Effect of MD1003 in Progressive Multiple Sclerosis (SPI2)

Phase 3

Terminated

Conditions: Multiple Sclerosis

Interventions: Drug: MD1003 100mg capsule
Drug: PLACEBO

Registration Number: NCT02936037

Lead Sponsor: MedDay Pharmaceuticals SA

Brief 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.

Detailed Description: Not available

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 642

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
GROUP 2	MD1003 100mg capsule	MD1003 capsule, 1 capsule tid (morning,noon and evening) for 15 months and up to 27 months.
GROUP 1	PLACEBO	Placebo capsule, 1 capsule tid (morning,noon and evening) for 15 months and up to 27 months.

Primary Outcome Measures

Name	Time	Method
Proportion of Patients Improved on Either Expanded Disability Status Scale (EDSS) or Time to Walk 25 Feet (TW25)	15 months	Proportion of patients improved on either Expanded Disability Status Scale (EDSS) or time to walk 25 feet (TW25) : - 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) or - with improved TW25 of at least 20% at Month 12 and Month15 compared to the lowest of the two EDSS and TW25\* scores among inclusion and randomization visits. \*The lowest TW25 value recorded among the four values obtained during the inclusion and randomization visits will be considered as the baseline TW25 value.

Secondary Outcome Measures

Name	Time	Method
Mean Change in TW25 Between M0 and M15	15 months
Time to 12-Weeks Confirmed EDSS Progression	3 to 27 months	12-weeks EDSS progression is defined by an increase of at least 1 point for baseline EDSS 3.5 to 5.5 and of at least 0.5 point for baseline EDSS 6 to 6.5 with respective confirmation 12 weeks later. Date of 12-weeks confirmed EDSS progression will be the first date of an EDSS progression (as defined above) that is confirmed 12 weeks later.
CGI-I Score (Clinical Global Impression of Change - Improvement), Evaluated Both by the Patient (SGI) and by the Evaluating Physician (CGI)	15 months

Trial Locations

Locations (92): MS Center of California
🇺🇸
Newport Beach, California, United States
Hospital Santa Caterina
🇪🇸
Salt, Girona, Spain
Nemocnice Teplice
🇨🇿
Teplice, Czechia
Vseobecna fakultni nemocnice v Praze
🇨🇿
Praha, Czechia
Brain and Mind Centre/University of Sydney
🇦🇺
Sydney, New South Wales, Australia
Barts And The London School Of Medicine And Dentistry Institute
🇬🇧
London, United Kingdom
Fakultni nemocnice v Motole
🇨🇿
Praha, Czechia
Sahlgrenska Universitetssjukhus - MS Center forskningsenheten
🇸🇪
Göteborg, Sweden
Tyne Hospitals NHS Foundation
🇬🇧
Newcastle upon Tyne, United Kingdom
Austin Hospital
🇦🇺
Heidelberg, Victoria, Australia
The Johns Hopkins Outpatient Center
🇺🇸
Baltimore, Maryland, United States
Nemocnice Jihlava
🇨🇿
Jihlava, Czechia
Hospital Regional Universitario de Málaga
🇪🇸
Malaga, Spain
doc. MUDr. Radomir Talab, CSc., neurologie
🇨🇿
Hradec Králové, Czechia
Fachkrankenhaus Hubertusburg
🇩🇪
Wermsdorf, Sachsen, Germany
MultipEL Studies Institut für klinische Studien GbR
🇩🇪
Hamburg, Germany
Hostipal Universitario Quirónsalud Madrid
🇪🇸
Pozuelo de Alarcón, Madrid, Spain
Hospital del Mar Servicio de Neurología
🇪🇸
Barcelona, Spain
Institute of Neurological Sciences
🇬🇧
Glasgow, United Kingdom
Hospital Clínico San Carlos
🇪🇸
Madrid, Spain
Hospital Universitari Vall d'Hebron
🇪🇸
Barcelona, Spain
Ondokuz Mayis University Medical Faculty
🇹🇷
Samsun, Turkey
University of Chicago Medical Center-Duchossois Center for Advanced Medicine (DCAM)
🇺🇸
Chicago, Illinois, United States
Harvard Medical School - Brigham and Women's Hospital - Center for Neurologic Diseases
🇺🇸
Boston, Massachusetts, United States
Cleveland Clinic Mellen Center for MS
🇺🇸
Cleveland, Ohio, United States
Mayo Clinic Scottsdale
🇺🇸
Scottsdale, Arizona, United States
Yale New Haven Hospital
🇺🇸
North Haven, Connecticut, United States
Northwestern University - Feinberg School of Medicine
🇺🇸
Chicago, Illinois, United States
Holy Name Hospital
🇺🇸
Teaneck, New Jersey, United States
New Orleans Center for Clinical Research
🇺🇸
Knoxville, Tennessee, United States
Charité - Universitätsmedizin Berlin / NeuroCure Clinical Research Center
🇩🇪
Berlin, Germany
Heinrich-Heine-Universität Düsseldorf
🇩🇪
Dusseldorf, Germany
The University of Edinburgh
🇬🇧
Edinburgh, United Kingdom
University of Miami Miller School of Medicine
🇺🇸
Miami, Florida, United States
Jordan Research And Education Institute Of Alta Bates Summit
🇺🇸
Berkeley, California, United States
University of Southern California Keck School of Medicine
🇺🇸
Los Angeles, California, United States
Neuro-Pain Medical Center
🇺🇸
Fresno, California, United States
Mount Sinai School of Medicine - Corinne Goldsmith Dickinson Center for MS
🇺🇸
New York, New York, United States
Columbia University Medical Center
🇺🇸
New York, New York, United States
The University of New Mexico - Multiple Sclerosis Specialty Clinic
🇺🇸
Albuquerque, New Mexico, United States
UBMD Neurology
🇺🇸
Buffalo, New York, United States
Washington University School of Medicine
🇺🇸
Saint Louis, Missouri, United States
State University of New York (SUNY)
🇺🇸
Stony Brook, New York, United States
Raleigh Neurology Associates, P.A.
🇺🇸
Raleigh, North Carolina, United States
University of Texas Southwestern Medical Center
🇺🇸
Dallas, Texas, United States
Central Texas Neurology Consultants
🇺🇸
Round Rock, Texas, United States
Virginia Mason Medical Center
🇺🇸
Seattle, Washington, United States
University of Virginia Health System
🇺🇸
Charlottesville, Virginia, United States
Rowe Neurology Institute
🇺🇸
Lenexa, Kansas, United States
Minneapolis Clinic of Neurology, LTD
🇺🇸
Golden Valley, Minnesota, United States
University of Rochester Medical Center
🇺🇸
Rochester, New York, United States
UCSF Multiple Sclerosis Center
🇺🇸
San Francisco, California, United States
Vanderbilt Comprehensive Multiple Sclerosis Center
🇺🇸
Nashville, Tennessee, United States
Wayne State University - Comp Clinic and MS Center
🇺🇸
Detroit, Michigan, United States
Karolinska University Hospital - Neurologmottagningen
🇸🇪
Stockholm, Sweden
University College London Institute of Neurology / National Hospital for Neurology & Neurosurgery
🇬🇧
London, United Kingdom
Salford Royal Hospital
🇬🇧
Salford, United Kingdom
St. Michael's Hospital
🇨🇦
Toronto, Ontario, Canada
Hopital de Notre Dame
🇨🇦
Montréal, Quebec, Canada
Universitätsklinikum Leipzig A.ö.R. - Klinik und Poliklinik
🇩🇪
Leipzig, Sachsen, Germany
Poliklinik für Neurologie Universitätsklinikum Ulm
🇩🇪
Ulm, Germany
Twoja Przychodnia Centrum Medyczne Nowa Sol
🇵🇱
Nowa Sol, Poland
Nova Clinical Research, LLC
🇺🇸
Bradenton, Florida, United States
Vancouver Hospital and Health Sciences Centre
🇨🇦
Vancouver, British Columbia, Canada
Burnaby Hospital
🇨🇦
Burnaby, British Columbia, Canada
University of Colorado Denver
🇺🇸
Aurora, Colorado, United States
UC Davis Health System
🇺🇸
Sacramento, California, United States
University of South Florida - Neurology
🇺🇸
Tampa, Florida, United States
Providence Multiple Sclerosis Center
🇺🇸
Portland, Oregon, United States
Barrow Neurology Clinics (BNC)
🇺🇸
Phoenix, Arizona, United States
Ospedale San Raffaele, IRCCS
🇮🇹
Milano, Italy
Nova Scotia Rehabilitation Center
🇨🇦
Halifax, Nova Scotia, Canada
The Royal Melbourne Hospital
🇦🇺
Parkville, Victoria, Australia
Ochsner Health System
🇺🇸
New Orleans, Louisiana, United States
UZ Gent
🇧🇪
Halle, Oost-Vlaanderen, Belgium
Montreal Neurologic Institute
🇨🇦
Montreal, Quebec, Canada
Neuro Centrum Science GmbH
🇩🇪
Erbach, Germany
COPERNICUS PL sp z o.o.,Szpital im. M.Kopernika Oddział Neurologiczny
🇵🇱
Gdansk, Poland
AO S.Andrea, Università degli Studi di Roma La Sapienza
🇮🇹
Roma, Italy
UZ Antwerpen
🇧🇪
Edegem, Antwerpen, Belgium
Jessa Ziekenhuis - Campus Virga Jesse
🇧🇪
Hasselt, Limburg, Belgium
Caritas Krankenhaus
🇩🇪
Bad Mergentheim, Germany
Neuropoint GmbH
🇩🇪
Ulm, Germany
Nasz Lekarz Ośrodek Badań Klinicznych
🇵🇱
Bydgoszcz, Poland
Centrum Medyczne Pratia Warszawa
🇵🇱
Warszawa, Poland
Hôpital universitaire Dr George L-Dumont university Hospital
🇨🇦
Moncton, New Brunswick, Canada
Servicio de Neurología Hospital Vithas Nisa Aljarafe
🇪🇸
Castilleja de la Cuesta, Sevilla, Spain
Ludwig-Maximilians Universität München
🇩🇪
München, Germany
Valeomed Kft
🇭🇺
Esztergom, Hungary
Ottawa Hospital General Campus
🇨🇦
Ottawa, Ontario, Canada
Thomas Jefferson University
🇺🇸
Philadelphia, Pennsylvania, United States
University of Kansas Medical Center
🇺🇸
Kansas City, Kansas, United States