Study of ravulizumab in adults and adolescents with HSCT-TMA
- Conditions
- Hematopoietic stem cell transplant-associated thrombotic microangiopathyMedDRA version: 20.0Level: PTClassification code 10043645Term: Thrombotic microangiopathySystem Organ Class: 10005329 - Blood and lymphatic system disordersTherapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]
- Registration Number
- EUCTR2020-000144-61-BE
- Lead Sponsor
- Alexion Pharmaceuticals, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 114
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
• De novo anemia OR the 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 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
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
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 or suspicion 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
- Primary Outcome Measures
Name Time Method Main Objective: To assess the efficacy of ravulizumab versus placebo in the treatment of adult and adolescent participants<br>with 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 dysfunction in renal system, cardiovascular system, pulmonary system, CNS, and GI system through 26 weeks and 52 weeks<br>3. Change from baseline eGRF at Week 26 and Week 52<br>4. TMA relapse during the follow-up period<br>5 .Overall survival by 26 weeks and 52 weeks<br>6.Non-relapse mortality;Timepoint(s) of evaluation of this end point: Week 26 and Week 52