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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02936037




Registration number
NCT02936037
Ethics application status
Date submitted
14/10/2016
Date registered
18/10/2016
Date last updated
23/11/2020

Titles & IDs
Public title
Effect of MD1003 in Progressive Multiple Sclerosis (SPI2)
Scientific title
Effect of MD1003 in Progressive Multiple Sclerosis: a Randomized Double Blind Placebo Controlled Study
Secondary ID [1] 0 0
MD1003CT2016-01MS-SPI2
Universal Trial Number (UTN)
Trial acronym
SPI2
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Multiple Sclerosis 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - PLACEBO

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

Experimental: GROUP 2 - MD1003 capsule, 1 capsule tid (morning,noon and evening) for 15 months and up to 27 months.


Treatment: Drugs: PLACEBO
an inactive substance
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Proportion of Patients Improved on Either Expanded Disability Status Scale (EDSS) or Time to Walk 25 Feet (TW25)
Timepoint [1] 0 0
15 months
Secondary outcome [1] 0 0
Time to 12-Weeks Confirmed EDSS Progression
Timepoint [1] 0 0
3 to 27 months
Secondary outcome [2] 0 0
CGI-I Score (Clinical Global Impression of Change - Improvement), Evaluated Both by the Patient (SGI) and by the Evaluating Physician (CGI)
Timepoint [2] 0 0
15 months
Secondary outcome [3] 0 0
Mean Change in TW25 Between M0 and M15
Timepoint [3] 0 0
15 months

Eligibility
Key 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"
Minimum age
18 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/12/2016
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
23/04/2020
Sample size
Target
Accrual to date
Final
642
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 0 0
Brain and Mind Centre/University of Sydney - Sydney
Recruitment hospital [2] 0 0
Austin Hospital - Heidelberg
Recruitment hospital [3] 0 0
The Royal Melbourne Hospital - Parkville
Recruitment postcode(s) [1] 0 0
2050 - Sydney
Recruitment postcode(s) [2] 0 0
3084 - Heidelberg
Recruitment postcode(s) [3] 0 0
3050 - Parkville
Recruitment outside Australia
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Arizona
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California
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Czechia
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Hradec Králové
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Czechia
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Jihlava
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Czechia
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Praha
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Teplice
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Germany
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Berlin
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Erbach
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Ulm
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Esztergom
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Milano
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Roma
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Gdansk
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Nowa Sol
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Girona
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Stockholm
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Turkey
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Samsun
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Edinburgh
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Glasgow
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London
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Newcastle upon Tyne
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United Kingdom
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Salford

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
MedDay Pharmaceuticals SA
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/study/NCT02936037
Trial related presentations / publications
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.
Public notes

Contacts
Principal investigator
Name 0 0
Bruce Cree, MD, PHD
Address 0 0
University of California, San Francisco
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT02936037