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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
148
Weight-based doses of ravulizumab will be administered intravenously as loading dose regimen followed by maintenance dosing every 8 weeks.
Matching placebo
Participants will receive medications, therapies, and interventions per standard hospital treatment protocols (unless specifically prohibited by the protocol).
Research Site
Tampa, Florida, United States
Research Site
Grosse Pointe Farms, Michigan, United States
Research Site
Durham, North Carolina, United States
Research Site
Pittsburgh, Pennsylvania, United States
Research Site
Seattle, Washington, United States
Research Site
Event Free Survival
Event free survival during the 26 weeks treatment period defined as the time from randomization until the first of the two following events: death and clinical worsening.
Time frame: 26 weeks (treatment period)
Time To TMA Response
Time frame: 26 weeks (treatment period)
Change from Baseline in eGFR
Time frame: 26 weeks (treatment period) and 52 weeks
Overall Survival
Time frame: Day 100, 26 weeks (treatment period), and 52 weeks
Non-relapse Mortality
Time frame: Day 100, 26 weeks (treatment period), and 52 weeks
Hematologic Response
Time frame: 26 weeks (treatment period)
TMA response and time to response for each individual component of TMA
Time frame: 26 weeks (treatment period)
Time to Hematologic Response
Time frame: 26 weeks (treatment period)
Hemoglobin Response
Time frame: 26 weeks (treatment period)
Partial Response
Time frame: 26 weeks (treatment period)
Loss of TMA Response
Time frame: 26 weeks (treatment period)
Duration of TMA Response
Time frame: 26 weeks (treatment period) and 52 weeks
Changes from Baseline in Haptoglobin, Platelets, LDH, and Hemoglobin
Time frame: 26 weeks (treatment period) and 52 weeks
Modified TMA Response
Time frame: 26 weeks (treatment period)
Change from baseline in TMA-associated organ dysfunction in renal system, cardiovascular system, pulmonary system, CNS, and GI system
Time frame: 26 weeks (treatment period) and 52 weeks
TMA Relapse
Time frame: Follow-up Period
Platelet Response
Time frame: 26 weeks (treatment period)
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Parkville, Australia
Research Site
Bruges, Belgium
Research Site
Brussels, Belgium
Research Site
Chênée, Belgium
Research Site
Yvoir, Belgium
...and 56 more locations