Effect of MD1003 in Progressive Multiple Sclerosis (SPI2)

NCT ID: NCT02936037

Last Updated: 2020-11-23

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

View full results

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

TERMINATED

Clinical Phase

PHASE3

Total Enrollment

642 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-12-31

Study Completion Date

2020-04-23

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Multiple Sclerosis

Keywords

Explore important study keywords that can help with search, categorization, and topic discovery.

progressive multiple sclerosis MS EDSS TW25 multiple sclerosis

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

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.
Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

GROUP 1

Placebo capsule, 1 capsule tid (morning,noon and evening) for 15 months and up to 27 months.

Group Type PLACEBO_COMPARATOR

PLACEBO

Intervention Type DRUG

an inactive substance

GROUP 2

MD1003 capsule, 1 capsule tid (morning,noon and evening) for 15 months and up to 27 months.

Group Type EXPERIMENTAL

MD1003 100mg capsule

Intervention Type DRUG

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

MD1003 100mg capsule

Intervention Type DRUG

PLACEBO

an inactive substance

Intervention Type DRUG

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

high dose biotin

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

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
Minimum Eligible Age

18 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

MedDay Pharmaceuticals SA

INDUSTRY

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Responsibility Role SPONSOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Bruce Cree, MD, PHD

Role: PRINCIPAL_INVESTIGATOR

University of California, San Francisco

Frederic Sedel, MD, PHD

Role: STUDY_DIRECTOR

Medday Pharmaceuticals

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Barrow Neurology Clinics (BNC)

Phoenix, Arizona, United States

Site Status

Mayo Clinic Scottsdale

Scottsdale, Arizona, United States

Site Status

Jordan Research And Education Institute Of Alta Bates Summit

Berkeley, California, United States

Site Status

Neuro-Pain Medical Center

Fresno, California, United States

Site Status

University of Southern California Keck School of Medicine

Los Angeles, California, United States

Site Status

MS Center of California

Newport Beach, California, United States

Site Status

UC Davis Health System

Sacramento, California, United States

Site Status

UCSF Multiple Sclerosis Center

San Francisco, California, United States

Site Status

University of Colorado Denver

Aurora, Colorado, United States

Site Status

Yale New Haven Hospital

North Haven, Connecticut, United States

Site Status

Nova Clinical Research, LLC

Bradenton, Florida, United States

Site Status

University of Miami Miller School of Medicine

Miami, Florida, United States

Site Status

University of South Florida - Neurology

Tampa, Florida, United States

Site Status

Northwestern University - Feinberg School of Medicine

Chicago, Illinois, United States

Site Status

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

Chicago, Illinois, United States

Site Status

University of Kansas Medical Center

Kansas City, Kansas, United States

Site Status

Rowe Neurology Institute

Lenexa, Kansas, United States

Site Status

Ochsner Health System

New Orleans, Louisiana, United States

Site Status

The Johns Hopkins Outpatient Center

Baltimore, Maryland, United States

Site Status

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

Boston, Massachusetts, United States

Site Status

Wayne State University - Comp Clinic and MS Center

Detroit, Michigan, United States

Site Status

Minneapolis Clinic of Neurology, LTD

Golden Valley, Minnesota, United States

Site Status

Washington University School of Medicine

St Louis, Missouri, United States

Site Status

Holy Name Hospital

Teaneck, New Jersey, United States

Site Status

The University of New Mexico - Multiple Sclerosis Specialty Clinic

Albuquerque, New Mexico, United States

Site Status

UBMD Neurology

Buffalo, New York, United States

Site Status

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

New York, New York, United States

Site Status

Columbia University Medical Center

New York, New York, United States

Site Status

University of Rochester Medical Center

Rochester, New York, United States

Site Status

State University of New York (SUNY)

Stony Brook, New York, United States

Site Status

Raleigh Neurology Associates, P.A.

Raleigh, North Carolina, United States

Site Status

Cleveland Clinic Mellen Center for MS

Cleveland, Ohio, United States

Site Status

Providence Multiple Sclerosis Center

Portland, Oregon, United States

Site Status

Thomas Jefferson University

Philadelphia, Pennsylvania, United States

Site Status

New Orleans Center for Clinical Research

Knoxville, Tennessee, United States

Site Status

Vanderbilt Comprehensive Multiple Sclerosis Center

Nashville, Tennessee, United States

Site Status

University of Texas Southwestern Medical Center

Dallas, Texas, United States

Site Status

Central Texas Neurology Consultants

Round Rock, Texas, United States

Site Status

University of Virginia Health System

Charlottesville, Virginia, United States

Site Status

Virginia Mason Medical Center

Seattle, Washington, United States

Site Status

Brain and Mind Centre/University of Sydney

Sydney, New South Wales, Australia

Site Status

Austin Hospital

Heidelberg, Victoria, Australia

Site Status

The Royal Melbourne Hospital

Parkville, Victoria, Australia

Site Status

UZ Antwerpen

Edegem, Antwerpen, Belgium

Site Status

Jessa Ziekenhuis - Campus Virga Jesse

Hasselt, Limburg, Belgium

Site Status

UZ Gent

Halle, Oost-Vlaanderen, Belgium

Site Status

Burnaby Hospital

Burnaby, British Columbia, Canada

Site Status

Vancouver Hospital and Health Sciences Centre

Vancouver, British Columbia, Canada

Site Status

Hôpital universitaire Dr George L-Dumont university Hospital

Moncton, New Brunswick, Canada

Site Status

Nova Scotia Rehabilitation Center

Halifax, Nova Scotia, Canada

Site Status

Ottawa Hospital General Campus

Ottawa, Ontario, Canada

Site Status

St. Michael's Hospital

Toronto, Ontario, Canada

Site Status

Hopital de Notre Dame

Montreal, Quebec, Canada

Site Status

Montreal Neurologic Institute

Montreal, Quebec, Canada

Site Status

doc. MUDr. Radomir Talab, CSc., neurologie

Hradec Králové, , Czechia

Site Status

Nemocnice Jihlava

Jihlava, , Czechia

Site Status

Vseobecna fakultni nemocnice v Praze

Prague, , Czechia

Site Status

Fakultni nemocnice v Motole

Prague, , Czechia

Site Status

Nemocnice Teplice

Teplice, , Czechia

Site Status

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

Leipzig, Saxony, Germany

Site Status

Fachkrankenhaus Hubertusburg

Wermsdorf, Saxony, Germany

Site Status

Caritas Krankenhaus

Bad Mergentheim, , Germany

Site Status

Charité - Universitätsmedizin Berlin / NeuroCure Clinical Research Center

Berlin, , Germany

Site Status

Heinrich-Heine-Universität Düsseldorf

Düsseldorf, , Germany

Site Status

Neuro Centrum Science GmbH

Erbach im Odenwald, , Germany

Site Status

MultipEL Studies Institut für klinische Studien GbR

Hamburg, , Germany

Site Status

Ludwig-Maximilians Universität München

München, , Germany

Site Status

Neuropoint GmbH

Ulm, , Germany

Site Status

Poliklinik für Neurologie Universitätsklinikum Ulm

Ulm, , Germany

Site Status

Valeomed Kft

Esztergom, , Hungary

Site Status

Ospedale San Raffaele, IRCCS

Milan, , Italy

Site Status

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

Roma, , Italy

Site Status

Nasz Lekarz Ośrodek Badań Klinicznych

Bydgoszcz, , Poland

Site Status

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

Gdansk, , Poland

Site Status

Twoja Przychodnia Centrum Medyczne Nowa Sol

Nowa Sól, , Poland

Site Status

Centrum Medyczne Pratia Warszawa

Warsaw, , Poland

Site Status

Hospital Santa Caterina

Salt, Girona, Spain

Site Status

Hostipal Universitario Quirónsalud Madrid

Pozuelo de Alarcón, Madrid, Spain

Site Status

Servicio de Neurología Hospital Vithas Nisa Aljarafe

Castilleja de la Cuesta, Sevilla, Spain

Site Status

Hospital del Mar Servicio de Neurología

Barcelona, , Spain

Site Status

Hospital Universitari Vall d'Hebron

Barcelona, , Spain

Site Status

Hospital Clínico San Carlos

Madrid, , Spain

Site Status

Hospital Regional Universitario de Málaga

Málaga, , Spain

Site Status

Sahlgrenska Universitetssjukhus - MS Center forskningsenheten

Gothenburg, , Sweden

Site Status

Karolinska University Hospital - Neurologmottagningen

Stockholm, , Sweden

Site Status

Ondokuz Mayis University Medical Faculty

Samsun, , Turkey (Türkiye)

Site Status

The University of Edinburgh

Edinburgh, , United Kingdom

Site Status

Institute of Neurological Sciences

Glasgow, , United Kingdom

Site Status

Barts And The London School Of Medicine And Dentistry Institute

London, , United Kingdom

Site Status

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

London, , United Kingdom

Site Status

Tyne Hospitals NHS Foundation

Newcastle upon Tyne, , United Kingdom

Site Status

Salford Royal Hospital

Salford, , United Kingdom

Site Status

Countries

Review the countries where the study has at least one active or historical site.

Netherlands United States Australia Belgium Canada Czechia Germany Hungary Italy Poland Spain Sweden Turkey (Türkiye) United Kingdom

References

Explore related publications, articles, or registry entries linked to this study.

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.

Reference Type DERIVED
PMID: 33222767 (View on PubMed)

Provided Documents

Download supplemental materials such as informed consent forms, study protocols, or participant manuals.

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

MD1003CT2016-01MS-SPI2

Identifier Type: -

Identifier Source: org_study_id