Arimoclomol in Amyotropic Lateral Sclerosis
- Registration Number
- NCT03491462
- Lead Sponsor
- ZevraDenmark
- Brief Summary
A multicenter, randomized, double-blind, placebo-controlled, parallel group trial to evaluate the efficacy and safety of arimoclomol in amyotropic lateral sclerosis (ALS)
- Detailed Description
Screening up to 4 weeks Treatment up to 76 weeks
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 245
- Subject meets revised El Escorial criteria for clinically possible, clinically probable / clinically probable ALS laboratory-supported, clinically definite ALS or clinically definite familial ALS laboratory-supported
- 18 months or less since first appearance of weakness (e.g. limb weakness, dysarthria, dysphagia, shortness of breath)
- ALS Functional Rating Scale-Revised (ALSFRS-R) equal to or above 35 and erect (seated) Slow Vital Capacity (SVC) % predicted equal to or above 70% at Screening
- Tracheostomy or use of non-invasive ventilation for more than 2 hours during waking hours at the time of Screening and Baseline
- Pregnant or breast-feeding
- Current or anticipated use of diaphragmatic pacing
- Any other relevant medically significant condition which could present risk to the subject or interfere with the assessment of safety or has an increased risk of causing death during the trial
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arimoclomol Arimoclomol 248 mg arimoclomol base (equivalent to 400 mg arimoclomol citrate) 3 times daily Placebo Placebo 248 mg matching placebo 3 times daily
- Primary Outcome Measures
Name Time Method Combined Assessment of Function and Survival (CAFS) Over 76 Weeks 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.
- Secondary Outcome Measures
Name Time Method Time to Permanent Assisted Ventilation (PAV) / Tracheostomy / Death Over 76 weeks 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
Change From Baseline to Week 76 (or End-of-trial) in the Revised ALS Functional Rating Scale (ALSFRS-R) Week 76 (or end of trial) 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.
Change From Baseline to Week 76 (or End-of-trial) in Percent (%) Predicted Slow Vital Capacity (SVC) Week 76 (or end of trial) 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.
Trial Locations
- Locations (29)
University of Miami
🇺🇸Miami, Florida, United States
Providence Brain & Spine Institute
🇺🇸Portland, Oregon, United States
Umeå University Hospital
🇸🇪Umeå, Sweden
University of Kansas Medical Center (KUMC) - Landon Center on Aging
🇺🇸Kansas City, Kansas, United States
Kantonsspital St.Gallen, Muskelzentrum/ALS Clinic
🇨🇭Saint Gallen, Switzerland
UC Irvine Health ALS and Neuromuscular Center
🇺🇸Orange, California, United States
St. Joseph's Hospital and Medical Center (SJHMC) - Barrow Neurological Institute (BNI) - The Gregory W. Fulton ALS and Neuromuscular Disease Center
🇺🇸Phoenix, Arizona, United States
HonorHealth Neurology
🇺🇸Phoenix, Arizona, United States
Hospital for Special Surgery
🇺🇸New York, New York, United States
University of Pensylvania, Perelman Center for Advanced Medicine - Penn Neuroscience Center
🇺🇸Philadelphia, Pennsylvania, United States
Catholic University Leuven
🇧🇪Leuven, Belgium
University of Texas Southwestern Medical Center
🇺🇸Dallas, Texas, United States
London Health Sciences Centre
🇨🇦London, Ontario, Canada
Groupe Hospitalier Pitie-Salpetriere - Centre d'Investigation Clinique Neurosciences 1422
🇫🇷Paris, France
Montreal Neurological Institute and Hospital
🇨🇦Montréal, Quebec, Canada
Centre Hospitalier Regional Universitaire (CHRU) Montpellier - Hopital Gui De Chauliac
🇫🇷Montpellier, France
Medizinische Hochschule Hannover (MHH) - Klinik fuer Neurologie
🇩🇪Hannover, Germany
Charite - Universitaetsmedizin Berlin - Campus Virchow-Klinikum (CVK) - Ambulanz fuer ALS und andere Motoneuronenerkrankungen
🇩🇪Berlin, Germany
Sunnybrook Health Sciences Centre
🇨🇦Toronto, Ontario, Canada
Instituti Clinica Scientifici Maugeri - IRCCS
🇮🇹Milano, Italy
Centrum Medyczne NeuroProtect
🇵🇱Warsaw, Poland
Azienda Ospedaliero Universitaria (AUO) di Torino - Citta'della Salute e della Scienza di Torino
🇮🇹Torino, Italy
Universitaetsklinikum Ulm - Klinik fuer Neurologie
🇩🇪Ulm, Germany
Citi Clinic
🇵🇱Warsaw, Poland
Hospital Universitario Vall d'Hebron ALS Unit. Consultas Externas; Office: 9-10-11
🇪🇸Barcelona, Spain
Leonard Wolfson Experimental Neurology Centre
🇬🇧London, United Kingdom
Hospital Carlos III - Hospital Universitario La Paz, ALS Unit
🇪🇸Madrid, Spain
University of Virginia Health System
🇺🇸Charlottesville, Virginia, United States
University Medical Center Utrecht
🇳🇱Utrecht, Netherlands