clotting in small blood vessels HSCT-TMA
Conditions
Interventions
During Stage 1, all participants will receive weight-based ravulizumab dosing
regimen plus best supportive care (BSC). During Stage 2, participants will be
randomized 1:1 to receive either the weigh
Sponsors
Alexion Pharmaceuticals
Eligibility
Age
12 Years to 64 Years
Inclusion criteria
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 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
Exclusion criteria
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 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| TMA response throughout 26 weeks. | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Time to TMA response 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 3. Change from baseline in eGFR at Week 26 and Week 52 4. TMA relapse during the follow-up period 5. Overall survival by 26 weeks and 52 weeks 6. Non-relapse mortality | — |
Countries
Netherlands
Outcome results
None listed