Arimoclomol in Amyotropic Lateral Sclerosis - Open Label Extension Trial

NCT03836716 | Terminated Phase 3 Results FDA Drug

• 1 other identifier: ORARIALS-02
• Study Type: interventional
• Target: 120
• Locations: 11 countries
• Sites: 23

Brief Summary

A multicenter, non-randomized, open label trial, to assess long term safety and efficacy of Arimoclomol in subjects with Amyotrophic Lateral Sclerosis (ALS) who have completed the ORARIALS-01 trial.

Conditions

Amyotrophic Lateral Sclerosis

Keywords

Arimoclomol; ALS

Outcome Measures

Primary Outcomes (17)

• Number of Participants With Treatment-emergent Adverse Events (TEAEs) Over the Open-label Treatment Period

  Adverse event (AE) data were collected throughout the trial until early termination. The average duration of exposure was 198.7 days (approximately 28 weeks; standard deviation 99.57 days; minimum 16 days, maximum 494 days). 58 participants (48.3%) were exposed less than 6 months; 55 participants (45.8%) were exposed 6 to less than 12 months; 7 participants (5.8%) were exposed 12 to less than 18 months. No participant was treated for 76 weeks. Participants with on-treatment TEAEs are reported. An on-treatment TEAE is any TEAE in the on-treatment period defined as the time from first dose of IMP until 14 days since the last preceding administration of IMP (either before a temporary IMP interruption with duration \>14 days or the last dose at the end of trial). A participant may have several on-treatment periods separated by interruption intervals.

  From Day 1 in ORARIALS-02 to Early Termination, an average of approximately 28 weeks

• Mean and Change From Baseline in Clinical Safety Laboratory Tests - Hematology (1)

  Standard hematology parameters. White blood cell differential count for basophils, eosinophils, leukocytes, lymphocytes, monocytes, and neutrophils, and platelet count.

  Week 76

• Mean and Change From Baseline in Clinical Safety Laboratory Tests - Hematology (2)

  Standard hematology parameters. Percentage of leukocytes were determined for basophils, eosinophils, lymphocytes, monocytes, and neutrophils

  Week 76

• Mean and Change From Baseline in Clinical Safety Laboratory Tests - Erythrocytes

  Standard hematology parameter.

  Week 76

• Mean and Change From Baseline in Clinical Safety Laboratory Tests - Hematocrit

  Standard hematology parameter.

  Week 76

• Mean and Change From Baseline in Clinical Safety Laboratory Tests - Hemoglobin

  Standard hematology parameter.

  Week 76

• Mean and Change From Baseline in Clinical Safety Laboratory Tests - Clinical Chemistry (1)

  Standard clinical chemistry parameters. Alanine Aminotransferase, Alkaline Phosphatase, Aspartate Aminotransferase, Creatine Kinase, Gamma Glutamyl Transferase, and Lactate Dehydrogenase.

  Week 76

• Mean and Change From Baseline in Clinical Safety Laboratory Tests - Clinical Chemistry (2)

  Standard clinical chemistry parameters. Calcium, Calcium Corrected, Cholesterol, Glucose, HDL Cholesterol, LDL Cholesterol, Potassium, Sodium, Triglycerides, and Urea Nitrogen.

  Week 76

• Mean and Change From Baseline in Clinical Safety Laboratory Tests - Clinical Chemistry (3)

  Standard clinical chemistry parameters. Bilirubin, Creatinine, Direct Bilirubin, and Indirect Bilirubin.

  Week 76

• Mean and Change From Baseline in Clinical Safety Laboratory Tests - Albumin and Protein

  Standard clinical chemistry parameters.

  Week 76

• Mean and Change From Baseline in Clinical Safety Laboratory Tests - Cystatin C

  Standard clinical chemistry parameter.

  Week 76

• Mean and Change From Baseline in Vital Signs - Blood Pressure

  Standard vital signs. Systolic and diastolic blood pressure.

  Week 76

• Mean and Change From Baseline in Vital Signs - Pulse Rate

  Standard vital signs measurement.

  Week 76

• Mean and Change From Baseline in Vital Signs - Respiratory Rate

  Standard vital signs measurement.

  Week 76

• Mean and Change From Baseline in Vital Signs - Temperature

  Standard vital signs measurement.

  Week 76

• Number of Participants With Potentially Clinically Significant Abnormalities in Clinical Safety Laboratory Tests and Vital Signs Over the Open-label Treatment Period

  Clinical safety laboratory data and vital signs were collected throughout the trial until early termination. The average duration of exposure was 198.7 days (approximately 28 weeks; standard deviation 99.57 days; minimum 16 days, maximum 494 days). 58 participants (48.3%) were exposed less than 6 months; 55 participants (45.8%) were exposed 6 to less than 12 months; 7 participants (5.8%) were exposed 12 to less than 18 months. No patient was treated for 76 weeks.

  From Day 1 in ORARIALS-02 to Early Termination, an average of approximately 28 weeks

• Columbia-Suicide Severity Rating Scale (C-SSRS) Over the Open-label Treatment Period

  The C-SSRS is a detailed questionnaire assessing both suicidal behavior and suicidal ideation through a series of simple, plain-language questions administered as an interview by a qualified investigator or delegate.

  From Day 1 in ORARIALS-02 to Early Termination, an average of approximately 28 weeks

Secondary Outcomes (2)

• Change in ALS Functional Rating Scale - Revised (ALSFRS-R) From Baseline to Week 76

  Week 76

• Change in Percentage (%) Predicted Slow Vital Capacity (SVC) From Baseline to Week 76 (for Subjects Who Did Not Meet the Survival Endpoint in the ORARIALS-01 Trial)

  76 weeks

Study Arms (1)

Arimoclomol

EXPERIMENTAL

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

Drug: Arimoclomol

Interventions

Arimoclomol DRUG

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

Arimoclomol

Eligibility Criteria

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

You may qualify if:

• Subject is able to comprehend and is willing to provide written informed consent and is capable and willing to comply with trial procedures, or in the circumstance that the subject is incompetent, informed consent/assent is provided in accordance with local regulation and/or procedures
• Subject has completed the ORARIALS-01 trial (i.e., met one of the surrogate survival endpoints of tracheostomy or PAV or has completed the 76 weeks randomized treatment period)
• Subject completed ORARIALS-01 while on treatment, where on treatment is defined as having taken the last dose of IMP within 2 weeks of the End of Trial visit (whether at week 76 or prior)

You may not qualify if:

• Known or suspected allergy or intolerance to the IMP (Arimoclomol or constituents)
• Exposure to any other investigational treatment, advanced therapy medicinal product or use of any other prohibited concomitant medications
• Women who are lactating or pregnant, or men or women unwilling to use a highly effective method of birth control if not surgically sterile (defined as bilateral tubal ligation, bilateral oophorectomy, or hysterectomy for women; vasectomy for men) for female participants until 4 weeks after last dose and for male participants until 3 months after last dose. Pre-menopausal women must have a negative pregnancy test prior to dosing with trial medication.
• Any of the following medically significant conditions:
• Clinically significant renal or hepatic disease OR clinical laboratory assessment (results ≥ 3 times the upper limit of normal \[ULN\] for aspartate aminotransferase and/or alanine aminotransferase, bilirubin ≥ 2 times the ULN, or creatinine ≥ 1.5 times the ULN).
• Any new condition or worsening of existing condition which, in the opinion of the investigator, would put the subject at undue risk.
• Any serious adverse event or moderate/severe adverse event from the ORARIALS-01 trial which is ongoing at the time of transitioning to ORARIALS-02 and assessed as probably related to IMP

Sponsors & Collaborators

• ZevraDenmark: lead

Study Sites (23)

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

UC Irvine Health ALS and Neuromuscular Center

Orange, California, 92868, United States

Location

University of Miami

Miami, Florida, 33136, 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 Virginia Health System

Charlottesville, Virginia, 22908, United States

Location

Catholic University Leuven

Leuven, Belgium

Location

London Health Sciences Centre

London, Ontario, N6A 5A5, 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

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

Leonard Wolfson Experimental Neurology Centre

London, WC1N 3BG, United Kingdom

Location

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

Limitations and Caveats

Early termination led to data for a limited number of patients. No conclusions can be drawn from the laboratory results due to data for only a few patients.

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: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Non-randomized open label

Study Record Dates

• First Submitted: February 7, 2019
• First Posted: February 11, 2019
• Study Start: September 19, 2019
• Primary Completion: July 2, 2021
• Study Completion: July 2, 2021
• Last Updated: August 24, 2023
• Results First Posted: August 24, 2023

Record last verified: 2023-08

Locations

NL (1); GB (1); CA (1); IT (2); FR (2); US (7); DE (3); BE (1); PL (2); ES (2); SE (1)