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)
- Conditions
- clotting in small blood vesselsHSCT-TMA10064477
- Registration Number
- NL-OMON54406
- Lead Sponsor
- Alexion Pharmaceuticals
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- Not specified
- Target Recruitment
- 3
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 or platelet transfusion refractoriness • De
novo anemia or increase in transfusion requirements • Either one of the
following markers of hemolysis * LDH > ULN for age * Presence of
schistocytes >= 2 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 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
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
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>TMA response throughout 26 weeks.</p><br>
- Secondary Outcome Measures
Name Time Method <p>1. Time to TMA response<br /><br>2. Change from baseline in TMA-associated organ dysfunction in renal system,<br /><br>cardiovascular system, pulmonary system, CNS, and GI system through 26 weeks<br /><br>and 52 weeks<br /><br>3. Change from baseline in eGFR at Week 26 and Week 52<br /><br>4. TMA relapse during the follow-up period<br /><br>5. Overall survival by 26 weeks and 52 weeks<br /><br>6. Non-relapse mortality</p><br>