Clinical trial NCT03836716: Arimoclomol in Amyotropic Lateral Sclerosis - Open Label Extension Trial
Official title: Open Label, Non-randomized Extension Trial to Assess Long Term Safety and Efficacy of Arimoclomol in Subjects With Amyotropic Lateral Sclerosis Who Have Completed the ORARIALS-01 Trial
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Amyotrophic Lateral Sclerosis
Keywords: Arimoclomol
ALS
Lead sponsor: ZevraDenmark
Sponsor class: INDUSTRY
First posted: 2019-02-11
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Non-randomized open label
Primary purpose: TREATMENT

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.

Detailed description: The planned duration of the open-label trial was 152 weeks, but the trial was terminated early as a consequence of the results of ORARIALS-01 which did not meet any of its efficacy endpoints. Therefore, the actual mean duration of open-label treatment was approximately 28 weeks (range approximately 2 to 71 weeks).

Eligibility criteria: Inclusion Criteria:

* 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)

Exclusion Criteria:

* 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:

  1. 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).
  2. 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

Primary outcomes:
measure: Number of Participants With Treatment-emergent Adverse Events (TEAEs) Over the Open-label Treatment Period
timeFrame: From Day 1 in ORARIALS-02 to Early Termination, an average of approximately 28 weeks
measure: Mean and Change From Baseline in Clinical Safety Laboratory Tests - Hematology (1)
timeFrame: Week 76
measure: Mean and Change From Baseline in Clinical Safety Laboratory Tests - Hematology (2)
timeFrame: Week 76
measure: Mean and Change From Baseline in Clinical Safety Laboratory Tests - Erythrocytes
timeFrame: Week 76
measure: Mean and Change From Baseline in Clinical Safety Laboratory Tests - Hematocrit
timeFrame: Week 76
measure: Mean and Change From Baseline in Clinical Safety Laboratory Tests - Hemoglobin
timeFrame: Week 76
measure: Mean and Change From Baseline in Clinical Safety Laboratory Tests - Clinical Chemistry (1)
timeFrame: Week 76
measure: Mean and Change From Baseline in Clinical Safety Laboratory Tests - Clinical Chemistry (2)
timeFrame: Week 76
measure: Mean and Change From Baseline in Clinical Safety Laboratory Tests - Clinical Chemistry (3)
timeFrame: Week 76
measure: Mean and Change From Baseline in Clinical Safety Laboratory Tests - Albumin and Protein
timeFrame: Week 76
measure: Mean and Change From Baseline in Clinical Safety Laboratory Tests - Cystatin C
timeFrame: Week 76
measure: Mean and Change From Baseline in Vital Signs - Blood Pressure
timeFrame: Week 76
measure: Mean and Change From Baseline in Vital Signs - Pulse Rate
timeFrame: Week 76
measure: Mean and Change From Baseline in Vital Signs - Respiratory Rate
timeFrame: Week 76
measure: Mean and Change From Baseline in Vital Signs - Temperature
timeFrame: Week 76
measure: Number of Participants With Potentially Clinically Significant Abnormalities in Clinical Safety Laboratory Tests and Vital Signs Over the Open-label Treatment Period
timeFrame: From Day 1 in ORARIALS-02 to Early Termination, an average of approximately 28 weeks
measure: Columbia-Suicide Severity Rating Scale (C-SSRS) Over the Open-label Treatment Period
timeFrame: From Day 1 in ORARIALS-02 to Early Termination, an average of approximately 28 weeks
Secondary outcomes:
measure: Change in ALS Functional Rating Scale - Revised (ALSFRS-R) From Baseline to Week 76
timeFrame: Week 76
measure: 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)
timeFrame: 76 weeks
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: St. Joseph's Hospital and Medical Center (SJHMC) - Barrow Neurological Institute (BNI) - The Gregory W. Fulton ALS and Neuromuscular Disease Center
state: Arizona
city: Orange
country: United States
facility: UC Irvine Health ALS and Neuromuscular Center
state: California
city: Miami
country: United States
facility: University of Miami
state: Florida
city: New York
country: United States
facility: Hospital for Special Surgery
state: New York
city: Portland
country: United States
facility: Providence Brain & Spine Institute
state: Oregon
city: Philadelphia
country: United States
facility: University of Pensylvania, Perelman Center for Advanced Medicine - Penn Neuroscience Center
state: Pennsylvania
city: Charlottesville
country: United States
facility: University of Virginia Health System
state: Virginia
city: Leuven
country: Belgium
facility: Catholic University Leuven
city: London
country: Canada
facility: London Health Sciences Centre
state: Ontario
city: Montpellier
country: France
facility: Centre Hospitalier Regional Universitaire (CHRU) Montpellier - Hopital Gui De Chauliac
city: Paris
country: France
facility: Groupe Hospitalier Pitie-Salpetriere - Centre d'Investigation Clinique Neurosciences 1422
city: Berlin
country: Germany
facility: Charite - Universitaetsmedizin Berlin - Campus Virchow-Klinikum (CVK) - Ambulanz fuer ALS und andere Motoneuronenerkrankungen
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover (MHH) - Klinik fuer Neurologie
city: Ulm
country: Germany
facility: Universitaetsklinikum Ulm - Klinik fuer Neurologie
city: Milano
country: Italy
facility: Instituti Clinica Scientifici Maugeri
city: Torino
country: Italy
facility: Azienda Ospedaliero Universitaria (AUO) di Torino - Citta'della Salute e della Scienza di Torino
city: Utrecht
country: Netherlands
facility: University Medical Center Utrecht
city: Warsaw
country: Poland
facility: Centrum Medyczne NeuroProtect
city: Warsaw
country: Poland
facility: Citi Clinic
city: Barcelona
country: Spain
facility: Hospital Universitario Vall d'Hebron ALS Unit. Consultas Externas; Office: 9-10-11
city: Madrid
country: Spain
facility: Hospital Carlos III - Hospital Universitario La Paz, ALS Unit
city: Umeå
country: Sweden
facility: Umeå University Hospital
city: London
country: United Kingdom
facility: Leonard Wolfson Experimental Neurology Centre
Study officials:
affiliation: University of Miami
name: Michael Benatar, MD PhD
role: PRINCIPAL_INVESTIGATOR
References: