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Arimoclomol in Amyotropic Lateral Sclerosis

Primary Purpose

Amyotrophic Lateral Sclerosis

Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Arimoclomol
Placebo
Sponsored by
ZevraDenmark
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Amyotrophic Lateral Sclerosis focused on measuring Arimoclomol, ALS

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Subject meets revised El Escorial criteria for clinically possible, clinically probable / Clinically probable ALS laboratory-supported or clinically definite ALS, or familial ALS
  • 18 months or less since first appearance of weakness (e.g. limb weakness, dysarthria, dysphagia, shortness of breath).
  • ALSFRS-R equal to or above 35 and erect (seated) 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 or 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

Sites / Locations

  • St. Joseph's Hospital and Medical Center (SJHMC) - Barrow Neurological Institute (BNI) - The Gregory W. Fulton ALS and Neuromuscular Disease Center
  • HonorHealth Neurology
  • UC Irvine Health ALS and Neuromuscular Center
  • University of Miami
  • University of Kansas Medical Center (KUMC) - Landon Center on Aging
  • Hospital for Special Surgery
  • Providence Brain & Spine Institute
  • University of Pensylvania, Perelman Center for Advanced Medicine - Penn Neuroscience Center
  • University of Texas Southwestern Medical Center
  • University of Virginia Health System
  • Catholic University Leuven
  • London Health Sciences Centre
  • Sunnybrook Health Sciences Centre
  • Montreal Neurological Institute and Hospital
  • 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 - IRCCS
  • 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
  • Kantonsspital St.Gallen, Muskelzentrum/ALS Clinic
  • Leonard Wolfson Experimental Neurology Centre

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Arimoclomol

Placebo

Arm Description

248 mg arimoclomol base (equivalent to 400 mg arimoclomol citrate) 3 times daily

248 mg matching placebo 3 times daily

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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
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.
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.

Full Information

First Posted
March 27, 2018
Last Updated
August 22, 2023
Sponsor
ZevraDenmark
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1. Study Identification

Unique Protocol Identification Number
NCT03491462
Brief Title
Arimoclomol in Amyotropic Lateral Sclerosis
Official Title
A Phase 3, Randomised, Placebo-Controlled Trial of Arimoclomol in Amyotropic Lateral Sclerosis
Study Type
Interventional

2. Study Status

Record Verification Date
August 2023
Overall Recruitment Status
Completed
Study Start Date
July 31, 2018 (Actual)
Primary Completion Date
December 18, 2020 (Actual)
Study Completion Date
December 18, 2020 (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
Yes

5. Study Description

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

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
Parallel Assignment
Model Description
Placebo-controlled, parallel group
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
Double-blind
Allocation
Randomized
Enrollment
245 (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
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
248 mg matching placebo 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
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
2 matched placebo capsules taken 3 times daily
Primary Outcome Measure Information:
Title
Combined Assessment of Function and Survival (CAFS)
Description
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.
Time Frame
Over 76 Weeks
Secondary Outcome Measure Information:
Title
Time to Permanent Assisted Ventilation (PAV) / Tracheostomy / Death
Description
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
Time Frame
Over 76 weeks
Title
Change From Baseline to Week 76 (or End-of-trial) in the Revised ALS Functional Rating Scale (ALSFRS-R)
Description
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.
Time Frame
Week 76 (or end of trial)
Title
Change From Baseline to Week 76 (or End-of-trial) in Percent (%) Predicted Slow Vital Capacity (SVC)
Description
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.
Time Frame
Week 76 (or end of trial)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
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
HonorHealth Neurology
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85018
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
University of Kansas Medical Center (KUMC) - Landon Center on Aging
City
Kansas City
State/Province
Kansas
ZIP/Postal Code
66160
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 Texas Southwestern Medical Center
City
Dallas
State/Province
Texas
ZIP/Postal Code
75390
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
ZIP/Postal Code
3000
Country
Belgium
Facility Name
London Health Sciences Centre
City
London
State/Province
Ontario
ZIP/Postal Code
N6A 5A5
Country
Canada
Facility Name
Sunnybrook Health Sciences Centre
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M4N 3M5
Country
Canada
Facility Name
Montreal Neurological Institute and Hospital
City
Montréal
State/Province
Quebec
ZIP/Postal Code
H3A 2B4
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 - IRCCS
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
Kantonsspital St.Gallen, Muskelzentrum/ALS Clinic
City
Saint Gallen
ZIP/Postal Code
9007
Country
Switzerland
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

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