Title : Design of a proposed phase III trial following the HORIZON phase II study
Abstract:
Multiple Sclerosis (MS) is an autoimmune disease that affects children and adults nationwide. The goal of this research is to improve the quality of life for patients living with the sometimes debilitating symptoms of MS, specifically through the use of the mRNA-1195 vaccine (also known as the Epstein Barr Virus vaccine). We designed a multicenter, randomized, placebo controlled, masked Phase III trial enrolling 400 adults (18–55) with early relapsing MS who are EBV-seropositive, with follow-up through Day 887. Participants would receive vaccinations on Day 1, ~Day 85, and ~Day 176, remain on standard MS management (as an add-on approach), and be monitored using clinical assessments, standardized assessment of disability outcomes, immune response labs, and neurological imaging at baseline, Month 12, and end-of-study. The proposed primary efficacy endpoint was time to first new disease activity through Day 887. First new disease activity was defined as a clinical attack and/or new or enlarging MRI lesions, based on previous studies. Statistical power calculations (n=200 per arm, SD=1.0, two-sided α=0.05) indicated low power for a small effect (Δ=0.10; 17%) but strong power for moderate-to-large effects (Δ=0.30; 85.1%; Δ≥1.0; ~100%). A high-level budget estimate for a 10-site, 400- participant trial (excluding vaccine manufacturing) ranged from ~$25M to $177M, reflecting variability in site operations, imaging, labs, and monitoring intensity. This report outlines a feasible and ethically considered Phase III trial design to test whether adding mRNA-1195 vaccination to standard MS care reduces disease activity. The proposed sample size is well-powered to detect clinically meaningful effects (about 30% or larger), and the cost ranges provide a realistic planning framework for future clinical trial implementation. Next steps include finalizing dose and eligibility details based on Phase II results and, if adult safety and efficacy signals are strong, planning stepwise evaluation in adolescents with pediatric-onset MS.
