Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register   allows you to search for protocol and results information on:
  • interventional clinical trials that were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC
  • clinical trials conducted outside the EU/EEA that are linked to European paediatric-medicine development

    • EU/EEA interventional clinical trials approved under or transitioned to the Clinical Trial Regulation 536/2014 are publicly accessible through the
    Clinical Trials Information System (CTIS).

    The EU Clinical Trials Register currently displays   43874   clinical trials with a EudraCT protocol, of which   7293   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

    Phase 1 trials conducted solely on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).  
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Download PDF

    Clinical Trial Results:
    Effect of MD1003 in amyotrophic lateral sclerosis: a randomized, double blind placebo controlled study

    Summary
    EudraCT number
    		 2015-005810-31
    Trial protocol
    		 FR  
    Global end of trial date
    24 May 2018

    Results information
    Results version number
    		 v1(current)
    This version publication date
    15 Aug 2020
    First version publication date
    15 Aug 2020
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    MD1003CT2015-02-ALS
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT03114215
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    MedDay Pharmaceuticals
    Sponsor organisation address
    24-26 rue de la pépinière, PARIS, France,
    Public contact
    Clinical Trial Information, MEDDAY PHARMACEUTICALS, +33 181516666,
    Scientific contact
    Clinical Trial Information, MEDDAY PHARMACEUTICALS, +33 181516666,
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    12 Jun 2017
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    12 Jun 2017
    Global end of trial reached?
    Yes
    Global end of trial date
    24 May 2018
    Was the trial ended prematurely?
    Yes
    General information about the trial
    Main objective of the trial
    Investigation of the safety of biotin in ALS
    Protection of trial subjects
    signature of an ICF at the beginning of the stufy before any assessment.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    29 Jun 2016
    Long term follow-up planned
    Yes
    Long term follow-up rationale
    		 Safety, Efficacy, Ethical reason
    Long term follow-up duration
    		 12 Months
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    France: 30
    Worldwide total number of subjects
    30
    EEA total number of subjects
    30
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    20
    From 65 to 84 years
    10
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 all patients were randomized from the June 29th 2016 to November 15th 2016 at the Principale investigator'site in Montpellier.

    Pre-assignment
    Screening details
    		 all patients screened were randomized in this study. no screen failure.

    Pre-assignment period milestones
    Number of subjects started
    		 30
    Number of subjects completed
    		 30

    Period 1
    Period 1 title
    Double-blind (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Monitor, Data analyst, Carer, Assessor
    Blinding implementation details
    Each product, active or placebo will be conditioned in size one capsules having the same aspect. The capsules will contain the same quantity of white powder, with the same aspect and taste (biotin has no taste). Placebo capsules will thus contain 100 mg more lactose in replacement of biotin.

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Placebo
    Arm description
    		 placebo arm 10 patients in placebo arm
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    300 mg/day (100 mg tid)

    Arm title
    		 active arm
    Arm description
    		 20 patients in the active arm
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Biotin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    300 mg/day (100 mg tid)

    Number of subjects in period 1
    		Placebo active arm
    Started
    10
    20
    Completed
    9
    18
    Not completed
    1
    2
         Adverse event, serious fatal
    1
    2

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Double-blind
    Reporting group description
    		 -

    Reporting group values
    		 Double-blind Total
    Number of subjects
    		 30 30
    Age categorical
    adults patients from 18 to 164 yers
    Units: Subjects
        In utero
    		 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0
        Newborns (0-27 days)
    		 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0
        Children (2-11 years)
    		 0 0
        Adolescents (12-17 years)
    		 0 0
        Adults (18-64 years)
    		 20 20
        From 65-84 years
    		 10 10
        85 years and over
    		 0 0
    Gender categorical
    Units: Subjects
        Female
    		 9 9
        Male
    		 21 21
    Subject analysis sets

    Subject analysis set title
    FAS
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    This population included all randomized patients who received at least one dose of study medication and with at least one assessment at screening or baseline. In case of error in treatment allocation, the actual treatment received was used.

    Subject analysis set title
    SAFETY ANALYSIS SET
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    This population included all patients who received at least one dose of study medication. In case of error in treatment allocation, the actual treatment received was used. This set was used for the safety analyses.

    Subject analysis set title
    PER PROTOCOL
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    This population included all patients of the FAS with an assessment of ALSFRS-R at baseline and at M6 and without major protocol deviations. This set was used in the sensitivity analyses to assess the impact of early death and the impact of protocol deviations.

    Subject analysis sets values
    		 FAS SAFETY ANALYSIS SET PER PROTOCOL
    Number of subjects
    30
    30
    26
    Age categorical
    adults patients from 18 to 164 yers
    Units: Subjects
        In utero
    0
        Preterm newborn infants (gestational age < 37 wks)
    0
        Newborns (0-27 days)
    0
        Infants and toddlers (28 days-23 months)
    0
        Children (2-11 years)
    0
        Adolescents (12-17 years)
    0
        Adults (18-64 years)
    20
        From 65-84 years
    10
        85 years and over
    0
    Age continuous
    Units:
        
    ( )
    ( )
    ( )
    Gender categorical
    Units: Subjects
        Female
    9
        Male
    21

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    Placebo
    Reporting group description
    		 placebo arm 10 patients in placebo arm

    Reporting group title
    active arm
    Reporting group description
    		 20 patients in the active arm

    Subject analysis set title
    FAS
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    This population included all randomized patients who received at least one dose of study medication and with at least one assessment at screening or baseline. In case of error in treatment allocation, the actual treatment received was used.

    Subject analysis set title
    SAFETY ANALYSIS SET
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    This population included all patients who received at least one dose of study medication. In case of error in treatment allocation, the actual treatment received was used. This set was used for the safety analyses.

    Subject analysis set title
    PER PROTOCOL
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    This population included all patients of the FAS with an assessment of ALSFRS-R at baseline and at M6 and without major protocol deviations. This set was used in the sensitivity analyses to assess the impact of early death and the impact of protocol deviations.

    Primary: Safety Primary Endpoint

    		 Close Top of page
    End point title
    		 Safety Primary Endpoint
    End point description
    • Recording of adverse events in the two groups • Laboratory testing (haematology and biochemistry panel) o RBC, WBC, platelets o Ferritin, CPK o Electrolytes, creatinine, glycaemia o AST, ALT, bilirubin, GGT, alkaline phosphatase o Triglyceride, cholesterol o Haemostasis: APPT, PT
    End point type
    Primary
    End point timeframe
    Do reported treatment-emergent adverse events (TEAEs) and serious TEAEs allow to detect a signal of safety concerns in the first 6 months of treatment?
    End point values
    		 Placebo active arm SAFETY ANALYSIS SET
    Number of subjects analysed
    10
    20
    30
    Units: percent
        number (not applicable)
    60
    60
    30
    Statistical analysis title
    		 mann-Whitney U
    Comparison groups
    Placebo v active arm
    Number of subjects included in analysis
    30
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.493
    Method
    		 Wilcoxon (Mann-Whitney)
    Confidence interval

    Secondary: Motor disability: ALSFRS-R scale

    		 Close Top of page
    End point title
    		 Motor disability: ALSFRS-R scale
    End point description
    End point type
    Secondary
    End point timeframe
    6 months
    End point values
    		 Placebo active arm FAS
    Number of subjects analysed
    10
    20
    30
    Units: score
        median (inter-quartile range (Q1-Q3))
    -2.5 (-8.0 to -1.0)
    -4.0 (-10.0 to -2.0)
    -3.5 (-8.0 to -1.0)
    No statistical analyses for this end point

    Secondary: Disease severity - Severity score

    		 Close Top of page
    End point title
    		 Disease severity - Severity score
    End point description
    End point type
    Secondary
    End point timeframe
    6 months
    End point values
    		 Placebo active arm FAS
    Number of subjects analysed
    10
    20
    30
    Units: score
        median (standard deviation)
    -5.500 ( 7.990 )
    -7.100 ( 8.265 )
    -1.600 ( 7.900 )
    No statistical analyses for this end point

    Secondary: Respiratory parameters - Slow vital capacity (SVC)

    		 Close Top of page
    End point title
    		 Respiratory parameters - Slow vital capacity (SVC)
    End point description
    End point type
    Secondary
    End point timeframe
    6 Months
    End point values
    		 Placebo active arm FAS
    Number of subjects analysed
    0 [1]
    0 [2]
    30
    Units: mean
        arithmetic mean (standard error)
    ( )
    ( )
    4.24 ( 7.50 )
    Notes
    [1] - This analyse is not performed per reporting group (MD1003 / placebo). Only overall is available.
    [2] - This analyse is not performed per reporting group (MD1003 / placebo). Only overall is available.
    No statistical analyses for this end point

    Secondary: Respiratory parameters - maximal inspiratory pressure (MIP)

    		 Close Top of page
    End point title
    		 Respiratory parameters - maximal inspiratory pressure (MIP)
    End point description
    End point type
    Secondary
    End point timeframe
    6 Months
    End point values
    		 Placebo active arm FAS
    Number of subjects analysed
    0 [3]
    0 [4]
    30
    Units: MEAN
        arithmetic mean (standard error)
    ( )
    ( )
    4.91 ( 8.12 )
    Notes
    [3] - This analyse is not performed per reporting group (MD1003 / placebo). Only overall is available.
    [4] - This analyse is not performed per reporting group (MD1003 / placebo). Only overall is available.
    No statistical analyses for this end point

    Secondary: Respiratory parameters - sniff nasal inspiratory pressure (SNIP)

    		 Close Top of page
    End point title
    		 Respiratory parameters - sniff nasal inspiratory pressure (SNIP)
    End point description
    End point type
    Secondary
    End point timeframe
    6 months
    End point values
    		 Placebo active arm FAS
    Number of subjects analysed
    0 [5]
    0 [6]
    30
    Units: MEAN
        arithmetic mean (standard error)
    ( )
    ( )
    12.78 ( 7.45 )
    Notes
    [5] - This analyse is not performed per reporting group (MD1003 / placebo). Only overall is available.
    [6] - This analyse is not performed per reporting group (MD1003 / placebo). Only overall is available.
    No statistical analyses for this end point

    Secondary: Weight

    		 Close Top of page
    End point title
    		 Weight
    End point description
    End point type
    Secondary
    End point timeframe
    6 months
    End point values
    		 Placebo active arm FAS
    Number of subjects analysed
    0 [7]
    0 [8]
    30
    Units: mean
        arithmetic mean (standard error)
    ( )
    ( )
    -1.63 ( 1.29 )
    Notes
    [7] - This analyse is not performed per reporting group (MD1003 / placebo). Only overall is available.
    [8] - This analyse is not performed per reporting group (MD1003 / placebo). Only overall is available.
    No statistical analyses for this end point

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    at each visit
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    19.0
    Reporting groups
    Reporting group title
    Placebo
    Reporting group description
    		 placebo arm 10 patients in placebo arm

    Reporting group title
    active arm
    Reporting group description
    		 20 patients in the active arm

    Serious adverse events
    		 Placebo active arm
    Total subjects affected by serious adverse events
         subjects affected / exposed
    2 / 10 (20.00%)
    4 / 20 (20.00%)
         number of deaths (all causes)
    1
    2
         number of deaths resulting from adverse events
    1
    2
    Injury, poisoning and procedural complications
    Fall
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 20 (5.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Surgical and medical procedures
    Gastrostomy
         subjects affected / exposed
    0 / 10 (0.00%)
    2 / 20 (10.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    Cardiac disorders
    Cardiac arrest
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    Myocardial infarction
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ear and labyrinth disorders
    Vertigo
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 20 (5.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Acute respiratory failure
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 20 (5.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    Frequency threshold for reporting non-serious adverse events: 0%
    Non-serious adverse events
    		 Placebo active arm
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    6 / 10 (60.00%)
    12 / 20 (60.00%)
    Vascular disorders
    Hypertension
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 20 (5.00%)
         occurrences all number
    0
    1
    Orthostatic hypotension
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 20 (5.00%)
         occurrences all number
    0
    1
    Surgical and medical procedures
    Gastrostomy
         subjects affected / exposed
    0 / 10 (0.00%)
    2 / 20 (10.00%)
         occurrences all number
    0
    2
    Hip arthroplasty
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 20 (5.00%)
         occurrences all number
    0
    1
    Respiratory, thoracic and mediastinal disorders
    Acute respiratory failure
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 20 (5.00%)
         occurrences all number
    0
    1
    Psychiatric disorders
    Anxiety
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 20 (5.00%)
         occurrences all number
    0
    1
    Injury, poisoning and procedural complications
    Fall
         subjects affected / exposed
    1 / 10 (10.00%)
    2 / 20 (10.00%)
         occurrences all number
    1
    2
    Cardiac disorders
    Cardiac arrest
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 20 (0.00%)
         occurrences all number
    1
    0
    Myocardial infarction
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 20 (0.00%)
         occurrences all number
    1
    0
    Nervous system disorders
    Complex regional pain syndrome
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 20 (5.00%)
         occurrences all number
    1
    1
    Restless legs syndrome
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 20 (5.00%)
         occurrences all number
    0
    1
    Presyncope
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 20 (0.00%)
         occurrences all number
    1
    0
    Ear and labyrinth disorders
    Vertigo
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 20 (5.00%)
         occurrences all number
    0
    1
    Skin and subcutaneous tissue disorders
    Erythema
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 20 (5.00%)
         occurrences all number
    0
    1
    Rash maculo-papular
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 20 (5.00%)
         occurrences all number
    0
    1
    Renal and urinary disorders
    Urinary retention
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 20 (5.00%)
         occurrences all number
    0
    1
    Musculoskeletal and connective tissue disorders
    Tendonitis
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 20 (0.00%)
         occurrences all number
    1
    0
    Infections and infestations
    Bronchitis
         subjects affected / exposed
    1 / 10 (10.00%)
    1 / 20 (5.00%)
         occurrences all number
    1
    1
    Urinary tract infection
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 20 (5.00%)
         occurrences all number
    0
    1
    Metabolism and nutrition disorders
    Hypertriglyceridaemia
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 20 (0.00%)
         occurrences all number
    1
    0

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    24 Jun 2016
    change of factory for the secondary packaging and labelling.
    14 Apr 2017
    addition of 12 months of open label extension

    Interruptions (globally)
    Were there any global interruptions to the trial? No

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported

    Online references
    http://www.ncbi.nlm.nih.gov/pubmed/32140672
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

    European Medicines Agency © 1995-Wed May 08 23:17:29 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA