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A multicenter, randomized, double-blind, placebo-controlled, parallel group trial to evaluate the efficacy and safety of arimoclomol in amyotropic lateral sclerosis (ALS)
Screening up to 4 weeks Treatment up to 76 weeks
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Arimoclomol | Experimental | 248 mg arimoclomol base (equivalent to 400 mg arimoclomol citrate) 3 times daily |
|
| Placebo | Placebo Comparator | 248 mg matching placebo 3 times daily |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Arimoclomol | Drug | 2 capsules (2 x 124 mg arimoclomol base; equivalent to 2 x 200 mg arimoclomol citrate) taken 3 times daily |
|
| Measure | Description | Time Frame |
|---|---|---|
| Combined Assessment of Function and Survival (CAFS) | Combined Assessment of Function and Survival (CAFS) is a composite endpoint that includes 1) the change from baseline in revised ALS functional rating scale (ALSFRS-R) and 2) the survival endpoint (time to permanent assisted ventilation [PAV], tracheostomy or death). On the ALSFRS-R, 12 functions are rated on 5-point ordinal rating scales (from 0 to 4) with a total score range (minimum and maximum score) of 0-48 (sum of all 12 items). The higher the score the better functioning. For the survival endpoint, the longer time to PAV, tracheostomy, or death the better outcome. A patient's CAFS score represents a patient's rank in the study based on comparing the patient's outcome for both the change in ALSFRS-R and the time to event (PAV, tracheostomy, or death) to the outcome for all other patients in the study in a pairwise fashion. A higher rank score (range 0-1) is considered a better outcome. The reported values are the mean rank scores in each group for the composite endpoint. | Over 76 Weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Time to Permanent Assisted Ventilation (PAV) / Tracheostomy / Death | Time from baseline to one of the events (PAV / tracheostomy / death). PAV is defined as the first of 7 consecutive days on which PAV was used for >22 hours/day | Over 76 weeks |
| Change From Baseline to Week 76 (or End-of-trial) in the Revised ALS Functional Rating Scale (ALSFRS-R) |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Michael Benatar, MD PhD | University of Miami | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| St. Joseph's Hospital and Medical Center (SJHMC) - Barrow Neurological Institute (BNI) - The Gregory W. Fulton ALS and Neuromuscular Disease Center | Phoenix | Arizona | 85013 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 38782015 | Derived | Benatar M, Hansen T, Rom D, Geist MA, Blaettler T, Camu W, Kuzma-Kozakiewicz M, van den Berg LH, Morales RJ, Chio A, Andersen PM, Pradat PF, Lange D, Van Damme P, Mora G, Grudniak M, Elliott M, Petri S, Olney N, Ladha S, Goyal NA, Meyer T, Hanna MG, Quinn C, Genge A, Zinman L, Jabari D, Shoesmith C, Ludolph AC, Neuwirth C, Nations S, Shefner JM, Turner MR, Wuu J, Bennett R, Dang H, Sundgreen C; ORARIALS-01 trial team. Safety and efficacy of arimoclomol in patients with early amyotrophic lateral sclerosis (ORARIALS-01): a randomised, double-blind, placebo-controlled, multicentre, phase 3 trial. Lancet Neurol. 2024 Jul;23(7):687-699. doi: 10.1016/S1474-4422(24)00134-0. Epub 2024 May 20. |
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| ID | Title | Description |
|---|---|---|
| FG000 | Arimoclomol (up to 76 Weeks) | Arimoclomol base 248 mg 3 times daily for up to 76 weeks |
| FG001 | Placebo (up to 76 Weeks) | Matching placebo 3 times daily for up to 76 weeks |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Jun 8, 2020 | May 12, 2023 |
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Placebo-controlled, parallel group
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Double-blind
| Placebo | Drug | 2 matched placebo capsules taken 3 times daily |
|
The ALSFRS-R score is based on a rating scale where 12 functions are rated on 5-point ordinal rating scales (from 0 to 4) with a maximum score of 48 (sum of all 12 items). The higher the score the better functioning. |
| Week 76 (or end of trial) |
| Change From Baseline to Week 76 (or End-of-trial) in Percent (%) Predicted Slow Vital Capacity (SVC) | Slow Vital Capacity (SVC) is a measure of breathing function. SVC measures the volume that can be exhaled from a full inhalation after exhaling to a maximum as slowly as possible. The percent (%) of predicted SVC is reported. | Week 76 (or end of trial) |
| HonorHealth Neurology | Phoenix | Arizona | 85018 | United States |
| UC Irvine Health ALS and Neuromuscular Center | Orange | California | 92868 | United States |
| University of Miami | Miami | Florida | 33136 | United States |
| University of Kansas Medical Center (KUMC) - Landon Center on Aging | Kansas City | Kansas | 66160 | United States |
| Hospital for Special Surgery | New York | New York | 10021 | United States |
| Providence Brain & Spine Institute | Portland | Oregon | 97213 | United States |
| University of Pensylvania, Perelman Center for Advanced Medicine - Penn Neuroscience Center | Philadelphia | Pennsylvania | 19107 | United States |
| University of Texas Southwestern Medical Center | Dallas | Texas | 75390 | United States |
| University of Virginia Health System | Charlottesville | Virginia | 22908 | United States |
| Catholic University Leuven | Leuven | 3000 | Belgium |
| London Health Sciences Centre | London | Ontario | N6A 5A5 | Canada |
| Sunnybrook Health Sciences Centre | Toronto | Ontario | M4N 3M5 | Canada |
| Montreal Neurological Institute and Hospital | Montreal | Quebec | H3A 2B4 | Canada |
| Centre Hospitalier Regional Universitaire (CHRU) Montpellier - Hopital Gui De Chauliac | Montpellier | 34295 | France |
| Groupe Hospitalier Pitie-Salpetriere - Centre d'Investigation Clinique Neurosciences 1422 | Paris | 75013 | France |
| Charite - Universitaetsmedizin Berlin - Campus Virchow-Klinikum (CVK) - Ambulanz fuer ALS und andere Motoneuronenerkrankungen | Berlin | 13353 | Germany |
| Medizinische Hochschule Hannover (MHH) - Klinik fuer Neurologie | Hanover | 30625 | Germany |
| Universitaetsklinikum Ulm - Klinik fuer Neurologie | Ulm | 89081 | Germany |
| Instituti Clinica Scientifici Maugeri - IRCCS | Milan | 20138 | Italy |
| Azienda Ospedaliero Universitaria (AUO) di Torino - Citta'della Salute e della Scienza di Torino | Torino | 10126 | Italy |
| University Medical Center Utrecht | Utrecht | 3584CX | Netherlands |
| Centrum Medyczne NeuroProtect | Warsaw | 01-684 | Poland |
| Citi Clinic | Warsaw | 02-473 | Poland |
| Hospital Universitario Vall d'Hebron ALS Unit. Consultas Externas; Office: 9-10-11 | Barcelona | 08035 | Spain |
| Hospital Carlos III - Hospital Universitario La Paz, ALS Unit | Madrid | 28046 | Spain |
| Umeå University Hospital | Umeå | 90737 | Sweden |
| Kantonsspital St.Gallen, Muskelzentrum/ALS Clinic | Sankt Gallen | 9007 | Switzerland |
| Leonard Wolfson Experimental Neurology Centre | London | WC1N 3BG | United Kingdom |
| COMPLETED |
|
| NOT COMPLETED |
|
|
All participants in the modified intention-to-treat (mITT) population
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| ID | Title | Description |
|---|---|---|
| BG000 | Arimoclomol (up to 76 Weeks) | Arimoclomol base 248 mg 3 times daily for up to 76 weeks |
| BG001 | Placebo (up to 76 Weeks) | Matching placebo 3 times daily for up to 76 weeks |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
| |||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||
| Race (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||
| Revised ALS Functional Rating Scale (ALSFRS-R) | The ALSFRS-R score is based on a rating scale where 12 functions are rated on 5-point ordinal rating scales (from 0 to 4) with a maximum score of 48 (sum of all 12 items). The higher the score the better functioning. | Mean | Standard Deviation | units on a scale |
| ||||||||||||||
| Percent (%) Predicted Slow Vital Capacity (SVC) | Slow Vital Capacity (SVC) is a measure of breathing function. SVC measures the volume that can be exhaled from a full inhalation after exhaling to a maximum as slowly as possible. The percent (%) of predicted SVC is reported. | Mean | Standard Deviation | percent (%) predicted SVC |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Combined Assessment of Function and Survival (CAFS) | Combined Assessment of Function and Survival (CAFS) is a composite endpoint that includes 1) the change from baseline in revised ALS functional rating scale (ALSFRS-R) and 2) the survival endpoint (time to permanent assisted ventilation [PAV], tracheostomy or death). On the ALSFRS-R, 12 functions are rated on 5-point ordinal rating scales (from 0 to 4) with a total score range (minimum and maximum score) of 0-48 (sum of all 12 items). The higher the score the better functioning. For the survival endpoint, the longer time to PAV, tracheostomy, or death the better outcome. A patient's CAFS score represents a patient's rank in the study based on comparing the patient's outcome for both the change in ALSFRS-R and the time to event (PAV, tracheostomy, or death) to the outcome for all other patients in the study in a pairwise fashion. A higher rank score (range 0-1) is considered a better outcome. The reported values are the mean rank scores in each group for the composite endpoint. | modified intention-to-treat (mITT) | Posted | Mean | Standard Deviation | score on a scale | Over 76 Weeks |
|
|
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Time to Permanent Assisted Ventilation (PAV) / Tracheostomy / Death | Time from baseline to one of the events (PAV / tracheostomy / death). PAV is defined as the first of 7 consecutive days on which PAV was used for >22 hours/day | modified intention-to-treat (mITT) | Posted | Median | Inter-Quartile Range | days | Over 76 weeks |
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Change From Baseline to Week 76 (or End-of-trial) in the Revised ALS Functional Rating Scale (ALSFRS-R) | The ALSFRS-R score is based on a rating scale where 12 functions are rated on 5-point ordinal rating scales (from 0 to 4) with a maximum score of 48 (sum of all 12 items). The higher the score the better functioning. | modified intention-to-treat (mITT) | Posted | Mean | Standard Deviation | units on a scale | Week 76 (or end of trial) |
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Change From Baseline to Week 76 (or End-of-trial) in Percent (%) Predicted Slow Vital Capacity (SVC) | Slow Vital Capacity (SVC) is a measure of breathing function. SVC measures the volume that can be exhaled from a full inhalation after exhaling to a maximum as slowly as possible. The percent (%) of predicted SVC is reported. | modified intention-to-treat (mITT) | Posted | Mean | Standard Deviation | percent (%) predicted SVC | Week 76 (or end of trial) |
|
|
From first dose of study medication up to 76 weeks. Assessed every week.
The safety population included all participants not on edaravone at baseline who received any amount of study medication.
The safety analysis included all events occurring during the on-treatment observation period which started at the date of first administration of study medication and until 14 days following the latest administration of study medication (in case of interruption of treatment) or last dose of study medication, or end of trial, whichever is earliest.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Arimoclomol (up to 76 Weeks) | Arimoclomol base 248 mg 3 times daily for up to 76 weeks | 29 | 160 | 36 | 160 | 149 | 160 |
| EG001 | Placebo (up to 76 Weeks) | Matching placebo 3 times daily for up to 76 weeks | 18 | 79 | 20 | 79 | 71 | 79 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Pulmonary embolism | Respiratory, thoracic and mediastinal disorders | MedDRA (21.1) | Systematic Assessment |
| |
| Pneumonia aspiration | Respiratory, thoracic and mediastinal disorders | MedDRA (21.1) | Systematic Assessment |
| |
| Respiratory failure | Respiratory, thoracic and mediastinal disorders | MedDRA (21.1) | Systematic Assessment |
| |
| Hypoxia | Respiratory, thoracic and mediastinal disorders | MedDRA (21.1) | Systematic Assessment |
| |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA (21.1) | Systematic Assessment |
| |
| Stridor | Respiratory, thoracic and mediastinal disorders | MedDRA (21.1) | Systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA (21.1) | Systematic Assessment |
| |
| Respiratory tract infection | Infections and infestations | MedDRA (21.1) | Systematic Assessment |
| |
| Bronchitis | Infections and infestations | MedDRA (21.1) | Systematic Assessment |
| |
| Diverticulitis | Infections and infestations | MedDRA (21.1) | Systematic Assessment |
| |
| Infection | Infections and infestations | MedDRA (21.1) | Systematic Assessment |
| |
| Influenza | Infections and infestations | MedDRA (21.1) | Systematic Assessment |
| |
| Lower respiratory tract infection | Infections and infestations | MedDRA (21.1) | Systematic Assessment |
| |
| Lung infection | Infections and infestations | MedDRA (21.1) | Systematic Assessment |
| |
| Myocardial infarction | Cardiac disorders | MedDRA (21.1) | Systematic Assessment |
| |
| Acute coronary syndrome | Cardiac disorders | MedDRA (21.1) | Systematic Assessment |
| |
| Acute myocardial infarction | Cardiac disorders | MedDRA (21.1) | Systematic Assessment |
| |
| Cardiac arrest | Cardiac disorders | MedDRA (21.1) | Systematic Assessment |
| |
| Cardiac failure acute | Cardiac disorders | MedDRA (21.1) | Systematic Assessment |
| |
| Femur fracture | Injury, poisoning and procedural complications | MedDRA (21.1) | Systematic Assessment |
| |
| Forearm fracture | Injury, poisoning and procedural complications | MedDRA (21.1) | Systematic Assessment |
| |
| Injury | Injury, poisoning and procedural complications | MedDRA (21.1) | Systematic Assessment |
| |
| Procedural complication | Injury, poisoning and procedural complications | MedDRA (21.1) | Systematic Assessment |
| |
| Hepatic enzyme increased | Investigations | MedDRA (21.1) | Systematic Assessment |
| |
| Transaminases increased | Investigations | MedDRA (21.1) | Systematic Assessment |
| |
| Medical observation | Investigations | MedDRA (21.1) | Systematic Assessment |
| |
| Deep vein thrombosis | Vascular disorders | MedDRA (21.1) | Systematic Assessment |
| |
| Circulatory collapse | Vascular disorders | MedDRA (21.1) | Systematic Assessment |
| |
| Phlebitis | Vascular disorders | MedDRA (21.1) | Systematic Assessment |
| |
| Cerebrovascular accident | Nervous system disorders | MedDRA (21.1) | Systematic Assessment |
| |
| Paraesthesia | Nervous system disorders | MedDRA (21.1) | Systematic Assessment |
| |
| Subarachnoid haemorrhage | Nervous system disorders | MedDRA (21.1) | Systematic Assessment |
| |
| Transient ischaemic attack | Nervous system disorders | MedDRA (21.1) | Systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA (21.1) | Systematic Assessment |
| |
| Oesophageal perforation | Gastrointestinal disorders | MedDRA (21.1) | Systematic Assessment |
| |
| Medical device site inflammation | General disorders | MedDRA (21.1) | Systematic Assessment |
| |
| Non-cardiac chest pain | General disorders | MedDRA (21.1) | Systematic Assessment |
| |
| Sudden death | General disorders | MedDRA (21.1) | Systematic Assessment |
| |
| Anxiety | Psychiatric disorders | MedDRA (21.1) | Systematic Assessment |
| |
| Assisted suicide | Psychiatric disorders | MedDRA (21.1) | Systematic Assessment |
| |
| Bipolar disorder | Psychiatric disorders | MedDRA (21.1) | Systematic Assessment |
| |
| Diplopia | Eye disorders | MedDRA (21.1) | Systematic Assessment |
| |
| Pupils unequal | Eye disorders | MedDRA (21.1) | Systematic Assessment |
| |
| Fistula | Musculoskeletal and connective tissue disorders | MedDRA (21.1) | Systematic Assessment |
| |
| Osteoarthritis | Musculoskeletal and connective tissue disorders | MedDRA (21.1) | Systematic Assessment |
| |
| Cholecystitis acute | Hepatobiliary disorders | MedDRA (21.1) | Systematic Assessment |
| |
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA (21.1) | Systematic Assessment |
| |
| Rectal cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (21.1) | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Headache | Nervous system disorders | MedDRA (21.1) | Systematic Assessment |
| |
| Fall | Injury, poisoning and procedural complications | MedDRA (21.1) | Systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA (21.1) | Systematic Assessment |
| |
| Insomnia | Psychiatric disorders | MedDRA (21.1) | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA (21.1) | Systematic Assessment |
| |
| Nasopharyngitis | Infections and infestations | MedDRA (21.1) | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA (21.1) | Systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA (21.1) | Systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA (21.1) | Systematic Assessment |
| |
| Dizziness | Nervous system disorders | MedDRA (21.1) | Systematic Assessment |
| |
| Oedema peripheral | General disorders | MedDRA (21.1) | Systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA (21.1) | Systematic Assessment |
| |
| Post lumbar puncture syndrome | Injury, poisoning and procedural complications | MedDRA (21.1) | Systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA (21.1) | Systematic Assessment |
| |
| Depression | Psychiatric disorders | MedDRA (21.1) | Systematic Assessment |
| |
| Influenza | Infections and infestations | MedDRA (21.1) | Systematic Assessment |
| |
| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | MedDRA (21.1) | Systematic Assessment |
| |
| Contusion | Injury, poisoning and procedural complications | MedDRA (21.1) | Systematic Assessment |
| |
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA (21.1) | Systematic Assessment |
| |
| Bronchitis | Infections and infestations | MedDRA (21.1) | Systematic Assessment |
| |
| Alanine aminotransferase increased | Investigations | MedDRA (21.1) | Systematic Assessment |
| |
| Dyspepsia | Gastrointestinal disorders | MedDRA (21.1) | Systematic Assessment |
| |
| Fatigue | General disorders | MedDRA (21.1) | Systematic Assessment |
| |
| Hyperhidrosis | Skin and subcutaneous tissue disorders | MedDRA (21.1) | Systematic Assessment |
| |
| Rash | Skin and subcutaneous tissue disorders | MedDRA (21.1) | Systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | MedDRA (21.1) | Systematic Assessment |
| |
| Procedural pain | Injury, poisoning and procedural complications | MedDRA (21.1) | Systematic Assessment |
| |
| Flatulence | Gastrointestinal disorders | MedDRA (21.1) | Systematic Assessment |
| |
| Hypertension | Vascular disorders | MedDRA (21.1) | Systematic Assessment |
| |
| Sleep disorder | Psychiatric disorders | MedDRA (21.1) | Systematic Assessment |
| |
| Gastrooesophageal reflux disease | Gastrointestinal disorders | MedDRA (21.1) | Systematic Assessment |
|
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Medical Affairs | Zevra Denmark A/S | +1-888-289-5607 | medicalaffairs@zevra.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Apr 19, 2021 | May 12, 2023 | SAP_001.pdf |
Not provided
| ID | Term |
|---|---|
| D000690 | Amyotrophic Lateral Sclerosis |
| ID | Term |
|---|---|
| D013118 | Spinal Cord Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D016472 | Motor Neuron Disease |
| D019636 | Neurodegenerative Diseases |
| D057177 | TDP-43 Proteinopathies |
| D009468 | Neuromuscular Diseases |
| D057165 | Proteostasis Deficiencies |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| C486387 | arimoclomol |
Not provided
Not provided
Not provided
| Male |
|
| Not Hispanic or Latino |
|
| Unknown or Not Reported |
|
| Asian |
|
| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
|
|
|