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   44334   clinical trials with a EudraCT protocol, of which   7366   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:
    Open-label, Non-randomised Extension Trial to Assess the Long-Term Safety and Efficacy of 1200 mg/day Arimoclomol 400 mg Three Times a Day (t.i.d.) in Subjects with Amyotrophic Lateral Sclerosis (ALS) who have Completed the ORARIALS-01 Trial

    Summary
    EudraCT number
    		 2019-000374-39
    Trial protocol
    		 GB   SE   BE   PL   DE   NL   ES   IT  
    Global end of trial date
    11 May 2021

    Results information
    Results version number
    		 v1(current)
    This version publication date
    16 Oct 2024
    First version publication date
    16 Oct 2024
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    ORARIALS-02
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT03836716
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Zevra Denmark A/S
    Sponsor organisation address
    Nordre Fasanvej 215, Frederiksberg, Denmark, 2000
    Public contact
    Medical Affairs, Zevra Denmark A/S, +1 8882895607, medicalaffairs@zevra.com
    Scientific contact
    Medical Affairs, Zevra Denmark A/S, +1 8882895607, medicalaffairs@zevra.com
    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
    05 Jan 2022
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    11 May 2021
    Was the trial ended prematurely?
    Yes
    General information about the trial
    Main objective of the trial
    A multicenter, non-randomized, open label trial, to assess long term safety and efficacy of Arimoclomol in subjects with Amyotrophic Lateral Sclerosis (ALS) who have completed the ORARIALS-01 trial. The planned duration of the open-label trial was 152 weeks, but the trial was terminated early as a consequence of the results of ORARIALS-01 which did not meet any of its efficacy endpoints. Therefore, the actual mean duration of open-label treatment was approximately 28 weeks (range approximately 2 to 71 weeks).
    Protection of trial subjects
    Trial were conducted in accordance with their protocol and with the following: • Consensus ethical principles derived from international guidelines including the current version of the Declaration of Helsinki and Council for International Organizations of Medical Sciences International Ethical Guidelines. • Current version of applicable ICH GCP guidelines. • Applicable laws and regulations.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    01 May 2019
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Netherlands: 10
    Country: Number of subjects enrolled
    Poland: 15
    Country: Number of subjects enrolled
    Spain: 15
    Country: Number of subjects enrolled
    Sweden: 5
    Country: Number of subjects enrolled
    United Kingdom: 2
    Country: Number of subjects enrolled
    Belgium: 5
    Country: Number of subjects enrolled
    France: 17
    Country: Number of subjects enrolled
    Germany: 7
    Country: Number of subjects enrolled
    Italy: 14
    Country: Number of subjects enrolled
    United States: 28
    Country: Number of subjects enrolled
    Canada: 2
    Worldwide total number of subjects
    120
    EEA total number of subjects
    88
    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)
    86
    From 65 to 84 years
    34
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 Roll-over of 120 subjects who completed the ORARIALS 01 trial (i.e., met one of the surrogate survival endpoints of tracheostomy or PAV or has completed the 76 weeks randomized treatment period).

    Pre-assignment
    Screening details
    		 Screening was up to 4 weeks prior to Baseline if a washout period for an investigational treatment was required and to allow for laboratory re-tests (if required). Patients excluded with cilinically significant renal or hepatic disease OR clinical laboratory assessment.

    Period 1
    Period 1 title
    Overall trial (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Not applicable
    Blinding used
    		 Not blinded
    Blinding implementation details
    Open-label extension.

    Arms
    Arm title
    		 Arimoclomol (Open-label)
    Arm description
    		 248 mg arimoclomol base 3 times daily
    Arm type
    		 Experimental

    Investigational medicinal product name
    Arimoclomol
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule, hard
    Routes of administration
    Oral use
    Dosage and administration details
    Arimoclomol 2 × 124 mg capsules were taken orally t.i.d.

    Number of subjects in period 1
    		Arimoclomol (Open-label)
    Started
    120
    Completed
    0
    Not completed
    120
         Adverse event, serious fatal
    22
         Consent withdrawn by subject
    8
         Adverse event, non-fatal
    3
         Study terminated by sponsor
    87

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Overall trial
    Reporting group description
    		 -

    Reporting group values
    		 Overall trial Total
    Number of subjects
    		 120 120
    Age categorical
    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)
    		 86 86
        From 65-84 years
    		 34 34
        85 years and over
    		 0 0
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 57.6 ( 10.30 ) -
    Gender categorical
    Units: Subjects
        Female
    		 36 36
        Male
    		 84 84

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    Arimoclomol (Open-label)
    Reporting group description
    		 248 mg arimoclomol base 3 times daily

    Primary: Number of Participants with Treatment-emergent Adverse Events (TEAEs) Over the Open-label Treatment Period

    		 Close Top of page
    End point title
    		 Number of Participants with Treatment-emergent Adverse Events (TEAEs) Over the Open-label Treatment Period [1]
    End point description
    Adverse event (AE) data were collected throughout the trial until early termination. The average duration of exposure was 198.7 days (approximately 28 weeks; standard deviation 99.57 days; minimum 16 days, maximum 494 days). 58 participants (48.3%) were exposed less than 6 months; 55 participants (45.8%) were exposed 6 to less than 12 months; 7 participants (5.8%) were exposed 12 to less than 18 months. No participant was treated for 76 weeks. Participants with on-treatment TEAEs are reported. An on-treatment TEAE is any TEAE in the on-treatment period defined as the time from first dose of IMP until 14 days since the last preceding administration of IMP (either before a temporary IMP interruption with duration >14 days or the last dose at the end of trial). A participant may have several on-treatment periods separated by interruption intervals.
    End point type
    Primary
    End point timeframe
    From Day 1 in ORARIALS-02 to Early Termination, an average of approximately 28 weeks
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Early termination of trial.
    End point values
    		 Arimoclomol (Open-label)
    Number of subjects analysed
    120
    Units: Participants
        Mild TEAEs
    34
        Moderate TEAEs
    44
        Severe TEAEs
    15
        Treatment-related TEAEs
    31
        Probably related TEAEs
    9
        Possibly related TEAEs
    22
        Not related TEAEs
    62
        Serious TEAEs (SAEs)
    21
        Treatment-related serious TEAEs
    1
        TEAEs leading to IMP withdrawal
    9
        TEAEs leading to IMP interruption
    12
        Treatment-emergent adverse events (TEAEs)
    93
    No statistical analyses for this end point

    Primary: Mean and Change from Baseline in Clinical Safety Laboratory Tests - Hematology (1)

    		 Close Top of page
    End point title
    		 Mean and Change from Baseline in Clinical Safety Laboratory Tests - Hematology (1) [2]
    End point description
    Standard hematology parameters. White blood cell differential count for basophils, eosinophils, leukocytes, lymphocytes, monocytes, and neutrophils, and platelet count. Data only available for 2 participants at Week 76 since the trial was terminated early by the sponsor as a consequence of the results of ORARIALS-01 which did not meet any of its efficacy endpoints.
    End point type
    Primary
    End point timeframe
    Week 76
    Notes
    [2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Early termination of trial.
    End point values
    		 Arimoclomol (Open-label)
    Number of subjects analysed
    2
    Units: 10^9 cells/L
    arithmetic mean (standard deviation)
        Basophils, Week 76 *Mean (Standard Deviation) | Un
    0.030 ( 0.0000 )
        Basophils, change from baseline to Week 76*
    -0.015 ( 0.0071 )
        Eosinophils, Week 76*
    0.150 ( 0.0071 )
        Eosinophils, change from baseline to Week 76*
    -0.070 ( 0.0424 )
        Leukocytes, Week 76*
    9.120 ( 3.1537 )
        Leukocytes, change from baseline to Week 76*
    -0.565 ( 2.4395 )
        Lymphocytes, Week 76*
    1.445 ( 0.4738 )
        Lymphocytes, change from baseline to Week 76*
    -0.365 ( 0.3041 )
        Monocytes, Week 76*
    0.460 ( 0.1414 )
        Monocytes, change from baseline to Week 76*
    -0.055 ( 0.0212 )
        Neutrophils, Segmented, Week 76*
    7.030 ( 3.4648 )
        Neutrophils, Segmented, change from baseline to We
    -0.070 ( 2.8001 )
        Platelets, Week 76*
    334.0 ( 114.55 )
        Platelets, change from baseline to Week 76*
    62.5 ( 103.94 )
    No statistical analyses for this end point

    Primary: Mean and Change from Baseline in Clinical Safety Laboratory Tests - Hematology (2)

    		 Close Top of page
    End point title
    		 Mean and Change from Baseline in Clinical Safety Laboratory Tests - Hematology (2) [3]
    End point description
    Standard hematology parameters. White blood cell differential count for basophils, eosinophils, leukocytes, lymphocytes, monocytes, and neutrophils, and platelet count. Data only available for 2 participants at Week 76 since the trial was terminated early by the sponsor as a consequence of the results of ORARIALS-01 which did not meet any of its efficacy endpoints.
    End point type
    Primary
    End point timeframe
    Week 76
    Notes
    [3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Early termination of trial.
    End point values
    		 Arimoclomol (Open-label)
    Number of subjects analysed
    2
    Units: percentage of leukocytes
    arithmetic mean (standard deviation)
        Basophils/Leukocytes
    0.40 ( 0.141 )
        Basophils/Leukocytes, change from baseline
    -0.05 ( 0.212 )
        Eosinophils/Leukocytes
    1.70 ( 0.424 )
        Eosinophils/Leukocytes, change from baseline
    -0.50 ( 0.849 )
        Lymphocytes/Leukocytes
    17.85 ( 11.384 )
        Lymphocytes/Leukocytes, change from baseline
    -0.95 ( 8.132 )
        Monocytes/Leukocytes
    5.05 ( 0.212 )
        Monocytes/Leukocytes, change from baseline
    -0.20 ( 1.556 )
        Neutrophils/Leukocytes
    74.95 ( 12.092 )
        Neutrophils/Leukocytes, change from baseline
    1.70 ( 10.607 )
    No statistical analyses for this end point

    Primary: Mean and Change from Baseline in Clinical Safety Laboratory Tests- Erthrocytes

    		 Close Top of page
    End point title
    		 Mean and Change from Baseline in Clinical Safety Laboratory Tests- Erthrocytes [4]
    End point description
    Standard hematology parameters. Percentage of leukocytes were determined for basophils, eosinophils, lymphocytes, monocytes, and neutrophils. Data only available for 2 participants at Week 76 since the trial was terminated early by the sponsor as a consequence of the results of ORARIALS-01 which did not meet any of its efficacy endpoints.
    End point type
    Primary
    End point timeframe
    Week 76
    Notes
    [4] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Early termination of trial.
    End point values
    		 Arimoclomol (Open-label)
    Number of subjects analysed
    2
    Units: 10^12 cells/L
    arithmetic mean (standard deviation)
        Erythrocytes
    3.70 ( 0.000 )
        Erythrocytes, change from baseline
    -0.40 ( 0.707 )
    No statistical analyses for this end point

    Primary: Mean and Change from Baseline in Clinical Safety Laboratory Tests - Hematocrit

    		 Close Top of page
    End point title
    		 Mean and Change from Baseline in Clinical Safety Laboratory Tests - Hematocrit [5]
    End point description
    Standard hematology parameter. Data only available for 2 participants at Week 76 since the trial was terminated early by the sponsor as a consequence of the results of ORARIALS-01 which did not meet any of its efficacy endpoints.
    End point type
    Primary
    End point timeframe
    Week 76
    Notes
    [5] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Early termination of trial.
    End point values
    		 Arimoclomol (Open-label)
    Number of subjects analysed
    2
    Units: L of cells / L of blood
    arithmetic mean (standard deviation)
        Hematocrit
    0.345 ( 0.0071 )
        Hematocrit, change from baseline
    -0.025 ( 0.0636 )
    No statistical analyses for this end point

    Primary: Mean and Change from Baseline in Clinical Safety Laboratory Tests - Hemoglobin

    		 Close Top of page
    End point title
    		 Mean and Change from Baseline in Clinical Safety Laboratory Tests - Hemoglobin [6]
    End point description
    End point type
    Primary
    End point timeframe
    Week 76
    Notes
    [6] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Early termination of trial.
    End point values
    		 Arimoclomol (Open-label)
    Number of subjects analysed
    2
    Units: g/L
    arithmetic mean (standard deviation)
        Hemoglobin
    115.5 ( 3.54 )
        Hemoglobin, change from baseline
    -14.0 ( 21.21 )
    No statistical analyses for this end point

    Primary: Mean and Change from Baseline in Clinical Safety Laboratory Tests - Cystatin C

    		 Close Top of page
    End point title
    		 Mean and Change from Baseline in Clinical Safety Laboratory Tests - Cystatin C [7]
    End point description
    Standard clinical chemistry parameter. Data only available for 2 participants at Week 76 since the trial was terminated early by the sponsor as a consequence of the results of ORARIALS-01 which did not meet any of its efficacy endpoints.
    End point type
    Primary
    End point timeframe
    Week 76
    Notes
    [7] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Early termination of trial.
    End point values
    		 Arimoclomol (Open-label)
    Number of subjects analysed
    2
    Units: mg/L
    arithmetic mean (standard deviation)
        Cystatin C
    1.310 ( 0.7495 )
        Cystatin C, change from baseline
    0.350 ( 0.6364 )
    No statistical analyses for this end point

    Primary: Number of Participants with potentially clinically significant abnormalities in Clinical Safety Laboratory Tests and Vital Signs Over the Open-Label Treatment Period

    		 Close Top of page
    End point title
    		 Number of Participants with potentially clinically significant abnormalities in Clinical Safety Laboratory Tests and Vital Signs Over the Open-Label Treatment Period [8]
    End point description
    Clinical safety laboratory data and vital signs were collected throughout the trial until early termination. The average duration of exposure was 198.7 days (approximately 28 weeks; standard deviation 99.57 days; minimum 16 days, maximum 494 days). 58 participants (48.3%) were exposed less than 6 months; 55 participants (45.8%) were exposed 6 to less than 12 months; 7 participants (5.8%) were exposed 12 to less than 18 months. No patient was treated for 76 weeks. Safety analysis set: All enrolled patients that received at least one dose of arimoclomol.
    End point type
    Primary
    End point timeframe
    From Day 1 in ORARIALS-02 to Early Termination, an average of approximately 28 weeks
    Notes
    [8] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Early termination of trial.
    End point values
    		 Arimoclomol (Open-label)
    Number of subjects analysed
    120 [9]
    Units: Participants
    number (not applicable)
        Hemoglobin (g/​L) <= 95 (Females) <= 115 (Males)
    10
        Hemoglobin (g/​L) >= 165 (Females), >= 185 (Males)
    0
        Erythrocytes (10^12/​L) <= 3.5 (F), <= 3.8 (M)
    16
        Erythrocytes (10^12/​L) >= 6.0 (F), >= 7.0 (M)
    0
        Hematocrit <= 0.32 (Females), <= 0.37 (Males)
    21
        Hematocrit >= 0.5 (Females), >= 0.55 (Males)
    0
        Leukocytes (10^9/​L) <= 2.8
    0
        Leukocytes (10^9/​L) >= 16
    3
        Neutrophils/​Leukocytes (%) <= 20
    0
        Neutrophils/​Leukocytes (%) >= 85
    3
        Eosinophils/​Leukocytes (%) >= 10
    1
        Basophils/​Leukocytes (%) >= 10
    0
        Lymphocytes/​Leukocytes (%) <= 10
    6
        Lymphocytes/​Leukocytes (%) >= 75
    0
        Monocytes/​Leukocytes (%) >= 15
    0
        Platelets (10^9/​L) <= 75
    0
        Platelets (10^9/​L) >= 600
    0
        Aspartate Aminotransferase (U/​L) >= 3 x ULN
    0
        Alanine Aminotransferase (U/​L) >= 3 x ULN
    7
        Bilirubin (umol/​L) >= 34
    2
        Direct Bilirubin (umol/​L) >= 12
    0
        Indirect Bilirubin (umol/​L) >= 22
    4
        Alkaline Phosphatase (U/​L) >= 3 x ULN
    1
        Gamma Glutamyl Transferase (U/​L) >= 200
    4
        Creatinine (umol/​L) >= 1.5 x ULN
    1
        Urea Nitrogen (mmol/​L) >= 11
    7
        Sodium (mmol/​L) <= 125
    2
        Sodium (mmol/​L) >= 155
    1
        Potassium (mmol/​L) <= 3.0
    4
        Potassium (mmol/​L) >= 6.0
    0
        Calcium (mmol/​L) <= 1.8
    0
        Calcium (mmol/​L) >= 3.0
    2
        Glucose (mmol/​L) <= 3.9 (Fasting=No or blank)
    8
        Glucose (mmol/​L) >= 11.1 (Fasting=No or blank)
    7
        Glucose (mmol/​L) <= 3.5 (Fasting=Yes)
    0
        Glucose (mmol/​L) >= 7.0 (Fasting=Yes)
    7
        Protein (g/​L) <= 45
    1
        Protein (g/​L) >= 95
    0
        Albumin (g/​L) <= 27
    2
        Cholesterol (mmol/​L) >= 7.8 (Fasting=No or blank)
    15
        Cholesterol (mmol/​L) >= 6.2 (Fasting=Yes)
    15
        Triglycerides (mmol/​L) >= 5.65 (Fasting=No/blank)
    6
        Triglycerides (mmol/​L) >= 4.2 (Fasting=Yes)
    3
        LDL Cholesterol (mmol/​L) >= 5.3 (Fasting=No/blank
    13
        LDL Cholesterol (mmol/​L) >= 4.9 (Fasting=Yes)
    7
        HDL Cholesterol (mmol/​L) <= 0.8 (Fasting=No/blank
    11
        HDL Cholesterol (mmol/​L) <= 0.9 (Fasting=Yes)
    2
        Creatine Kinase (U/​L) >= 400 (F) >= 750 (M)
    20
        Lactate Dehydrogenase (U/​L) >= 750
    0
        Pulse Rate <50 and decrease from BL>=15 beats/min
    0
        PR >120 and increase from BL of >=15 beats/min
    0
        Diastolic BP <=50 and decrease from BL of>=15 mmHg
    1
        Diastolic BP >105 and increase from BL of>=15 mmHg
    6
        Systolic BP<=90 and decrease from BL of >= 20 mmHg
    3
        Systolic BP>180 and increase from BL of >= 20 mmHg
    0
    Notes
    [9] - Safety analysis set: all patients enrolled that received at least 1 dose of arimoclomol
    No statistical analyses for this end point

    Primary: Columbia-Suicide Severity Rating Scale (C-SSRS) Over the Open-Label Treatment Period

    		 Close Top of page
    End point title
    		 Columbia-Suicide Severity Rating Scale (C-SSRS) Over the Open-Label Treatment Period [10]
    End point description
    The C-SSRS is a detailed questionnaire assessing both suicidal behavior and suicidal ideation through a series of simple, plain-language questions administered as an interview by a qualified investigator or delegate. Safety analysis set: All enrolled patients who received at least one dose of arimoclomol.
    End point type
    Primary
    End point timeframe
    From Day 1 in ORARIALS-02 to Early Termination, an average of approximately 28 weeks
    Notes
    [10] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Early termination of trial.
    End point values
    		 Arimoclomol (Open-label)
    Number of subjects analysed
    120
    Units: Participants
        Suicidal ideation(yes on any 1 following 5 items)
    16
        Wish to be Dead
    15
        Non-specific active suicidal thoughts
    10
        Active Suicidal ideation w/ any methods(not Plan)
    5
        Active suicidal ideation w/ some intent, w/o plan
    1
        Active Suicidal ideation w/ specific Plan & Intent
    0
        Suicidal Behavior (yes any 1 of following 5 item)
    0
        Preparatory acts or behavior
    0
        Aborted Attempt
    0
        Interrupted Attempt
    0
        Actual Attempt (non-fatal)
    0
        Completed Suicide
    0
        Suicidal ideation/Behavior(Y to any above 10 items
    16
        Self-injurious Behavior without suicidal intent
    0
    No statistical analyses for this end point

    Secondary: Change in ALS Functional Rating Scale - Revised (ALSFRS-R) From Baseline to Week 76

    		 Close Top of page
    End point title
    		 Change in ALS Functional Rating Scale - Revised (ALSFRS-R) From Baseline to Week 76
    End point description
    The ALSFRS-R is an ordinal rating scale used to determine subjects' subjective assessment of their capability and independence with 12 functional activities ('speech', 'salivation', 'swallowing', handwriting', 'cutting food and handling utensils', 'dressing and hygiene', 'turning in bed and adjusting bed clothes', 'walking', 'dyspnoea', 'orthopnoea' and 'respiratory insufficiency'). Each activity is rated on a 5-point scale (from 0 [no ability] to 4 [normal]), giving a maximal ALSFRS-R score of 48. A lower score corresponds to a lower capability and independence. Data were not collected at Week 76 since the trial was terminated early by the sponsor as a consequence of the results of ORARIALS-01 which did not meet any of its efficacy endpoints.
    End point type
    Secondary
    End point timeframe
    Week 76
    End point values
    		 Arimoclomol (Open-label)
    Number of subjects analysed
    0 [11]
    Units: ALSFRS-R scale
        arithmetic mean (standard deviation)
    ( )
    Notes
    [11] - Data were not collected as trial was terminated early by the sponsor as a consequence of ORARIALS-01
    No statistical analyses for this end point

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    AE's collected throughout the trial until early termination. Average duration of exposure was 198.7 days (approximately 28 weeks).
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    21.1
    Reporting groups
    Reporting group title
    Arimoclomol (Open-label)
    Reporting group description
    		 -

    Serious adverse events
    		 Arimoclomol (Open-label)
    Total subjects affected by serious adverse events
         subjects affected / exposed
    21 / 120 (17.50%)
         number of deaths (all causes)
    23
         number of deaths resulting from adverse events
    Investigations
    False positive investigation result
         subjects affected / exposed
    1 / 120 (0.83%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Injury, poisoning and procedural complications
    Rib fracture
         subjects affected / exposed
    1 / 120 (0.83%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Cardiac disorders
    Cardiac arrest
         subjects affected / exposed
    1 / 120 (0.83%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    Cardiac failure
         subjects affected / exposed
    1 / 120 (0.83%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Coronary artery disease
         subjects affected / exposed
    1 / 120 (0.83%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Gastrointestinal disorders
    Ileus
         subjects affected / exposed
    1 / 120 (0.83%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    Respiratory, thoracic and mediastinal disorders
    Pneumonia aspiration
         subjects affected / exposed
    3 / 120 (2.50%)
         occurrences causally related to treatment / all
    0 / 3
         deaths causally related to treatment / all
    0 / 1
    Acute respiratory failure
         subjects affected / exposed
    2 / 120 (1.67%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Pulmonary embolism
         subjects affected / exposed
    2 / 120 (1.67%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Chronic obstructive pulmonary disease
         subjects affected / exposed
    1 / 120 (0.83%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    Dyspnoea
         subjects affected / exposed
    1 / 120 (0.83%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Pneumothorax
         subjects affected / exposed
    1 / 120 (0.83%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    1 / 120 (0.83%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Urinary incontinence
         subjects affected / exposed
    1 / 120 (0.83%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Infections and infestations
    Pneumonia
         subjects affected / exposed
    7 / 120 (5.83%)
         occurrences causally related to treatment / all
    0 / 7
         deaths causally related to treatment / all
    0 / 3
    Clostridium difficile infection
         subjects affected / exposed
    1 / 120 (0.83%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Corona virus infection
         subjects affected / exposed
    1 / 120 (0.83%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Respiratory tract infection
         subjects affected / exposed
    1 / 120 (0.83%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 2%
    Non-serious adverse events
    		 Arimoclomol (Open-label)
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    91 / 120 (75.83%)
    Investigations
    Cystatin C increased
         subjects affected / exposed
    7 / 120 (5.83%)
         occurrences all number
    7
    Alanine aminotransferase increased
         subjects affected / exposed
    4 / 120 (3.33%)
         occurrences all number
    5
    Gamma-glutamyltransferase increased
         subjects affected / exposed
    3 / 120 (2.50%)
         occurrences all number
    4
    Injury, poisoning and procedural complications
    Fall
         subjects affected / exposed
    8 / 120 (6.67%)
         occurrences all number
    12
    Head injury
         subjects affected / exposed
    3 / 120 (2.50%)
         occurrences all number
    3
    Vascular disorders
    Hypertension
         subjects affected / exposed
    3 / 120 (2.50%)
         occurrences all number
    3
    Cardiac disorders
    Tachycardia
         subjects affected / exposed
    3 / 120 (2.50%)
         occurrences all number
    3
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    6 / 120 (5.00%)
         occurrences all number
    6
    Leukocytosis
         subjects affected / exposed
    3 / 120 (2.50%)
         occurrences all number
    3
    Gastrointestinal disorders
    Constipation
         subjects affected / exposed
    8 / 120 (6.67%)
         occurrences all number
    8
    Flatulence
         subjects affected / exposed
    3 / 120 (2.50%)
         occurrences all number
    3
    Gastrooesophageal reflux disease
         subjects affected / exposed
    3 / 120 (2.50%)
         occurrences all number
    3
    Diarrhoea
         subjects affected / exposed
    4 / 120 (3.33%)
         occurrences all number
    4
    Nausea
         subjects affected / exposed
    5 / 120 (4.17%)
         occurrences all number
    6
    Psychiatric disorders
    Anxiety
         subjects affected / exposed
    4 / 120 (3.33%)
         occurrences all number
    4
    Depression
         subjects affected / exposed
    3 / 120 (2.50%)
         occurrences all number
    3
    Musculoskeletal and connective tissue disorders
    Muscle spasms
         subjects affected / exposed
    3 / 120 (2.50%)
         occurrences all number
    3
    Pain in extremity
         subjects affected / exposed
    3 / 120 (2.50%)
         occurrences all number
    3
    Infections and infestations
    Urinary tract infection
         subjects affected / exposed
    7 / 120 (5.83%)
         occurrences all number
    8
    Corona virus infection
         subjects affected / exposed
    6 / 120 (5.00%)
         occurrences all number
    6
    Fungal skin infection
         subjects affected / exposed
    3 / 120 (2.50%)
         occurrences all number
    3
    Metabolism and nutrition disorders
    Type 2 diabetes mellitus
         subjects affected / exposed
    4 / 120 (3.33%)
         occurrences all number
    4
    Decreased appetite
         subjects affected / exposed
    4 / 120 (3.33%)
         occurrences all number
    4
    Hypokalaemia
         subjects affected / exposed
    3 / 120 (2.50%)
         occurrences all number
    3

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    19 Jul 2019
    Protocol version 3.0 added in-clinic visits in response to an urgent safety measure that was initiated by the DMC in response to cases of elevated transaminases. To monitorelevated transaminases, the remote visits 3, 5, and 7 (Week 8, 16, and 24) was to in-person visits and a blood sample was to be taken. This was done to enable routine monitoring of patients monthly for the first 6 months of the trial, as recommended by the DMC.

    Interruptions (globally)
    Were there any global interruptions to the trial? Yes
    Date
    Interruption
    Restart date
    11 May 2021
    As a consequence of the results of ORARIALS-01 which did not meet any of its efficacy endpoints. The planned duration was 152 weeks. After termination, the actual mean duration of treatment was approx. 28 weeks (range approx. 2 to 71 weeks).
    -

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
    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-Mon May 05 04:27:12 CEST 2025 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA