Effect of MD1003 in progressive multiple sclerosis with walking impairment

• Register: EUCTR
• Last refreshed on: 28 September 2020
• Main ID: EUCTR2016-000700-29-DE
• Date of registration: 16/11/2016
• Prospective Registration: Yes
• Primary sponsor: MEDDAY PHARMACEUTICALS SA
• Public title: Effect of MD1003 in progressive multiple sclerosis with walking impairment
• Scientific title: Effect of MD1003 in progressive multiple sclerosis: a randomized double-blind placebo-controlled study. - SPI2
• Date of first enrolment: 08/03/2017
• Target sample size: 754
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2016-000700-29
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: yes; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: yes; Other: no; Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Australia, Belgium, Canada, Czech Republic, Germany, Hungary, Italy, Netherlands, Poland, Spain, Sweden, Turkey, United Kingdom, United States

Contacts

• Name: Clinical Trials Information Desk
• Affiliation: Medday Pharmaceuticals

• Name: Clinical Trials Information Desk
• Affiliation: Medday Pharmaceuticals

Key inclusion & exclusion criteria

Inclusion criteria:
1. Patient aged 18-65 years old
2. Signed and dated written informed consent form in accordance with local regulations: having freely given their written informed consent to participate in the study
3. Diagnosis of primary or secondary progressive MS fulfilling revised McDonald criteria (2010) and Lublin criteria (2014)
4. 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
5. EDSS at inclusion from 3.5 to 6.5
6. TW25 < 40 seconds
7. 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”

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 745
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 9

Exclusion criteria:
1. Clinical evidence of a relapse in 24 months prior to inclusion
2. Treatment with any product containing biotin as single ingredient within six months prior to inclusion (multivitamin supplementation authorized if biotin < 1mg per day)
3. Concomitant treatment with fampridine at inclusion or in the 30 days prior to inclusion
4. New immunosuppressive/immunomodulatory drug initiated less than 90 days prior to inclusion
5. Treatment with botulinium toxin (except for cosmetic purpose) initiated within 6 months prior to inclusion
6. In-patient rehabilitation program within the 3 months prior to inclusion
7. Pregnancy, breastfeeding or women with childbearing potential without acceptable form of contraception
8. Men unwilling to use an acceptable form of contraception
9. Any general chronic handicapping/incapacitating disease other than MS
10. Any serious disease necessitating biological follow-up with biological tests using biotinylated antibodies or substrates
11. Past history of rhabdomyolysis/metabolic myopathy
12. Known fatty acids beta oxidation defect
13. 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
14. Patients with hypersensitivity or any contra-indication to Gadolinium
15. Patients with uncontrolled hepatic disorder, renal or cardiovascular disease, or cancer
16. Laboratory tests out of normal ranges considered by the investigator as clinically significant with regards to the study continuation
17. Patients with history or presence of alcohol abuse or drug addiction
18. Untreated or uncontrolled psychiatric disorders, especially suicidal risk assessed by Columbia-Suicide Severity Rating Scale (C-SSRS)
19. Participation in another research study involving an investigational product (IP) in the 90 days prior to inclusion, or planned use during the study duration
20. Patients likely to be non-compliant to the study procedures or for whom a long-term follow-up seems to be difficult to achieve
21. Relapse that occurs between inclusion and randomization visit


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Multiple sclerosis
MedDRA version: 20.1 Level: PT Classification code 10028245 Term: Multiple sclerosis System Organ Class: 10029205 - Nervous system disorders

Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

Intervention(s)

Product Name: D-Biotin
Product Code: MD1003
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: D-BIOTIN
CAS Number: 58-85-5
Current Sponsor code: MD1003
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

Primary Outcome(s)

Secondary Objective: To evaluate the safety of MD1003

Main Objective: To demonstrate the superiority of MD1003, 300 mg/day, over placebo to clinically improve patients with progressive multiple sclerosis (MS).

Primary end point(s): Primary efficacy endpoint:
Proportions of patients:
- 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 M12 and M15

The baseline score for EDSS will be the lowest (best) value obtained during either the inclusion or randomization visit.
The baseline value for TW25 will be the best mean of the 2 scores
obtained at either the inclusion or randomization visit (the lowest mean between the 2 visits).

The TW25 value at visit M12 and M15 is defined as the mean of the two TW25 attempts at each visit.

Timepoint(s) of evaluation of this end point: - month 12 and 15

Secondary Outcome(s)

Secondary end point(s): Secondary efficacy endpoints
1. Time to EDSS progression confirmed at 12 weeks
2. Mean difference between treatment arms in CGI at M15;
3. Mean difference between treatment arms in SGI at M15;
4. Mean change in TW25 between M0 and M15
5. Mean change in TW25 score between M0 and the last visit in doubleblind phase of any particular patient (M15, M18, M21, M24 or M27 or Early Termination).


Exploratory endpoints
- 1. Brain MRI measuresments will assess the following endpoints between M0 and M15 (and between M0 and M27 and every year until the end of the study)
a. Percent whole brain volume
b. Percent thalamic volume
c. Percent cortical grey matter volume
d. Brain water content evaluated by Pseudo T2 relaxation time
e. NAA/Cr in a subset of sites acquiring MRS

2. Remote monitoring of ambulation
3. Multiple Sclerosis Quality of Life-54 (MSQOL54) and Caregiver health-related quality of life in Multiple Sclerosis (CAREQOL-MS) subscores and composite scores
4. Subscores of the Kurtzke functional score
5. Symbol digit modalities test (SDMT)

Safety evaluation
a. Recording of AEs
b. Laboratory testing (standard hematology and biochemistry panel)
c. ECG: PR, QRS, QT and RR interval, HR and QTcF, wave morphology, rhythm and conduction
d. Brain MRI: new or enlarging T2 lesions and Gd+ lesions
e. Columbia-Suicide Severity Rating Scale

Timepoint(s) of evaluation of this end point: Week 12, Month 15, Month 27, the last visit in double-blind phase (M15,
M18, M21, M24 or M27 or Early Termination)

Secondary ID(s)

NCT02936037

MD1003CT2016-01MS-SPI2

2016-000700-29-CZ

Source(s) of Monetary Support

Medday pharmaceuticals SA

Ethics review

Status: Approved
Approval date: 01/02/2017
Contact: