The baseline characteristics analysis of the CALLIPER trial has revealed distinct patterns in progressive multiple sclerosis patients, particularly noting lower rates of inflammatory activity compared to previous major clinical trials. The findings, presented at the 2025 ACTRIMS Forum in West Palm Beach, Florida, offer new insights into trial design and treatment approaches for progressive MS.
Patient Demographics and Disease Distribution
The phase 2 CALLIPER trial, investigating vidofludimus calcium, enrolled 278 patients across different progressive MS subtypes. The distribution showed 59.5% with nonactive secondary progressive MS (SPMS), 7.9% with active SPMS, and 35.2% with primary progressive MS (PPMS). Dr. Robert J. Fox, staff neurologist at the Mellen Center for Multiple Sclerosis at Cleveland Clinic, led the comparative analysis of baseline characteristics.
Key Differences in Inflammatory Activity
While demographic factors such as age, sex, and EDSS scores aligned closely with previous trials, CALLIPER demonstrated notably lower rates of inflammatory activity. In the PPMS cohort, only 17.8% of patients showed gadolinium-enhancing (Gd+) lesions, compared to 26.5% in the ORATORIO trial. The difference was even more pronounced in nonactive SPMS patients, where just 6.8% exhibited Gd+ lesions, versus 12.6% in the HERCULES trial.
Implications for Treatment Approaches
"This presentation compared those enrolled in the study to other progressive MS trials, such as ORATORIO with ocrelizumab, HERCULES with nonrelapsing secondary progressive MS, and others," noted Dr. Fox. The reduced proportion of patients with gadolinium-enhancing lesions suggests a potential shift in treatment focus toward compartmentalized central nervous system inflammation rather than peripheral-driven pathology.
Trial Design and Future Directions
The unique patient characteristics observed in CALLIPER may influence future clinical trial designs for progressive MS treatments. The findings emphasize the importance of carefully defining patient populations and understanding how variations across studies might impact outcomes. Topline results from the CALLIPER trial are expected in April 2025, potentially offering new insights into the effectiveness of vidofludimus calcium as a selective DHODH inhibitor and Nurr1 activator.
The trial's focus on both SPMS and PPMS populations, combined with its distinct inflammatory profile, positions CALLIPER as a significant contributor to the evolving landscape of progressive MS treatment research. These findings may help shape more targeted therapeutic approaches for patients with progressive forms of MS, where treatment options have historically been limited.
