Ravulizumab in Thrombotic Microangiopathy After Hematopoietic Stem Cell Transplant

NCT ID: NCT04543591

Last Updated: 2025-11-12

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE3

Total Enrollment

148 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-12-10

Study Completion Date

2026-03-20

Brief Summary

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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.

Detailed Description

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Conditions

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Thrombotic Microangiopathy

Keywords

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

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Ravulizumab

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).

Group Type EXPERIMENTAL

Ravulizumab

Intervention Type BIOLOGICAL

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

Best supportive care

Intervention Type OTHER

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

Placebo

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

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type OTHER

Matching placebo

Best supportive care

Intervention Type OTHER

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

Interventions

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Ravulizumab

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

Intervention Type BIOLOGICAL

Placebo

Matching placebo

Intervention Type OTHER

Best supportive care

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

Intervention Type OTHER

Other Intervention Names

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Ultomiris, ALXN1210

Eligibility Criteria

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Inclusion Criteria

1. 12 years of age or older at time of consent/assent.
2. Received HSCT within the past 12 months.
3. Diagnosis of TMA that persists for at least 72 hours after initial management of any triggering agent/condition.
4. A TMA diagnosis based on meeting the laboratory-based criteria during the Screening Period and/or ≤14 days prior to the Screening Period.
5. Body weight ≥ 30 kilograms at Screening or ≤7 days prior to the start of the Screening Period (date of consent).
6. Female participants of childbearing potential and male participants with female partners of childbearing potential must use highly effective contraception.
7. 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.
8. Participants or their legally authorized representative must be capable of giving signed informed consent or assent.

Exclusion Criteria

1. Thrombotic thrombocytopenic purpura (TTP) evidenced by ADAMTS13 deficiency
2. Known Shiga toxin-related hemolytic uremic syndrome as demonstrated by positive test.
3. Positive direct Coombs test indicative of a clinically significant immune-mediated hemolysis not due to TMA.
4. Clinical diagnosis of disseminated intravascular coagulation (DIC).
5. Known bone marrow/graft failure for the current HSCT.
6. Diagnosis of veno-occlusive disease which is unresolved at the time of Screening.
7. Human immunodeficiency virus (HIV) infection.
8. Unresolved meningococcal disease.
9. Presence of sepsis requiring vasopressor support.
10. Pregnancy or breastfeeding.
11. Hypersensitivity to murine proteins or to one of the excipients of ravulizumab.
12. 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.
13. Respiratory failure requiring mechanical ventilation.
14. Acute and/or chronic heart failure with an ejection fraction ≤ 40%.
15. Previously or currently treated with a complement inhibitor.
16. Participation in an interventional treatment study of any therapy for TMA.
Minimum Eligible Age

12 Years

Maximum Eligible Age

100 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Alexion Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Research Site

Tampa, Florida, United States

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Grosse Pointe Farms, Michigan, United States

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Durham, North Carolina, United States

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Pittsburgh, Pennsylvania, United States

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Seattle, Washington, United States

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Parkville, , Australia

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Bruges, , Belgium

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Brussels, , Belgium

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Chênée, , Belgium

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Yvoir, , Belgium

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Cerqueira César, , Brazil

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Florianópolis, , Brazil

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Jaú, , Brazil

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Porto Alegre, , Brazil

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Porto Alegre, , Brazil

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Rio de Janeiro, , Brazil

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São José do Rio Preto, , Brazil

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São Paulo, , Brazil

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Calgary, Alberta, Canada

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Shanghai, , China

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Suzhou, , China

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Tianjin, , China

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Angers, , France

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La Tronche, , France

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Nice, , France

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Hamburg, , Germany

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Ulm, , Germany

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Athens, , Greece

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Pátrai, , Greece

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Thessaloniki, , Greece

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Halfa, , Israel

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Ramat Gan, , Israel

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Roma, , Italy

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Udine, , Italy

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Akita, , Japan

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Anjo, , Japan

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Chiba, , Japan

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Fukushima, , Japan

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Isehara-shi, , Japan

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Kurashiki-shi, , Japan

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Minatoku, , Japan

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Okayama, , Japan

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Osaka, , Japan

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Osakasayama-shi, , Japan

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Sapporo, , Japan

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Suita-shi, , Japan

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Tsukuba, , Japan

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Wakayama, , Japan

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Groningen, , Netherlands

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Goyang-si, , South Korea

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Seoul, , South Korea

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Seoul, , South Korea

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Seoul, , South Korea

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Barcelona, , Spain

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Granada, , Spain

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L'Hospitalet de Llobregat, , Spain

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Madrid, , Spain

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Madrid, , Spain

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Madrid, , Spain

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Madrid, , Spain

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Málaga, , Spain

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Pamplona, , Spain

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Salamanca, , Spain

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Seville, , Spain

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Huddinge, , Sweden

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London, , United Kingdom

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Nottingham, , United Kingdom

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Countries

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Poland United States Australia Belgium Brazil Canada China France Germany Greece Israel Italy Japan Netherlands South Korea Spain Sweden United Kingdom

Other Identifiers

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ALXN1210-TMA-313

Identifier Type: -

Identifier Source: org_study_id