Study of ravulizumab in adults and adolescents 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: EUCTR2020-000144-61-PL
• Lead Sponsor: Alexion Pharmaceuticals, Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2021-11-09
• Last Update Posted: 2 April 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 114

Inclusion Criteria

1.12 years of age or older, at the time of signing the informed consent form (ICF)
2.participants who received HSCT within the past 12 months at the time of Screening
3.A TMA diagnosis, based on meeting all of the following criteria during the Screening Period and/or = 14 days prior to the Screening Period:
• De novo thrombocytopenia
•Any one of the following markers of hemolysis:
- LDH > ULN for age
- Presence of schistocytes = 2 per high power field (HPF) or = 1% in
peripheral blood smear
• Proteinuria on spot urinalysis
• Presence of hypertension
4.Participants must have HSCT-TMA that persists despite initial management of any triggering condition (persists for at least 72 hours after management of triggering agent/condition)
• Withdrawal or dose reduction of the offending agent (eg, CNIs)
• Treatment of any underlying infection
• Treatment of underlying GVHD
5. Body weight = 30 kg at Screening or = 7 days prior to the start of the Screening Period (date of consent).
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 (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
7.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.
8.Capable of giving signed informed consent or assent which includes compliance with the requirements and restrictions listed in the informed consent and in this protocol

Are the trial subjects under 18? yes
Number of subjects for this age range: 10
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 92
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 12

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. Clinical Diagnosis of disseminated intravascular coagulation (DIC)
5.Known bone marrow/graft failure
6.Diagnosis of veno-occlusive disease (VOD), regardless of severity
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. Any ongoing or history of medical or psychological conditions unrelated to HSCT-TMA that, could increase the risk to the participant by participating in the study or confound the outcome of the study. Including but not limited to, major cardiac, pulmonary, renal, endocrine, or hepatic disease
13.Previously or currently treated with a complement inhibitor

Study & Design

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