Objective: To assess whether treatment with the generic drug domperidone can reduce the progression of disability in secondary progressive multiple sclerosis (SPMS), we conducted a phase 2 futility trial following the Simon two-stage design.

Methods: We enrolled patients in an open-label, Simon two-stage, single-center, phase 2, single-arm futility trial at the Calgary MS Clinic if they met the following criteria: age 18 to 60 years, SPMS, screening EDSS score of 4.0 to 6.5 and screening T25FW of 9 seconds or more. Patients received domperidone 10mg QID for one year. The primary outcome was worsening of disability, defined as worsening of the T25FW performance by 20% or more at 12 months compared to at baseline. This trial is registered with ClinicalTrials.gov, number NCT02308137.

Results: Between February 13^th, 2015 and January 3^rd, 2020, 110 patients were screened, 81 received treatment, 64 completed follow-up, of whom 62 were analysed. The study did not meet its primary endpoint: 22 of 62 (35%) patients experienced significant worsening of disability, which is close to the expected proportion of 40%, and above the pre-defined futility threshold. Patients with higher prolactin levels during the study had a significantly lower risk of disability progression, which may warrant further investigation. Domperidone treatment was reasonably well tolerated, but adverse events occurred in 84% and serious adverse events in 15% of patients.

Conclusions: Domperidone treatment could not reject futility in reducing disability progression in SPMS. The Simon two-stage trial model may be a useful model for phase 2 studies in progressive MS.

Classification of Evidence: This study provides Class III evidence that in individuals with secondary progressive multiple sclerosis participating in a futility trial, domperidone treatment could not reject futility in reducing disability progression at 12 months.