Arimoclomol in Amyotropic Lateral Sclerosis

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

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

Study Overview

• Status: Completed
• Conditions: Amyotrophic Lateral Sclerosis
• Intervention / Treatment: Drug: Arimoclomol; Drug: Placebo

Detailed Description

Screening up to 4 weeks Treatment up to 76 weeks

• Study Type: Interventional
• Enrollment (Actual): 245
• Phase: Phase 3

Contacts and Locations

Study Locations

• Belgium
  • Leuven, Belgium, 3000
    • Catholic University Leuven
• Canada
  • Ontario
    • London, Ontario, Canada, N6A 5A5
      • London Health Sciences Centre
    • Toronto, Ontario, Canada, M4N 3M5
      • Sunnybrook Health Sciences Centre
  • Quebec
    • Montréal, Quebec, Canada, H3A 2B4
      • Montreal Neurological Institute and Hospital
• France
  • Montpellier, France, 34295
    • Centre Hospitalier Regional Universitaire (CHRU) Montpellier - Hopital Gui De Chauliac
  • Paris, France, 75013
    • Groupe Hospitalier Pitie-Salpetriere - Centre d'Investigation Clinique Neurosciences 1422
• Germany
  • Berlin, Germany, 13353
    • Charite - Universitaetsmedizin Berlin - Campus Virchow-Klinikum (CVK) - Ambulanz fuer ALS und andere Motoneuronenerkrankungen
  • Hannover, Germany, 30625
    • Medizinische Hochschule Hannover (MHH) - Klinik fuer Neurologie
  • Ulm, Germany, 89081
    • Universitaetsklinikum Ulm - Klinik fuer Neurologie
• Italy
  • Milano, Italy, 20138
    • Instituti Clinica Scientifici Maugeri - IRCCS
  • Torino, Italy, 10126
    • Azienda Ospedaliero Universitaria (AUO) di Torino - Citta'della Salute e della Scienza di Torino
• Netherlands
  • Utrecht, Netherlands, 3584CX
    • University Medical Center Utrecht
• Poland
  • Warsaw, Poland, 01-684
    • Centrum Medyczne NeuroProtect
  • Warsaw, Poland, 02-473
    • Citi Clinic
• Spain
  • Barcelona, Spain, 08035
    • Hospital Universitario Vall d'Hebron ALS Unit. Consultas Externas; Office: 9-10-11
  • Madrid, Spain, 28046
    • Hospital Carlos III - Hospital Universitario La Paz, ALS Unit
• Sweden
  • Umeå, Sweden, 90737
    • Umeå University Hospital
• Switzerland
  • Saint Gallen, Switzerland, 9007
    • Kantonsspital St.Gallen, Muskelzentrum/ALS Clinic
• United Kingdom
  • London, United Kingdom, WC1N 3BG
    • Leonard Wolfson Experimental Neurology Centre
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85013
      • 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, 85018
      • HonorHealth Neurology
  • California
    • Orange, California, United States, 92868
      • UC Irvine Health ALS and Neuromuscular Center
  • Florida
    • Miami, Florida, United States, 33136
      • University of Miami
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • University of Kansas Medical Center (KUMC) - Landon Center on Aging
  • New York
    • New York, New York, United States, 10021
      • Hospital for Special Surgery
  • Oregon
    • Portland, Oregon, United States, 97213
      • Providence Brain & Spine Institute
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • University of Pensylvania, Perelman Center for Advanced Medicine - Penn Neuroscience Center
  • Texas
    • Dallas, Texas, United States, 75390
      • University of Texas Southwestern Medical Center
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • University of Virginia Health System

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arimoclomol; 248 mg arimoclomol base (equivalent to 400 mg arimoclomol citrate) 3 times daily	Drug: Arimoclomol; 2 capsules (2 x 124 mg arimoclomol base; equivalent to 2 x 200 mg arimoclomol citrate) taken 3 times daily
Placebo Comparator: Placebo; 248 mg matching placebo 3 times daily	Drug: Placebo; 2 matched placebo capsules taken 3 times daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Secondary Outcome Measures

Outcome Measure	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)	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)

Collaborators and Investigators

• Sponsor: ZevraDenmark
• Investigators: Principal Investigator: Michael Benatar, MD PhD, University of Miami

Study record dates

Study Major Dates

• Study Start (Actual): July 31, 2018
• Primary Completion (Actual): December 18, 2020
• Study Completion (Actual): December 18, 2020

Study Registration Dates

• First Submitted: March 27, 2018
• First Submitted That Met QC Criteria: April 6, 2018
• First Posted (Actual): April 9, 2018

Study Record Updates

• Last Update Posted (Actual): August 24, 2023
• Last Update Submitted That Met QC Criteria: August 22, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: ALS; Arimoclomol
• Additional Relevant MeSH Terms: Pathologic Processes; Metabolic Diseases; Central Nervous System Diseases; Nervous System Diseases; Neuromuscular Diseases; Neurodegenerative Diseases; Spinal Cord Diseases; TDP-43 Proteinopathies; Proteostasis Deficiencies; Sclerosis; Motor Neuron Disease; Amyotrophic Lateral Sclerosis
• Other Study ID Numbers: ORARIALS-01

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No