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.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
139
The ravulizumab OBDS is a biological-device combination product consisting of a prefilled cartridge containing ravulizumab SC and an on-body injector.
Administered by IV infusion. Ravulizumab IV doses will be based on participant body weight.
Ctrough Serum Concentration of Ravulizumab
Time frame: Predose at Day 71
Ctrough Serum Concentration of Ravulizumab at Day 351
Time frame: Predose at Day 351
Free Serum Complement Component 5 (C5) Concentrations at Day 71
Time frame: Predose at Day 71
Free Serum Complement Component 5 (C5) Concentrations at Day 351
Time frame: Predose at Day 351
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
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
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
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Research Site
Los Angeles, California, United States
Research Site
Liverpool, Australia
Research Site
Parkville, Australia
Research Site
Vienna, Austria
Research Site
Antwerp, Belgium
Research Site
Brussels, Belgium
Research Site
Hasselt, Belgium
Research Site
Leuven, Belgium
Research Site
Botucatu, Brazil
Research Site
Ribeirão Preto, Brazil
...and 41 more locations
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
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
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
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
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
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
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
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
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