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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
Timepoint [1] 0 0
Day 29 through Day 183
Primary outcome [2] 0 0
Percentage Of Participants Who Achieved Transfusion Avoidance (TA)
Timepoint [2] 0 0
Baseline through Day 183
Secondary outcome [1] 0 0
Percentage Of Participants With Breakthrough Hemolysis (BTH)
Timepoint [1] 0 0
Baseline through Day 183
Secondary outcome [2] 0 0
Percent Change From Baseline In LDH Levels
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
Timepoint [3] 0 0
Baseline, Day 183
Secondary outcome [4] 0 0
Percentage Of Participants With Stabilized Hemoglobin Levels
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
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United States of America
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Texas
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Argentina
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Buenos Aires
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Argentina
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Córdoba
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Austria
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Linz
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Austria
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Vienna
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Belgium
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Bruxelles
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Belgium
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Hasselt
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Belgium
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Leuven
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Brazil
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Rio De Janeiro
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Brazil
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Salvador
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Brazil
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Sao Paulo
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Canada
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Alberta
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Canada
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Ontario
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Czechia
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Plzen
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Czechia
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Prague
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Estonia
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Tallinn
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France
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Limoges
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France
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MONTPELLIER Cedex 5
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France
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Paris Cedex 10
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France
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Pierre Benite
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France
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Poitiers
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France
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Rennes Cedex 9
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Germany
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Aachen
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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
Country [28] 0 0
Italy
State/province [28] 0 0
Firenze
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Italy
State/province [29] 0 0
Milano
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Italy
State/province [30] 0 0
Napoli
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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
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Japan
State/province [35] 0 0
Hamamatsu-shi
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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
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Japan
State/province [43] 0 0
Okayama-shi
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Japan
State/province [44] 0 0
Osakasayama-shi
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Japan
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Sapporo-shi
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Japan
State/province [46] 0 0
Shimotsuke-shi
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Japan
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Shinjuku-ku
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Japan
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Suita
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Japan
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Tokorozawa-shi
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Japan
State/province [50] 0 0
Tokyo
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Japan
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Toyoake-shi
Country [52] 0 0
Japan
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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
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Korea, Republic of
State/province [59] 0 0
Jung-gu
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Korea, Republic of
State/province [60] 0 0
Seoul
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Korea, Republic of
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Songpa-gu
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Korea, Republic of
State/province [62] 0 0
Suwon-si
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Korea, Republic of
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Ulsan
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Malaysia
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George
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Malaysia
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Johor Bahru
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Malaysia
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Kota Bharu
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Malaysia
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Kota Kinabalu
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Malaysia
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Kuching
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Malaysia
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Miri
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Malaysia
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Sibu
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Mexico
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Monterrey
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Poland
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Gdansk
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Poland
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Warszawa
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Russian Federation
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Arkhangelsk
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Russian Federation
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Barnaul
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Russian Federation
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Irkutsk
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Russian Federation
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Kirov
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Russian Federation
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Moscow
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Russian Federation
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Murmansk
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Russian Federation
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Novosibirsk
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Russian Federation
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Omsk
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Russian Federation
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Petrozavodsk
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Russian Federation
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Rostov-on-Don
Country [84] 0 0
Russian Federation
State/province [84] 0 0
Saint-Petersburg
Country [85] 0 0
Russian Federation
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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
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Spain
State/province [90] 0 0
Madrid
Country [91] 0 0
Spain
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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
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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.
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/study/NCT02946463
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.
Schwartz CE, Stark RB, Borowiec K, Nolte S, Myren KJ. Norm-based comparison of the quality-of-life impact of ravulizumab and eculizumab in paroxysmal nocturnal hemoglobinuria. Orphanet J Rare Dis. 2021 Sep 15;16(1):389. doi: 10.1186/s13023-021-02016-8.
Schrezenmeier H, Kulasekararaj A, Mitchell L, Sicre de Fontbrune F, Devos T, Okamoto S, Wells R, Rottinghaus ST, Liu P, Ortiz S, Lee JW, Socie G. One-year efficacy and safety of ravulizumab in adults with paroxysmal nocturnal hemoglobinuria naive to complement inhibitor therapy: open-label extension of a randomized study. Ther Adv Hematol. 2020 Oct 24;11:2040620720966137. doi: 10.1177/2040620720966137. eCollection 2020.
Ishiyama K, Nakao S, Usuki K, Yonemura Y, Ikezoe T, Uchiyama M, Mori Y, Fukuda T, Okada M, Fujiwara SI, Noji H, Rottinghaus S, Aguzzi R, Yokosawa J, Nishimura JI, Kanakura Y, Okamoto S. Results from multinational phase 3 studies of ravulizumab (ALXN1210) versus eculizumab in adults with paroxysmal nocturnal hemoglobinuria: subgroup analysis of Japanese patients. Int J Hematol. 2020 Oct;112(4):466-476. doi: 10.1007/s12185-020-02934-6. Epub 2020 Aug 31.
Brodsky RA, Peffault de Latour R, Rottinghaus ST, Roth A, Risitano AM, Weitz IC, Hillmen P, Maciejewski JP, Szer J, Lee JW, Kulasekararaj AG, Volles L, Damokosh AI, Ortiz S, Shafner L, Liu P, Hill A, Schrezenmeier H. Characterization of breakthrough hemolysis events observed in the phase 3 randomized studies of ravulizumab versus eculizumab in adults with paroxysmal nocturnal hemoglobinuria. Haematologica. 2021 Jan 1;106(1):230-237. doi: 10.3324/haematol.2019.236877.
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
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT02946463