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Abstract: INFO27

Evaluating Ravulizumab in Thrombotic Microangiopathy Associated With a Trigger: Rationale and Design of a Global Phase 3 Randomized, Double-Blind, Placebo-Controlled Study

Session Information

  • Informational Posters
    November 04, 2021 | Location: On-Demand, Virtual Only
    Abstract Time: 10:00 AM - 12:00 PM

Category: Genetic Diseases of the Kidneys

  • No subcategory defined

Authors

  • Khawaja, Zeeshan, Alexion Pharmaceuticals, Inc., Boston, Massachusetts, United States
  • Wang, Edward, Alexion Pharmaceuticals, Inc., Boston, Massachusetts, United States
  • Konig, Elsa, Alexion Pharmaceuticals, Inc., Boston, Massachusetts, United States
  • Chen, Peter, Alexion Pharmaceuticals, Inc., Boston, Massachusetts, United States
  • Parikh, Samir V., The Ohio State University Wexner Medical Center, Columbus, Ohio, United States
Description

Ravulizumab, a monoclonal antibody specific for C5, is approved in the US for treatment of atypical hemolytic uremic syndrome (aHUS) to inhibit complement-mediated thrombotic microangiopathy (TMA). Pivotal Phase 3 trials in aHUS included patients with primary disease and TMAs following renal transplant and pregnancy, yet excluded TMA caused by other triggers. Complement involvement in the pathophysiology of TMA associated with one or more triggers (secondary TMA) is not fully understood and the benefit of terminal complement blockade in these cases requires further evidence. This Phase 3 randomized, placebo-controlled, global trial (NCT04743804) investigates efficacy and safety of ravulizumab in patients with TMA associated with a trigger (Figure). Randomization will be stratified by dialysis status and primary trigger type. Adults with severe acute kidney injury and diagnosis of TMA (based on protocol-defined criteria: thrombocytopenia, microangiopathic hemolytic anemia, elevated lactate dehydrogenase) associated with at least one trigger (autoimmune disease [lupus nephritis, systemic sclerosis-associated TMA], infection, solid organ transplant, drugs or malignant hypertension) will be included. Exclusion criteria include postpartum aHUS, aHUS-associated mutations, TMA due to hematopoietic stem cell transplantation, chronic kidney disease with eGFR ≤45 mL/min/1.73 m2, primary or secondary glomerular diseases (other than lupus), familial or acquired ADAMTS13 deficiency (activity <5%) or a positive direct Coombs’ test. The primary outcome is complete TMA response during the 26-week treatment period. Additional outcomes include time to complete TMA response, TMA response duration, hematologic response and renal response assessed by change in eGFR and by dialysis requirement. Safety will be assessed through Week 26 and Week 52.

Figure. Study design, dosing schedule and key endpoints.

Funding

  • Study funded by Alexion Pharmaceuticals, Inc.