Efficacy and Safety Study of Narsoplimab in Pediatric Patients With High-Risk Hematopoietic Stem Cell Transplant TMA

Inclusion Criteria20

• Age at least 28 days and less than 18 years prior to informed consent (Visit 0).
• Have informed consent from at least one parent or legal guardian as required by local law and regulation. Patient informed consent will be required if the patient has reached the local legal age of majority.
• Assent from patients as required by local law and regulation.
• Have received an allogeneic hematopoietic stem cell transplant for the treatment of benign or malignant disease.
• Have a diagnosis of HSCT-TMA defined as meeting both of the following criteria:
• Platelet count \< 50,000/mL or a decrease in platelet count \> 50% from the highest value obtained following transplant.
• Evidence of microangiopathic hemolysis (presence of schistocytes, serum lactate dehydrogenase \[LDH\] \> upper limit of normal (\[ULN\], or haptoglobin \< lower limit of normal \[LLN\])
• Have at least one of the following HSCT-TMA high-risk criteria:
• HSCT-TMA persistence \> 2 weeks following modification of calcineurin inhibitors or sirolimus OR
• Have evidence of high-risk HSCT-TMA defined as at least one of the following:
• Spot protein/creatinine ratio \> 2 mg/mg
• Serum creatinine \> 1.5 x the creatinine level prior to TMA development
• Biopsy-proven gastrointestinal TMA
• TMA-related neurological abnormality
• Pericardial or pleural effusion without alternative explanation
• Pulmonary hypertension without alternative explanation
• Have Grade III or Grade IV graft-versus-host disease (GVHD) or, in the opinion of the Investigator, risk for development of Grade III or Grade IV GVHD if immunosuppression were to be modified
• Have elevated serum C5b-9 (\> 244 ng/mL)
• If sexually active and of childbearing potential (for female pediatric patients, defined as starting at onset of menses), must agree to practice a highly effective method of birth control throughout study drug treatment and for at least 12 weeks after the last dose of study drug, such method of birth control defined as one that results in a low failure rate (i.e., less than 1% per year) when used consistently and correctly, such as implants, injectables, combined oral contraceptives, some intrauterine devices, sexual abstinence (abstinence is acceptable when it is in line with the patient's preferred and usual lifestyle and is defined as complete abstinence of sexual intercourse, not periodic abstinence or withdrawal), or vasectomized partner.
• Male patients must be willing to avoid fathering children for at least 12 weeks following the last dose of study medication.