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Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/ct2/show/NCT02946463
Registration number
NCT02946463
Ethics application status
Date submitted
25/10/2016
Date registered
27/10/2016
Date last updated
14/05/2024
Titles & IDs
Public title
ALXN1210 (Ravulizumab) Versus Eculizumab in Complement Inhibitor Treatment-Naïve Adult Participants With Paroxysmal Nocturnal Hemoglobinuria (PNH)
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Scientific title
A Phase 3, Randomized, Open-Label, Active-Controlled Study of ALXN1210 Versus Eculizumab in Complement Inhibitor-Naïve Adult Patients With Paroxysmal Nocturnal Hemoglobinuria (PNH)
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Secondary ID [1]
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2016-002025-11
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Secondary ID [2]
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ALXN1210-PNH-301
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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 (PNH)
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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
Other interventions - Eculizumab
Experimental: Ravulizumab -
Active Comparator: Eculizumab -
Other interventions: Ravulizumab
All treatments were given as intravenous (IV) infusions. For participants weighing =40 to <60 kilogram (kg): 2400 mg was given as a single loading dose, followed by 3000 mg as maintenance dose. For participants weighing =60 to <100 kg: 2700 mg was given as a loading dose, followed by 3300 mg as maintenance dose. For participants weighing =100 kg: 3000 mg was given as a loading dose, followed by 3600 mg as maintenance dose.
Other interventions: Eculizumab
All treatments were given as IV infusions. Participants were administered induction doses of 600 mg followed by maintenance doses of 900 mg.
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Intervention code [1]
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Other interventions
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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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Proportion Of Participants With Normalization Of Lactate Dehydrogenase (LDH) Levels
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Assessment method [1]
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LDH is an indicator of intravascular hemolysis that occurs in participants with paroxysmal nocturnal hemoglobinuria (PNH). A decrease in LDH from above the upper limit of normal (ULN) to below the ULN indicates reduction (improvement) in hemolysis. Normalization of LDH levels (LDH-N) was LDH levels less than or equal to 1 x ULN, from Day 29 through Day 183. The ULN for LDH is 246 U/L.
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Timepoint [1]
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Day 29 through Day 183
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Primary outcome [2]
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Percentage Of Participants Who Achieved Transfusion Avoidance (TA)
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Assessment method [2]
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Transfusion avoidance was defined as the percentage of participants who remained transfusion free and did not require a transfusion per protocol-specified guidelines through Day 183.
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Timepoint [2]
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Baseline through Day 183
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Secondary outcome [1]
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Percentage Of Participants With Breakthrough Hemolysis (BTH)
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Assessment method [1]
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Breakthrough hemolysis was defined as at least 1 new or worsening symptom or sign of intravascular hemolysis (fatigue, hemoglobinuria, abdominal pain, shortness of breath [dyspnea], anemia [hemoglobin <10 gram/deciliter (g/dL)], major adverse vascular event [MAVE, including thrombosis], dysphagia, or erectile dysfunction) in the presence of elevated LDH =2 × ULN, after prior LDH reduction to <1.5 × ULN on therapy.
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Timepoint [1]
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Baseline through Day 183
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Secondary outcome [2]
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Percent Change From Baseline In LDH Levels
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Assessment method [2]
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Baseline is defined as the average of all available assessments of LDH levels prior to first study drug dose. Estimates are based on Mixed Model for Repeated Measures (MMRM) that includes treatment group, history of transfusion (as a categorical variable based on the stratification factor levels) and baseline LDH level (as a continuous variable), study visit and study visit by treatment group interaction. An unstructured covariance structure was used.
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Timepoint [2]
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Baseline, Day 183
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Secondary outcome [3]
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Change From Baseline In Quality Of Life As Assessed By The Functional Assessment Of Chronic Illness Therapy (FACIT)-Fatigue
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Assessment method [3]
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FACIT-Fatigue score ranges from 0 to 52, with a higher score indicating less fatigue. Baseline is defined as the last non-missing value prior to first dose of study drug. Estimates are based on MMRM that includes treatment group, the observed stratification randomization indicators (history of transfusion and LDH) and baseline FACIT-Fatigue level, study visit, and study visit by treatment group interaction. An unstructured covariance structure was used.
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Timepoint [3]
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Baseline, Day 183
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Secondary outcome [4]
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Percentage Of Participants With Stabilized Hemoglobin Levels
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Assessment method [4]
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Stabilized hemoglobin was defined as avoidance of a =2 g/dL decrease in hemoglobin level from baseline in the absence of transfusion through Day 183.
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Timepoint [4]
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Baseline through Day 183
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Eligibility
Key inclusion criteria
Criteria For Patient Cohort Originally Enrolled in ALXN1210-PNH-301 Study: Inclusion
Criteria: 1. Male or female =18 years of age. 2. PNH diagnosis confirmed by documented by
high-sensitivity flow cytometry. 3. Presence of 1 or more of the following PNH-related
signs or symptoms within 3 months of screening: fatigue, hemoglobinuria, abdominal pain,
shortness of breath (dyspnea), anemia (hemoglobin <10 gram/deciliter), history of a major
adverse vascular event (including thrombosis), dysphagia, or erectile dysfunction; or
history of packed red blood cells (pRBC) transfusion due to PNH. 4. Lactate dehydrogenase
(LDH) level =1.5 times the upper limit of normal at screening. 5. Documented meningococcal
vaccination not more than 3 years prior to, or at the time of, initiating study treatment.
6. Female participants of childbearing potential must use highly effective contraception
starting at screening and continuing until at least 8 months after the last dose of
ravulizumab. 7. Willing and able to give written informed consent and comply with study
visit schedule.
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Minimum age
No limit
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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
1. Treatment with a complement inhibitor at any time.
2. History of bone marrow transplantation. 3. Body weight <40 kg. 4. Females who are
pregnant, breastfeeding, or who have a positive pregnancy test at screening or Day 1. 5.
Participation in another interventional clinical study or use of any experimental therapy
within 30 days before initiation of study drug on Day 1 in this study or within 5
half-lives of that investigational product, whichever is greater. 6. History of or ongoing
major cardiac, pulmonary, renal, endocrine, or hepatic disease that, in the opinion of the
investigator or sponsor, would preclude participation. 7. 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). Eligibility Criteria For Roll-over Cohort: 1. All
participants regardless of age, who are currently receiving ALXN1210 IV in an ongoing
ALXN1210 study in patients with PNH 2. Participants must be willing and able to give
written informed consent and to comply with all Extension study visits and procedures,
including the use of any data collection device(s) to directly record patient data 3.
Females of childbearing potential and male patients with female partners of childbearing
potential must use highly effective contraception continuing until at least 8 months after
the last dose of ravulizumab.
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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
12/12/2016
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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
28/02/2023
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Sample size
Target
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Accrual to date
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Final
272
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Recruitment in Australia
Recruitment state(s)
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Recruitment hospital [1]
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Research Site - Perth
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Recruitment postcode(s) [1]
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6000 - Perth
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Recruitment outside Australia
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Ufa
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Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
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Name
Alexion Pharmaceuticals, Inc.
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Ethics approval
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Summary
Brief summary
The primary purpose of this study was to assess the noninferiority of ravulizumab compared to
eculizumab in adult participants with PNH who had never been treated with a complement
inhibitor (treatment-naïve).
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Trial website
https://clinicaltrials.gov/ct2/show/NCT02946463
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Trial related presentations / publications
Lee JW, Sicre de Fontbrune F, Wong Lee Lee L, Pessoa V, Gualandro S, Fureder W, Ptushkin V, Rottinghaus ST, Volles L, Shafner L, Aguzzi R, Pradhan R, Schrezenmeier H, Hill A. Ravulizumab (ALXN1210) vs eculizumab in adult patients with PNH naive to complement inhibitors: the 301 study. Blood. 2019 Feb 7;133(6):530-539. doi: 10.1182/blood-2018-09-876136. Epub 2018 Dec 3.
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Public notes
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Contacts
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Contact person for scientific queries
Summary Results
For IPD and results data, please see
https://clinicaltrials.gov/ct2/show/NCT02946463
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