Effect of MD1003 in Progressive Multiple Sclerosis (SPI2)

Multiple Sclerosis Clinical Trial

— SPI2  

Official title:

Effect of MD1003 in Progressive Multiple Sclerosis: a Randomized Double Blind Placebo Controlled Study

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02936037
• Other study ID #: MD1003CT2016-01MS-SPI2
• Status: Terminated
• Phase: Phase 3
• Start date: December 2016
• Est. completion date: April 23, 2020

Study information

• Verified date: October 2020
• Source: MedDay Pharmaceuticals SA
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 642
• Est. completion date: April 23, 2020
• Est. primary completion date: November 15, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Multiple Sclerosis
• Multiple Sclerosis, Chronic Progressive
• Sclerosis

Intervention

Drug:
• MD1003 100mg capsule

• PLACEBO
an inactive substance

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
MedDay Pharmaceuticals SA

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Canada,  Czechia,  Germany,  Hungary,  Italy,  Poland,  Spain,  Sweden,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Brain MRI Changes Between M0 and M15		15 months
Other	Remote Monitoring of Ambulation		27 months
Other	(MSQOL54) & (CAREQOL-MS) Subscores and Composite Scores		15 months
Other	Subscores of the Kurtzke Functional Score		15 months
Other	Symbol Digit Modalities Test (SDMT)		15 months
Primary	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	Time to 12-Weeks Confirmed EDSS Progression	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.	3 to 27 months
Secondary	CGI-I Score (Clinical Global Impression of Change - Improvement), Evaluated Both by the Patient (SGI) and by the Evaluating Physician (CGI)		15 months
Secondary	Mean Change in TW25 Between M0 and M15		15 months

External Links

•   Sponsor