Effect of MD1003 in Progressive Multiple Sclerosis (SPI2)

NCT02936037 | Terminated Phase 3 Results DMC

• 1 other identifier: MD1003CT2016-01MS-SPI2
• Study Type: interventional
• Target: 642
• Locations: 13 countries
• Sites: 92

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.

Conditions

Multiple Sclerosis

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Proportion of Patients Improved on Either Expanded Disability Status Scale (EDSS) or Time to Walk 25 Feet (TW25)

  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.

  15 months

Secondary Outcomes (3)

• Time to 12-Weeks Confirmed EDSS Progression

  3 to 27 months

• CGI-I Score (Clinical Global Impression of Change - Improvement), Evaluated Both by the Patient (SGI) and by the Evaluating Physician (CGI)

  15 months

• Mean Change in TW25 Between M0 and M15

  15 months

Other Outcomes (5)

• Brain MRI Changes Between M0 and M15

  15 months

• Remote Monitoring of Ambulation

  27 months

• (MSQOL54) & (CAREQOL-MS) Subscores and Composite Scores

  15 months

Study Arms (2)

GROUP 1

PLACEBO COMPARATOR

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

Drug: PLACEBO

GROUP 2

EXPERIMENTAL

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

Drug: MD1003 100mg capsule

Interventions

MD1003 100mg capsule DRUG

Also known as: high dose biotin

GROUP 2

PLACEBO DRUG

an inactive substance

GROUP 1

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)
• 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"

You may not qualify if:

• 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)
• Patients likely to be non-compliant to the study procedures or for whom a long-term follow-up seems to be difficult to achieve

Sponsors & Collaborators

• MedDay Pharmaceuticals SA: lead

Study Sites (92)

Barrow Neurology Clinics (BNC)

Phoenix, Arizona, 85013, United States

Location

Mayo Clinic Scottsdale

Scottsdale, Arizona, 85259, United States

Location

Jordan Research And Education Institute Of Alta Bates Summit

Berkeley, California, 94705, United States

Location

Neuro-Pain Medical Center

Fresno, California, 93710, United States

Location

University of Southern California Keck School of Medicine

Los Angeles, California, 90033, United States

Location

MS Center of California

Newport Beach, California, 92663, United States

Location

UC Davis Health System

Sacramento, California, 95817, United States

Location

UCSF Multiple Sclerosis Center

San Francisco, California, 94158, United States

Location

University of Colorado Denver

Aurora, Colorado, 80045, United States

Location

Yale New Haven Hospital

North Haven, Connecticut, 06473, United States

Location

Nova Clinical Research, LLC

Bradenton, Florida, 34209, United States

Location

University of Miami Miller School of Medicine

Miami, Florida, 33136, United States

Location

University of South Florida - Neurology

Tampa, Florida, 33612, United States

Location

Northwestern University - Feinberg School of Medicine

Chicago, Illinois, 60611, United States

Location

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

Chicago, Illinois, 60637, United States

Location

University of Kansas Medical Center

Kansas City, Kansas, 66160, United States

Location

Rowe Neurology Institute

Lenexa, Kansas, 66214, United States

Location

Ochsner Health System

New Orleans, Louisiana, 70121, United States

Location

The Johns Hopkins Outpatient Center

Baltimore, Maryland, 21287, United States

Location

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

Boston, Massachusetts, 02115, United States

Location

Wayne State University - Comp Clinic and MS Center

Detroit, Michigan, 48201, United States

Location

Minneapolis Clinic of Neurology, LTD

Golden Valley, Minnesota, 55422, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Holy Name Hospital

Teaneck, New Jersey, 07666, United States

Location

The University of New Mexico - Multiple Sclerosis Specialty Clinic

Albuquerque, New Mexico, 87131, United States

Location

UBMD Neurology

Buffalo, New York, 14203, United States

Location

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

New York, New York, 10029, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

University of Rochester Medical Center

Rochester, New York, 14642, United States

Location

State University of New York (SUNY)

Stony Brook, New York, 11794, United States

Location

Raleigh Neurology Associates, P.A.

Raleigh, North Carolina, 27607, United States

Location

Cleveland Clinic Mellen Center for MS

Cleveland, Ohio, 44195, United States

Location

Providence Multiple Sclerosis Center

Portland, Oregon, 97225, United States

Location

Thomas Jefferson University

Philadelphia, Pennsylvania, 19107, United States

Location

New Orleans Center for Clinical Research

Knoxville, Tennessee, 37920, United States

Location

Vanderbilt Comprehensive Multiple Sclerosis Center

Nashville, Tennessee, 37215, United States

Location

University of Texas Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

Central Texas Neurology Consultants

Round Rock, Texas, 78681, United States

Location

University of Virginia Health System

Charlottesville, Virginia, 22903, United States

Location

Virginia Mason Medical Center

Seattle, Washington, 98101, United States

Location

Brain and Mind Centre/University of Sydney

Sydney, New South Wales, 2050, Australia

Location

Austin Hospital

Heidelberg, Victoria, 3084, Australia

Location

The Royal Melbourne Hospital

Parkville, Victoria, 3050, Australia

Location

UZ Antwerpen

Edegem, Antwerpen, 2650, Belgium

Location

Jessa Ziekenhuis - Campus Virga Jesse

Hasselt, Limburg, 3500, Belgium

Location

UZ Gent

Halle, Oost-Vlaanderen, 9000, Belgium

Location

Burnaby Hospital

Burnaby, British Columbia, V5G 2X6, Canada

Location

Vancouver Hospital and Health Sciences Centre

Vancouver, British Columbia, V6T 2B5, Canada

Location

Hôpital universitaire Dr George L-Dumont university Hospital

Moncton, New Brunswick, E1C 2Z3, Canada

Location

Nova Scotia Rehabilitation Center

Halifax, Nova Scotia, B3H 4K4, Canada

Location

Ottawa Hospital General Campus

Ottawa, Ontario, ON K1H 8L6, Canada

Location

St. Michael's Hospital

Toronto, Ontario, M5B 1W8, Canada

Location

Hopital de Notre Dame

Montreal, Quebec, H2L 4M1, Canada

Location

Montreal Neurologic Institute

Montreal, Quebec, H3A 2B4, Canada

Location

doc. MUDr. Radomir Talab, CSc., neurologie

Hradec Králové, 500 03, Czechia

Location

Nemocnice Jihlava

Jihlava, 586 33, Czechia

Location

Vseobecna fakultni nemocnice v Praze

Prague, 128 21, Czechia

Location

Fakultni nemocnice v Motole

Prague, 150 06, Czechia

Location

Nemocnice Teplice

Teplice, 415 29, Czechia

Location

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

Leipzig, Saxony, 04103, Germany

Location

Fachkrankenhaus Hubertusburg

Wermsdorf, Saxony, 04779, Germany

Location

Caritas Krankenhaus

Bad Mergentheim, 97980, Germany

Location

Charité - Universitätsmedizin Berlin / NeuroCure Clinical Research Center

Berlin, 10117, Germany

Location

Heinrich-Heine-Universität Düsseldorf

Düsseldorf, 40225, Germany

Location

Neuro Centrum Science GmbH

Erbach im Odenwald, 64711, Germany

Location

MultipEL Studies Institut für klinische Studien GbR

Hamburg, 22179, Germany

Location

Ludwig-Maximilians Universität München

München, 81377, Germany

Location

Neuropoint GmbH

Ulm, 89073, Germany

Location

Poliklinik für Neurologie Universitätsklinikum Ulm

Ulm, 89081, Germany

Location

Valeomed Kft

Esztergom, 2500, Hungary

Location

Ospedale San Raffaele, IRCCS

Milan, 20132, Italy

Location

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

Roma, 00189, Italy

Location

Nasz Lekarz Ośrodek Badań Klinicznych

Bydgoszcz, 85-794, Poland

Location

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

Gdansk, 80-803, Poland

Location

Twoja Przychodnia Centrum Medyczne Nowa Sol

Nowa Sól, 67-100, Poland

Location

Centrum Medyczne Pratia Warszawa

Warsaw, 01-868, Poland

Location

Hospital Santa Caterina

Salt, Girona, 17190, Spain

Location

Hostipal Universitario Quirónsalud Madrid

Pozuelo de Alarcón, Madrid, 28223, Spain

Location

Servicio de Neurología Hospital Vithas Nisa Aljarafe

Castilleja de la Cuesta, Sevilla, 41950, Spain

Location

Hospital del Mar Servicio de Neurología

Barcelona, 08003, Spain

Location

Hospital Universitari Vall d'Hebron

Barcelona, 08035, Spain

Location

Hospital Clínico San Carlos

Madrid, 28040, Spain

Location

Hospital Regional Universitario de Málaga

Málaga, 29010, Spain

Location

Sahlgrenska Universitetssjukhus - MS Center forskningsenheten

Gothenburg, 413 45, Sweden

Location

Karolinska University Hospital - Neurologmottagningen

Stockholm, 171 76, Sweden

Location

Ondokuz Mayis University Medical Faculty

Samsun, 55139, Turkey (Türkiye)

Location

The University of Edinburgh

Edinburgh, EH16 4SB, United Kingdom

Location

Institute of Neurological Sciences

Glasgow, G51 4TF, United Kingdom

Location

Barts And The London School Of Medicine And Dentistry Institute

London, E1 2AT, United Kingdom

Location

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

London, WC1N 3BG, United Kingdom

Location

Tyne Hospitals NHS Foundation

Newcastle upon Tyne, NE1 4LP, United Kingdom

Location

Salford Royal Hospital

Salford, M6 8HD, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 33222767 DERIVED

MeSH Terms

Conditions

Multiple Sclerosis; Multiple Sclerosis, Chronic Progressive

Interventions

Biotin

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Coenzymes; Enzymes and Coenzymes

Results Point of Contact

• Title: Dr Frédéric SEDEL, Chief Scientific Officer and Co-founder
• Organization: MedDay Pharmaceuticals

frederic.sedel@medday-pharma.com

+33180401440

Study Officials

• Bruce Cree, MD, PHD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

• Frederic Sedel, MD, PHD

  Medday Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: October 14, 2016
• First Posted: October 18, 2016
• Study Start: December 1, 2016
• Primary Completion: November 15, 2019
• Study Completion: April 23, 2020
• Last Updated: November 23, 2020
• Results First Posted: November 23, 2020

Record last verified: 2020-10

Data Sharing

• IPD Sharing: Will not share

Locations

BE (3); ES (7); SE (2); US (40); TU (1); GB (6); CZ (5); DE (10); CA (8); AU (3); IT (2); PL (4); HU (1)