EDSS and Timed 25 Foot Walk Correlate with Spinal Cord Areas: Baseline Results from the SPI2 Clinical Trial of MD-1003 (high-dose biotin) in Progressive Multiple Sclerosis (P3.2-023)

Objective: To determine whether clinical measures of disability (timed 25-foot walk [T25FW] and Expanded Disability Status Scale [EDSS]) correlate with total cervical spinal cord area as measured by MRI by phase-sensitive inversion recovery (PSIR) imaging in a phase 3 randomized clinical trial for progressive multiple sclerosis (MS).

Background: Cross-sectional studies indicated a strong relationship between MS disability and spinal cord areas but these metrics have not been investigated in a multi-center dataset or within the context of a randomized controlled trial. The SPI2 study is a phase 3, placebo-controlled, randomized trial investigating the efficacy and safety of MD1003 (high-dose biotin) in 642 participants with progressive forms of MS.

Design/Methods: Spinal cord MRI was acquired at 60 of 92 study centers that had Phillips or Siemens 1.5 or 3.0 Tesla MRI scanners. Sites with General Electric scanners did not participate. PSIR sequences at vertebral disc levels C2–C3 and C3–C4 were acquired at baseline (prior to randomization). Total cord areas were measured using a semi-automatic method. LASSO subset selection regression models were used to correlate the average total cord areas with sex, disease duration, onset age, disease course, and combinations of T25FW and EDSS.

Results: Baseline cervical spinal cord MRI scans were available for 120 primary progressive MS (PPMS) and 204 secondary progressive MS (SPMS) participants. A model including both walk time and EDSS had: R²=0.15 with onset age (p<.0001) and (T25FW p<.0001) significantly contributing. A model without T25FW had R²=0.14 with onset age (p<.0001) and EDSS (p=.0002) significantly contributing. Disease course (secondary progressive MS vs primary progressive MS) was not significant in these relationships.

Conclusions: These results demonstrate the feasibility of implementing cross-platform, PSIR cervical cord MRI in a global, multi-center, multi-platform, phase 3 clinical trial. These results validate proposed correlations between total cervical cord areas using PSIR MRI and clinical disability outcomes.

Disclosure: Dr. Block has nothing to disclose. Dr. Alexander has nothing to disclose. Dr. Papinutto has nothing to disclose. Dr. Rajesh has nothing to disclose. Dr. Gundel has nothing to disclose. Dr. Arnold has nothing to disclose. Dr. SEDEL has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with MedDay. Dr. SEDEL holds stock and/or stock options in MedDay stocks as part of employee’s compensation, which sponsored research in which Dr. SEDEL was involved as an investigator. Dr. Cree has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities from Abbvie, Akili, Biogen, EMD Serono, GeNeuro and Novartis. Dr. Henry has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Consultancy from Novartis, Medday, Roche, Sanofi-Genzyme, Abbvie. Educational programs from Sanofi-Genzyme, TEVA. Dr. Henry has received research support from Research support from Sanofi-Genzyme, Roche/Genentech, Medday.