Insights on Baseline Characteristics From Major Clinical Trials in Progressive Multiple Sclerosis: Robert J. Fox, MD

WATCH TIME: 4 minutes

“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. What we found is that the demographics, including age and sex, were fairly similar between the trials.”

Research has shown that progressive multiple sclerosis (MS) leads to ongoing neurological disability in patients, with limited therapeutic options. Key clinical trials like ORATORIO (NCT01194570), EXPAND (NCT01665144), MS-STAT2 (NCT03387670), and HERCULES (NCT04411641) have examined treatments for progressive forms of MS. Another trial, CALLIPER (NCT05054140), is an ongoing phase 2, randomized, placebo-controlled study investigating vidofludimus calcium, a selective DHODH inhibitor and Nurr1 activator, for its potential neuroprotective effects in secondary progressive MS (SPMS) and primary progressive MS (PPMS).

A recent analysis presented at the 2025 Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum, held February 27 to March 1, in West Palm Beach, Florida, aimed to compare the baseline characteristics of patients from CALLIPER with those from other major MS trials to assess how these differences might influence trial outcomes.¹ Led by by Robert J. Fox, MD, a staff neurologist at the Mellen Center for Multiple Sclerosis at Cleveland Clinic, the CALLIPER trial enrolled 278 patients, with 59.5% having nonactive SPMS, 7.9% having active SPMS, and 35.2% having PPMS.

Baseline data from CALLIPER, while blinded, showed that patient characteristics such as age, sex, and EDSS scores were similar across the clinical trials. However, differences in focal inflammation were noted, with fewer patients showing gadolinium-enhancing (Gd+) lesions at baseline compared with other trials. In CALLIPER’s PPMS group, 17.8% had Gd+ lesions, compared with 26.5% in ORATORIO. For nonactive SPMS, only 6.8% had Gd+ lesions, compared with 12.6% in HERCULES. Topline results of CALLIPER are anticipated to be reported in April 2025.

In a recent interview with NeurologyLive^®, Fox discussed the implications of the reduced proportion of patients with gadolinium-enhancing lesions in the CALLIPER trial. He highlighted how these findings may shape future treatment strategies for progressive MS by emphasizing the potential for therapies to target compartmentalized central nervous system inflammation rather than peripheral-driven pathology.

Fox also explored how the CALLIPER trial’s unique patient characteristics could influence the design of future clinical trials for progressive MS, stressing the importance of carefully defining patient populations and considering variations across studies. Addressing the challenges in comparing different progressive MS trials, he proposed strategies for harmonizing trial methodologies to improve consistency and reliability in future research.

Click here for coverage of 2025 ACTRIMS Forum.

REFERENCES
1. Fox R, Sciacca V, Wolf C, et al. Baseline Characteristics Across Major Clinical Trials in Progressive Multiple Sclerosis: Insights from ORATORIO, EXPAND, MS-STAT2, HERCULES, and CALLIPER. Presented at ACTRIMS Forum 2025; February 27 to March 1; West Palm Beach, Florida. P102.