Back to resultsArimoclomol in Amyotropic Lateral Sclerosis - Open Label Extension Trial
Primary Purpose
Amyotrophic Lateral Sclerosis
Status
Terminated
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Arimoclomol
Sponsored by
About this trial
This is an interventional treatment trial for Amyotrophic Lateral Sclerosis focused on measuring Arimoclomol, ALS
Eligibility Criteria
Inclusion Criteria:
- Subject is able to comprehend and is willing to provide written informed consent and is capable and willing to comply with trial procedures, or in the circumstance that the subject is incompetent, informed consent/assent is provided in accordance with local regulation and/or procedures
- Subject has 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)
- Subject completed ORARIALS-01 while on treatment, where on treatment is defined as having taken the last dose of IMP within 2 weeks of the End of Trial visit (whether at week 76 or prior)
Exclusion Criteria:
- Known or suspected allergy or intolerance to the IMP (Arimoclomol or constituents)
- Exposure to any other investigational treatment, advanced therapy medicinal product or use of any other prohibited concomitant medications
- Women who are lactating or pregnant, or men or women unwilling to use a highly effective method of birth control if not surgically sterile (defined as bilateral tubal ligation, bilateral oophorectomy, or hysterectomy for women; vasectomy for men) for female participants until 4 weeks after last dose and for male participants until 3 months after last dose. Pre-menopausal women must have a negative pregnancy test prior to dosing with trial medication.
Any of the following medically significant conditions:
- Clinically significant renal or hepatic disease OR clinical laboratory assessment (results ≥ 3 times the upper limit of normal [ULN] for aspartate aminotransferase and/or alanine aminotransferase, bilirubin ≥ 2 times the ULN, or creatinine ≥ 1.5 times the ULN).
- Any new condition or worsening of existing condition which, in the opinion of the investigator, would put the subject at undue risk.
- Any serious adverse event or moderate/severe adverse event from the ORARIALS-01 trial which is ongoing at the time of transitioning to ORARIALS-02 and assessed as probably related to IMP
Sites / Locations
- St. Joseph's Hospital and Medical Center (SJHMC) - Barrow Neurological Institute (BNI) - The Gregory W. Fulton ALS and Neuromuscular Disease Center
- UC Irvine Health ALS and Neuromuscular Center
- University of Miami
- Hospital for Special Surgery
- Providence Brain & Spine Institute
- University of Pensylvania, Perelman Center for Advanced Medicine - Penn Neuroscience Center
- University of Virginia Health System
- Catholic University Leuven
- London Health Sciences Centre
- Centre Hospitalier Regional Universitaire (CHRU) Montpellier - Hopital Gui De Chauliac
- Groupe Hospitalier Pitie-Salpetriere - Centre d'Investigation Clinique Neurosciences 1422
- Charite - Universitaetsmedizin Berlin - Campus Virchow-Klinikum (CVK) - Ambulanz fuer ALS und andere Motoneuronenerkrankungen
- Medizinische Hochschule Hannover (MHH) - Klinik fuer Neurologie
- Universitaetsklinikum Ulm - Klinik fuer Neurologie
- Instituti Clinica Scientifici Maugeri
- Azienda Ospedaliero Universitaria (AUO) di Torino - Citta'della Salute e della Scienza di Torino
- University Medical Center Utrecht
- Centrum Medyczne NeuroProtect
- Citi Clinic
- Hospital Universitario Vall d'Hebron ALS Unit. Consultas Externas; Office: 9-10-11
- Hospital Carlos III - Hospital Universitario La Paz, ALS Unit
- Umeå University Hospital
- Leonard Wolfson Experimental Neurology Centre
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Arimoclomol
Arm Description
248 mg arimoclomol base (equivalent to 400 mg arimoclomol citrate) 3 times daily
Outcomes
Primary Outcome Measures
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Over the Open-label Treatment Period
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.
Mean and Change From Baseline in Clinical Safety Laboratory Tests - Hematology (1)
Standard hematology parameters. White blood cell differential count for basophils, eosinophils, leukocytes, lymphocytes, monocytes, and neutrophils, and platelet count.
Mean and Change From Baseline in Clinical Safety Laboratory Tests - Hematology (2)
Standard hematology parameters. Percentage of leukocytes were determined for basophils, eosinophils, lymphocytes, monocytes, and neutrophils
Mean and Change From Baseline in Clinical Safety Laboratory Tests - Erythrocytes
Standard hematology parameter.
Mean and Change From Baseline in Clinical Safety Laboratory Tests - Hematocrit
Standard hematology parameter.
Mean and Change From Baseline in Clinical Safety Laboratory Tests - Hemoglobin
Standard hematology parameter.
Mean and Change From Baseline in Clinical Safety Laboratory Tests - Clinical Chemistry (1)
Standard clinical chemistry parameters. Alanine Aminotransferase, Alkaline Phosphatase, Aspartate Aminotransferase, Creatine Kinase, Gamma Glutamyl Transferase, and Lactate Dehydrogenase.
Mean and Change From Baseline in Clinical Safety Laboratory Tests - Clinical Chemistry (2)
Standard clinical chemistry parameters. Calcium, Calcium Corrected, Cholesterol, Glucose, HDL Cholesterol, LDL Cholesterol, Potassium, Sodium, Triglycerides, and Urea Nitrogen.
Mean and Change From Baseline in Clinical Safety Laboratory Tests - Clinical Chemistry (3)
Standard clinical chemistry parameters. Bilirubin, Creatinine, Direct Bilirubin, and Indirect Bilirubin.
Mean and Change From Baseline in Clinical Safety Laboratory Tests - Albumin and Protein
Standard clinical chemistry parameters.
Mean and Change From Baseline in Clinical Safety Laboratory Tests - Cystatin C
Standard clinical chemistry parameter.
Mean and Change From Baseline in Vital Signs - Blood Pressure
Standard vital signs. Systolic and diastolic blood pressure.
Mean and Change From Baseline in Vital Signs - Pulse Rate
Standard vital signs measurement.
Mean and Change From Baseline in Vital Signs - Respiratory Rate
Standard vital signs measurement.
Mean and Change From Baseline in Vital Signs - Temperature
Standard vital signs measurement.
Number of Participants With Potentially Clinically Significant Abnormalities in Clinical Safety Laboratory Tests and Vital Signs Over the Open-label Treatment Period
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.
Columbia-Suicide Severity Rating Scale (C-SSRS) Over the Open-label Treatment Period
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.
Secondary Outcome Measures
Change in ALS Functional Rating Scale - Revised (ALSFRS-R) From Baseline to Week 76
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.
Change in Percentage (%) Predicted Slow Vital Capacity (SVC) From Baseline to Week 76 (for Subjects Who Did Not Meet the Survival Endpoint in the ORARIALS-01 Trial)
Slow vital capacity (SVC) measures the volume that can be exhaled from a full inhalation after exhaling to a maximum as slowly as possible. Predicted SVC was derived per European Community of Coal and Steel (ECCS) reference equations:
If male: Predicted SVC = 0.061 x height (cm) - 0.028 x age (years) - 4.65
If female: Predicted SVC = 0.0466 x height (cm) - 0.024 x age (years) - 3.28
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03836716
Brief Title
Arimoclomol in Amyotropic Lateral Sclerosis - Open Label Extension Trial
Official Title
Open Label, Non-randomized Extension Trial to Assess Long Term Safety and Efficacy of Arimoclomol in Subjects With Amyotropic Lateral Sclerosis Who Have Completed the ORARIALS-01 Trial
Study Type
Interventional
2. Study Status
Record Verification Date
August 2023
Overall Recruitment Status
Terminated
Why Stopped
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).
Study Start Date
September 19, 2019 (Actual)
Primary Completion Date
July 2, 2021 (Actual)
Study Completion Date
July 2, 2021 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
ZevraDenmark
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
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.
Detailed Description
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).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Amyotrophic Lateral Sclerosis
Keywords
Arimoclomol, ALS
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Single Group Assignment
Model Description
Non-randomized open label
Masking
None (Open Label)
Allocation
N/A
Enrollment
120 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Arimoclomol
Arm Type
Experimental
Arm Description
248 mg arimoclomol base (equivalent to 400 mg arimoclomol citrate) 3 times daily
Intervention Type
Drug
Intervention Name(s)
Arimoclomol
Intervention Description
2 capsules (2 x 124 mg arimoclomol base; equivalent to 2 x 200 mg arimoclomol citrate) taken 3 times daily
Primary Outcome Measure Information:
Title
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Over the Open-label Treatment Period
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.
Time Frame
From Day 1 in ORARIALS-02 to Early Termination, an average of approximately 28 weeks
Title
Mean and Change From Baseline in Clinical Safety Laboratory Tests - Hematology (1)
Description
Standard hematology parameters. White blood cell differential count for basophils, eosinophils, leukocytes, lymphocytes, monocytes, and neutrophils, and platelet count.
Time Frame
Week 76
Title
Mean and Change From Baseline in Clinical Safety Laboratory Tests - Hematology (2)
Description
Standard hematology parameters. Percentage of leukocytes were determined for basophils, eosinophils, lymphocytes, monocytes, and neutrophils
Time Frame
Week 76
Title
Mean and Change From Baseline in Clinical Safety Laboratory Tests - Erythrocytes
Description
Standard hematology parameter.
Time Frame
Week 76
Title
Mean and Change From Baseline in Clinical Safety Laboratory Tests - Hematocrit
Description
Standard hematology parameter.
Time Frame
Week 76
Title
Mean and Change From Baseline in Clinical Safety Laboratory Tests - Hemoglobin
Description
Standard hematology parameter.
Time Frame
Week 76
Title
Mean and Change From Baseline in Clinical Safety Laboratory Tests - Clinical Chemistry (1)
Description
Standard clinical chemistry parameters. Alanine Aminotransferase, Alkaline Phosphatase, Aspartate Aminotransferase, Creatine Kinase, Gamma Glutamyl Transferase, and Lactate Dehydrogenase.
Time Frame
Week 76
Title
Mean and Change From Baseline in Clinical Safety Laboratory Tests - Clinical Chemistry (2)
Description
Standard clinical chemistry parameters. Calcium, Calcium Corrected, Cholesterol, Glucose, HDL Cholesterol, LDL Cholesterol, Potassium, Sodium, Triglycerides, and Urea Nitrogen.
Time Frame
Week 76
Title
Mean and Change From Baseline in Clinical Safety Laboratory Tests - Clinical Chemistry (3)
Description
Standard clinical chemistry parameters. Bilirubin, Creatinine, Direct Bilirubin, and Indirect Bilirubin.
Time Frame
Week 76
Title
Mean and Change From Baseline in Clinical Safety Laboratory Tests - Albumin and Protein
Description
Standard clinical chemistry parameters.
Time Frame
Week 76
Title
Mean and Change From Baseline in Clinical Safety Laboratory Tests - Cystatin C
Description
Standard clinical chemistry parameter.
Time Frame
Week 76
Title
Mean and Change From Baseline in Vital Signs - Blood Pressure
Description
Standard vital signs. Systolic and diastolic blood pressure.
Time Frame
Week 76
Title
Mean and Change From Baseline in Vital Signs - Pulse Rate
Description
Standard vital signs measurement.
Time Frame
Week 76
Title
Mean and Change From Baseline in Vital Signs - Respiratory Rate
Description
Standard vital signs measurement.
Time Frame
Week 76
Title
Mean and Change From Baseline in Vital Signs - Temperature
Description
Standard vital signs measurement.
Time Frame
Week 76
Title
Number of Participants With Potentially Clinically Significant Abnormalities in Clinical Safety Laboratory Tests and Vital Signs Over the Open-label Treatment Period
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.
Time Frame
From Day 1 in ORARIALS-02 to Early Termination, an average of approximately 28 weeks
Title
Columbia-Suicide Severity Rating Scale (C-SSRS) Over the Open-label Treatment Period
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.
Time Frame
From Day 1 in ORARIALS-02 to Early Termination, an average of approximately 28 weeks
Secondary Outcome Measure Information:
Title
Change in ALS Functional Rating Scale - Revised (ALSFRS-R) From Baseline to Week 76
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.
Time Frame
Week 76
Title
Change in Percentage (%) Predicted Slow Vital Capacity (SVC) From Baseline to Week 76 (for Subjects Who Did Not Meet the Survival Endpoint in the ORARIALS-01 Trial)
Description
Slow vital capacity (SVC) measures the volume that can be exhaled from a full inhalation after exhaling to a maximum as slowly as possible. Predicted SVC was derived per European Community of Coal and Steel (ECCS) reference equations:
If male: Predicted SVC = 0.061 x height (cm) - 0.028 x age (years) - 4.65
If female: Predicted SVC = 0.0466 x height (cm) - 0.024 x age (years) - 3.28
Time Frame
76 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Subject is able to comprehend and is willing to provide written informed consent and is capable and willing to comply with trial procedures, or in the circumstance that the subject is incompetent, informed consent/assent is provided in accordance with local regulation and/or procedures
Subject has 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)
Subject completed ORARIALS-01 while on treatment, where on treatment is defined as having taken the last dose of IMP within 2 weeks of the End of Trial visit (whether at week 76 or prior)
Exclusion Criteria:
Known or suspected allergy or intolerance to the IMP (Arimoclomol or constituents)
Exposure to any other investigational treatment, advanced therapy medicinal product or use of any other prohibited concomitant medications
Women who are lactating or pregnant, or men or women unwilling to use a highly effective method of birth control if not surgically sterile (defined as bilateral tubal ligation, bilateral oophorectomy, or hysterectomy for women; vasectomy for men) for female participants until 4 weeks after last dose and for male participants until 3 months after last dose. Pre-menopausal women must have a negative pregnancy test prior to dosing with trial medication.
Any of the following medically significant conditions:
Clinically significant renal or hepatic disease OR clinical laboratory assessment (results ≥ 3 times the upper limit of normal [ULN] for aspartate aminotransferase and/or alanine aminotransferase, bilirubin ≥ 2 times the ULN, or creatinine ≥ 1.5 times the ULN).
Any new condition or worsening of existing condition which, in the opinion of the investigator, would put the subject at undue risk.
Any serious adverse event or moderate/severe adverse event from the ORARIALS-01 trial which is ongoing at the time of transitioning to ORARIALS-02 and assessed as probably related to IMP
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Michael Benatar, MD PhD
Organizational Affiliation
University of Miami
Official's Role
Principal Investigator
Facility Information:
Facility Name
St. Joseph's Hospital and Medical Center (SJHMC) - Barrow Neurological Institute (BNI) - The Gregory W. Fulton ALS and Neuromuscular Disease Center
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85013
Country
United States
Facility Name
UC Irvine Health ALS and Neuromuscular Center
City
Orange
State/Province
California
ZIP/Postal Code
92868
Country
United States
Facility Name
University of Miami
City
Miami
State/Province
Florida
ZIP/Postal Code
33136
Country
United States
Facility Name
Hospital for Special Surgery
City
New York
State/Province
New York
ZIP/Postal Code
10021
Country
United States
Facility Name
Providence Brain & Spine Institute
City
Portland
State/Province
Oregon
ZIP/Postal Code
97213
Country
United States
Facility Name
University of Pensylvania, Perelman Center for Advanced Medicine - Penn Neuroscience Center
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19107
Country
United States
Facility Name
University of Virginia Health System
City
Charlottesville
State/Province
Virginia
ZIP/Postal Code
22908
Country
United States
Facility Name
Catholic University Leuven
City
Leuven
Country
Belgium
Facility Name
London Health Sciences Centre
City
London
State/Province
Ontario
ZIP/Postal Code
N6A 5A5
Country
Canada
Facility Name
Centre Hospitalier Regional Universitaire (CHRU) Montpellier - Hopital Gui De Chauliac
City
Montpellier
ZIP/Postal Code
34295
Country
France
Facility Name
Groupe Hospitalier Pitie-Salpetriere - Centre d'Investigation Clinique Neurosciences 1422
City
Paris
ZIP/Postal Code
75013
Country
France
Facility Name
Charite - Universitaetsmedizin Berlin - Campus Virchow-Klinikum (CVK) - Ambulanz fuer ALS und andere Motoneuronenerkrankungen
City
Berlin
ZIP/Postal Code
13353
Country
Germany
Facility Name
Medizinische Hochschule Hannover (MHH) - Klinik fuer Neurologie
City
Hannover
ZIP/Postal Code
30625
Country
Germany
Facility Name
Universitaetsklinikum Ulm - Klinik fuer Neurologie
City
Ulm
ZIP/Postal Code
89081
Country
Germany
Facility Name
Instituti Clinica Scientifici Maugeri
City
Milano
ZIP/Postal Code
20138
Country
Italy
Facility Name
Azienda Ospedaliero Universitaria (AUO) di Torino - Citta'della Salute e della Scienza di Torino
City
Torino
ZIP/Postal Code
10126
Country
Italy
Facility Name
University Medical Center Utrecht
City
Utrecht
ZIP/Postal Code
3584CX
Country
Netherlands
Facility Name
Centrum Medyczne NeuroProtect
City
Warsaw
ZIP/Postal Code
01-684
Country
Poland
Facility Name
Citi Clinic
City
Warsaw
ZIP/Postal Code
02-473
Country
Poland
Facility Name
Hospital Universitario Vall d'Hebron ALS Unit. Consultas Externas; Office: 9-10-11
City
Barcelona
ZIP/Postal Code
08035
Country
Spain
Facility Name
Hospital Carlos III - Hospital Universitario La Paz, ALS Unit
City
Madrid
ZIP/Postal Code
28046
Country
Spain
Facility Name
Umeå University Hospital
City
Umeå
ZIP/Postal Code
90737
Country
Sweden
Facility Name
Leonard Wolfson Experimental Neurology Centre
City
London
ZIP/Postal Code
WC1N 3BG
Country
United Kingdom
12. IPD Sharing Statement
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Arimoclomol in Amyotropic Lateral Sclerosis - Open Label Extension Trial
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