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Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/study/NCT03748823
Registration number
NCT03748823
Ethics application status
Date submitted
19/11/2018
Date registered
21/11/2018
Titles & IDs
Public title
Ravulizumab Subcutaneous (SC) Versus Ravulizumab Intravenous (IV) in Adults With Paroxysmal Nocturnal Hemoglobinuria (PNH) Currently Treated With Eculizumab
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Scientific title
A Phase 3, Randomized, Parallel-Group, Multicenter, Open-Label, Pharmacokinetic, Noninferiority Study of Ravulizumab Administered Subcutaneously Versus Intravenously in Adult Patients With Paroxysmal Nocturnal Hemoglobinuria Currently Treated With Eculizumab
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Secondary ID [1]
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2017-002370-39
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Secondary ID [2]
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ALXN1210-PNH-303
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Universal Trial Number (UTN)
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Trial acronym
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Linked study record
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Health condition
Health condition(s) or problem(s) studied:
Paroxysmal Nocturnal Hemoglobinuria
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Condition category
Condition code
Blood
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Haematological diseases
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Intervention/exposure
Study type
Interventional
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Description of intervention(s) / exposure
Other interventions - Ravulizumab OBDS
Treatment: Other - Ravulizumab
Experimental: Ravulizumab SC Treatment Group - In the Randomized Treatment Period, participants will receive an IV loading dose of ravulizumab on Day 1 followed by SC maintenance doses of ravulizumab administered via the ravulizumab OBDS on Day 15 and every week (qw) thereafter for a total of 10 weeks of study treatment.
In the Extension Period, ravulizumab SC will be administered via the ravulizumab OBDS from Day 71 qw through Day 1274.
Active comparator: Ravulizumab IV Treatment Group - In the Randomized Treatment Period, participants will receive an IV loading dose of ravulizumab on Day 1 followed by IV maintenance doses of ravulizumab on Day 15.
In the Extension Period, ravulizumab SC will be administered via the ravulizumab OBDS from Day 71 qw through Day 1274.
Other interventions: Ravulizumab OBDS
The ravulizumab OBDS is a biological-device combination product consisting of a prefilled cartridge containing ravulizumab SC and an on-body injector.
Treatment: Other: Ravulizumab
Administered by IV infusion. Ravulizumab IV doses will be based on participant body weight.
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Intervention code [1]
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Other interventions
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Intervention code [2]
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Treatment: Other
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Comparator / control treatment
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Control group
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Outcomes
Primary outcome [1]
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Ctrough Serum Concentration of Ravulizumab
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Assessment method [1]
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Timepoint [1]
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Predose at Day 71
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Secondary outcome [1]
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Ctrough Serum Concentration of Ravulizumab at Day 351
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Assessment method [1]
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Timepoint [1]
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Predose at Day 351
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Secondary outcome [2]
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Free Serum Complement Component 5 (C5) Concentrations at Day 71
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Assessment method [2]
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Timepoint [2]
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Predose at Day 71
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Secondary outcome [3]
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Free Serum Complement Component 5 (C5) Concentrations at Day 351
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Assessment method [3]
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Timepoint [3]
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Predose at Day 351
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Secondary outcome [4]
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Percent Change From Baseline in Lactate Dehydrogenase (LDH) Levels at Day 71
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Assessment method [4]
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Baseline was defined as the last assessment prior to first study drug dose. Lactate dehydrogenase samples impacted by tabletop hemolysis were excluded from the analysis.
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Timepoint [4]
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Baseline, Day 71
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Secondary outcome [5]
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Percent Change From Baseline in Lactate Dehydrogenase Levels at Day 351
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Assessment method [5]
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Subcutaneous baseline was defined as the last assessment prior to first dose of subcutaneous treatment. Lactate dehydrogenase samples impacted by tabletop hemolysis were excluded from the analysis.
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Timepoint [5]
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Baseline, Day 351
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Secondary outcome [6]
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Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Subscale Version 4 Score at Day 71
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Assessment method [6]
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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; total scores range from 0 to 52 with 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.
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Timepoint [6]
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Baseline, Day 71
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Secondary outcome [7]
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Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue Scale Version 4 Score at Day 351
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Assessment method [7]
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FACIT-fatigue scale is a 13-item questionnaire that assesses self-reported fatigue and its impact upon daily activities and function over the preceding 7 days; total scores range from 0 to 52 with 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.
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Timepoint [7]
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Baseline, Day 351
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Secondary outcome [8]
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Change From Baseline in Treatment Administration Satisfaction Questionnaire (TASQ) Score at Day 71
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Assessment method [8]
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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.
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Timepoint [8]
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Baseline, Day 71
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Secondary outcome [9]
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Change From Baseline in Treatment Administration Satisfaction Questionnaire (TASQ) Score at Day 351
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Assessment method [9]
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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.
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Timepoint [9]
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Baseline, Day 351
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Secondary outcome [10]
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Percentage of Participants Who Experienced Breakthrough Hemolysis up to Day 71
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Assessment method [10]
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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.
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Timepoint [10]
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Baseline up to Day 71
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Secondary outcome [11]
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Percentage of Participants Who Experienced Breakthrough Hemolysis up to Day 351
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Assessment method [11]
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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.
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Timepoint [11]
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Baseline up to Day 351
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Secondary outcome [12]
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Percentage of Participants Who Achieved Transfusion Avoidance up to Day 71
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Assessment method [12]
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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.
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Timepoint [12]
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Baseline up to Day 71
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Secondary outcome [13]
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Percentage of Participants Who Achieved Transfusion Avoidance up to Day 351
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Assessment method [13]
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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.
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Timepoint [13]
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Baseline up to Day 351
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Secondary outcome [14]
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Percentage of Participants Who Maintained Stabilized Hemoglobin up to Day 71
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Assessment method [14]
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Stabilized hemoglobin (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.
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Timepoint [14]
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Baseline up to Day 71
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Secondary outcome [15]
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Percentage of Participants Who Maintained Stabilized Hemoglobin up to Day 351
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Assessment method [15]
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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.
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Timepoint [15]
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Baseline up to Day 351
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Eligibility
Key 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.
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Minimum age
18
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Maximum age
No limit
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Sex
Both males and females
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Can healthy volunteers participate?
No
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Key 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.
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Study design
Purpose of the study
Treatment
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Allocation to intervention
Randomised controlled trial
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Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
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Methods used to generate the sequence in which subjects will be randomised (sequence generation)
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Masking / blinding
Open (masking not used)
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Who is / are masked / blinded?
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Intervention assignment
Parallel
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Other design features
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Phase
Phase 3
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Type of endpoint/s
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Statistical methods / analysis
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Recruitment
Recruitment status
Completed
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Data analysis
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Reason for early stopping/withdrawal
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Other reasons
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Date of first participant enrolment
Anticipated
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Actual
19/02/2019
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Date of last participant enrolment
Anticipated
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Actual
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Date of last data collection
Anticipated
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Actual
31/08/2023
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Sample size
Target
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Accrual to date
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Final
139
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Recruitment in Australia
Recruitment state(s)
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Recruitment hospital [1]
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Research Site - Liverpool
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Recruitment hospital [2]
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Research Site - Parkville
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Recruitment postcode(s) [1]
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2170 - Liverpool
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Recruitment postcode(s) [2]
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3050 - Parkville
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Recruitment outside Australia
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United States of America
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California
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Austria
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Vienna
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Antwerpen
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Bruxelles
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Hasselt
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Leuven
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Brazil
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Brazil
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Brazil
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Ontario
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Helsinki
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Montpellier Cedex 5
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Nantes cedex 01
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Rennes Cedex 9
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Badalona
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Donostia
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Las Palmas de Gran Canaria
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Madrid
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Majadahonda
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Uppsala
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Adana
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Istambul
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Istanbul
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Izmir
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Funding & Sponsors
Primary sponsor type
Commercial sector/industry
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Name
Alexion Pharmaceuticals, Inc.
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Address
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Ethics approval
Ethics application status
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Summary
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.
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Trial website
https://clinicaltrials.gov/study/NCT03748823
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Trial related presentations / publications
Yenerel MN, Sicre de Fontbrune F, Piatek C, Sahin F, Fureder W, Ortiz S, Ogawa M, Ozol-Godfrey A, Sierra JR, Szer J. Phase 3 Study of Subcutaneous Versus Intravenous Ravulizumab in Eculizumab-Experienced Adult Patients with PNH: Primary Analysis and 1-Year Follow-Up. Adv Ther. 2023 Jan;40(1):211-232. doi: 10.1007/s12325-022-02339-3. Epub 2022 Oct 22.
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Public notes
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Contacts
Principal investigator
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Contact person for scientific queries
Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
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No/undecided IPD sharing reason/comment
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What supporting documents are/will be available?
No Supporting Document Provided
Type
Other Details
Attachment
Study protocol
https://cdn.clinicaltrials.gov/large-docs/23/NCT03748823/Prot_000.pdf
Statistical analysis plan
https://cdn.clinicaltrials.gov/large-docs/23/NCT03748823/SAP_001.pdf
Results publications and other study-related documents
No documents have been uploaded by study researchers.
Results are available at
https://clinicaltrials.gov/study/NCT03748823