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)

Phase 3

Active, not recruiting

Conditions: Hematopoietic stem cell transplant-associated thrombotic microangiopathy

Registration Number: 2023-510107-22-00

Lead Sponsor: Alexion Pharmaceuticals Inc.

Brief Summary: To assess the efficacy of ravulizumab versus placebo in the treatment of adult and adolescent participants with HSCT-TMA.

Detailed Description: Not available

Recruitment & Eligibility

Status: Ongoing, recruitment ended

Sex: Not specified

Target Recruitment: 61

Inclusion Criteria

12 years of age or older, at the time of signing the informed consent form (ICF)

Participants who received HSCT within the past 12 months at the time of Screening)

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 or platelet transfusion refractoriness •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 • De novo anemia OR the presence of hypertension

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)

Body weight ≥ 30 kg at Screening or ≤ 7 days prior to the start of the Screening Period (date of consent).

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 revaccinated 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

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.

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

Exclusion Criteria

Known familial or acquired 'a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13' (ADAMTS13) deficiency (activity < 5%).

Presence of sepsis requiring vasopressor support within 7 days prior to enrollment

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

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

Previously or currently treated with a complement inhibitor

Pregnancy or breastfeeding

Known Shiga toxin-related hemolytic uremic syndrome (ST-HUS)

Positive direct Coombs test result

Clinical diagnosis of disseminated intravascular coagulation (DIC)

Known bone marrow/graft failure for the current HSCT

Diagnosis of veno-occlusive disease (VOD)

Human immunodeficiency virus (HIV) infection evidenced by HIV-1 or HIV-2 antibody titer

Unresolved meningococcal disease

Study & Design

Study Type: Not specified

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Event free survival during the 26-week Treatment Period defined as the time from randomization until the first of the two following events: Death and Clinical worsening		Event free survival during the 26-week Treatment Period defined as the time from randomization until the first of the two following events: Death and Clinical worsening

Secondary Outcome Measures

Name	Time	Method
Overall survival by Day 100, Week 26		Overall survival by Day 100, Week 26
Non-relapse mortality during the 26-week Treatment Period		Non-relapse mortality during the 26-week Treatment Period
Number of TMA response criteria met during the 26-week Treatment Period		Number of TMA response criteria met during the 26-week Treatment Period
Hematologic response during the 26-week Treatment Period		Hematologic response during the 26-week Treatment Period
Change from baseline in eGFR at Week 26		Change from baseline in eGFR at Week 26

Trial Locations

Locations (57): Universitair Medisch Centrum Groningen
🇳🇱
Groningen, Netherlands
University Hospital Maastricht
🇳🇱
Maastricht, Netherlands
Region Skane Skanes Universitetssjukhus
🇸🇪
Lund, Sweden
Karolinska University Hospital
🇸🇪
Huddinge, Sweden
Hospital Universitario De Salamanca
🇪🇸
Salamanca, Spain
Hospital Universitario De La Princesa
🇪🇸
Madrid, Spain
Hospital Universitario Regional De Malaga
🇪🇸
Malaga, Spain
Hospital Universitario Y Politecnico La Fe
🇪🇸
Valencia, Spain
Clinica Universidad De Navarra
🇪🇸
Pamplona, Spain
Hospital Universitario Puerta De Hierro De Majadahonda
🇪🇸
Majadahonda, Spain
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Universitair Medisch Centrum Groningen
🇳🇱Groningen, Netherlands
Carin Hazenberg
Site contact
+31503616151
c.l.e.hazenberg@umcg.nl