NCT04743804TerminatedPhase 3
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 enrollmentStarted: June 29, 2021Last updated:
Conditions
Interventions
Drugs
Trial Snapshot
- Phase
- Phase 3
- Status
- Terminated
- Enrollment
- 16
- Locations
- 1
- Primary Endpoint
- Number of Participants With Complete Thrombotic Microangiopathy (TMA) Response at Week 26
Study 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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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
- •Presence of sepsis requiring vasopressors within 7 days prior to or during Screening
- •Presence of monoclonal gammopathy including but not limited to multiple myeloma
- •Known bone marrow insufficiency or failure evidenced by cytopenias
- •Unresolved N. meningitidis infection
- •History of malignancy within 5 years of Screening with the exception of nonmelanoma skin cancer or carcinoma in situ of the cervix that has been treated with no evidence of recurrence
- •Use of any complement inhibitors within the past 3 years
- •Respiratory failure requiring mechanical ventilation
Arms & Interventions
Placebo
Placebo Comparator
Intervention: Placebo (Other)
Ravulizumab
Experimental
Intervention: Ravulizumab (Biological)
Ravulizumab
Experimental
Intervention: Best Supportive Care (Other)
Placebo
Placebo Comparator
Intervention: Best Supportive Care (Other)
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.
Secondary Outcomes
- Time to Complete TMA Response(Baseline through Week 26)
- Number of Participants With Renal Response at Week 26(Week 26)
- Number of Participants With Hematologic Response at Week 26(Week 26)
- Number of Participants On Dialysis at Week 26(Week 26)
- Change From Baseline in eGFR at Week 26(Baseline, Week 26)
Investigators
Study Sites (1)
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