Arimoclomol in Amyotropic Lateral Sclerosis

Amyotrophic Lateral Sclerosis Clinical Trial

Official title:

A Phase 3, Randomised, Placebo-Controlled Trial of Arimoclomol in Amyotropic Lateral Sclerosis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03491462
• Other study ID #: ORARIALS-01
• Status: Completed
• Phase: Phase 3
• Start date: July 31, 2018
• Est. completion date: December 18, 2020

Study information

• Verified date: August 2023
• Source: ZevraDenmark
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

A multicenter, randomized, double-blind, placebo-controlled, parallel group trial to evaluate the efficacy and safety of arimoclomol in amyotropic lateral sclerosis (ALS)

Description:

Screening up to 4 weeks Treatment up to 76 weeks

Recruitment information / eligibility

• Status: Completed
• Enrollment: 245
• Est. completion date: December 18, 2020
• Est. primary completion date: December 18, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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

Related Conditions & MeSH terms

• Amyotrophic Lateral Sclerosis
• Motor Neuron Disease
• Sclerosis

Intervention

Drug:
• Arimoclomol
2 capsules (2 x 124 mg arimoclomol base; equivalent to 2 x 200 mg arimoclomol citrate) taken 3 times daily
• Placebo
2 matched placebo capsules taken 3 times daily

Locations

Country	Name	City	State
Belgium	Catholic University Leuven	Leuven
Canada	London Health Sciences Centre	London	Ontario
Canada	Montreal Neurological Institute and Hospital	Montréal	Quebec
Canada	Sunnybrook Health Sciences Centre	Toronto	Ontario
France	Centre Hospitalier Regional Universitaire (CHRU) Montpellier - Hopital Gui De Chauliac	Montpellier
France	Groupe Hospitalier Pitie-Salpetriere - Centre d'Investigation Clinique Neurosciences 1422	Paris
Germany	Charite - Universitaetsmedizin Berlin - Campus Virchow-Klinikum (CVK) - Ambulanz fuer ALS und andere Motoneuronenerkrankungen	Berlin
Germany	Medizinische Hochschule Hannover (MHH) - Klinik fuer Neurologie	Hannover
Germany	Universitaetsklinikum Ulm - Klinik fuer Neurologie	Ulm
Italy	Instituti Clinica Scientifici Maugeri - IRCCS	Milano
Italy	Azienda Ospedaliero Universitaria (AUO) di Torino - Citta'della Salute e della Scienza di Torino	Torino
Netherlands	University Medical Center Utrecht	Utrecht
Poland	Centrum Medyczne NeuroProtect	Warsaw
Poland	Citi Clinic	Warsaw
Spain	Hospital Universitario Vall d'Hebron ALS Unit. Consultas Externas; Office: 9-10-11	Barcelona
Spain	Hospital Carlos III - Hospital Universitario La Paz, ALS Unit	Madrid
Sweden	Umeå University Hospital	Umeå
Switzerland	Kantonsspital St.Gallen, Muskelzentrum/ALS Clinic	Saint Gallen
United Kingdom	Leonard Wolfson Experimental Neurology Centre	London
United States	University of Virginia Health System	Charlottesville	Virginia
United States	University of Texas Southwestern Medical Center	Dallas	Texas
United States	University of Kansas Medical Center (KUMC) - Landon Center on Aging	Kansas City	Kansas
United States	University of Miami	Miami	Florida
United States	Hospital for Special Surgery	New York	New York
United States	UC Irvine Health ALS and Neuromuscular Center	Orange	California
United States	University of Pensylvania, Perelman Center for Advanced Medicine - Penn Neuroscience Center	Philadelphia	Pennsylvania
United States	HonorHealth Neurology	Phoenix	Arizona
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	Providence Brain & Spine Institute	Portland	Oregon

Sponsors (1)

Lead Sponsor	Collaborator
ZevraDenmark

Countries where clinical trial is conducted

United States,  Belgium,  Canada,  France,  Germany,  Italy,  Netherlands,  Poland,  Spain,  Sweden,  Switzerland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
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.	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	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.	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.	Week 76 (or end of trial)