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Clinical Trial 20871

Cancer Type: Malignant Hematology
Study Type: Treatment
NCT#: NCT04543591

Phase: Phase III
Principal Investigator: Nishihori, Taiga

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Overview

Study Title

A Phase 3, Open-label, Randomized, Multicenter Study of Ravulizumab in Adult and Adolescent Participants who have Thrombotic Microangiopathy (TMA) after Hematopoietic Stem Cell Transplant (HSCT)

Summary

This study will evaluate the efficacy, safety, pharmacokinetics, and pharmacodynamics of ravulizumab in adult and adolescent participants with hematopoietic stem cell transplant-associated thrombotic microangiopathy (HSCT-TMA). In Stage 1, an open-label, single-arm period, the dosing regimen will be confirmed. In Stage 2, participants will be randomized to receive either blinded ravulizumab plus best supportive care or matching placebo plus best supportive care. The treatment period is 26 weeks (open-label for Stage 1, and randomized, double-blind, and placebo-controlled for Stage 2) followed by a 26-week follow-up period.

Objective

Primary: To assess the efficacy of ravulizumab plus BSC versus BSC-only in the treatment of adult and adolescent participants with HSCT-TMA Secondary: To characterize TMA response after treatment with ravulizumab. To assess improvement in organ dysfunction. To assess TMA relapse and duration of response. To assess overall survival. To assess non-relapse mortality. To assess platelet response.

Treatments

Therapies

Therapy (NOS)

Medications

Placebo (); Ravulizumab ()

Inclusion Criteria

Inclusion Criteria:

  • 12 years of age or older
  • Received HSCT within the past 12 months at time of screening
  • Must have HSCT-TMA that persists despite initial management of any triggering conditions (persists for at least 72 hours after management of triggering agent/condition): Withdrawal or dose reduction of the triggering agent, treatment of any underlying infection, treatment of underlying GVHD.
  • Diagnosis of TMA based on meeting all of the criteria outlined in protocol
  • Body weight > 30 kilograms.
  • Female participants of childbearing potential and male participants with female partners of childbearing potential must use highly effective contraception starting at screening and continuing until at least 8 months after the last dose of study intervention
  • Participants must be vaccinated against meningococcal infections if clinically feasible, according to institutional guidelines for immune reconstitution after HSCT. Participants > Other criteria may apply

  • Exclusion Criteria

  • Known familial or acquired 'a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13' deficiency (activity > Known Shiga toxin-related hemolytic uremic syndrome
  • Positive direct Coombs test result which in the judgment of the Investigator is indicative of a clinically significant immune-mediated hemolysis not due to TMA.
  • Clinical diagnosis of disseminated intravascular coagulation in the judgment of the investigator, utilizing the International Society of Thrombosis and Haemostasis (ISTH) scoring criteria outlined in protocol.
  • Known bone marrow/graft failure
  • Diagnosis of veno-occlusive disease, unresolved at the time of screening.
  • Known human immunodeficiency virus (HIV) infection evidenced by positive HIV-1 or HIV-2 antibody titer obtained at screening. A documented negative HIV-1 and HIV-2 test within 6 months prior to screening is also acceptable to confirm eligibility.
  • Unresolved meningococcal disease
  • Presence of sepsis requiring vasopressor support within 7 days prior to enrollment
  • Pregnancy or breastfeeding
  • Hypersensitivity to murine proteins or to 1 of the excipients of ravulizumab
  • Any ongoing or history of medical or psychological conditions unrelated to HSCT-TMA that, in the opinion of the investigator, could increase the risk to the participant by participating in the study or confound the outcome of the study.
  • Respiratory failure from any cause requiring mechanical ventilation (including intubation, bilevel positive airway pressure [BiPAP], or continuous positive airway pressure [CPAP] within 72 hours prior to enrollment.
  • Acute and/or chronic heart failure with an ejection fracture greater than or equal to 40%
  • Other exclusions apply

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