants experienced BTH.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

1. Participants from birth up to <18 years of age and weighing ≥ 5 kilograms at the time of consent.

2. PNH diagnosis confirmed by documented high-sensitivity flow cytometry.

3. Presence of 1 or more of the following PNH-related signs or symptoms within 3 months of Screening: fatigue, hemoglobinuria, abdominal pain, shortness of breath (dyspnea), anemia, history of a major adverse vascular event (including thrombosis), dysphagia, or erectile dysfunction; or history of packed red blood cell transfusion due to PNH.

4. Lactate dehydrogenase (LDH) level ≥ 1.5 × upper limit of normal (ULN) for participants not being treated with eculizumab at screening and LDH level ≤ 1.5 × ULN for participants taking eculizumab.

5. Documented meningococcal vaccination not more than 3 years prior to dosing, and vaccination against Streptococcus pneumoniae and Haemophilus influenzae.

6. Female participants of childbearing potential must use highly effective contraception starting at screening and continuing until at least 8 months after the last dose of ravulizumab.

Exclusion Criteria:

1. History of bone marrow transplantation.

2. History of or ongoing major cardiac, pulmonary, renal, endocrine, or hepatic disease that, in the opinion of the investigator or sponsor, would preclude participation.

3. Unstable medical conditions (for example, myocardial ischemia, active gastrointestinal bleed, severe congestive heart failure, anticipated need for major surgery within 6 months of randomization, coexisting chronic anemia unrelated to PNH).

4. Females who are pregnant or breastfeeding or who have a positive pregnancy test at screening or Day 1.

5. Participation in another interventional clinical study or use of any experimental therapy within 30 days before initiation of study drug on Day 1 in this study or within 5 half-lives of that investigational product, whichever is greater.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Clinical Trial Site	Atlanta	Georgia	United States	30329
2	Clinical Trial Site	Milwaukee	Wisconsin	United States	53226
3	Clinical Trial Site	Paris		France
4	Clinical Trial Site	Utrecht		Netherlands
5	Clinical Trial Site	Oslo		Norway
6	Clinical Trial Site	Moscow		Russian Federation
7	Clinical Trial Site	Saint Petersburg		Russian Federation
8	Clinical Trial Site	Leeds		United Kingdom
9	Clinical Trial Site	London		United Kingdom

Sponsors and Collaborators

• Alexion Pharmaceuticals

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol - Apr 22, 2020
• Statistical Analysis Plan - May 8, 2020

More Information

Publications

None provided.

• Responsible Party: Alexion Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT03406507
• Other Study ID Numbers: ALXN1210-PNH-304; 2017-002820-26
• First Posted: Jan 23, 2018
• Last Update Posted: Aug 17, 2022
• Last Verified: Aug 1, 2022

• 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
• Keywords provided by Alexion Pharmaceuticals: Ravulizumab; ALXN1210; Ultomiris; Pharmacokinetics; Pharmacodynamics
• Additional relevant MeSH terms: Hemoglobinuria; Hemoglobinuria, Paroxysmal; Ravulizumab

Study Results

Participant Flow

Recruitment Details	Thirteen participants, from birth to < 18 years, were planned to be enrolled to ensure at least 10 evaluable participants would complete the 26-week Primary Evaluation Period. Participants were recruited from 9 sites across 6 countries (United States, United Kingdom, France, Netherlands, Russia, and Norway).

Arm/Group Title	Treatment Naïve	Eculizumab Experienced
Arm/Group Description	Complement inhibitor treatment-naïve participants received weight-based doses of ravulizumab.	Eculizumab-experienced participants received weight-based doses of ravulizumab.
Period Title: Primary Evaluation Period
STARTED	5	8
Received at Least 1 Dose of Study Drug	5	8
COMPLETED	5	8
NOT COMPLETED	0	0
Period Title: Primary Evaluation Period
STARTED	5	8
Received at Least 1 Dose of Study Drug	5	8
COMPLETED	0	2
NOT COMPLETED	5	6

Baseline Characteristics

Arm/Group Title	Treatment Naïve	Eculizumab Experienced	Total
Arm/Group Description	Complement inhibitor treatment-naïve participants received weight-based doses of ravulizumab.	Eculizumab-experienced participants received weight-based doses of ravulizumab.	Total of all reporting groups
Overall Participants	5	8	13
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	14.4 (2.19)	14.4 (3.07)	14.4 (2.66)
Sex: Female, Male (Count of Participants)
Female	1 20%	7 87.5%	8 61.5%
Male	4 80%	1 12.5%	5 38.5%
Race/Ethnicity, Customized (Count of Participants)
Race - Undisclosed	5 100%	8 100%	13 100%
Ethnicity - Undisclosed	5 100%	8 100%	13 100%

Outcome Measures

1. Primary Outcome

Title	Maximum Observed Serum Concentration (Cmax) Of Ravulizumab
Description	Blood samples for determination of ravulizumab Cmax were collected before and after administration of study drug at designated time points. Results are reported in micrograms/milliliter (μg/mL).
Time Frame	Week 1 (Day 1), Week 2 (Day 15), Week 10 (Day 71), and Week 18 (Day 127)

Outcome Measure Data

Analysis Population Description

Pharmacokinetic (PK): Participants enrolled into the study who received at least 1 dose of ravulizumab and who had evaluable interim PK data. One treatment-naïve participant was excluded due to receipt of packed red blood cell transfusions during study. The PK set was used for all PK analyses.

Arm/Group Title	Treatment Naïve	Eculizumab Experienced
Arm/Group Description	Complement inhibitor treatment-naïve participants received weight-based doses of ravulizumab.	Eculizumab-experienced participants received weight-based doses of ravulizumab.
Measure Participants	4	8
Day 1: End of Infusion	733.00 (106.436)	884.63 (170.842)
Day 15: End of Infusion	1230.00 (234.663)	1612.50 (211.441)
Day 71: End of Infusion	1487.50 (330.593)	1581.43 (207.961)
Day 127: End of Infusion	1490.00 (398.079)	1705.00 (164.751)

2. Primary Outcome

Title	Trough Serum Concentration (Ctrough) Of Ravulizumab
Description	Blood samples for determination of ravulizumab Ctrough were collected before and after administration of study drug at designated time points. Trough serum concentration was measured at end of dosing interval at steady state. Results are reported in μg/mL.
Time Frame	Week 2 (Day 15), Week 10 (Day 71), Week 18 (Day 127), Week 26 (Day 183)

Outcome Measure Data

Analysis Population Description

Pharmacokinetic (PK): participants enrolled into the study who received at least 1 dose of ravulizumab and who had evaluable interim PK data. One treatment naïve participant was excluded due to receipt of packed red blood cell transfusions during study. The PK set was used for all PK analyses.

Arm/Group Title	Treatment Naïve	Eculizumab Experienced
Arm/Group Description	Complement inhibitor treatment-naïve participants received weight-based doses of ravulizumab.	Eculizumab-experienced participants received weight-based doses of ravulizumab.
Measure Participants	4	8
Day 15: Predose	368.25 (54.119)	452.25 (68.312)
Day 71: Predose	418.00 (93.833)	521.00 (72.870)
Day 127: Predose	480.75 (171.179)	567.88 (56.847)
Day 183: Predose	494.50 (105.402)	565.63 (68.980)

3. Primary Outcome

Title	Mean Accumulation Ratio For Cmax Of Ravulizumab Following The Last Maintenance Dose Relative To The First Maintenance Dose
Description	Blood samples for determination of ravulizumab accumulation ratio for Cmax were collected before and after administration of study drug at designated time points. The accumulation ratio was calculated as Cmax from the last maintenance dose (Week 18) divided by Cmax from the first maintenance dose (Week 2).
Time Frame	Week 18

Outcome Measure Data

Analysis Population Description

Pharmacokinetic (PK): participants enrolled into the study who received at least 1 dose of ravulizumab and who had evaluable interim PK data. One treatment naïve participant was excluded due to receipt of packed red blood cell transfusions during study. The PK set was used for all PK analyses.

Arm/Group Title	Treatment Naïve	Eculizumab Experienced
Arm/Group Description	Complement inhibitor treatment-naïve participants received weight-based doses of ravulizumab.	Eculizumab-experienced participants received weight-based doses of ravulizumab.
Measure Participants	4	8
Mean (Standard Deviation) [Ratio]	1.2122 (0.24070)	1.0630 (0.06872)

4. Primary Outcome

Title	Change In Free Complement Component C5 (C5) Concentrations Over Time
Description	Blood samples for determination of free C5 were collected before and after administration of study drug at designated time points.
Time Frame	Baseline, Weeks 2, 10, 18, and 26 (end of infusion)

Outcome Measure Data

Analysis Population Description

Pharmacodynamic: all participants who received at least 1 dose of ravulizumab and who had evaluable pharmacodynamic data.

Arm/Group Title	Treatment Naïve	Eculizumab Experienced
Arm/Group Description	Complement inhibitor treatment-naïve participants received weight-based doses of ravulizumab.	Eculizumab-experienced participants received weight-based doses of ravulizumab.
Measure Participants	5	8
Week 2	-105.319 (17.1118)	0.000 (0.0000)
Week 10	-105.310 (17.1139)	0.003 (0.0052)
Week 18	-105.320 (17.1165)	0.006 (0.0067)
Week 26	-105.320 (17.1184)	0.006 (0.0070)

5. Primary Outcome

Title	Change In Chicken Red Blood Cell (cRBC) Hemolytic Activity Over Time
Description	Blood samples for determination of cRBC hemolytic activity were collected before and after administration of study drug at designated time points.
Time Frame	Baseline, Weeks 2, 10, 18, and 26

Outcome Measure Data

Analysis Population Description

Pharmacodynamic: all participants who received at least 1 dose of ravulizumab and who had evaluable pharmacodynamic data.

Arm/Group Title	Treatment Naïve	Eculizumab Experienced
Arm/Group Description	Complement inhibitor treatment-naïve participants received weight-based doses of ravulizumab.	Eculizumab-experienced participants received weight-based doses of ravulizumab.
Measure Participants	5	8
Week 2	-93.120 (9.2589)	1.950 (2.8158)
Week 10	-93.240 (9.2411)	3.971 (9.2094)
Week 18	-96.925 (4.5434)	2.775 (5.6729)
Week 26	-96.775 (4.8162)	7.025 (12.6803)

6. Secondary Outcome

Title	Percentage Change From Baseline At Week 26 In Lactate Dehydrogenase (LDH) Levels
Description	Blood and urine samples for determination of LDH levels were collected at designated time points. Baseline was defined as the average of all assessments analyzed by the central laboratory prior to first study drug administration.
Time Frame	Baseline, Week 26

Outcome Measure Data

Analysis Population Description

Full Analysis: all participants who received at least 1 dose of ravulizumab and had at least 1 efficacy assessment after the first infusion of ravulizumab.

Arm/Group Title	Treatment Naïve	Eculizumab Experienced
Arm/Group Description	Complement inhibitor treatment-naïve participants received weight-based doses of ravulizumab.	Eculizumab-experienced participants received weight-based doses of ravulizumab.
Measure Participants	5	8
Mean (Standard Deviation) [Percent Change]	-47.91 (52.716)	4.65 (44.702)

7. Secondary Outcome

Title	Percentage Of Participants Who Achieved Transfusion Avoidance (TA)
Description	Transfusion avoidance was defined as the proportion of participants who remained transfusion-free and did not require a transfusion according to protocol-specified guidelines. Point estimates and 2-sided 95% exact confidence intervals (CIs) were computed. Participants who withdrew from the study due to lack of efficacy during the Primary Evaluation Period were considered as non-responders and were counted in the group needing transfusion. For participants who withdrew from the study for any other reason during the Primary Evaluation Period, their data up to the time of withdrawal was used to assess TA.
Time Frame	Week 26

Outcome Measure Data

Analysis Population Description

Full Analysis: all participants who received at least 1 dose of ravulizumab and had at least 1 efficacy assessment after the first infusion of ravulizumab.

Arm/Group Title	Treatment Naïve	Eculizumab Experienced
Arm/Group Description	Complement inhibitor treatment-naïve participants received weight-based doses of ravulizumab.	Eculizumab-experienced participants received weight-based doses of ravulizumab.
Measure Participants	5	8
Number (95% Confidence Interval) [Percentage of Participants]	60.0 1200%	100.0 1250%

8. Secondary Outcome

Title	Change In Quality Of Life (QoL) From Baseline To Week 26
Description	Quality of life was measured by Pediatric Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue Questionnaire (participants ≥ 5 years of age), a 13-item questionnaire that assesses fatigue and its impact upon daily activities and function over the preceding 7 days. Each item is scored on a 5-point scale, and total scores range from 0 to 52, with a higher score indicating better QoL. The scoring guideline for the Pediatric FACIT-Fatigue instrument was used to calculate a FACIT-Fatigue score. Changes from baseline in FACIT-Fatigue scores were summarized at baseline and at the study visits where this assessment was collected up to Day 183 (Week 26). At each study visit, the proportion of participants who showed an improvement of at least 3 points for the Pediatric FACIT-Fatigue scores were summarized by point estimates and 2-sided 95% exact CIs.
Time Frame	Baseline, Week 26

Outcome Measure Data

Analysis Population Description

Full Analysis: all participants who received at least 1 dose of ravulizumab and had at least 1 efficacy assessment after the first infusion of ravulizumab.

Arm/Group Title	Treatment Naïve	Eculizumab Experienced
Arm/Group Description	Complement inhibitor treatment-naïve participants received weight-based doses of ravulizumab.	Eculizumab-experienced participants received weight-based doses of ravulizumab.
Measure Participants	5	8
Mean (Standard Deviation) [units on a scale]	3.40 (6.107)	1.28 (5.235)

9. Secondary Outcome

Title	Percentage Of Participants With Stabilized Hemoglobin At Week 26
Description	Stabilized hemoglobin was defined as avoidance of a ≥ 2 g/dL decrease in hemoglobin level from baseline in the absence of transfusion through Week 26. Point estimates and 2-sided 95% exact CIs were computed. Participants who withdrew from the study due to lack of efficacy during the Primary Evaluation Period were considered as non-responders and were counted in the group who did not meet the stabilized hemoglobin definition. For participants who withdrew from the study for any other reason during the Primary Evaluation Period, their data up to the time of withdrawal were used to assess stabilized hemoglobin.
Time Frame	Week 26

Outcome Measure Data

Analysis Population Description

Full Analysis: all participants who received at least 1 dose of ravulizumab and had at least 1 efficacy assessment after the first infusion of ravulizumab.

Arm/Group Title	Treatment Naïve	Eculizumab Experienced
Arm/Group Description	Complement inhibitor treatment-naïve participants received weight-based doses of ravulizumab.	Eculizumab-experienced participants received weight-based doses of ravulizumab.
Measure Participants	5	8
Number (95% Confidence Interval) [Percentage of Participants]	60.0 1200%	75.0 937.5%

10. Secondary Outcome

Title	Percentage Change In Free Hemoglobin From Baseline To Week 26
Description	Percentage change from baseline in free hemoglobin was summarized at all study visits up to Day 183 (Week 26). Baseline was defined as the last non-missing assessment value prior to the first study drug infusion.
Time Frame	Baseline, Week 26

Outcome Measure Data

Analysis Population Description

Full Analysis: all participants who received at least 1 dose of ravulizumab and had at least 1 efficacy assessment after the first infusion of ravulizumab.

Arm/Group Title	Treatment Naïve	Eculizumab Experienced
Arm/Group Description	Complement inhibitor treatment-naïve participants received weight-based doses of ravulizumab.	Eculizumab-experienced participants received weight-based doses of ravulizumab.
Measure Participants	5	8
Mean (Standard Deviation) [Percentage Change]	87.32 (226.816)	-15.29 (71.780)

11. Secondary Outcome

Title	Percentage Of Participants With Breakthrough Hemolysis (BTH) At Week 26
Description	Breakthrough hemolysis was defined as at least one new or worsening symptom or sign of intravascular hemolysis (fatigue, hemoglobinuria, abdominal pain, shortness of breath [dyspnea], anemia, major adverse vascular event [including thrombosis], dysphagia, or erectile dysfunction) in the presence of elevated LDH as follows: for participants who entered the study naïve to complement inhibitor treatment, elevated LDH ≥ 2 × the upper limit of normal (ULN) after prior LDH reduction to < 1.5 × ULN on therapy; for participants who entered the study stabilized on eculizumab treatment, elevated LDH ≥ 2 × ULN. Participants who withdrew from the study due to lack of efficacy during the Primary Evaluation Period were considered as non-responders and were counted in the group with BTH. For participants who withdrew from the study for any other reason during the Primary Evaluation Period, their data up to the time of withdrawal were used to assess BTH. No participants experienced BTH.
Time Frame	Week 26

Outcome Measure Data

Analysis Population Description

Full Analysis: all participants who received at least 1 dose of ravulizumab and had at least 1 efficacy assessment after the first infusion of ravulizumab.

Arm/Group Title	Treatment Naïve	Eculizumab Experienced
Arm/Group Description	Complement inhibitor treatment-naïve participants received weight-based doses of ravulizumab.	Eculizumab-experienced participants received weight-based doses of ravulizumab.
Measure Participants	5	8
Count of Participants [Participants]	0 0%	0 0%

12. Primary Outcome

Title	Mean Accumulation Ratio For Ctrough Of Ravulizumab Following The Last Maintenance Dose Relative To The First Maintenance Dose
Description	Blood samples for determination of ravulizumab accumulation ratio for Ctrough were collected before and after administration of study drug at designated time points. The accumulation ratio was calculated as Ctrough from the last maintenance dose (Week 18) divided by Ctrough from the first maintenance dose (Week 2).
Time Frame	Week 18

Outcome Measure Data

Analysis Population Description

Pharmacokinetic (PK): participants enrolled into the study who received at least 1 dose of ravulizumab and who had evaluable interim PK data. One treatment naïve participant was excluded due to receipt of packed red blood cell transfusions during study. The PK set was used for all PK analyses.

Arm/Group Title	Treatment Naïve	Eculizumab Experienced
Arm/Group Description	Complement inhibitor treatment-naïve participants received weight-based doses of ravulizumab.	Eculizumab-experienced participants received weight-based doses of ravulizumab.
Measure Participants	4	8
Mean (Standard Deviation) [Ratio]	1.2208 (0.32490)	1.0700 (0.09089)

Adverse Events

Time Frame	Day 1 through Week 26.
Arm/Group Title	Treatment Naïve		Eculizumab Experienced
Arm/Group Description	Complement inhibitor treatment-naïve participants received weight-based doses of ravulizumab.		Eculizumab-experienced participants received weight-based doses of ravulizumab.
All Cause Mortality
	Treatment Naïve		Eculizumab Experienced
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/5 (0%)		0/8 (0%)
Serious Adverse Events
	Treatment Naïve		Eculizumab Experienced
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/5 (20%)		2/8 (25%)
General disorders
Device related thrombosis	1/5 (20%)	1	0/8 (0%)	0
Multiple organ dysfunction syndrome	1/5 (20%)	1	0/8 (0%)	0
Infections and infestations
Device related sepsis	1/5 (20%)	1	0/8 (0%)	0
Septic shock	1/5 (20%)	1	0/8 (0%)	0
Staphylococcal infection	1/5 (20%)	1	0/8 (0%)	0
Viral upper respiratory tract infection	0/5 (0%)	0	1/8 (12.5%)	1
Investigations
Influenza A virus test positive	0/5 (0%)	0	1/8 (12.5%)	1
Other (Not Including Serious) Adverse Events
	Treatment Naïve		Eculizumab Experienced
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/5 (80%)		7/8 (87.5%)
Blood and lymphatic system disorders
Anemia	0/5 (0%)	0	1/8 (12.5%)	1
Ear and labyrinth disorders
Ear pain	0/5 (0%)	0	1/8 (12.5%)	2
Endocrine disorders
Cushing's syndrome	1/5 (20%)	1	0/8 (0%)	0
Gastrointestinal disorders
Abdominal pain	0/5 (0%)	0	2/8 (25%)	2
Constipation	0/5 (0%)	0	1/8 (12.5%)	1
Dysphagia	0/5 (0%)	0	1/8 (12.5%)	1
Nausea	0/5 (0%)	0	1/8 (12.5%)	1
Vomiting	0/5 (0%)	0	1/8 (12.5%)	1
Diarrhea	0/5 (0%)	0	1/8 (12.5%)	1
Rectal hemorrhage	0/5 (0%)	0	1/8 (12.5%)	1
General disorders
Fatigue	0/5 (0%)	0	1/8 (12.5%)	1
Pyrexia	1/5 (20%)	1	0/8 (0%)	0
Hepatobiliary disorders
Hyperbilirubinemia	1/5 (20%)	1	0/8 (0%)	0
Immune system disorders
Serum sickness	1/5 (20%)	1	0/8 (0%)	0
Infections and infestations
Nasopharyngitis	1/5 (20%)	1	1/8 (12.5%)	1
Cystitis	0/5 (0%)	0	1/8 (12.5%)	1
Hordeolum	0/5 (0%)	0	1/8 (12.5%)	1
Paronychia	1/5 (20%)	1	0/8 (0%)	0
Pharyngitis	0/5 (0%)	0	1/8 (12.5%)	1
Rhinitis	0/5 (0%)	0	1/8 (12.5%)	1
Sinusitis	0/5 (0%)	0	1/8 (12.5%)	1
Upper respiratory tract infection	0/5 (0%)	0	1/8 (12.5%)	1
Urinary tract infection	0/5 (0%)	0	1/8 (12.5%)	1
Injury, poisoning and procedural complications
Electric shock	0/5 (0%)	0	1/8 (12.5%)	1
Sunburn	0/5 (0%)	0	1/8 (12.5%)	1
Wound	0/5 (0%)	0	1/8 (12.5%)	1
Investigations
Blood pressure increased	1/5 (20%)	1	0/8 (0%)	0
Metabolism and nutrition disorders
Decreased appetite	0/5 (0%)	0	1/8 (12.5%)	1
Musculoskeletal and connective tissue disorders
Arthralgia	1/5 (20%)	1	0/8 (0%)	0
Neck pain	0/5 (0%)	0	1/8 (12.5%)	1
Pain in extremity	0/5 (0%)	0	1/8 (12.5%)	1
Nervous system disorders
Headache	1/5 (20%)	1	1/8 (12.5%)	1
Dizziness	0/5 (0%)	0	1/8 (12.5%)	1
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain	0/5 (0%)	0	1/8 (12.5%)	1
Rhinitis allergic	0/5 (0%)	0	1/8 (12.5%)	1
Skin and subcutaneous tissue disorders
Pruritus	0/5 (0%)	0	1/8 (12.5%)	1
Vascular disorders
Hematoma	0/5 (0%)	0	1/8 (12.5%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.