Study of ravulizumab in pediatric participants with HSCT-TMA

Phase 1

• Conditions: hematopoietic stem cell transplant-associated thrombotic microangiopathy; MedDRA version: 20.0Level: PTClassification code 10043645Term: Thrombotic microangiopathySystem Organ Class: 10005329 - Blood and lymphatic system disorders; Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]

• Registration Number: EUCTR2020-000761-16-FR
• Lead Sponsor: Alexion Pharmaceuticals, Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2020-09-09
• Last Update Posted: 26 February 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 40

Inclusion Criteria

1. 1 month of age up to < 18 years of age at the time of signing the informed consent
2. Participants who received HSCT within the past 6 months at the time of Screening
3. A TMA diagnosis, based on all of the following criteria occurring simultaneously:
• De novo thrombocytopenia or platelet transfusion refractoriness, where:
• De novo anemia or increase in transfusion requirements
• Either one of the following markers of hemolysis:
-Lactate dehydrogenase > 1.5 × ULN or,
- Presence of schistocytes = 2 high power field (HPF)
• Proteinuria on spot urinalysis
• Presence of hypertension
4. Participants must have HSCT-TMA that persists for at least 72 hours after initial management of any triggering agent/condition
5.Body weight = 5 kg at Screening
6. Male or female Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies
7. Vaccinated against meningococcal infections if clinically feasible, according to institutional guidelines for immune reconstitution after HSCT. Participants must be re-vaccinated against Haemophilus influenzae type b (Hib) 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 posttransplant infection prophylaxis guidances including coverage against N. meningiditis for at least 2 weeks after meningococcal vaccination. Participants who cannot receive meningococcal vaccine should receive antibiotic prophylaxis coverage against N. meningiditis the entire Treatment Period and for 8 months following the final dose of ravulizumab.
8. Participants or their legally authorized representative must be capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent or assent form and in this protocol

Are the trial subjects under 18? yes
Number of subjects for this age range: 40
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1. Known familial or acquired ‘a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13’ (ADAMTS13) deficiency (activity < 5%)
2. Known Shiga toxin-related hemolytic uremic syndrome (ST-HUS)
3. Positive direct Coombs test
4. Diagnosis or suspicion of disseminated intravascular coagulation (DIC)
5. Known bone marrow/graft failure
6. Diagnosis of veno-occlusive disease (VOD)
7. Human immunodeficiency virus (HIV) infection (evidenced by 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

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To assess the efficacy of ravulizumab plus BSC in the treatment of HSCT-TMA;Secondary Objective: Safety and tolerability of ALXN1210 and additional efficacy measures ;Primary end point(s): TMA response ;Timepoint(s) of evaluation of this end point: Throughout 26 Weeks

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): 1. Time to TMA response<br>2. Change from baseline in TMA-associated organ dysfunctiond in renal system, cardiovascular system, pulmonary system, CNS, and GI system at 6 months and 1 year<br>3. TMA relapse during the study <br>4. Overall survival at 6 months and 1 year<br>5. Non-relapse mortality (<br>6. Platelet response<br>7. Hematologic response<br>;Timepoint(s) of evaluation of this end point: Week 26 and Week 52