Ensayos clínicos

Inclusion Criteria:

• Male and female patients aged ≥ 18 years at the time of informed consent form (ICF) signature.
• Received allogeneic HSCT from a related or unrelated, human leukocyte antigen-matched or mismatched donor. Patients having received any of the following stem cell sources are eligible: granulocyte colony stimulating factor mobilized peripheral blood stem cells, bone marrow, umbilical cord blood.
• Diagnosis of TA-TMA established by histologic evidence of microangiopathy in any biopsied organ OR, as per the laboratory markers below, indicating TMA:
  • De novo or progressing thrombocytopenia (platelet count < 50 x 10^9/L or > 50 % decrease in platelet count from the highest value achieved after transplantation); AND
  • Elevated LDH (> 1.5 x ULN); AND
  • At least 1 additional laboratory criteria among the following:
  • Schistocytes on the peripheral blood smear (≥ 2 per hpf); OR
  • De novo anemia (hemoglobin < LLN or anemia requiring PRBC transfusion support as per local institutional standard); OR
  • Proteinuria (rUPCR ≥ 2 mg/mg); OR
  • Elevated plasma concentration of sC5b-9 above ULN.
• Have a diagnosis of TA-TMA that persists despite initial management of any triggering condition.
• Have at least 1 sign/symptom of organ dysfunction:
  • Kidney: doubling of serum creatinine compared with pre-HSCT level or patient receiving renal replacement therapy or proteinuria ≥ 30 mg/dL AND rUPCR ≥ 2 mg/mg;
  • Lungs: hypoxemia or any need for noninvasive or invasive positive pressure ventilation;
  • Cardiovascular: pulmonary hypertension diagnosed by a cardiologist using cardiac catheterization, or pulmonary hypertension criteria on echocardiography or arterial hypertension, defined by systolic blood pressure (BP) ≥ 140 mmHg and/or diastolic BP ≥ 90 mmHg at baseline or hypertension requiring > 2 medications (excluding diuretics);
  • Serositis: clinically significant pleural effusion or pericardial effusion requiring surgical therapy (e.g., pericardiocentesis/ thoracocentesis);
  • CNS: seizures attributable to posterior reversible encephalopathy syndrome;
  • GI tract: presence of biopsy-proven GI TA-TMA. Patients with GI bleeding (hematemesis or hematochezia) will be excluded.
• Women of childbearing potential, defined as any women who have experienced menarche and who are NOT permanently sterile or postmenopausal, must have a negative serum pregnancy test at screening and agree to use protocol-defined methods of contraception for the duration of the study and 8 weeks after their last IMP dose.
  • Note: Postmenopausal is defined as having had 12 consecutive months with no menses without an alternative medical cause.
• Men must agree to the following for the duration of the study and 8 weeks after their last dose of IMP:
  • Avoid fathering a child;
  • Use protocol-defined methods of contraception;
  • Refrain from donating sperm.
• Patient and/or legally authorized representative must be capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the ICF.

Exclusion Criteria:

• Positive direct Coombs test.
• Known familial or acquired ADAMTS13 deficiency.
• Known Shiga toxin‐related hemolytic uremic syndrome.
• Known bone marrow or graft failure.
• Diagnosis of disseminated intravascular coagulation.
• Diagnosis of VOD.
• Active GI bleeding (hematemesis or hematochezia) at baseline.
• Body weight < 30 kg and > 100 kg.
• Uncontrolled systemic bacterial or fungal infection, presence or suspicion of sepsis.
• Previously or currently treated with a complement inhibitor (approved or investigational).
• Pregnancy or breastfeeding.
• Positive human immunodeficiency virus antibody at screening or documented in pre-HSCT medical record.
• Hepatitis C virus detectable by polymerase chain reaction at screening or documented in pre-HSCT medical record.
• Chronic inactive hepatitis B virus with viral loads > 1000 IU/mL (> 5000 copies/mL) at screening or documented in pre-HSCT medical record. Eligible patients who are chronic active carriers (≤ 1000 IU/mL) must receive prophylactic antiviral treatment (e.g., entecavir, tenofovir, lamivudine) according to local country guidelines.
• Inability to cooperate with study procedures or any condition that, in the opinion of the investigator, could increase the patient’s risk by participating in the study or confound the outcome of the study.

Eligibility last updated 2/2/22. Questions regarding updates should be directed to the study team contact.