Arimoclomol in Amyotropic Lateral Sclerosis

NCT03491462 | Completed Phase 3 Results DMC FDA Drug

• 1 other identifier: ORARIALS-01
• Study Type: interventional
• Target: 245
• Locations: 12 countries
• Sites: 29

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)

Conditions

Amyotrophic Lateral Sclerosis

Keywords

Arimoclomol; ALS

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• Time to Permanent Assisted Ventilation (PAV) / Tracheostomy / Death

  Over 76 weeks

• 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)

• Change From Baseline to Week 76 (or End-of-trial) in Percent (%) Predicted Slow Vital Capacity (SVC)

  Week 76 (or end of trial)

Study Arms (2)

Arimoclomol

EXPERIMENTAL

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

Drug: Arimoclomol

Placebo

PLACEBO COMPARATOR

248 mg matching placebo 3 times daily

Drug: Placebo

Interventions

Arimoclomol DRUG

2 capsules (2 x 124 mg arimoclomol base; equivalent to 2 x 200 mg arimoclomol citrate) taken 3 times daily

Arimoclomol

Placebo DRUG

2 matched placebo capsules taken 3 times daily

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• ZevraDenmark: lead

Study Sites (29)

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

Location

HonorHealth Neurology

Phoenix, Arizona, 85018, United States

Location

UC Irvine Health ALS and Neuromuscular Center

Orange, California, 92868, United States

Location

University of Miami

Miami, Florida, 33136, United States

Location

University of Kansas Medical Center (KUMC) - Landon Center on Aging

Kansas City, Kansas, 66160, United States

Location

Hospital for Special Surgery

New York, New York, 10021, United States

Location

Providence Brain & Spine Institute

Portland, Oregon, 97213, United States

Location

University of Pensylvania, Perelman Center for Advanced Medicine - Penn Neuroscience Center

Philadelphia, Pennsylvania, 19107, United States

Location

University of Texas Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

University of Virginia Health System

Charlottesville, Virginia, 22908, United States

Location

Catholic University Leuven

Leuven, 3000, Belgium

Location

London Health Sciences Centre

London, Ontario, N6A 5A5, Canada

Location

Sunnybrook Health Sciences Centre

Toronto, Ontario, M4N 3M5, Canada

Location

Montreal Neurological Institute and Hospital

Montreal, Quebec, H3A 2B4, Canada

Location

Centre Hospitalier Regional Universitaire (CHRU) Montpellier - Hopital Gui De Chauliac

Montpellier, 34295, France

Location

Groupe Hospitalier Pitie-Salpetriere - Centre d'Investigation Clinique Neurosciences 1422

Paris, 75013, France

Location

Charite - Universitaetsmedizin Berlin - Campus Virchow-Klinikum (CVK) - Ambulanz fuer ALS und andere Motoneuronenerkrankungen

Berlin, 13353, Germany

Location

Medizinische Hochschule Hannover (MHH) - Klinik fuer Neurologie

Hanover, 30625, Germany

Location

Universitaetsklinikum Ulm - Klinik fuer Neurologie

Ulm, 89081, Germany

Location

Instituti Clinica Scientifici Maugeri - IRCCS

Milan, 20138, Italy

Location

Azienda Ospedaliero Universitaria (AUO) di Torino - Citta'della Salute e della Scienza di Torino

Torino, 10126, Italy

Location

University Medical Center Utrecht

Utrecht, 3584CX, Netherlands

Location

Centrum Medyczne NeuroProtect

Warsaw, 01-684, Poland

Location

Citi Clinic

Warsaw, 02-473, Poland

Location

Hospital Universitario Vall d'Hebron ALS Unit. Consultas Externas; Office: 9-10-11

Barcelona, 08035, Spain

Location

Hospital Carlos III - Hospital Universitario La Paz, ALS Unit

Madrid, 28046, Spain

Location

Umeå University Hospital

Umeå, 90737, Sweden

Location

Kantonsspital St.Gallen, Muskelzentrum/ALS Clinic

Sankt Gallen, 9007, Switzerland

Location

Leonard Wolfson Experimental Neurology Centre

London, WC1N 3BG, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 38782015 DERIVED

MeSH Terms

Conditions

Amyotrophic Lateral Sclerosis

Interventions

arimoclomol

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Motor Neuron Disease; Neurodegenerative Diseases; TDP-43 Proteinopathies; Neuromuscular Diseases; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases

Results Point of Contact

• Title: Medical Affairs
• Organization: Zevra Denmark A/S

medicalaffairs@zevra.com

+1-888-289-5607

Study Officials

• Michael Benatar, MD PhD

  University of Miami

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Double-blind
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Placebo-controlled, parallel group

Study Record Dates

• First Submitted: March 27, 2018
• First Posted: April 9, 2018
• Study Start: July 31, 2018
• Primary Completion: December 18, 2020
• Study Completion: December 18, 2020
• Last Updated: August 24, 2023
• Results First Posted: August 24, 2023

Record last verified: 2023-08

Locations

DE (3); ES (2); IT (2); SE (1); PL (2); GB (1); FR (2); BE (1); CH (1); NL (1); CA (3); US (10)