Presentation (CTI)

OBJECTIVES: Neuromyelitis optica spectrum disorder (NMOSD) is a severe autoimmune condition characterized by relapses and resulting disability, making the investigation of new effective treatments crucial. In the BCD-132-6/AQUARELLE trial we planned to conduct an unanchored matching-adjusted indirect comparison (MAIC) to compare efficacy of new anti-CD20 antibody Divozilimab against the N-MOmentum placebo group, with the primary objective being to demonstrate superiority in reducing annualized relapse rate (ARR) in patients with NMOSD. Objective is to estimate the minimum effective sample size (ESS) required to demonstrate superiority of Divozilimab to placebo in reducing adjudicated ARR by ≥90% over 6 months.
METHODS: A systematic review was conducted to identify relevant trials. First, we developed a meta-regression model (adjusting for sex, age, AQP4-IgG status, race, EDSS score and prior therapy) using external trial data. We then used individual patient characteristics at screening at the BCD-132-6/AQUARELLE trial and extrapolated the 6-month ARR for them. Finally, we simulated an unanchored MAICs with a weighted annualized relapse rate ratio (ARRR) of Divozilimab versus placebo, decreasing the ESS, and estimated the minimum ESS required for 90% power.
RESULTS: The predicted unadjusted 6-month ARR for Divozilimab was 0.116 (95% CI: 0.030, 0.212), and 0.155 (95% CI: 0.042, 0.335) after MAIC weighting. The 6-month ARR versus placebo was 0.117 (90% CI 0.045; 0.214) for unweighted value, and 0.156 (90% CI 0.050; 0.315) for weighted value. The ESS for the Divozilimab group was 61. The minimum ESS required to achieve 90% power was 35 patients.
CONCLUSIONS: Simulation modelling predicts the 6-month ARR of 0.116 (90% CI: 0.030; 0.212) for Divozilimab, corresponding to ARR of 0.117 (90% CI: 0.050; 0.315) versus placebo. A minimum sample size of 35 patients receiving Divozilimab is predicted to provide ≥90% power to demonstrate superiority based on the primary objective.