Ravulizumab in Thrombotic Microangiopathy after Hematopoietic Stem Cell Transplant

Study identifier:ALXN1210-TMA-313

ClinicalTrials.gov identifier:NCT04543591

EudraCT identifier:N/A

CTIS identifier:N/A

Recruiting

Official Title

A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Multicenter Study of Ravulizumab in Adult and Adolescent Participants who have Thrombotic Microangiopathy (TMA) after Hematopoietic Stem Cell Transplant (HSCT)

Medical condition

Thrombotic Microangiopathy

Phase

Phase 3

Healthy volunteers

Study drug

Sex

All

Estimated Enrollment

130

Study type

Interventional

Age

12 Years - n/a

Date

Study Start Date: 10 Dec 2020

Estimated Primary Completion Date: 25 Jun 2025

Estimated Study Completion Date: 26 Dec 2025

Study design

Allocation: Randomized
Endpoint Classification: -
Intervention Model: Parallel Assignment
Masking: -
Primary Purpose: Treatment

Verification:

Verified 01 Aug 2024 by Alexion Pharmaceuticals, Inc.

Collaborators

Inclusion and exclusion criteria

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.

Sort by status

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Arms	Assigned Interventions
Experimental: 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).	Biological/Vaccine: Ravulizumab Weight-based doses of ravulizumab will be administered intravenously as loading dose regimen followed by maintenance dosing every 8 weeks. Other Name: Ultomiris, ALXN1210 Other: Best supportive care Participants will receive medications, therapies, and interventions per standard hospital treatment protocols (unless specifically prohibited by the protocol).
Placebo Comparator: Placebo In Stage 2, participants randomized to the placebo arm will receive matching placebo plus BSC.	Other: Placebo Matching placebo Other: Best supportive care Participants will receive medications, therapies, and interventions per standard hospital treatment protocols (unless specifically prohibited by the protocol).

Contacts

Contact

Alexion Pharmaceuticals, Inc. (Sponsor)

1-855-752-2356

[email protected]