Ravulizumab in Thrombotic Microangiopathy After Hematopoietic Stem Cell Transplant

NCT04543591 | Completed Phase 3 DMC FDA Drug

• 1 other identifier: ALXN1210-TMA-313
• Study Type: interventional
• Target: 148
• Locations: 17 countries
• Sites: 66

Brief Summary

This study will evaluate the efficacy, safety, pharmacokinetics, and pharmacodynamics of ravulizumab in adult and adolescent participants with hematopoietic stem cell transplant-associated thrombotic microangiopathy (HSCT-TMA). In Stage 1, an open-label, single-arm period, the dosing regimen will be confirmed. In Stage 2, participants will be randomized to receive either blinded ravulizumab plus best supportive care or matching placebo plus best supportive care. The treatment period is 26 weeks (open-label for Stage 1, and randomized, double-blind, and placebo-controlled for Stage 2) followed by a 26-week follow-up period.

Conditions

Thrombotic Microangiopathy

Keywords

Thrombotic Microangiopathy (TMA) Ultomiris; Ravulizumab; Hematopoietic Stem Cell Transplant (HSCT) Transplant-associated TMA; HSCT-TMA

Outcome Measures

Primary Outcomes (1)

• Event Free Survival

  Event free survival during the 26 weeks treatment period defined as the time from randomization until the first of the two following events: death and clinical worsening.

  26 weeks (treatment period)

Secondary Outcomes (16)

• Time To TMA Response

  26 weeks (treatment period)

• Change from Baseline in eGFR

  26 weeks (treatment period) and 52 weeks

• Overall Survival

  Day 100, 26 weeks (treatment period), and 52 weeks

• Non-relapse Mortality

  Day 100, 26 weeks (treatment period), and 52 weeks

• Hematologic Response

  26 weeks (treatment period)

Study Arms (2)

Ravulizumab

EXPERIMENTAL

In Stage 1, all participants will receive open-label ravulizumab plus Best Supportive Care (BSC). In Stage 2, participants will receive blinded ravulizumab plus Best Supportive Care (BSC).

Biological: Ravulizumab; Other: Best supportive care

Placebo

PLACEBO COMPARATOR

In Stage 2, participants randomized to the placebo arm will receive matching placebo plus BSC.

Other: Placebo; Other: Best supportive care

Interventions

Placebo OTHER

Matching placebo

Placebo

Best supportive care OTHER

Participants will receive medications, therapies, and interventions per standard hospital treatment protocols (unless specifically prohibited by the protocol).

Placebo; Ravulizumab

Ravulizumab BIOLOGICAL

Weight-based doses of ravulizumab will be administered intravenously as loading dose regimen followed by maintenance dosing every 8 weeks.

Also known as: Ultomiris, ALXN1210

Ravulizumab

Eligibility Criteria

• Age: 12 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• years of age or older at time of consent/assent.
• Received HSCT within the past 12 months.
• Diagnosis of TMA that persists for at least 72 hours after initial management of any triggering agent/condition.
• A TMA diagnosis based on meeting the laboratory-based criteria during the Screening Period and/or ≤14 days prior to the Screening Period.
• Body weight ≥ 30 kilograms at Screening or ≤7 days prior to the start of the Screening Period (date of consent).
• Female participants of childbearing potential and male participants with female partners of childbearing potential must use highly effective contraception.
• Participants must be vaccinated against meningococcal infections if clinically feasible. Participants who cannot receive meningococcal vaccine should receive antibiotic prophylaxis. Participants \<18 years of age must be re-vaccinated against Haemophilus influenzae type b (Hib) and Streptococcus pneumoniae if clinically feasible.
• Participants or their legally authorized representative must be capable of giving signed informed consent or assent.

You may not qualify if:

• Thrombotic thrombocytopenic purpura (TTP) evidenced by ADAMTS13 deficiency
• Known Shiga toxin-related hemolytic uremic syndrome as demonstrated by positive test.
• Positive direct Coombs test indicative of a clinically significant immune-mediated hemolysis not due to TMA.
• Clinical diagnosis of disseminated intravascular coagulation (DIC).
• Known bone marrow/graft failure for the current HSCT.
• Diagnosis of veno-occlusive disease which is unresolved at the time of Screening.
• Human immunodeficiency virus (HIV) infection.
• Unresolved meningococcal disease.
• Presence of sepsis requiring vasopressor support.
• Pregnancy or breastfeeding.
• Hypersensitivity to murine proteins or to one of the excipients of ravulizumab.
• Any ongoing or history of medical or psychological conditions unrelated to HSCT-TMA that could increase the risk to the participant or confound the outcome of the study.
• Respiratory failure requiring mechanical ventilation.
• Acute and/or chronic heart failure with an ejection fraction ≤ 40%.
• Previously or currently treated with a complement inhibitor.

Sponsors & Collaborators

• Alexion Pharmaceuticals, Inc.: lead

Study Sites (66)

Research Site

Tampa, Florida, 33612, United States

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Grosse Pointe Farms, Michigan, 48236, United States

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Durham, North Carolina, 27705, United States

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Pittsburgh, Pennsylvania, 15232, United States

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Seattle, Washington, 98109, United States

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Parkville, 3050, Australia

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Bruges, 8000, Belgium

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Brussels, 1200, Belgium

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Chênée, 4032, Belgium

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Yvoir, 5530, Belgium

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Cerqueira César, 05403-000, Brazil

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Florianópolis, 88034-000, Brazil

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Jaú, 17210-080, Brazil

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Porto Alegre, 90035-903, Brazil

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Porto Alegre, 90110-270, Brazil

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Rio de Janeiro, 20230-130, Brazil

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São José do Rio Preto, 15090-000, Brazil

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São Paulo, 05.403-010, Brazil

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Calgary, Alberta, T2N 4N1, Canada

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Suzhou, 215006, China

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Tianjin, 300020, China

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Angers, 49033, France

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La Tronche, 38043, France

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Nice, 06200, France

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Hamburg, 20246, Germany

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Ulm, 89081, Germany

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Athens, 12462, Greece

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Pátrai, 26504, Greece

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Thessaloniki, 57010, Greece

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Halfa, 31096, Israel

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Ramat Gan, 52621, Israel

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Roma, 00168, Italy

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Udine, 33100, Italy

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Akita, 010-8543, Japan

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Anjo, 446-8602, Japan

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Chiba, 260-8677, Japan

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Fukushima, 960-1295, Japan

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Isehara-shi, 259-1193, Japan

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Kurashiki-shi, 710-8602, Japan

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Minatoku, 105-8470, Japan

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Okayama, 700-8558, Japan

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Osaka, 545-8586, Japan

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Osakasayama-shi, 589-8511, Japan

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Sapporo, 060-8638, Japan

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Suita-shi, 565-0871, Japan

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Tsukuba, 305-8576, Japan

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Wakayama, 641-8510, Japan

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Groningen, 9713 GZ, Netherlands

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Goyang-si, 10408, South Korea

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Seoul, 03080, South Korea

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Seoul, 03722, South Korea

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Seoul, 06351, South Korea

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Barcelona, 08036, Spain

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Granada, 18014, Spain

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L'Hospitalet de Llobregat, 08908, Spain

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Madrid, 28007, Spain

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Madrid, 28034, Spain

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Madrid, 28040, Spain

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Madrid, 28046, Spain

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Málaga, 29010, Spain

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Pamplona, 31008, Spain

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Salamanca, 37007, Spain

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Seville, 41013, Spain

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Huddinge, 141 57, Sweden

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London, W12 0HS, United Kingdom

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Nottingham, NG5 1PB, United Kingdom

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MeSH Terms

Conditions

Thrombotic Microangiopathies

Interventions

ravulizumab

Condition Hierarchy (Ancestors)

Thrombocytopenia; Blood Platelet Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Cytopenia

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 17, 2020
• First Posted: September 10, 2020
• Study Start: December 10, 2020
• Primary Completion: September 19, 2025
• Study Completion: March 20, 2026
• Last Updated: April 9, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

BR (8); ES (11); GR (3); US (5); CA (1); CN (2); JP (14); GB (2); IT (2); SE (1); BE (4); IL (2); DE (2); AU (1); NL (1); KR (4); FR (3)