Trial Outcomes & Findings for Ravulizumab Subcutaneous (SC) Versus Ravulizumab Intravenous (IV) in Adults With Paroxysmal Nocturnal Hemoglobinuria (PNH) Currently Treated With Eculizumab (NCT NCT03748823)

NCT ID: NCT03748823

Last Updated: 2024-09-19

Results Overview

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

139 participants

Primary outcome timeframe

Predose at Day 71

Results posted on

2024-09-19

Participant Flow

Participants were stratified by weight group (≥40 to \<60 kilogram \[kg\] and ≥60 to \<100 kg) and then randomized in a 2:1 ratio to 2 treatment groups.

Participant milestones

Participant milestones
Measure	Ravulizumab Intravenous (IV)/Subcutaneous (SC) Treatment Group During the Randomized Treatment Period, participants received a weight-based single loading dose (2400 to 2700 milligrams \[mg\]) of ravulizumab IV on Day 1, followed by a maintenance weight-based dose (3000 to 3300 mg) of ravulizumab IV on Day 15. During the Extension Period (Day 71 up to Day 1275), participants received 490 mg of ravulizumab SC once every week (qw).	Ravulizumab SC/SC Treatment Group During the Randomized Treatment Period, participants received a weight-based single loading dose (2400 to 2700 mg) of ravulizumab SC on Day 1, followed by maintenance weight-based doses (490 mg) of ravulizumab SC qw from Days 15 to 64. During the Extension Period (Day 71 up to Day 1275), participants received 490 mg of ravulizumab SC qw.
Randomized Treatment Period STARTED	46	90
Randomized Treatment Period Received at Least 1 Dose of Study Drug	46	90
Randomized Treatment Period Treated and Not Included in Analysis	1	6
Randomized Treatment Period Full Analysis Set	45	84
Randomized Treatment Period Safety Analysis Set	45	84
Randomized Treatment Period COMPLETED	44	84
Randomized Treatment Period NOT COMPLETED	2	6
Extension Period STARTED	44	83
Extension Period Received at Least 1 Dose of Study Drug	44	83
Extension Period Treated But Not Included in the Analysis	1	6
Extension Period COMPLETED	31	64
Extension Period NOT COMPLETED	13	19

Reasons for withdrawal

Reasons for withdrawal
Measure	Ravulizumab Intravenous (IV)/Subcutaneous (SC) Treatment Group During the Randomized Treatment Period, participants received a weight-based single loading dose (2400 to 2700 milligrams \[mg\]) of ravulizumab IV on Day 1, followed by a maintenance weight-based dose (3000 to 3300 mg) of ravulizumab IV on Day 15. During the Extension Period (Day 71 up to Day 1275), participants received 490 mg of ravulizumab SC once every week (qw).	Ravulizumab SC/SC Treatment Group During the Randomized Treatment Period, participants received a weight-based single loading dose (2400 to 2700 mg) of ravulizumab SC on Day 1, followed by maintenance weight-based doses (490 mg) of ravulizumab SC qw from Days 15 to 64. During the Extension Period (Day 71 up to Day 1275), participants received 490 mg of ravulizumab SC qw.
Randomized Treatment Period Withdrawal by Subject	1	0
Randomized Treatment Period Site Source Document Deviations	1	6
Extension Period Withdrawal by Subject	9	12
Extension Period Death	2	2
Extension Period Other than Specified	0	1
Extension Period Protocol Violation	1	0
Extension Period Lost to Follow-up	0	1
Extension Period Lack of Efficacy	0	1
Extension Period Physician Decision	1	2

Baseline Characteristics

Ravulizumab Subcutaneous (SC) Versus Ravulizumab Intravenous (IV) in Adults With Paroxysmal Nocturnal Hemoglobinuria (PNH) Currently Treated With Eculizumab

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Ravulizumab IV/SC Treatment Group n=45 Participants During the Randomized Treatment Period, participants received a weight-based single loading dose (2400 to 2700 mg) of ravulizumab IV on Day 1, followed by a maintenance weight-based dose (3000 to 3300 mg) of ravulizumab IV on Day 15. During the Extension Period (Day 71 up to Day 1275), participants received 490 mg of ravulizumab SC qw.	Ravulizumab SC/SC Treatment Group n=84 Participants During the Randomized Treatment Period, participants received a weight-based single loading dose (2400 to 2700 mg) of ravulizumab SC on Day 1, followed by maintenance weight-based doses (490 mg) of ravulizumab SC qw from Days 15 to 64. During the Extension Period (Day 71 up to Day 1275), participants received 490 mg of ravulizumab SC qw.	Total n=129 Participants Total of all reporting groups
Age, Continuous	46.4 years STANDARD_DEVIATION 13.22 • n=5 Participants	45.3 years STANDARD_DEVIATION 14.47 • n=7 Participants	45.7 years STANDARD_DEVIATION 14.00 • n=5 Participants
Sex: Female, Male Female	25 Participants n=5 Participants	44 Participants n=7 Participants	69 Participants n=5 Participants
Sex: Female, Male Male	20 Participants n=5 Participants	40 Participants n=7 Participants	60 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	7 Participants n=5 Participants	15 Participants n=7 Participants	22 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	29 Participants n=5 Participants	53 Participants n=7 Participants	82 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	9 Participants n=5 Participants	16 Participants n=7 Participants	25 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Asian	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	4 Participants n=5 Participants	3 Participants n=7 Participants	7 Participants n=5 Participants
Race (NIH/OMB) White	29 Participants n=5 Participants	63 Participants n=7 Participants	92 Participants n=5 Participants
Race (NIH/OMB) More than one race	2 Participants n=5 Participants	4 Participants n=7 Participants	6 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	7 Participants n=5 Participants	14 Participants n=7 Participants	21 Participants n=5 Participants

PRIMARY outcome

Timeframe: Predose at Day 71

Population: Pharmacokinetic (PK) analysis set included all participants who had evaluable PK data.

Outcome measures

Outcome measures
Measure	Ravulizumab IV/SC Treatment Group n=43 Participants During the Randomized Treatment Period, participants received a weight-based single loading dose (2400 to 2700 mg) of ravulizumab IV on Day 1, followed by a maintenance weight-based dose (3000 to 3300 mg) of ravulizumab IV on Day 15. During the Extension Period (Day 71 up to Day 1275), participants received 490 mg of ravulizumab SC qw.	Ravulizumab SC/SC Treatment Group n=70 Participants During the Randomized Treatment Period, participants received a weight-based single loading dose (2400 to 2700 mg) of ravulizumab SC on Day 1, followed by maintenance weight-based doses (490 mg) of ravulizumab SC qw from Days 15 to 64. During the Extension Period (Day 71 up to Day 1275), participants received 490 mg of ravulizumab SC qw.
Ctrough Serum Concentration of Ravulizumab	457.58 micrograms/milliliter (µg/mL) Standard Deviation 108.491	578.70 micrograms/milliliter (µg/mL) Standard Deviation 140.819

SECONDARY outcome

Timeframe: Predose at Day 351

Population: SC treated full analysis set included all participants who had signed informed consent, were randomized, received at least 1 dose of ravulizumab SC, and were not excluded from analysis. Here, Number of Participants Analyzed signifies those participants who were evaluable for this outcome measure.

Outcome measures

Outcome measures
Measure	Ravulizumab IV/SC Treatment Group n=34 Participants During the Randomized Treatment Period, participants received a weight-based single loading dose (2400 to 2700 mg) of ravulizumab IV on Day 1, followed by a maintenance weight-based dose (3000 to 3300 mg) of ravulizumab IV on Day 15. During the Extension Period (Day 71 up to Day 1275), participants received 490 mg of ravulizumab SC qw.	Ravulizumab SC/SC Treatment Group n=74 Participants During the Randomized Treatment Period, participants received a weight-based single loading dose (2400 to 2700 mg) of ravulizumab SC on Day 1, followed by maintenance weight-based doses (490 mg) of ravulizumab SC qw from Days 15 to 64. During the Extension Period (Day 71 up to Day 1275), participants received 490 mg of ravulizumab SC qw.
Ctrough Serum Concentration of Ravulizumab at Day 351	712.79 µg/mL Standard Deviation 203.180	737.65 µg/mL Standard Deviation 208.894

SECONDARY outcome

Timeframe: Predose at Day 71

Population: Pharmacodynamic (PD) analysis set included all participants who received at least 1 dose of ravulizumab and who had evaluable PD data. Here, Number of Participants Analyzed signifies those participants who were evaluable for this outcome measure.

Outcome measures

Outcome measures
Measure	Ravulizumab IV/SC Treatment Group n=44 Participants During the Randomized Treatment Period, participants received a weight-based single loading dose (2400 to 2700 mg) of ravulizumab IV on Day 1, followed by a maintenance weight-based dose (3000 to 3300 mg) of ravulizumab IV on Day 15. During the Extension Period (Day 71 up to Day 1275), participants received 490 mg of ravulizumab SC qw.	Ravulizumab SC/SC Treatment Group n=83 Participants During the Randomized Treatment Period, participants received a weight-based single loading dose (2400 to 2700 mg) of ravulizumab SC on Day 1, followed by maintenance weight-based doses (490 mg) of ravulizumab SC qw from Days 15 to 64. During the Extension Period (Day 71 up to Day 1275), participants received 490 mg of ravulizumab SC qw.
Free Serum Complement Component 5 (C5) Concentrations at Day 71	0.072193 µg/mL Standard Deviation 0.0245225	0.059458 µg/mL Standard Deviation 0.0182180

SECONDARY outcome

Timeframe: Predose at Day 351

Outcome measures

Outcome measures
Measure	Ravulizumab IV/SC Treatment Group n=33 Participants During the Randomized Treatment Period, participants received a weight-based single loading dose (2400 to 2700 mg) of ravulizumab IV on Day 1, followed by a maintenance weight-based dose (3000 to 3300 mg) of ravulizumab IV on Day 15. During the Extension Period (Day 71 up to Day 1275), participants received 490 mg of ravulizumab SC qw.	Ravulizumab SC/SC Treatment Group n=73 Participants During the Randomized Treatment Period, participants received a weight-based single loading dose (2400 to 2700 mg) of ravulizumab SC on Day 1, followed by maintenance weight-based doses (490 mg) of ravulizumab SC qw from Days 15 to 64. During the Extension Period (Day 71 up to Day 1275), participants received 490 mg of ravulizumab SC qw.
Free Serum Complement Component 5 (C5) Concentrations at Day 351	0.071627 µg/mL Standard Deviation 0.0227980	0.069711 µg/mL Standard Deviation 0.0208784

SECONDARY outcome

Timeframe: Baseline, Day 71

Population: Full analysis set included all participants who had signed informed consent, were randomized, received at least 1 dose of ravulizumab, and were not excluded from analysis. Here, Number of Participants Analyzed signifies those participants who were evaluable for this outcome measure.

Baseline was defined as the last assessment prior to first study drug dose. LDH samples impacted by tabletop hemolysis were excluded from the analysis.

Outcome measures

Outcome measures
Measure	Ravulizumab IV/SC Treatment Group n=43 Participants During the Randomized Treatment Period, participants received a weight-based single loading dose (2400 to 2700 mg) of ravulizumab IV on Day 1, followed by a maintenance weight-based dose (3000 to 3300 mg) of ravulizumab IV on Day 15. During the Extension Period (Day 71 up to Day 1275), participants received 490 mg of ravulizumab SC qw.	Ravulizumab SC/SC Treatment Group n=82 Participants During the Randomized Treatment Period, participants received a weight-based single loading dose (2400 to 2700 mg) of ravulizumab SC on Day 1, followed by maintenance weight-based doses (490 mg) of ravulizumab SC qw from Days 15 to 64. During the Extension Period (Day 71 up to Day 1275), participants received 490 mg of ravulizumab SC qw.
Percent Change From Baseline in Lactate Dehydrogenase (LDH) Levels at Day 71	5.73 percent change Standard Deviation 29.716	2.57 percent change Standard Deviation 33.883

SECONDARY outcome

Timeframe: Baseline, Day 351

SC baseline was defined as the last assessment prior to first dose of SC treatment. LDH samples impacted by tabletop hemolysis were excluded from the analysis.

Outcome measures

Outcome measures
Measure	Ravulizumab IV/SC Treatment Group n=34 Participants During the Randomized Treatment Period, participants received a weight-based single loading dose (2400 to 2700 mg) of ravulizumab IV on Day 1, followed by a maintenance weight-based dose (3000 to 3300 mg) of ravulizumab IV on Day 15. During the Extension Period (Day 71 up to Day 1275), participants received 490 mg of ravulizumab SC qw.	Ravulizumab SC/SC Treatment Group n=73 Participants During the Randomized Treatment Period, participants received a weight-based single loading dose (2400 to 2700 mg) of ravulizumab SC on Day 1, followed by maintenance weight-based doses (490 mg) of ravulizumab SC qw from Days 15 to 64. During the Extension Period (Day 71 up to Day 1275), participants received 490 mg of ravulizumab SC qw.
Percent Change From Baseline in LDH Levels at Day 351	-0.83 percent change Standard Deviation 17.225	1.74 percent change Standard Deviation 21.905

SECONDARY outcome

Timeframe: Baseline, Day 71

FACIT-fatigue subscale is a 13-item questionnaire that assesses self-reported fatigue and its impact upon daily activities and function over the preceding 7 days. Items are scored on a 5 point Likert-type scale. Item scores ranged from 0 ("not at all") to 4 ("very much"). The total, summed score ranged from 0 to 52; lower scores indicating greater fatigue and higher score indicating better health-related quality of life. Baseline was defined as the last non-missing value prior to the first dose of study drug.

Outcome measures

Outcome measures
Measure	Ravulizumab IV/SC Treatment Group n=44 Participants During the Randomized Treatment Period, participants received a weight-based single loading dose (2400 to 2700 mg) of ravulizumab IV on Day 1, followed by a maintenance weight-based dose (3000 to 3300 mg) of ravulizumab IV on Day 15. During the Extension Period (Day 71 up to Day 1275), participants received 490 mg of ravulizumab SC qw.	Ravulizumab SC/SC Treatment Group n=80 Participants During the Randomized Treatment Period, participants received a weight-based single loading dose (2400 to 2700 mg) of ravulizumab SC on Day 1, followed by maintenance weight-based doses (490 mg) of ravulizumab SC qw from Days 15 to 64. During the Extension Period (Day 71 up to Day 1275), participants received 490 mg of ravulizumab SC qw.
Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Subscale Version 4 Score at Day 71	-0.83 units on a scale Standard Deviation 7.378	1.21 units on a scale Standard Deviation 7.882

SECONDARY outcome

Timeframe: Baseline, Day 351

Outcome measures

Outcome measures
Measure	Ravulizumab IV/SC Treatment Group n=70 Participants During the Randomized Treatment Period, participants received a weight-based single loading dose (2400 to 2700 mg) of ravulizumab IV on Day 1, followed by a maintenance weight-based dose (3000 to 3300 mg) of ravulizumab IV on Day 15. During the Extension Period (Day 71 up to Day 1275), participants received 490 mg of ravulizumab SC qw.	Ravulizumab SC/SC Treatment Group During the Randomized Treatment Period, participants received a weight-based single loading dose (2400 to 2700 mg) of ravulizumab SC on Day 1, followed by maintenance weight-based doses (490 mg) of ravulizumab SC qw from Days 15 to 64. During the Extension Period (Day 71 up to Day 1275), participants received 490 mg of ravulizumab SC qw.
Change From Baseline in FACIT-Fatigue Scale Version 4 Score at Day 351	2.57 units on a scale Standard Deviation 7.178	—

SECONDARY outcome

Timeframe: Baseline, Day 71

The Treatment Administration Satisfaction Questionnaire (TASQ) is a 19-item questionnaire that assesses treatment administration satisfaction across 5 domains: physical impact, psychological impact, impact on activities of daily living, convenience, and satisfaction. Each domain offers up to 5 response options; lower scores indicate a more positive response. Scoring is completed by summing each of the 5 domains. Total TASQ scores during the study ranged from 0 to 367, with a lower score indicating greater satisfaction with treatment administration.

Outcome measures

Outcome measures
Measure	Ravulizumab IV/SC Treatment Group n=43 Participants During the Randomized Treatment Period, participants received a weight-based single loading dose (2400 to 2700 mg) of ravulizumab IV on Day 1, followed by a maintenance weight-based dose (3000 to 3300 mg) of ravulizumab IV on Day 15. During the Extension Period (Day 71 up to Day 1275), participants received 490 mg of ravulizumab SC qw.	Ravulizumab SC/SC Treatment Group n=78 Participants During the Randomized Treatment Period, participants received a weight-based single loading dose (2400 to 2700 mg) of ravulizumab SC on Day 1, followed by maintenance weight-based doses (490 mg) of ravulizumab SC qw from Days 15 to 64. During the Extension Period (Day 71 up to Day 1275), participants received 490 mg of ravulizumab SC qw.
Change From Baseline in Treatment Administration Satisfaction Questionnaire (TASQ) Score at Day 71	-7.00 units on a scale Standard Deviation 34.581	-70.54 units on a scale Standard Deviation 70.522

SECONDARY outcome

Timeframe: Baseline, Day 351

Population: SC treated full analysis set included all participants who had signed informed consent, were randomized, received at least 1 dose of ravulizumab SC, and were not excluded from analysis. Here, Number of Participants analyzed signifies those participants who were evaluable for this outcome measure. This outcome measure was planned to be reported for ravulizumab SC/SC treatment group only.

Outcome measures

Outcome measures
Measure	Ravulizumab IV/SC Treatment Group n=72 Participants During the Randomized Treatment Period, participants received a weight-based single loading dose (2400 to 2700 mg) of ravulizumab IV on Day 1, followed by a maintenance weight-based dose (3000 to 3300 mg) of ravulizumab IV on Day 15. During the Extension Period (Day 71 up to Day 1275), participants received 490 mg of ravulizumab SC qw.	Ravulizumab SC/SC Treatment Group During the Randomized Treatment Period, participants received a weight-based single loading dose (2400 to 2700 mg) of ravulizumab SC on Day 1, followed by maintenance weight-based doses (490 mg) of ravulizumab SC qw from Days 15 to 64. During the Extension Period (Day 71 up to Day 1275), participants received 490 mg of ravulizumab SC qw.
Change From Baseline in Treatment Administration Satisfaction Questionnaire (TASQ) Score at Day 351	-69.29 units on a scale Standard Deviation 80.068	—

SECONDARY outcome

Timeframe: Baseline up to Day 71

Population: Full analysis set included all participants who had signed informed consent, were randomized, received at least 1 dose of ravulizumab, and were not excluded from analysis.

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 \[hemoglobin \<10 grams/deciliter (g/dL)\], major adverse vascular event \[MAVE, including thrombosis\], dysphagia, or erectile dysfunction) in the presence of elevated LDH ≥2\*upper limit of normal (ULN). Denominator for a percentage was participants with at least one post-baseline data for the period. For Through Day 71, only visits with data were used to assess breakthrough hemolysis.

Outcome measures

Outcome measures
Measure	Ravulizumab IV/SC Treatment Group n=45 Participants During the Randomized Treatment Period, participants received a weight-based single loading dose (2400 to 2700 mg) of ravulizumab IV on Day 1, followed by a maintenance weight-based dose (3000 to 3300 mg) of ravulizumab IV on Day 15. During the Extension Period (Day 71 up to Day 1275), participants received 490 mg of ravulizumab SC qw.	Ravulizumab SC/SC Treatment Group n=84 Participants During the Randomized Treatment Period, participants received a weight-based single loading dose (2400 to 2700 mg) of ravulizumab SC on Day 1, followed by maintenance weight-based doses (490 mg) of ravulizumab SC qw from Days 15 to 64. During the Extension Period (Day 71 up to Day 1275), participants received 490 mg of ravulizumab SC qw.
Percentage of Participants Who Experienced Breakthrough Hemolysis up to Day 71	2.2 percentage of participants Interval 0.06 to 11.77	1.2 percentage of participants Interval 0.03 to 6.46

SECONDARY outcome

Timeframe: Baseline up to Day 351

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 \[hemoglobin \<10 g/dL\], major adverse vascular event \[MAVE, including thrombosis\], dysphagia, or erectile dysfunction) in the presence of elevated LDH ≥2\*ULN. Denominator for a percentage was participants with at least one post-baseline data for the period.

Outcome measures

Outcome measures
Measure	Ravulizumab IV/SC Treatment Group n=44 Participants During the Randomized Treatment Period, participants received a weight-based single loading dose (2400 to 2700 mg) of ravulizumab IV on Day 1, followed by a maintenance weight-based dose (3000 to 3300 mg) of ravulizumab IV on Day 15. During the Extension Period (Day 71 up to Day 1275), participants received 490 mg of ravulizumab SC qw.	Ravulizumab SC/SC Treatment Group n=84 Participants During the Randomized Treatment Period, participants received a weight-based single loading dose (2400 to 2700 mg) of ravulizumab SC on Day 1, followed by maintenance weight-based doses (490 mg) of ravulizumab SC qw from Days 15 to 64. During the Extension Period (Day 71 up to Day 1275), participants received 490 mg of ravulizumab SC qw.
Percentage of Participants Who Experienced Breakthrough Hemolysis up to Day 351	4.5 percentage of participants Interval 0.56 to 15.47	3.6 percentage of participants Interval 0.74 to 10.08

SECONDARY outcome

Timeframe: Baseline up to Day 71

Population: Full analysis set included all participants who had signed informed consent, were randomized, received at least 1 dose of ravulizumab, and were not excluded from analysis.

Transfusion Avoidance was defined as participants who remained transfusion free and did not require a transfusion after the first dose of study drug through the period of interest. Percentages are based on participants with any post-baseline data for the period. For Through Day 71, only visits with data were used to assess transfusion avoidance.

Outcome measures

Outcome measures
Measure	Ravulizumab IV/SC Treatment Group n=45 Participants During the Randomized Treatment Period, participants received a weight-based single loading dose (2400 to 2700 mg) of ravulizumab IV on Day 1, followed by a maintenance weight-based dose (3000 to 3300 mg) of ravulizumab IV on Day 15. During the Extension Period (Day 71 up to Day 1275), participants received 490 mg of ravulizumab SC qw.	Ravulizumab SC/SC Treatment Group n=84 Participants During the Randomized Treatment Period, participants received a weight-based single loading dose (2400 to 2700 mg) of ravulizumab SC on Day 1, followed by maintenance weight-based doses (490 mg) of ravulizumab SC qw from Days 15 to 64. During the Extension Period (Day 71 up to Day 1275), participants received 490 mg of ravulizumab SC qw.
Percentage of Participants Who Achieved Transfusion Avoidance up to Day 71	86.7 percentage of participants Interval 73.21 to 94.95	94.0 percentage of participants Interval 86.65 to 98.04

SECONDARY outcome

Timeframe: Baseline up to Day 351

Transfusion Avoidance was defined as participants who remained transfusion free and did not require a transfusion after the first dose of study drug through the period of interest. Denominator for a percentage was participants with at least one post-baseline data for the period.

Outcome measures

Outcome measures
Measure	Ravulizumab IV/SC Treatment Group n=44 Participants During the Randomized Treatment Period, participants received a weight-based single loading dose (2400 to 2700 mg) of ravulizumab IV on Day 1, followed by a maintenance weight-based dose (3000 to 3300 mg) of ravulizumab IV on Day 15. During the Extension Period (Day 71 up to Day 1275), participants received 490 mg of ravulizumab SC qw.	Ravulizumab SC/SC Treatment Group n=84 Participants During the Randomized Treatment Period, participants received a weight-based single loading dose (2400 to 2700 mg) of ravulizumab SC on Day 1, followed by maintenance weight-based doses (490 mg) of ravulizumab SC qw from Days 15 to 64. During the Extension Period (Day 71 up to Day 1275), participants received 490 mg of ravulizumab SC qw.
Percentage of Participants Who Achieved Transfusion Avoidance up to Day 351	79.5 percentage of participants Interval 64.7 to 90.2	85.7 percentage of participants Interval 76.38 to 92.39

SECONDARY outcome

Timeframe: Baseline up to Day 71

SHg was defined as the avoidance of a ≥2 g/dL decrease in hemoglobin level from Baseline (defined as the last assessment prior to the first dose of the study drug) in the absence of transfusion to the end of the period of interest. Percentages were based on participants with at least one post-baseline data for the period. For Through Day 71, only visits with data were used to assess SHg.

Outcome measures

Outcome measures
Measure	Ravulizumab IV/SC Treatment Group n=44 Participants During the Randomized Treatment Period, participants received a weight-based single loading dose (2400 to 2700 mg) of ravulizumab IV on Day 1, followed by a maintenance weight-based dose (3000 to 3300 mg) of ravulizumab IV on Day 15. During the Extension Period (Day 71 up to Day 1275), participants received 490 mg of ravulizumab SC qw.	Ravulizumab SC/SC Treatment Group n=78 Participants During the Randomized Treatment Period, participants received a weight-based single loading dose (2400 to 2700 mg) of ravulizumab SC on Day 1, followed by maintenance weight-based doses (490 mg) of ravulizumab SC qw from Days 15 to 64. During the Extension Period (Day 71 up to Day 1275), participants received 490 mg of ravulizumab SC qw.
Percentage of Participants Who Maintained Stabilized Hemoglobin (SHg) up to Day 71	81.8 percentage of participants Interval 67.29 to 91.81	93.6 percentage of participants Interval 85.67 to 97.89

SECONDARY outcome

Timeframe: Baseline up to Day 351

Population: SC treated full analysis set included all participants who had signed informed consent, were randomized, received at least 1 dose of ravulizumab SC, and were not excluded from analysis. Here, Number of Participants analyzed signifies those participants who were evaluable for this outcome measure.

SHg was defined as the avoidance of a ≥2 g/dL decrease in hemoglobin level from SC Baseline (defined as the last assessment prior to the first dose of SC treatment) in the absence of transfusion to the end of the period of interest. Denominator for a percentage was participants with at least one post-baseline data for the period. Visits were based on the number of days since first dose of SC treatment.

Outcome measures

Outcome measures
Measure	Ravulizumab IV/SC Treatment Group n=44 Participants During the Randomized Treatment Period, participants received a weight-based single loading dose (2400 to 2700 mg) of ravulizumab IV on Day 1, followed by a maintenance weight-based dose (3000 to 3300 mg) of ravulizumab IV on Day 15. During the Extension Period (Day 71 up to Day 1275), participants received 490 mg of ravulizumab SC qw.	Ravulizumab SC/SC Treatment Group n=79 Participants During the Randomized Treatment Period, participants received a weight-based single loading dose (2400 to 2700 mg) of ravulizumab SC on Day 1, followed by maintenance weight-based doses (490 mg) of ravulizumab SC qw from Days 15 to 64. During the Extension Period (Day 71 up to Day 1275), participants received 490 mg of ravulizumab SC qw.
Percentage of Participants Who Maintained SHg up to Day 351	72.7 percentage of participants Interval 57.21 to 85.04	83.5 percentage of participants Interval 73.51 to 90.94

Adverse Events

Ravulizumab IV/SC Treatment Group

Serious events: 16 serious events

Other events: 44 other events

Deaths: 2 deaths

Ravulizumab SC/SC Treatment Group

Serious events: 30 serious events

Other events: 83 other events

Deaths: 2 deaths

Serious adverse events

Other adverse events

Additional Information

Alexion Pharmaceuticals Inc.

Phone: 855-752-2356

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Ravulizumab IV/SC Treatment Group n=45 participants at risk During the Randomized Treatment Period, participants received a weight-based single loading dose (2400 to 2700 mg) of ravulizumab IV on Day 1, followed by a maintenance weight-based dose (3000 to 3300 mg) of ravulizumab IV on Day 15. During the Extension Period (Day 71 up to Day 1275), participants received 490 mg of ravulizumab SC qw.	Ravulizumab SC/SC Treatment Group n=84 participants at risk During the Randomized Treatment Period, participants received a weight-based single loading dose (2400 to 2700 mg) of ravulizumab SC on Day 1, followed by maintenance weight-based doses (490 mg) of ravulizumab SC qw from Days 15 to 64. During the Extension Period (Day 71 up to Day 1275), participants received 490 mg of ravulizumab SC qw.
Blood and lymphatic system disorders Anaemia	8.9% 4/45 • Baseline up to approximately 3.5 years Safety analysis set included all participants who received at least 1 dose of ravulizumab and were not excluded from analysis.	14.3% 12/84 • Baseline up to approximately 3.5 years Safety analysis set included all participants who received at least 1 dose of ravulizumab and were not excluded from analysis.
Blood and lymphatic system disorders Haemolysis	8.9% 4/45 • Baseline up to approximately 3.5 years Safety analysis set included all participants who received at least 1 dose of ravulizumab and were not excluded from analysis.	11.9% 10/84 • Baseline up to approximately 3.5 years Safety analysis set included all participants who received at least 1 dose of ravulizumab and were not excluded from analysis.
Gastrointestinal disorders Diarrhoea	6.7% 3/45 • Baseline up to approximately 3.5 years Safety analysis set included all participants who received at least 1 dose of ravulizumab and were not excluded from analysis.	20.2% 17/84 • Baseline up to approximately 3.5 years Safety analysis set included all participants who received at least 1 dose of ravulizumab and were not excluded from analysis.
Gastrointestinal disorders Abdominal pain	13.3% 6/45 • Baseline up to approximately 3.5 years Safety analysis set included all participants who received at least 1 dose of ravulizumab and were not excluded from analysis.	11.9% 10/84 • Baseline up to approximately 3.5 years Safety analysis set included all participants who received at least 1 dose of ravulizumab and were not excluded from analysis.
Gastrointestinal disorders Nausea	11.1% 5/45 • Baseline up to approximately 3.5 years Safety analysis set included all participants who received at least 1 dose of ravulizumab and were not excluded from analysis.	10.7% 9/84 • Baseline up to approximately 3.5 years Safety analysis set included all participants who received at least 1 dose of ravulizumab and were not excluded from analysis.
Gastrointestinal disorders Vomiting	6.7% 3/45 • Baseline up to approximately 3.5 years Safety analysis set included all participants who received at least 1 dose of ravulizumab and were not excluded from analysis.	8.3% 7/84 • Baseline up to approximately 3.5 years Safety analysis set included all participants who received at least 1 dose of ravulizumab and were not excluded from analysis.
Gastrointestinal disorders Constipation	2.2% 1/45 • Baseline up to approximately 3.5 years Safety analysis set included all participants who received at least 1 dose of ravulizumab and were not excluded from analysis.	7.1% 6/84 • Baseline up to approximately 3.5 years Safety analysis set included all participants who received at least 1 dose of ravulizumab and were not excluded from analysis.
General disorders Pyrexia	15.6% 7/45 • Baseline up to approximately 3.5 years Safety analysis set included all participants who received at least 1 dose of ravulizumab and were not excluded from analysis.	23.8% 20/84 • Baseline up to approximately 3.5 years Safety analysis set included all participants who received at least 1 dose of ravulizumab and were not excluded from analysis.
General disorders Asthenia	6.7% 3/45 • Baseline up to approximately 3.5 years Safety analysis set included all participants who received at least 1 dose of ravulizumab and were not excluded from analysis.	15.5% 13/84 • Baseline up to approximately 3.5 years Safety analysis set included all participants who received at least 1 dose of ravulizumab and were not excluded from analysis.
General disorders Influenza like illness	0.00% 0/45 • Baseline up to approximately 3.5 years Safety analysis set included all participants who received at least 1 dose of ravulizumab and were not excluded from analysis.	8.3% 7/84 • Baseline up to approximately 3.5 years Safety analysis set included all participants who received at least 1 dose of ravulizumab and were not excluded from analysis.
General disorders Injection site erythema	2.2% 1/45 • Baseline up to approximately 3.5 years Safety analysis set included all participants who received at least 1 dose of ravulizumab and were not excluded from analysis.	8.3% 7/84 • Baseline up to approximately 3.5 years Safety analysis set included all participants who received at least 1 dose of ravulizumab and were not excluded from analysis.
General disorders Fatigue	6.7% 3/45 • Baseline up to approximately 3.5 years Safety analysis set included all participants who received at least 1 dose of ravulizumab and were not excluded from analysis.	8.3% 7/84 • Baseline up to approximately 3.5 years Safety analysis set included all participants who received at least 1 dose of ravulizumab and were not excluded from analysis.
Hepatobiliary disorders Cholelithiasis	6.7% 3/45 • Baseline up to approximately 3.5 years Safety analysis set included all participants who received at least 1 dose of ravulizumab and were not excluded from analysis.	4.8% 4/84 • Baseline up to approximately 3.5 years Safety analysis set included all participants who received at least 1 dose of ravulizumab and were not excluded from analysis.
Infections and infestations COVID-19	35.6% 16/45 • Baseline up to approximately 3.5 years Safety analysis set included all participants who received at least 1 dose of ravulizumab and were not excluded from analysis.	46.4% 39/84 • Baseline up to approximately 3.5 years Safety analysis set included all participants who received at least 1 dose of ravulizumab and were not excluded from analysis.
Infections and infestations Nasopharyngitis	17.8% 8/45 • Baseline up to approximately 3.5 years Safety analysis set included all participants who received at least 1 dose of ravulizumab and were not excluded from analysis.	13.1% 11/84 • Baseline up to approximately 3.5 years Safety analysis set included all participants who received at least 1 dose of ravulizumab and were not excluded from analysis.
Infections and infestations Upper respiratory tract infection	6.7% 3/45 • Baseline up to approximately 3.5 years Safety analysis set included all participants who received at least 1 dose of ravulizumab and were not excluded from analysis.	6.0% 5/84 • Baseline up to approximately 3.5 years Safety analysis set included all participants who received at least 1 dose of ravulizumab and were not excluded from analysis.
Infections and infestations Urinary tract infection	6.7% 3/45 • Baseline up to approximately 3.5 years Safety analysis set included all participants who received at least 1 dose of ravulizumab and were not excluded from analysis.	13.1% 11/84 • Baseline up to approximately 3.5 years Safety analysis set included all participants who received at least 1 dose of ravulizumab and were not excluded from analysis.
Infections and infestations Influenza	13.3% 6/45 • Baseline up to approximately 3.5 years Safety analysis set included all participants who received at least 1 dose of ravulizumab and were not excluded from analysis.	11.9% 10/84 • Baseline up to approximately 3.5 years Safety analysis set included all participants who received at least 1 dose of ravulizumab and were not excluded from analysis.
Musculoskeletal and connective tissue disorders Back pain	11.1% 5/45 • Baseline up to approximately 3.5 years Safety analysis set included all participants who received at least 1 dose of ravulizumab and were not excluded from analysis.	13.1% 11/84 • Baseline up to approximately 3.5 years Safety analysis set included all participants who received at least 1 dose of ravulizumab and were not excluded from analysis.
Musculoskeletal and connective tissue disorders Arthralgia	6.7% 3/45 • Baseline up to approximately 3.5 years Safety analysis set included all participants who received at least 1 dose of ravulizumab and were not excluded from analysis.	8.3% 7/84 • Baseline up to approximately 3.5 years Safety analysis set included all participants who received at least 1 dose of ravulizumab and were not excluded from analysis.
Musculoskeletal and connective tissue disorders Pain in extremity	11.1% 5/45 • Baseline up to approximately 3.5 years Safety analysis set included all participants who received at least 1 dose of ravulizumab and were not excluded from analysis.	10.7% 9/84 • Baseline up to approximately 3.5 years Safety analysis set included all participants who received at least 1 dose of ravulizumab and were not excluded from analysis.
Musculoskeletal and connective tissue disorders Myalgia	0.00% 0/45 • Baseline up to approximately 3.5 years Safety analysis set included all participants who received at least 1 dose of ravulizumab and were not excluded from analysis.	8.3% 7/84 • Baseline up to approximately 3.5 years Safety analysis set included all participants who received at least 1 dose of ravulizumab and were not excluded from analysis.
Nervous system disorders Headache	31.1% 14/45 • Baseline up to approximately 3.5 years Safety analysis set included all participants who received at least 1 dose of ravulizumab and were not excluded from analysis.	19.0% 16/84 • Baseline up to approximately 3.5 years Safety analysis set included all participants who received at least 1 dose of ravulizumab and were not excluded from analysis.
Nervous system disorders Dizziness	8.9% 4/45 • Baseline up to approximately 3.5 years Safety analysis set included all participants who received at least 1 dose of ravulizumab and were not excluded from analysis.	6.0% 5/84 • Baseline up to approximately 3.5 years Safety analysis set included all participants who received at least 1 dose of ravulizumab and were not excluded from analysis.
Product Issues Device delivery system issue	93.3% 42/45 • Baseline up to approximately 3.5 years Safety analysis set included all participants who received at least 1 dose of ravulizumab and were not excluded from analysis.	88.1% 74/84 • Baseline up to approximately 3.5 years Safety analysis set included all participants who received at least 1 dose of ravulizumab and were not excluded from analysis.
Respiratory, thoracic and mediastinal disorders Cough	13.3% 6/45 • Baseline up to approximately 3.5 years Safety analysis set included all participants who received at least 1 dose of ravulizumab and were not excluded from analysis.	7.1% 6/84 • Baseline up to approximately 3.5 years Safety analysis set included all participants who received at least 1 dose of ravulizumab and were not excluded from analysis.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	8.9% 4/45 • Baseline up to approximately 3.5 years Safety analysis set included all participants who received at least 1 dose of ravulizumab and were not excluded from analysis.	7.1% 6/84 • Baseline up to approximately 3.5 years Safety analysis set included all participants who received at least 1 dose of ravulizumab and were not excluded from analysis.
Respiratory, thoracic and mediastinal disorders Dyspnoea	6.7% 3/45 • Baseline up to approximately 3.5 years Safety analysis set included all participants who received at least 1 dose of ravulizumab and were not excluded from analysis.	2.4% 2/84 • Baseline up to approximately 3.5 years Safety analysis set included all participants who received at least 1 dose of ravulizumab and were not excluded from analysis.
Blood and lymphatic system disorders Neutropenia	4.4% 2/45 • Baseline up to approximately 3.5 years Safety analysis set included all participants who received at least 1 dose of ravulizumab and were not excluded from analysis.	7.1% 6/84 • Baseline up to approximately 3.5 years Safety analysis set included all participants who received at least 1 dose of ravulizumab and were not excluded from analysis.
Gastrointestinal disorders Toothache	8.9% 4/45 • Baseline up to approximately 3.5 years Safety analysis set included all participants who received at least 1 dose of ravulizumab and were not excluded from analysis.	11.9% 10/84 • Baseline up to approximately 3.5 years Safety analysis set included all participants who received at least 1 dose of ravulizumab and were not excluded from analysis.
Gastrointestinal disorders Dyspepsia	6.7% 3/45 • Baseline up to approximately 3.5 years Safety analysis set included all participants who received at least 1 dose of ravulizumab and were not excluded from analysis.	1.2% 1/84 • Baseline up to approximately 3.5 years Safety analysis set included all participants who received at least 1 dose of ravulizumab and were not excluded from analysis.
General disorders Infusion site erythema	6.7% 3/45 • Baseline up to approximately 3.5 years Safety analysis set included all participants who received at least 1 dose of ravulizumab and were not excluded from analysis.	4.8% 4/84 • Baseline up to approximately 3.5 years Safety analysis set included all participants who received at least 1 dose of ravulizumab and were not excluded from analysis.
Infections and infestations Gastroenteritis	11.1% 5/45 • Baseline up to approximately 3.5 years Safety analysis set included all participants who received at least 1 dose of ravulizumab and were not excluded from analysis.	6.0% 5/84 • Baseline up to approximately 3.5 years Safety analysis set included all participants who received at least 1 dose of ravulizumab and were not excluded from analysis.
Infections and infestations Paronychia	6.7% 3/45 • Baseline up to approximately 3.5 years Safety analysis set included all participants who received at least 1 dose of ravulizumab and were not excluded from analysis.	1.2% 1/84 • Baseline up to approximately 3.5 years Safety analysis set included all participants who received at least 1 dose of ravulizumab and were not excluded from analysis.
Injury, poisoning and procedural complications Post vaccination fever	8.9% 4/45 • Baseline up to approximately 3.5 years Safety analysis set included all participants who received at least 1 dose of ravulizumab and were not excluded from analysis.	7.1% 6/84 • Baseline up to approximately 3.5 years Safety analysis set included all participants who received at least 1 dose of ravulizumab and were not excluded from analysis.
Psychiatric disorders Insomnia	4.4% 2/45 • Baseline up to approximately 3.5 years Safety analysis set included all participants who received at least 1 dose of ravulizumab and were not excluded from analysis.	6.0% 5/84 • Baseline up to approximately 3.5 years Safety analysis set included all participants who received at least 1 dose of ravulizumab and were not excluded from analysis.
Psychiatric disorders Anxiety	2.2% 1/45 • Baseline up to approximately 3.5 years Safety analysis set included all participants who received at least 1 dose of ravulizumab and were not excluded from analysis.	6.0% 5/84 • Baseline up to approximately 3.5 years Safety analysis set included all participants who received at least 1 dose of ravulizumab and were not excluded from analysis.
Psychiatric disorders Depression	6.7% 3/45 • Baseline up to approximately 3.5 years Safety analysis set included all participants who received at least 1 dose of ravulizumab and were not excluded from analysis.	2.4% 2/84 • Baseline up to approximately 3.5 years Safety analysis set included all participants who received at least 1 dose of ravulizumab and were not excluded from analysis.
Renal and urinary disorders Haemoglobinuria	6.7% 3/45 • Baseline up to approximately 3.5 years Safety analysis set included all participants who received at least 1 dose of ravulizumab and were not excluded from analysis.	1.2% 1/84 • Baseline up to approximately 3.5 years Safety analysis set included all participants who received at least 1 dose of ravulizumab and were not excluded from analysis.
Reproductive system and breast disorders Intermenstrual bleeding	6.7% 3/45 • Baseline up to approximately 3.5 years Safety analysis set included all participants who received at least 1 dose of ravulizumab and were not excluded from analysis.	1.2% 1/84 • Baseline up to approximately 3.5 years Safety analysis set included all participants who received at least 1 dose of ravulizumab and were not excluded from analysis.
Skin and subcutaneous tissue disorders Rash	6.7% 3/45 • Baseline up to approximately 3.5 years Safety analysis set included all participants who received at least 1 dose of ravulizumab and were not excluded from analysis.	2.4% 2/84 • Baseline up to approximately 3.5 years Safety analysis set included all participants who received at least 1 dose of ravulizumab and were not excluded from analysis.
Vascular disorders Hypertension	6.7% 3/45 • Baseline up to approximately 3.5 years Safety analysis set included all participants who received at least 1 dose of ravulizumab and were not excluded from analysis.	3.6% 3/84 • Baseline up to approximately 3.5 years Safety analysis set included all participants who received at least 1 dose of ravulizumab and were not excluded from analysis.