A Phase 3, Randomized, Double-blind, Placebo-Controlled, Multicenter Study to Evaluate the Efficacy and Safety of Ravulizumab in Adult Participants Who Have Thrombotic Microangiopathy Associated With a Trigger

Alexion Pharmaceuticals, Inc.1 site in 1 country16 target enrollmentJune 29, 2021

ConditionsThrombotic Microangiopathy

InterventionsPlacebo Ravulizumab Best Supportive Care

DrugsRavulizumab

Overview

Phase: Phase 3
Intervention: Placebo
Conditions: Thrombotic Microangiopathy
Sponsor: Alexion Pharmaceuticals, Inc.
Enrollment: 16
Locations: 1
Primary Endpoint: Number of Participants With Complete Thrombotic Microangiopathy (TMA) Response at Week 26
Status: Terminated
Last Updated: last year

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

This study will investigate the efficacy and safety of ravulizumab compared to placebo in adult participants with thrombotic microangiopathy (TMA) associated with a trigger. Participants will be randomized to receive either ravulizumab plus best supportive care or placebo plus best supportive care. The treatment period is 26 weeks followed by a 26-week off-treatment follow-up period.

Registry

clinicaltrials.gov

Start Date

June 29, 2021

End Date

December 22, 2022

Last Updated

last year

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

Alexion Pharmaceuticals, Inc.

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•18 years of age or older
•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 ravulizumab
•TMA associated with a trigger (autoimmune disease, infection, solid organ transplant, drugs, and malignant hypertension)
•Vaccinated against meningococcal infection (Neisseria meningitidis), within 3 years prior to, or at the time of, randomization. Participants who initiate study drug treatment less than 2 weeks after receiving a meningococcal vaccine must receive appropriate prophylactic antibiotics for at least 2 weeks after the vaccination. If participant cannot receive the meningococcal vaccine, then participant must be willing to receive antibiotic prophylaxis coverage against N. meningitidis during the entire Treatment Period and for 8 months following the final dose of study drug. Additional vaccination (Haemophilus influenzae type b (Hib) and Streptococcus pneumoniae) may be considered based on individual patient condition.

Exclusion Criteria

•Any known gene mutation that causes atypical hemolytic uremic syndrome (aHUS)
•Postpartum aHUS
•Known chronic kidney disease
•TMA due to hematopoietic stem cell transplantation ≤ 12 months of Screening
•Primary and secondary glomerular diseases other than lupus
•Diagnosis of primary antiphospholipid antibody syndrome
•Shiga toxin-producing Escherichia coli infections including but not limited to Shiga toxin-related hemolytic uremic syndrome
•Known familial or acquired 'a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13' (ADAMTS13) deficiency (activity \< 5%)
•Positive direct Coombs test which in the judgement of the Investigator is indicative of a clinically significant immune-mediated hemolysis not due to TMA
•Clinical diagnosis of disseminated intravascular coagulation (DIC) in the judgement of the Investigator

Arms & Interventions

Placebo

Intervention: Placebo

Ravulizumab

Intervention: Ravulizumab

Ravulizumab

Intervention: Best Supportive Care

Placebo

Intervention: Best Supportive Care

Outcomes

Primary Outcomes

Number of Participants With Complete Thrombotic Microangiopathy (TMA) Response at Week 26

Time Frame: Week 26

TMA response required the following: 1) Normalization of platelet count without transfusion support during the prior 7 days. 2) Normalization of LDH. 3) Improvement in glomerular filtration rate (eGFR) of \>= 30% compared to baseline. Participants must meet each TMA criterion at 2 separate assessments obtained at least 24 hours apart, and any measurement in between.