Ravulizumab in Thrombotic Microangiopathy After Hematopoietic Stem Cell Transplant

• Status: Recruiting
• Trial end date: 2024-02-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Alexion Pharmaceuticals
• Treatments: Ravulizumab

Criteria

Inclusion Criteria:

1. 12 years of age or older.

2. Received HSCT within the past 6 months.

3. Diagnosis of TMA that persists despite initial management of any triggering condition.

4. Body weight ≥ 30 kilograms.

5. Female participants of childbearing potential and male participants with female partners of childbearing potential must use highly effective contraception starting at screening and continuing until at least 8 months after the last dose of study intervention.

6. Participants must be vaccinated against meningococcal infections if clinically feasible, according to institutional guidelines for immune reconstitution after HSCT. Participants < 18 years of age must be re-vaccinated against Haemophilus influenzae type b and Streptococcus pneumoniae if clinically feasible, according to institutional guidelines for immune reconstitution after HSCT. All participants should be administered coverage with prophylactic antibiotics according to institutional post-transplant infection prophylaxis guidances, including coverage against Neisseria meningitidis for at least 2 weeks after meningococcal vaccination. Participants who cannot receive meningococcal vaccine should receive antibiotic prophylaxis coverage against Neisseria meningitidis the entire Treatment Period and for 8 months following the final dose of study intervention.

Exclusion Criteria:

1. Known familial or acquired 'a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13' deficiency (activity < 5%).

2. Known Shiga toxin-related hemolytic uremic syndrome.

3. Positive direct Coombs test.

4. Diagnosis or suspicion of disseminated intravascular coagulation.

5. Known bone marrow/graft failure.

6. Diagnosis of veno-occlusive disease, regardless of severity.

7. Known human immunodeficiency virus (HIV) infection evidenced by positive HIV-1 or HIV-2 antibody titer.

8. Unresolved meningococcal disease.

9. Presence or suspicion of sepsis (treated or untreated) within 7 days prior to Screening.

10. Pregnancy or breastfeeding.

11. Hypersensitivity to murine proteins or to 1 of the excipients of ravulizumab.

12. Previously or currently treated with a complement inhibitor.