San Diego – In a phase 2 trial, .
“That was a striking result,” one of the study authors, Robert T. Naismith, MD, said in an interview prior to presenting the study at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis. “We’ll need to see how that translates into a possible clinical benefit.”
Dr. Robert T. Naismith
In a trial known as SPRINT-MS/NN 102, researchers led by principal investigator Robert Fox, MD, a neurologist at the Cleveland Clinic in Ohio, along with colleagues in the NeuroNEXT Network, randomized 255 subjects with primary or secondary progressive MS to receive either ibudilast up to 100 mg/day (50 mg twice daily) or matching placebo and followed them for 96 weeks. They assessed clinical and imaging outcomes every 24 weeks, and the primary outcome was change in brain atrophy as measured by brain parenchymal fraction (BPF) over 96 weeks. Secondary outcomes included magnetization transfer ratio (MTR), diffusion tensor imaging, and optical coherence tomography. Analysis was based on a modified intention-to-treat approach, and linear mixed effects modeling was used to estimate the rate of change within imaging measures for each treatment group.
The 255 subjects were enrolled at 28 U.S. sites and their last follow-up visit was completed on May 11, 2017. The retention rate through week 96 was 86%, or 219 patients. The researchers found that treatment with ibudilast was associated with a 48% slowing in the rate of decline in brain atrophy as measured by BPF. A per-protocol analysis yielded similar results (P = .045). In addition, no increased rate of serious adverse events and no opportunistic infections or cancer signals were observed. As for tolerability, 25% of subjects on placebo and 30% of those on ibudilast discontinued treatment (P = .30). The main treatment-related adverse events were gastrointestinal in nature (20% in the placebo group vs. 67% in the ibudilast group; P = .002), primarily nausea.
In the analysis of key secondary outcomes, the researchers found that the change in MTR in normal-appearing brain tissue was reduced –0.00558 for ibudilast and –0.03064 for placebo, which was a relative reduction of 82% in MTR decline. At the same time, the change in MTR in normal-appearing gray matter was reduced –0.00753 for ibudilast and –0.03210 for placebo, which was a relative reduction of 77% in MTR decline. No significant difference in white matter changes were observed in transverse diffusivity (P = .15) or longitudinal diffusivity (P = .73), compared with placebo.
For the secondary endpoint of disability, a blinded evaluator assessed Expanded Disability Status Scale (EDSS) score at baseline and every 24 weeks. The researchers used a time-to-event Kaplan-Meier analysis and a Cox proportional hazards model to determine time to confirmed EDSS progression not due to relapse. They found that the hazard ratio for progression in the ibudilast group, compared with the placebo group, was 0.74, with a 90% confidence interval of 0.47-1.17 (P = .29).
“Ibudilast is a novel therapy for progressive MS, with a positive phase 2 study,” Dr. Naismith concluded. “Safety and tolerability were favorable. Clinical endpoints from this trial will be forthcoming.”
The NeuroNEXT Network is supported by the National Institute of Neurological Disorders and Stroke. Dr. Naismith reported having no financial disclosures.
SOURCE: Naismith R et al. ACTRIMS Forum 2018 Abstract P029.