Effect of MD1003 in Progressive Multiple Sclerosis (SPI2) (SPI2)

• ClinicalTrials.gov Identifier: NCT02936037
• Recruitment Status: Terminated
• First Posted: October 18, 2016
• Results First Posted: November 23, 2020
• Last Update Posted: November 23, 2020
• Sponsor: MedDay Pharmaceuticals SA
• Information provided by (Responsible Party): MedDay Pharmaceuticals SA

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Multiple Sclerosis	Drug: MD1003 100mg capsule; Drug: PLACEBO	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 642 participants
• 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)
• Primary Purpose: Treatment
• Official Title: Effect of MD1003 in Progressive Multiple Sclerosis: a Randomized Double Blind Placebo Controlled Study
• Actual Study Start Date: December 2016
• Actual Primary Completion Date: November 15, 2019
• Actual Study Completion Date: April 23, 2020

Arms and Interventions

Arm	Intervention/treatment
Placebo Comparator: GROUP 1; Placebo capsule, 1 capsule tid (morning,noon and evening) for 15 months and up to 27 months.	Drug: PLACEBO; an inactive substance
Experimental: GROUP 2; MD1003 capsule, 1 capsule tid (morning,noon and evening) for 15 months and up to 27 months.	Drug: MD1003 100mg capsule; Other Name: high dose biotin

Outcome Measures

Primary Outcome Measures :

1. Proportion of Patients Improved on Either Expanded Disability Status Scale (EDSS) or Time to Walk 25 Feet (TW25) [ Time Frame: 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 :

1. Time to 12-Weeks Confirmed EDSS Progression [ Time Frame: 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.

2. CGI-I Score (Clinical Global Impression of Change - Improvement), Evaluated Both by the Patient (SGI) and by the Evaluating Physician (CGI) [ Time Frame: 15 months ]
3. Mean Change in TW25 Between M0 and M15 [ Time Frame: 15 months ]

Other Outcome Measures:

1. Brain MRI Changes Between M0 and M15 [ Time Frame: 15 months ]
2. Remote Monitoring of Ambulation [ Time Frame: 27 months ]
3. (MSQOL54) & (CAREQOL-MS) Subscores and Composite Scores [ Time Frame: 15 months ]
4. Subscores of the Kurtzke Functional Score [ Time Frame: 15 months ]
5. Symbol Digit Modalities Test (SDMT) [ Time Frame: 15 months ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 65 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

United States, Arizona

Barrow Neurology Clinics (BNC)

Phoenix, Arizona, United States, 85013

Mayo Clinic Scottsdale

Scottsdale, Arizona, United States, 85259

United States, California

Jordan Research And Education Institute Of Alta Bates Summit

Berkeley, California, United States, 94705

Neuro-Pain Medical Center

Fresno, California, United States, 93710

University of Southern California Keck School of Medicine

Los Angeles, California, United States, 90033

MS Center of California

Newport Beach, California, United States, 92663

UC Davis Health System

Sacramento, California, United States, 95817

UCSF Multiple Sclerosis Center

San Francisco, California, United States, 94158

United States, Colorado

University of Colorado Denver

Aurora, Colorado, United States, 80045

United States, Connecticut

Yale New Haven Hospital

North Haven, Connecticut, United States, 06473

United States, Florida

Nova Clinical Research, LLC

Bradenton, Florida, United States, 34209

University of Miami Miller School of Medicine

Miami, Florida, United States, 33136

University of South Florida - Neurology

Tampa, Florida, United States, 33612

United States, Illinois

Northwestern University - Feinberg School of Medicine

Chicago, Illinois, United States, 60611

University of Chicago Medical Center-Duchossois Center for Advanced Medicine (DCAM)

Chicago, Illinois, United States, 60637

United States, Kansas

University of Kansas Medical Center

Kansas City, Kansas, United States, 66160

Rowe Neurology Institute

Lenexa, Kansas, United States, 66214

United States, Louisiana

Ochsner Health System

New Orleans, Louisiana, United States, 70121

United States, Maryland

The Johns Hopkins Outpatient Center

Baltimore, Maryland, United States, 21287

United States, Massachusetts

Harvard Medical School - Brigham and Women's Hospital - Center for Neurologic Diseases

Boston, Massachusetts, United States, 02115

United States, Michigan

Wayne State University - Comp Clinic and MS Center

Detroit, Michigan, United States, 48201

United States, Minnesota

Minneapolis Clinic of Neurology, LTD

Golden Valley, Minnesota, United States, 55422

United States, Missouri

Washington University School of Medicine

Saint Louis, Missouri, United States, 63110

United States, New Jersey

Holy Name Hospital

Teaneck, New Jersey, United States, 07666

United States, New Mexico

The University of New Mexico - Multiple Sclerosis Specialty Clinic

Albuquerque, New Mexico, United States, 87131

United States, New York

UBMD Neurology

Buffalo, New York, United States, 14203

Mount Sinai School of Medicine - Corinne Goldsmith Dickinson Center for MS

New York, New York, United States, 10029

Columbia University Medical Center

New York, New York, United States, 10032

University of Rochester Medical Center

Rochester, New York, United States, 14642

State University of New York (SUNY)

Stony Brook, New York, United States, 11794

United States, North Carolina

Raleigh Neurology Associates, P.A.

Raleigh, North Carolina, United States, 27607

United States, Ohio

Cleveland Clinic Mellen Center for MS

Cleveland, Ohio, United States, 44195

United States, Oregon

Providence Multiple Sclerosis Center

Portland, Oregon, United States, 97225

United States, Pennsylvania

Thomas Jefferson University

Philadelphia, Pennsylvania, United States, 19107

United States, Tennessee

New Orleans Center for Clinical Research

Knoxville, Tennessee, United States, 37920

Vanderbilt Comprehensive Multiple Sclerosis Center

Nashville, Tennessee, United States, 37215

United States, Texas

University of Texas Southwestern Medical Center

Dallas, Texas, United States, 75390

Central Texas Neurology Consultants

Round Rock, Texas, United States, 78681

United States, Virginia

University of Virginia Health System

Charlottesville, Virginia, United States, 22903

United States, Washington

Virginia Mason Medical Center

Seattle, Washington, United States, 98101

Australia, New South Wales

Brain and Mind Centre/University of Sydney

Sydney, New South Wales, Australia, 2050

Australia, Victoria

Austin Hospital

Heidelberg, Victoria, Australia, 3084

The Royal Melbourne Hospital

Parkville, Victoria, Australia, 3050

Belgium

UZ Antwerpen

Edegem, Antwerpen, Belgium, 2650

Jessa Ziekenhuis - Campus Virga Jesse

Hasselt, Limburg, Belgium, 3500

UZ Gent

Halle, Oost-Vlaanderen, Belgium, 9000

Canada, British Columbia

Burnaby Hospital

Burnaby, British Columbia, Canada, V5G 2X6

Vancouver Hospital and Health Sciences Centre

Vancouver, British Columbia, Canada, V6T 2B5

Canada, New Brunswick

Hôpital universitaire Dr George L-Dumont university Hospital

Moncton, New Brunswick, Canada, E1C 2Z3

Canada, Nova Scotia

Nova Scotia Rehabilitation Center

Halifax, Nova Scotia, Canada, B3H 4K4

Canada, Ontario

Ottawa Hospital General Campus

Ottawa, Ontario, Canada, ON K1H 8L6

St. Michael's Hospital

Toronto, Ontario, Canada, M5B 1W8

Canada, Quebec

Montreal Neurologic Institute

Montreal, Quebec, Canada, H3A 2B4

Hopital de Notre Dame

Montréal, Quebec, Canada, H2L 4M1

Czechia

doc. MUDr. Radomir Talab, CSc., neurologie

Hradec Králové, Czechia, 500 03

Nemocnice Jihlava

Jihlava, Czechia, 586 33

Vseobecna fakultni nemocnice v Praze

Praha, Czechia, 128 21

Fakultni nemocnice v Motole

Praha, Czechia, 150 06

Nemocnice Teplice

Teplice, Czechia, 415 29

Germany

Universitätsklinikum Leipzig A.ö.R. - Klinik und Poliklinik

Leipzig, Sachsen, Germany, 04103

Fachkrankenhaus Hubertusburg

Wermsdorf, Sachsen, Germany, 04779

Caritas Krankenhaus

Bad Mergentheim, Germany, 97980

Charité - Universitätsmedizin Berlin / NeuroCure Clinical Research Center

Berlin, Germany, 10117

Heinrich-Heine-Universität Düsseldorf

Dusseldorf, Germany, 40225

Neuro Centrum Science GmbH

Erbach, Germany, 64711

MultipEL Studies Institut für klinische Studien GbR

Hamburg, Germany, 22179

Ludwig-Maximilians Universität München

München, Germany, 81377

Neuropoint GmbH

Ulm, Germany, 89073

Poliklinik für Neurologie Universitätsklinikum Ulm

Ulm, Germany, 89081

Hungary

Valeomed Kft

Esztergom, Hungary, 2500

Italy

Ospedale San Raffaele, IRCCS

Milano, Italy, 20132

AO S.Andrea, Università degli Studi di Roma La Sapienza

Roma, Italy, 00189

Poland

Nasz Lekarz Ośrodek Badań Klinicznych

Bydgoszcz, Poland, 85-794

COPERNICUS PL sp z o.o.,Szpital im. M.Kopernika Oddział Neurologiczny

Gdansk, Poland, 80-803

Twoja Przychodnia Centrum Medyczne Nowa Sol

Nowa Sol, Poland, 67-100

Centrum Medyczne Pratia Warszawa

Warszawa, Poland, 01-868

Spain

Hospital Santa Caterina

Salt, Girona, Spain, 17190

Hostipal Universitario Quirónsalud Madrid

Pozuelo de Alarcón, Madrid, Spain, 28223

Servicio de Neurología Hospital Vithas Nisa Aljarafe

Castilleja de la Cuesta, Sevilla, Spain, 41950

Hospital del Mar Servicio de Neurología

Barcelona, Spain, 08003

Hospital Universitari Vall d'Hebron

Barcelona, Spain, 08035

Hospital Clínico San Carlos

Madrid, Spain, 28040

Hospital Regional Universitario de Málaga

Malaga, Spain, 29010

Sweden

Sahlgrenska Universitetssjukhus - MS Center forskningsenheten

Göteborg, Sweden, 413 45

Karolinska University Hospital - Neurologmottagningen

Stockholm, Sweden, 171 76

Turkey

Ondokuz Mayis University Medical Faculty

Samsun, Turkey, 55139

United Kingdom

The University of Edinburgh

Edinburgh, United Kingdom, EH16 4SB

Institute of Neurological Sciences

Glasgow, United Kingdom, G51 4TF

Barts And The London School Of Medicine And Dentistry Institute

London, United Kingdom, E1 2AT

University College London Institute of Neurology / National Hospital for Neurology & Neurosurgery

London, United Kingdom, WC1N 3BG

Tyne Hospitals NHS Foundation

Newcastle upon Tyne, United Kingdom, NE1 4LP

Salford Royal Hospital

Salford, United Kingdom, M6 8HD

Sponsors and Collaborators

MedDay Pharmaceuticals SA

Investigators

• Principal Investigator: Bruce Cree, MD, PHD; University of California, San Francisco
• Study Director: Frederic Sedel, MD, PHD; Medday Pharmaceuticals

  Study Documents (Full-Text)

Documents provided by MedDay Pharmaceuticals SA:

Study Protocol  [PDF] November 12, 2018

Statistical Analysis Plan  [PDF] February 10, 2020

More Information

Additional Information:

Sponsor 

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Cree BAC, Cutter G, Wolinsky JS, Freedman MS, Comi G, Giovannoni G, Hartung HP, Arnold D, Kuhle J, Block V, Munschauer FE, Sedel F, Lublin FD; SPI2 investigative teams. Safety and efficacy of MD1003 (high-dose biotin) in patients with progressive multiple sclerosis (SPI2): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Neurol. 2020 Dec;19(12):988-997. doi: 10.1016/S1474-4422(20)30347-1. Epub 2020 Oct 23.

• Responsible Party: MedDay Pharmaceuticals SA
• ClinicalTrials.gov Identifier: NCT02936037
• Other Study ID Numbers: MD1003CT2016-01MS-SPI2
• First Posted: October 18, 2016
• Results First Posted: November 23, 2020
• Last Update Posted: November 23, 2020
• Last Verified: October 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

Keywords provided by MedDay Pharmaceuticals SA:

progressive multiple sclerosis; MS; EDSS; TW25; multiple sclerosis

Additional relevant MeSH terms:

Biotin; Multiple Sclerosis; Multiple Sclerosis, Chronic Progressive; Sclerosis; Pathologic Processes; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases; Vitamin B Complex; Vitamins; Micronutrients; Nutrients; Growth Substances; Physiological Effects of Drugs