Challenges in Rare Disease Clinical Trials: The PREVENT Trial for NMOSD

• Activity Number: 100 - Statistical Innovations for Drug Approval and Reimbursement for Rare Disease
• Type: Invited
• Date/Time: Monday, August 3, 2020 : 1:00 PM to 2:50 PM
• Sponsor: International Indian Statistical Association
• Author(s): Fanny O'Brien*
• Companies: Alexion
• Keywords: NMOSD; adjudication; time to first relapse; rare disease; eculizumab; aquaporin-4

Abstract

Neuromyelitis optica spectrum disorder is a rare, severe, disabling autoimmune inflammatory disorder of the central nervous system that targets aquaporin-4 (AQP4)-expressing cells, and predominately affects the optic nerves and spinal cord. In patients with NMOSD, disease progresses secondary to the disabilities that are accrued with each relapse. The PREVENT Study was a Phase 3, randomized, double-blind, placebo-controlled, multicenter study designed to evaluate the safety and efficacy of eculizumab for the treatment of patients with relapsing NMOSD. Eligible patients were randomized 2:1 to treatment arms: 1) eculizumab or 2) placebo. The primary efficacy endpoint was time to first adjudicated relapse. The study was designed to continue until the occurrence of 24 positively adjudicated relapses in 24 distinct patients. The trial was stopped after 23 prespecified adjudicated relapses, given the uncertainty in estimating when the final event would occur. On June 27, 2019, the FDA approved Soliris as the first treatment of NMOSD. This presentation will discuss the challenges of a time to event study in a rare disease.