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Safety and efficacy of MD1003 (high-dose biotin) in patients with progressive multiple sclerosis (SPI2) : a randomised, double-blind, placebo-controlled, phase 3 trial
- Source :
- The lancet neurology
- Publication Year :
- 2020
-
Abstract
- Background: There is an unmet need to develop therapeutic interventions directed at the neurodegeneration that underlies progression in multiple sclerosis. High-dose, pharmaceutical-grade biotin (MD1003) might enhance neuronal and oligodendrocyte energetics, resulting in improved cell function, repair, or survival. The MS-SPI randomised, double-blind, placebo-controlled study found that MD1003 improved disability outcomes over 12 months in patients with progressive multiple sclerosis. The SPI2 study was designed to assess the safety and efficacy of MD1003 in progressive forms of multiple sclerosis in a larger, more representative patient cohort. Methods: SPI2 was a randomised, double-blind, parallel-group, placebo-controlled trial done at 90 academic and community multiple sclerosis clinics across 13 countries. Patients were aged 18-65 years, had a diagnosis of primary or secondary progressive multiple sclerosis fulfilling the revised International Panel criteria and Lublin criteria, a Kurtzke pyramidal functional subscore of at least 2 (defined as minimal disability), an expanded disability status scale (EDSS) score of 3·5-6·5, a timed 25-foot walk (TW25) of less than 40 s, evidence of clinical disability progression, and no relapses in the 2 years before enrolment. Concomitant disease-modifying therapies were allowed. Patients were randomly assigned (1:1) by an independent statistician using an interactive web response system, with stratification by study site and disease history, to receive MD1003 (oral biotin 100 mg three times daily) or placebo. Participants, investigators, and assessors were masked to treatment assignment. The primary endpoint was a composite of the proportion of participants with confirmed improvement in EDSS or TW25 at month 12, confirmed at month 15, versus baseline. The primary endpoint was assessed in the intention-to-treat analysis set, after all participants completed the month 15 visit. Safety analyses included all participants who received at least one dose of MD1003. This trial is registered with ClinicalTrials.gov (NCT02936037) and the EudraCT database (2016-000700-29). Findings: From Feb 22, 2017, to June 8, 2018, 642 participants were randomly assigned MD1003 (n=326) or placebo (n=316). The double-blind, placebo-controlled phase of the study ended when the primary endpoint for the last-entered participant was assessed on Nov 15, 2019. The mean time in the placebo-controlled phase was 20·1 months (SD 5·3; range 15-27). For the primary outcome, 39 (12%) of 326 patients in the MD1003 group compared with 29 (9%) of 316 in the placebo group improved at month 12, with confirmation at month 15 (odds ratio 1·35 [95% CI 0·81-2·26]). Treatment-emergent adverse events occurred in 277 (84%) of 331 participants in the MD1003 group and in 264 (85%) of 311 in the placebo group. 87 (26%) of 331 participants in the MD1003 group and 82 (26%) of 311 participants in the placebo group had at least one serious treatment-emergent adverse event. One (
- Subjects :
- Adult
Male
0301 basic medicine
medicine.medical_specialty
Adolescent
Biotin
Placebo
Severity of Illness Index
law.invention
Young Adult
03 medical and health sciences
0302 clinical medicine
Double-Blind Method
Randomized controlled trial
law
Internal medicine
Outcome Assessment, Health Care
Severity of illness
Aged
Disease Progression
Female
Humans
Middle Aged
Multiple Sclerosis, Chronic Progressive
Vitamin B Complex
Walking Speed
Clinical endpoint
Medicine
Expanded Disability Status Scale
business.industry
Multiple sclerosis
medicine.disease
Clinical trial
030104 developmental biology
Cohort
Neurology (clinical)
Human medicine
business
030217 neurology & neurosurgery
Subjects
Details
- Language :
- English
- ISSN :
- 14744422
- Database :
- OpenAIRE
- Journal :
- The lancet neurology
- Accession number :
- edsair.doi.dedup.....96c5ad34bdeebea2fd1fc501717210a5