Effect of MD1003 in progressive multiple sclerosis with walking impairment

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 754

Inclusion Criteria

1. Patient aged 18-65 years old
2. Signed and dated written informed consent form in accordance with local regulations: having freely given their written informed consent to participate in the study
3. Diagnosis of primary or secondary progressive MS fulfilling revised McDonald criteria (2010) and Lublin criteria (2014)
4. Documented evidence of clinical disability progression within the 2 years prior to inclusion, i.e. a) progression of EDSS during the past two years of at least 1 point sustained for at least 6 months if inclusion EDSS is from 3.5 to 5.5 or at least 0.5 point increase sustained for at least 6 months if inclusion EDSS is from 6 to 6.5 or b) increase of TW25 by at least 20% in the last two years sustained for at least 6 months or c) other well-documented objective worsening validated by the Adjudication Committee
5. EDSS at inclusion from 3.5 to 6.5
6. TW25 < 40 seconds
7. Kurtzke pyramidal functional subscore =2 defined as minimal disability: patient complains of motor-fatigability or reduced performance in strenuous motor tasks (motor performance grade 1) and/or BMRC grade 4 in one or two muscle groups”

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 745
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 9

Exclusion Criteria

1. Clinical evidence of a relapse in 24 months prior to inclusion
2. Treatment with any product containing biotin as single ingredient within six months prior to inclusion (multivitamin supplementation authorized if biotin < 1mg per day)
3. Concomitant treatment with fampridine at inclusion or in the 30 days prior to inclusion
4. New immunosuppressive/immunomodulatory drug initiated less than 90 days prior to inclusion
5. Treatment with botulinium toxin (except for cosmetic purpose) initiated within 6 months prior to inclusion
6. In-patient rehabilitation program within the 3 months prior to inclusion
7. Pregnancy, breastfeeding or women with childbearing potential without acceptable form of contraception
8. Men unwilling to use an acceptable form of contraception
9. Any general chronic handicapping/incapacitating disease other than MS
10. Any serious disease necessitating biological follow-up with biological tests using biotinylated antibodies or substrates
11. Past history of rhabdomyolysis/metabolic myopathy
12. Known fatty acids beta oxidation defect
13. Known hypersensitivity or intolerance to biotin, analogues or excipients, patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption
14. Patients with hypersensitivity or any contra-indication to Gadolinium
15. Patients with uncontrolled hepatic disorder, renal or cardiovascular disease, or cancer
16. Laboratory tests out of normal ranges considered by the investigator as clinically significant with regards to the study continuation
17. Patients with history or presence of alcohol abuse or drug addiction
18. Untreated or uncontrolled psychiatric disorders, especially suicidal risk assessed by Columbia-Suicide Severity Rating Scale (C-SSRS)
19. Participation in another research study involving an investigational product (IP) in the 90 days prior to inclusion, or planned use during the study duration
20. Patients likely to be non-compliant to the study procedures or for whom a long-term follow-up seems to be difficult to achieve
21. Relapse that occurs between inclusion and randomization visit

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To confirm the superiority of MD1003, 300 mg/day, over placebo to clinically improve patients with not active progressive multiple sclerosis (MS).;Secondary Objective: To evaluate the safety of MD1003<br><br><br>;Primary end point(s): Primary efficacy endpoint:<br>Proportions of patients:<br>- with decreased EDSS at M12 confirmed at M15 (where decreased EDSS is defined as a decrease of at least 1 point if initial EDSS from 3.5 to 5.5 and of at least 0.5 point if initial EDSS from 6 to 6.5)<br>or<br>- with improved TW25 of at least 20% at M12 and M15<br>compared to the lowest of the two EDSS and TW25* scores among inclusion and randomization visits;Timepoint(s) of evaluation of this end point: - month 12 and 15

Secondary Outcome Measures

Name	Time	Method

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