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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/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)
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
Treatment: Other - Ravulizumab
Treatment: Other - Eculizumab

Experimental: Ravulizumab -

Active comparator: Eculizumab -


Treatment: Other: 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.

Treatment: Other: 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
Treatment: Other
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Proportion Of Participants With Normalization Of Lactate Dehydrogenase (LDH) Levels
Assessment method [1] 0 0
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.
Timepoint [1] 0 0
Day 29 through Day 183
Primary outcome [2] 0 0
Percentage Of Participants Who Achieved Transfusion Avoidance (TA)
Assessment method [2] 0 0
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)
Assessment method [1] 0 0
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 LDH Levels
Assessment method [2] 0 0
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
Assessment method [3] 0 0
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
Assessment method [4] 0 0
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
Criteria For Patient Cohort Originally Enrolled in ALXN1210-PNH-301 Study: 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
No limit
Maximum age
No limit
Sex
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). 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.

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
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
12/12/2016
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
28/02/2023
Sample size
Target
Accrual to date
Final
272
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Research Site - Perth
Recruitment postcode(s) [1] 0 0
6000 - Perth
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Texas
Country [3] 0 0
Argentina
State/province [3] 0 0
Buenos Aires
Country [4] 0 0
Argentina
State/province [4] 0 0
Córdoba
Country [5] 0 0
Austria
State/province [5] 0 0
Linz
Country [6] 0 0
Austria
State/province [6] 0 0
Vienna
Country [7] 0 0
Belgium
State/province [7] 0 0
Bruxelles
Country [8] 0 0
Belgium
State/province [8] 0 0
Hasselt
Country [9] 0 0
Belgium
State/province [9] 0 0
Leuven
Country [10] 0 0
Brazil
State/province [10] 0 0
Rio De Janeiro
Country [11] 0 0
Brazil
State/province [11] 0 0
Salvador
Country [12] 0 0
Brazil
State/province [12] 0 0
Sao Paulo
Country [13] 0 0
Canada
State/province [13] 0 0
Alberta
Country [14] 0 0
Canada
State/province [14] 0 0
Ontario
Country [15] 0 0
Czechia
State/province [15] 0 0
Plzen
Country [16] 0 0
Czechia
State/province [16] 0 0
Prague
Country [17] 0 0
Estonia
State/province [17] 0 0
Tallinn
Country [18] 0 0
France
State/province [18] 0 0
Limoges
Country [19] 0 0
France
State/province [19] 0 0
MONTPELLIER Cedex 5
Country [20] 0 0
France
State/province [20] 0 0
Paris Cedex 10
Country [21] 0 0
France
State/province [21] 0 0
Pierre Benite
Country [22] 0 0
France
State/province [22] 0 0
Poitiers
Country [23] 0 0
France
State/province [23] 0 0
Rennes Cedex 9
Country [24] 0 0
Germany
State/province [24] 0 0
Aachen
Country [25] 0 0
Germany
State/province [25] 0 0
Essen
Country [26] 0 0
Germany
State/province [26] 0 0
Ulm
Country [27] 0 0
Italy
State/province [27] 0 0
Ascoli Piceno
Country [28] 0 0
Italy
State/province [28] 0 0
Firenze
Country [29] 0 0
Italy
State/province [29] 0 0
Milano
Country [30] 0 0
Italy
State/province [30] 0 0
Napoli
Country [31] 0 0
Italy
State/province [31] 0 0
Vicenza
Country [32] 0 0
Japan
State/province [32] 0 0
Bunkyo-ku
Country [33] 0 0
Japan
State/province [33] 0 0
Fukuoka-Shi
Country [34] 0 0
Japan
State/province [34] 0 0
Fukushima-shi
Country [35] 0 0
Japan
State/province [35] 0 0
Hamamatsu-shi
Country [36] 0 0
Japan
State/province [36] 0 0
Kanazawa-shi
Country [37] 0 0
Japan
State/province [37] 0 0
Kitakyusyu-shi
Country [38] 0 0
Japan
State/province [38] 0 0
Koshigaya-shi
Country [39] 0 0
Japan
State/province [39] 0 0
Kumamoto-shi
Country [40] 0 0
Japan
State/province [40] 0 0
Nagoya-shi
Country [41] 0 0
Japan
State/province [41] 0 0
Nishinomiya-shi
Country [42] 0 0
Japan
State/province [42] 0 0
Ogaki-shi
Country [43] 0 0
Japan
State/province [43] 0 0
Okayama-shi
Country [44] 0 0
Japan
State/province [44] 0 0
Osakasayama-shi
Country [45] 0 0
Japan
State/province [45] 0 0
Sapporo-shi
Country [46] 0 0
Japan
State/province [46] 0 0
Shimotsuke-shi
Country [47] 0 0
Japan
State/province [47] 0 0
Shinjuku-ku
Country [48] 0 0
Japan
State/province [48] 0 0
Suita
Country [49] 0 0
Japan
State/province [49] 0 0
Tokorozawa-shi
Country [50] 0 0
Japan
State/province [50] 0 0
Tokyo
Country [51] 0 0
Japan
State/province [51] 0 0
Toyoake-shi
Country [52] 0 0
Japan
State/province [52] 0 0
Tsukuba-shi
Country [53] 0 0
Japan
State/province [53] 0 0
Wakayama-shi
Country [54] 0 0
Korea, Republic of
State/province [54] 0 0
Daejeon
Country [55] 0 0
Korea, Republic of
State/province [55] 0 0
Goyang-si
Country [56] 0 0
Korea, Republic of
State/province [56] 0 0
Incheon
Country [57] 0 0
Korea, Republic of
State/province [57] 0 0
Jeonju-si
Country [58] 0 0
Korea, Republic of
State/province [58] 0 0
JinJoo
Country [59] 0 0
Korea, Republic of
State/province [59] 0 0
Jung-gu
Country [60] 0 0
Korea, Republic of
State/province [60] 0 0
Seoul
Country [61] 0 0
Korea, Republic of
State/province [61] 0 0
Songpa-gu
Country [62] 0 0
Korea, Republic of
State/province [62] 0 0
Suwon-si
Country [63] 0 0
Korea, Republic of
State/province [63] 0 0
Ulsan
Country [64] 0 0
Malaysia
State/province [64] 0 0
George
Country [65] 0 0
Malaysia
State/province [65] 0 0
Johor Bahru
Country [66] 0 0
Malaysia
State/province [66] 0 0
Kota Bharu
Country [67] 0 0
Malaysia
State/province [67] 0 0
Kota Kinabalu
Country [68] 0 0
Malaysia
State/province [68] 0 0
Kuching
Country [69] 0 0
Malaysia
State/province [69] 0 0
Miri
Country [70] 0 0
Malaysia
State/province [70] 0 0
Sibu
Country [71] 0 0
Mexico
State/province [71] 0 0
Monterrey
Country [72] 0 0
Poland
State/province [72] 0 0
Gdansk
Country [73] 0 0
Poland
State/province [73] 0 0
Warszawa
Country [74] 0 0
Russian Federation
State/province [74] 0 0
Arkhangelsk
Country [75] 0 0
Russian Federation
State/province [75] 0 0
Barnaul
Country [76] 0 0
Russian Federation
State/province [76] 0 0
Irkutsk
Country [77] 0 0
Russian Federation
State/province [77] 0 0
Kirov
Country [78] 0 0
Russian Federation
State/province [78] 0 0
Moscow
Country [79] 0 0
Russian Federation
State/province [79] 0 0
Murmansk
Country [80] 0 0
Russian Federation
State/province [80] 0 0
Novosibirsk
Country [81] 0 0
Russian Federation
State/province [81] 0 0
Omsk
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Russian Federation
State/province [82] 0 0
Petrozavodsk
Country [83] 0 0
Russian Federation
State/province [83] 0 0
Rostov-on-Don
Country [84] 0 0
Russian Federation
State/province [84] 0 0
Saint-Petersburg
Country [85] 0 0
Russian Federation
State/province [85] 0 0
Saratov
Country [86] 0 0
Russian Federation
State/province [86] 0 0
St. Petersburg
Country [87] 0 0
Russian Federation
State/province [87] 0 0
Ufa
Country [88] 0 0
Serbia
State/province [88] 0 0
Belgrade
Country [89] 0 0
Singapore
State/province [89] 0 0
Singapore
Country [90] 0 0
Spain
State/province [90] 0 0
Madrid
Country [91] 0 0
Spain
State/province [91] 0 0
Majadahonda
Country [92] 0 0
Sweden
State/province [92] 0 0
Uppsala
Country [93] 0 0
Taiwan
State/province [93] 0 0
Changhua
Country [94] 0 0
Taiwan
State/province [94] 0 0
Hualien City
Country [95] 0 0
Taiwan
State/province [95] 0 0
Taichung
Country [96] 0 0
Taiwan
State/province [96] 0 0
Tainan
Country [97] 0 0
Taiwan
State/province [97] 0 0
Taipei
Country [98] 0 0
Thailand
State/province [98] 0 0
Bangkok
Country [99] 0 0
Thailand
State/province [99] 0 0
Songkhla
Country [100] 0 0
Turkey
State/province [100] 0 0
Eskisehir
Country [101] 0 0
United Kingdom
State/province [101] 0 0
Airdrie
Country [102] 0 0
United Kingdom
State/province [102] 0 0
Leeds
Country [103] 0 0
United Kingdom
State/province [103] 0 0
London

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Alexion Pharmaceuticals, Inc.
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

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

No information has been provided regarding IPD availability


What supporting documents are/will be available?

TypeOther DetailsAttachment
Study protocol
Statistical analysis plan



Results publications and other study-related documents

No documents have been uploaded by study researchers.

Results are available at https://clinicaltrials.gov/study/NCT02946463