Paroxysmal Nocturnal Hemoglobinuria
Conditions
Keywords
PNH
Brief summary
The primary objective of this study is to evaluate pharmacokinetics (PK) of ravulizumab administered subcutaneously via an on-body delivery system (OBDS) compared with intravenously administered ravulizumab in adult participants with PNH who are clinically stable on eculizumab for at least 3 months prior to study entry.
Detailed description
The study will consist of up to a 30-day Screening Period, a 10-week Randomized Treatment Period, and an Extension Period of up to 172 weeks.
Interventions
COMBINATION_PRODUCTRavulizumab OBDS
The ravulizumab OBDS is a biological-device combination product consisting of a prefilled cartridge containing ravulizumab SC and an on-body injector.
BIOLOGICALRavulizumab
Administered by IV infusion. Ravulizumab IV doses will be based on participant body weight.
Sponsors
Alexion Pharmaceuticals, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male or female ≥18 years of age * Treated with eculizumab for PNH for at least 3 months prior to Day 1 * LDH level ≤1.5 × upper limit of normal (ULN) at screening * PNH diagnosis confirmed by documented high-sensitivity flow cytometry. * Documented meningococcal vaccination not more than 3 years prior to, or at the time of, initiating study treatment. * Body weight ≥40 to \<100 kilogram (kg) * 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. * Willing and able to give written informed consent and comply with study visit schedule.
Exclusion criteria
* More than 1 LDH value \> 2 × ULN within the 3 months prior to study entry * History of bone marrow transplantation. * History of or ongoing major cardiac, pulmonary, renal, endocrine, or hepatic disease that, in the opinion of the Investigator or Sponsor, would preclude participation. * 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). * Females who are pregnant, breastfeeding or who have a positive pregnancy test at screening or Day 1. * 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Ctrough Serum Concentration of Ravulizumab | Predose at Day 71 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Free Serum Complement Component 5 (C5) Concentrations at Day 71 | Predose at Day 71 | — |
| Free Serum Complement Component 5 (C5) Concentrations at Day 351 | Predose at Day 351 | — |
| Percent Change From Baseline in Lactate Dehydrogenase (LDH) Levels at Day 71 | Baseline, Day 71 | Baseline was defined as the last assessment prior to first study drug dose. LDH samples impacted by tabletop hemolysis were excluded from the analysis. |
| Percent Change From Baseline in LDH Levels at Day 351 | 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. |
| Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Subscale Version 4 Score at Day 71 | 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. |
| Change From Baseline in FACIT-Fatigue Scale Version 4 Score at Day 351 | Baseline, Day 351 | 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 subcutaneous treatment. |
| Change From Baseline in Treatment Administration Satisfaction Questionnaire (TASQ) Score at Day 71 | 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. |
| Ctrough Serum Concentration of Ravulizumab at Day 351 | Predose at Day 351 | — |
| Percentage of Participants Who Experienced Breakthrough Hemolysis up to Day 71 | Baseline up to Day 71 | 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. |
| Percentage of Participants Who Experienced Breakthrough Hemolysis up to Day 351 | 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. |
| Percentage of Participants Who Achieved Transfusion Avoidance up to Day 71 | Baseline up to Day 71 | 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. |
| Percentage of Participants Who Achieved Transfusion Avoidance up to Day 351 | 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. |
| Percentage of Participants Who Maintained Stabilized Hemoglobin (SHg) up to Day 71 | 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. |
| Percentage of Participants Who Maintained SHg up to Day 351 | Baseline up to Day 351 | 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. |
| Change From Baseline in Treatment Administration Satisfaction Questionnaire (TASQ) Score at Day 351 | Baseline, Day 351 | 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. |
Countries
Australia, Austria, Belgium, Brazil, Canada, Finland, France, Italy, Netherlands, Russia, Spain, Sweden, Turkey (Türkiye), United States
Participant flow
Pre-assignment details
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.
Participants by arm
| Arm | Count |
|---|---|
| Ravulizumab IV/SC Treatment Group 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. | 45 |
| 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. | 84 |
| Total | 129 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Extension Period | Death | 2 | 2 |
| Extension Period | Lack of Efficacy | 0 | 1 |
| Extension Period | Lost to Follow-up | 0 | 1 |
| Extension Period | Other than Specified | 0 | 1 |
| Extension Period | Physician Decision | 1 | 2 |
| Extension Period | Protocol Violation | 1 | 0 |
| Extension Period | Withdrawal by Subject | 9 | 12 |
| Randomized Treatment Period | Site Source Document Deviations | 1 | 6 |
| Randomized Treatment Period | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Ravulizumab SC/SC Treatment Group | Total | Ravulizumab IV/SC Treatment Group |
|---|---|---|---|
| Age, Continuous | 45.3 years STANDARD_DEVIATION 14.47 | 45.7 years STANDARD_DEVIATION 14 | 46.4 years STANDARD_DEVIATION 13.22 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 15 Participants | 22 Participants | 7 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 53 Participants | 82 Participants | 29 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 16 Participants | 25 Participants | 9 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 7 Participants | 4 Participants |
| Race (NIH/OMB) More than one race | 4 Participants | 6 Participants | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 14 Participants | 21 Participants | 7 Participants |
| Race (NIH/OMB) White | 63 Participants | 92 Participants | 29 Participants |
| Sex: Female, Male Female | 44 Participants | 69 Participants | 25 Participants |
| Sex: Female, Male Male | 40 Participants | 60 Participants | 20 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 2 / 45 | 2 / 84 |
| other Total, other adverse events | 44 / 45 | 83 / 84 |
| serious Total, serious adverse events | 16 / 45 | 30 / 84 |
Outcome results
Primary
Ctrough Serum Concentration of Ravulizumab
Time frame: Predose at Day 71
Population: Pharmacokinetic (PK) analysis set included all participants who had evaluable PK data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ravulizumab IV/SC Treatment Group | Ctrough Serum Concentration of Ravulizumab | 457.58 micrograms/milliliter (µg/mL) | Standard Deviation 108.491 |
| Ravulizumab SC/SC Treatment Group | Ctrough Serum Concentration of Ravulizumab | 578.70 micrograms/milliliter (µg/mL) | Standard Deviation 140.819 |
p-value: <0.000190% CI: [1.16, 1.361]ANOVA
Secondary
Change From Baseline in FACIT-Fatigue Scale Version 4 Score at Day 351
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 subcutaneous treatment.
Time frame: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ravulizumab IV/SC Treatment Group | Change From Baseline in FACIT-Fatigue Scale Version 4 Score at Day 351 | 2.57 units on a scale | Standard Deviation 7.178 |
Secondary
Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Subscale Version 4 Score at 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.
Time frame: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ravulizumab IV/SC Treatment Group | 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 |
| Ravulizumab SC/SC Treatment Group | Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Subscale Version 4 Score at Day 71 | 1.21 units on a scale | Standard Deviation 7.882 |
Secondary
Change From Baseline in Treatment Administration Satisfaction Questionnaire (TASQ) Score at Day 351
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.
Time frame: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ravulizumab IV/SC Treatment Group | Change From Baseline in Treatment Administration Satisfaction Questionnaire (TASQ) Score at Day 351 | -69.29 units on a scale | Standard Deviation 80.068 |
Secondary
Change From Baseline in Treatment Administration Satisfaction Questionnaire (TASQ) Score at 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.
Time frame: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ravulizumab IV/SC Treatment Group | Change From Baseline in Treatment Administration Satisfaction Questionnaire (TASQ) Score at Day 71 | -7.00 units on a scale | Standard Deviation 34.581 |
| Ravulizumab SC/SC Treatment Group | Change From Baseline in Treatment Administration Satisfaction Questionnaire (TASQ) Score at Day 71 | -70.54 units on a scale | Standard Deviation 70.522 |
Secondary
Ctrough Serum Concentration of Ravulizumab at Day 351
Time frame: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ravulizumab IV/SC Treatment Group | Ctrough Serum Concentration of Ravulizumab at Day 351 | 712.79 µg/mL | Standard Deviation 203.18 |
| Ravulizumab SC/SC Treatment Group | Ctrough Serum Concentration of Ravulizumab at Day 351 | 737.65 µg/mL | Standard Deviation 208.894 |
Secondary
Free Serum Complement Component 5 (C5) Concentrations at Day 351
Time frame: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ravulizumab IV/SC Treatment Group | Free Serum Complement Component 5 (C5) Concentrations at Day 351 | 0.071627 µg/mL | Standard Deviation 0.022798 |
| Ravulizumab SC/SC Treatment Group | Free Serum Complement Component 5 (C5) Concentrations at Day 351 | 0.069711 µg/mL | Standard Deviation 0.0208784 |
Secondary
Free Serum Complement Component 5 (C5) Concentrations at Day 71
Time frame: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ravulizumab IV/SC Treatment Group | Free Serum Complement Component 5 (C5) Concentrations at Day 71 | 0.072193 µg/mL | Standard Deviation 0.0245225 |
| Ravulizumab SC/SC Treatment Group | Free Serum Complement Component 5 (C5) Concentrations at Day 71 | 0.059458 µg/mL | Standard Deviation 0.018218 |
Secondary
Percentage of Participants Who Achieved Transfusion Avoidance 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.
Time frame: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ravulizumab IV/SC Treatment Group | Percentage of Participants Who Achieved Transfusion Avoidance up to Day 351 | 79.5 percentage of participants |
| Ravulizumab SC/SC Treatment Group | Percentage of Participants Who Achieved Transfusion Avoidance up to Day 351 | 85.7 percentage of participants |
Secondary
Percentage of Participants Who Achieved Transfusion Avoidance up to Day 71
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.
Time frame: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ravulizumab IV/SC Treatment Group | Percentage of Participants Who Achieved Transfusion Avoidance up to Day 71 | 86.7 percentage of participants |
| Ravulizumab SC/SC Treatment Group | Percentage of Participants Who Achieved Transfusion Avoidance up to Day 71 | 94.0 percentage of participants |
Secondary
Percentage of Participants Who Experienced Breakthrough Hemolysis 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.
Time frame: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ravulizumab IV/SC Treatment Group | Percentage of Participants Who Experienced Breakthrough Hemolysis up to Day 351 | 4.5 percentage of participants |
| Ravulizumab SC/SC Treatment Group | Percentage of Participants Who Experienced Breakthrough Hemolysis up to Day 351 | 3.6 percentage of participants |
Secondary
Percentage of Participants Who Experienced Breakthrough Hemolysis up to Day 71
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.
Time frame: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ravulizumab IV/SC Treatment Group | Percentage of Participants Who Experienced Breakthrough Hemolysis up to Day 71 | 2.2 percentage of participants |
| Ravulizumab SC/SC Treatment Group | Percentage of Participants Who Experienced Breakthrough Hemolysis up to Day 71 | 1.2 percentage of participants |
Secondary
Percentage of Participants Who Maintained SHg up to Day 351
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.
Time frame: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ravulizumab IV/SC Treatment Group | Percentage of Participants Who Maintained SHg up to Day 351 | 72.7 percentage of participants |
| Ravulizumab SC/SC Treatment Group | Percentage of Participants Who Maintained SHg up to Day 351 | 83.5 percentage of participants |
Secondary
Percentage of Participants Who Maintained Stabilized Hemoglobin (SHg) 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.
Time frame: 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. Here, Number of Participants Analyzed signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ravulizumab IV/SC Treatment Group | Percentage of Participants Who Maintained Stabilized Hemoglobin (SHg) up to Day 71 | 81.8 percentage of participants |
| Ravulizumab SC/SC Treatment Group | Percentage of Participants Who Maintained Stabilized Hemoglobin (SHg) up to Day 71 | 93.6 percentage of participants |
Secondary
Percent Change From Baseline in Lactate Dehydrogenase (LDH) Levels at Day 71
Baseline was defined as the last assessment prior to first study drug dose. LDH samples impacted by tabletop hemolysis were excluded from the analysis.
Time frame: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ravulizumab IV/SC Treatment Group | Percent Change From Baseline in Lactate Dehydrogenase (LDH) Levels at Day 71 | 5.73 percent change | Standard Deviation 29.716 |
| Ravulizumab SC/SC Treatment Group | Percent Change From Baseline in Lactate Dehydrogenase (LDH) Levels at Day 71 | 2.57 percent change | Standard Deviation 33.883 |
Secondary
Percent Change From Baseline in LDH Levels at 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.
Time frame: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ravulizumab IV/SC Treatment Group | Percent Change From Baseline in LDH Levels at Day 351 | -0.83 percent change | Standard Deviation 17.225 |
| Ravulizumab SC/SC Treatment Group | Percent Change From Baseline in LDH Levels at Day 351 | 1.74 percent change | Standard Deviation 21.905 |