Effect of MD1003 in Progressive Multiple Sclerosis (SPI2)
Condition: Multiple Sclerosis
MeSH terms: Multiple Sclerosis; Multiple Sclerosis, Chronic Progressive; Sclerosis
Intervention: MD1003 100mg capsule; PLACEBO
Intervention description: an inactive substance
Intervention MeSH terms: Biotin
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: PART 1:
Total duration of Part 1 is 27 months. The randomized double-blind placebo-controlled period ranges from 15 to 27 months depending upon the randomization date of an individual patient.
Once the last month 15 evaluation of the study has been completed, patients will switch to the active drug at the next planned visit. Participants and study personnel will remain blinded as to the original treatment assignment.
Maximum duration of double-blind period per patient will be no longer than 27 months.
PART 2:
At the last evaluation of Part 1 (Visit 11/Month 27) all participants will be offered active treatment in an open label extension for 39 additional months (From V11/M27 to V18/M66).
The purpose of the active drug extension is to further define the safety of MD1003.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 642.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: progressive multiple sclerosis; MS; EDSS; TW25; multiple sclerosis

Summary:

      The purpose of this study is to demonstrate the superiority of MD1003 over placebo in the
      disability of patients suffering from progressive multiple sclerosis and especially those
      with gait impairment.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patient aged 18-65 years old

          -  Signed and dated written informed consent form in accordance with local regulations:
             having freely given their written informed consent to participate in the study

          -  Diagnosis of primary or secondary progressive MS fulfilling revised McDonald criteria
             (2010) and Lublin criteria (2014)

          -  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

          -  EDSS at inclusion from 3.5 to 6.5

          -  TW25 < 40 seconds at inclusion visit

          -  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"

        Exclusion Criteria:

          -  Clinical evidence of a relapse in 24 months prior to inclusion

          -  Treatment with any product containing biotin as single ingredient within six months
             prior to inclusion (multivitamin supplementation authorized if biotin < 1mg per day)

          -  Concomitant treatment with fampridine at inclusion or in the 30 days prior to
             inclusion

          -  New immunosuppressive/immunomodulatory drug initiated less than 90 days prior to
             inclusion

          -  Treatment with botulinum toxin (except for cosmetic purpose) initiated within 6 months
             prior to inclusion

          -  In-patient rehabilitation program within the 3 months prior to inclusion

          -  Pregnancy, breastfeeding or women with childbearing potential without acceptable form
             of contraception

          -  Men unwilling to use an acceptable form of contraception

          -  Any general chronic handicapping/incapacitating disease other than MS

          -  Any serious disease necessitating biological follow-up with biological tests using
             biotinylated antibodies or substrates

          -  Past history of rhabdomyolysis/metabolic myopathy

          -  Known fatty acids beta oxidation defect

          -  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

          -  Patients with hypersensitivity or any contra-indication to Gadolinium

          -  Patients with uncontrolled hepatic disorder, renal or cardiovascular disease, or
             cancer

          -  Laboratory tests out of normal ranges considered by the investigator as clinically
             significant with regards to the study continuation

          -  Patients with history or presence of alcohol abuse or drug addiction

          -  Untreated or uncontrolled psychiatric disorders, especially suicidal risk assessed by
             Columbia-Suicide Severity Rating Scale (C-SSRS)

          -  Participation in another research study involving an investigational product (IP) in
             the 90 days prior to inclusion, or planned use during the study duration

          -  Patients likely to be non-compliant to the study procedures or for whom a long-term
             follow-up seems to be difficult to achieve

          -  Relapse that occurs between inclusion and randomization visit