Ravulizumab in Thrombotic Microangiopathy After Hematopoietic Stem Cell Transplant

Inclusion criteria

• 12 years of age or older at time of consent/assent.
• Received HSCT within the past 12 months.
• Diagnosis of TMA that persists for at least 72 hours after initial management of any triggering agent/condition.
• A TMA diagnosis based on meeting the laboratory-based criteria during the Screening Period and/or ≤14 days prior to the Screening Period.
• Body weight ≥ 30 kilograms at Screening or ≤7 days prior to the start of the Screening Period (date of consent).
• Female participants of childbearing potential and male participants with female partners of childbearing potential must use highly effective contraception.
• Participants must be vaccinated against meningococcal infections if clinically feasible. Participants who cannot receive meningococcal vaccine should receive antibiotic prophylaxis. Participants <18 years of age must be re-vaccinated against Haemophilus influenzae type b (Hib) and Streptococcus pneumoniae if clinically feasible.
• Participants or their legally authorized representative must be capable of giving signed informed consent or assent.

Exclusion criteria

• Thrombotic thrombocytopenic purpura (TTP) evidenced by ADAMTS13 deficiency
• Known Shiga toxin-related hemolytic uremic syndrome as demonstrated by positive test.
• Positive direct Coombs test indicative of a clinically significant immune-mediated hemolysis not due to TMA.
• Clinical diagnosis of disseminated intravascular coagulation (DIC).
• Known bone marrow/graft failure for the current HSCT.
• Diagnosis of veno-occlusive disease which is unresolved at the time of Screening.
• Human immunodeficiency virus (HIV) infection.
• Unresolved meningococcal disease.
• Presence of sepsis requiring vasopressor support.
• Pregnancy or breastfeeding.
• Hypersensitivity to murine proteins or to one 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 or confound the outcome of the study.
• Respiratory failure requiring mechanical ventilation.
• Acute and/or chronic heart failure with an ejection fraction ≤ 40%.
• Previously or currently treated with a complement inhibitor.
• Participation in an interventional treatment study of any therapy for TMA.