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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT02946463




Registration number
NCT02946463
Ethics application status
Date submitted
25/10/2016
Date registered
27/10/2016
Date last updated
16/05/2019

Titles & IDs
Public title
ALXN1210 (Ravulizumab) Versus Eculizumab in Complement Inhibitor Treatment-Naïve Adult Participants With Paroxysmal Nocturnal Hemoglobinuria (PNH)
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)
Secondary ID [1] 0 0
2016-002025-11
Secondary ID [2] 0 0
ALXN1210-PNH-301
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Paroxysmal Nocturnal Hemoglobinuria (PNH) 0 0
Condition category
Condition code
Blood 0 0 0 0
Haematological diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Other interventions - Ravulizumab
Other interventions - Eculizumab

Experimental: Ravulizumab - Participants received weight-based doses of ravulizumab ranging from 2400 to 3000 milligram (mg) on Day 1. Thereafter, weight-based doses of ravulizumab ranging from 3000 to 3600 mg were administered on Day 15 and every 8 weeks thereafter for 26 weeks.
After completion of the Primary Evaluation Period, all participants had the opportunity to enter the Extension Period, wherein participants will receive weight-based doses of ravulizumab for up to 5 years.

Active Comparator: Eculizumab - Participants received 600 mg of eculizumab on Days 1, 8, 15, and 22, followed by 900 mg of eculizumab on Day 29 and every 2 weeks thereafter for 26 weeks.
After completion of the Primary Evaluation Period, all participants had the opportunity to enter the Extension Period, wherein participants will receive weight-based doses of ravulizumab for up to 5 years.


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.

Intervention code [1] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Proportion Of Participants With Normalization Of Lactate Dehydrogenase (LDH) Levels - LDH is an indicator of intravascular hemolysis that occurs in patients 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.
Timepoint [1] 0 0
Day 29 through Day 183
Primary outcome [2] 0 0
Percentage Of Participants Who Achieved Transfusion Avoidance (TA) - 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.
Timepoint [2] 0 0
Baseline through Day 183
Secondary outcome [1] 0 0
Percentage Of Participants With Breakthrough Hemolysis (BTH) - 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.
Timepoint [1] 0 0
Baseline through Day 183
Secondary outcome [2] 0 0
Percent Change From Baseline In Lactate Dehydrogenase (LDH) Levels - 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.
Timepoint [2] 0 0
Baseline, Day 183
Secondary outcome [3] 0 0
Change From Baseline In Quality Of Life As Assessed By The Functional Assessment Of Chronic Illness Therapy (FACIT)-Fatigue - 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.
Timepoint [3] 0 0
Baseline, Day 183
Secondary outcome [4] 0 0
Percentage Of Participants With Stabilized Hemoglobin Levels - 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.
Timepoint [4] 0 0
Baseline through Day 183

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
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).

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Clinical Trial Site - Perth
Recruitment postcode(s) [1] 0 0
- Perth
Recruitment outside Australia
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United States of America
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California
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Caba
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Córdoba
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Linz
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Vienna
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Hasselt
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Edmonton
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Toronto
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Plzen
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Praha
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Tallinn
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France
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Vienne
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France
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France
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France
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Paris
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France
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Pierre-Bénite
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France
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Rennes
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Germany
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Essen
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Germany
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Ulm
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Italy
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Ascoli Piceno
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Italy
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Firenze
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Milano
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Italy
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Napoli
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Vicenza
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Fukuoka
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Fukushima
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Hamamatsu-shi
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Kanazawa-shi
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Koshigaya-shi
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Kumamoto
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Nishinomiya-shi
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Sapporo
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Incheon
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Jeonju
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Seoul
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Ulsan
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Barnaul
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Rostov-na-Donu
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Saint Petersburg
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Saratov
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Ufa
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Singapore
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Singapore
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Spain
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Barcelona
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Spain
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Madrid
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Spain
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Majadahonda
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Sweden
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Uppsala
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Taiwan
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Chang-hua
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Taiwan
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Hualien City
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Taiwan
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Kaohsiung
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Taiwan
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Taichung
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Taiwan
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Tainan
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Taiwan
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Taipei
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Thailand
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Bangkok
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Thailand
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Songkhla
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Turkey
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Eskisehir
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United Kingdom
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Leeds
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United Kingdom
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London

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Alexion Pharmaceuticals
Address
Country

Ethics approval
Ethics application status

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).
Trial website
https://clinicaltrials.gov/show/NCT02946463
Trial related presentations / publications
Lee JW, Sicre de Fontbrune F, Wong Lee Lee L, Pessoa V, Gualandro S, Füreder 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.
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
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Email 0 0
Contact person for scientific queries

Summary results
Other publications