Phase II/III Randomized, Placebo-controlled Trial of Arimoclomol in SOD1 Positive Familial Amyotrophic Lateral Sclerosis

NCT00706147 | Completed Phase 2 DMC

• 2 other identifiers: 201007583517
• Study Type: interventional
• Target: 38
• Locations: 1 country
• Sites: 2

Brief Summary

The purpose of this study will be to demonstrate the safety, tolerability, and efficacy of arimoclomol in subjects with SOD1 positive familial Amyotrophic Lateral Sclerosis (ALS). This type of ALS is HEREDITARY (runs in families), and at least one other person in the family must have had ALS. Study hypotheses: Arimoclomol, taken at a dose of 200 mg three times daily will improve survival as defined by time to death, tracheostomy or permanent assisted ventilation. In addition, it will be safe and well tolerated in subjects with SOD1 positive familial ALS. Funding Source - FDA-OOPD

Conditions

Amyotrophic Lateral Sclerosis

Keywords

Hereditary ALS; Hereditary neurological disease; Lou Gehrig's Disease; Motor Neuron Disease; Amyotrophic Lateral Sclerosis (ALS); Familial ALS; Neuromuscular disease; SOD1 mutation; Superoxide dismutase; SOD1 positive ALS; inherited ALS

Outcome Measures

Primary Outcomes (1)

• Time to death, tracheostomy or permanent assisted ventilation will be the primary outcome measure.

  12 months

Secondary Outcomes (3)

• Rate of decline of ALSFRS-R (ALS functional rating scale-revised) over a period of up to 12 months.

  12 months

• Disease progression as measured by the rate of decline of FEV6.

  12 months

• Safety and tolerability of arimoclomol will be evaluated by using vital signs and weight, clinical laboratory measures, physical examination, report of adverse events, and the proportion of subjects completing the study on assigned treatment.

  12 months

Study Arms (2)

1

PLACEBO COMPARATOR

Drug: Placebo

2

ACTIVE COMPARATOR

Drug: Arimoclomol

Interventions

Arimoclomol DRUG

Drug: Arimoclomol capsules given three times per day

Also known as: Arimoclomol (BRX-345)

2

Placebo DRUG

Drug: Placebo capsules given three times per day

1

Eligibility Criteria

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

You may qualify if:

• Type of ALS that is hereditary (runs in families) only.
• El Escorial criteria for familial ALS and a family history of a pathogenic mutation in a gene known to be associated with ALS, such as the SOD1 gene.
• Willingness to undergo genetic testing and to learn the results.
• Demonstrable mutation in the SOD1 gene that is reported to be associated with a rapid rate of disease progression (i.e. A4V, A4T, C6F, C6G, V7E, L8Q, G10V, G41S, H43R, H48Q, D90V, G93A, D101H, D101Y, L106V, I112M, I112T, R115G, L126X, G127X, A145T, V148G, V148I) or possibly associated with rapidly progressive disease (E21G, G37R, L38V, D76Y, L84F, L84V, N86S, D90A het, G93R, I104F, I113T, L144F, L144S).
• Age 18 years or older; male or female.
• Capable of providing informed consent and complying with trial procedures.
• Diagnosis within less than 9 months of the anticipated date of the baseline visit AND study participants' subjective evaluation that they expect their physical condition to permit travel to the study site for both the baseline and 2-month study visits.
• Women must not be able to become pregnant (e.g. post menopausal for at least one year, surgically sterile, or practicing adequate birth control methods) for the duration of the study. Adequate contraception includes: oral contraception, implanted contraception, intrauterine device in place for at least 3 months, or barrier method in conjunction with spermicide.
• Women of childbearing potential must have a negative pregnancy test at screening visit and be non-lactating.
• Willing to remain on a stable dose of Riluzole or to remain off Riluzole for the duration of the trial.
• Identifiable local medical doctor to assist with urgent care of any medical complications that may arise.

You may not qualify if:

• History of known sensitivity or intolerability to Arimoclomol or to any other related compound.
• Exposure to any investigational drug within 30 days of the screening visit.
• Presence of any of the following clinical conditions:
• Substance abuse within the past year.
• Unstable cardiac, pulmonary, renal, hepatic, endocrine, hematologic, or active infectious disease.
• AIDS or AIDS-related complex.
• Unstable psychiatric illness defined as psychosis (hallucinations or delusions), untreated major depression within 90 days of the screening visit.
• Positive pregnancy test at screening visit.
• Screening laboratory values:
• Creatinine greater than 1.5.
• Alanine aminotransferase (ALT) or Aspartate aminotransferase (AST). greater than 3.0 times the upper limit of normal.
• Total bilirubin greater than 2.0 times the upper limit of normal.
• White blood cell (WBC) count less than 3,500/mm3.
• Platelet concentration less than 100,000/ul.
• Hematocrit level less than 33 for female or less than 35 for male.

Sponsors & Collaborators

• University of Miami: lead
• Massachusetts General Hospital: collaborator

Study Sites (2)

University of Miami Miller School of Medicine

Miami, Florida, 33136, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Related Publications (1)

• Benatar M, Wuu J, Andersen PM, Atassi N, David W, Cudkowicz M, Schoenfeld D. Randomized, double-blind, placebo-controlled trial of arimoclomol in rapidly progressive SOD1 ALS. Neurology. 2018 Feb 13;90(7):e565-e574. doi: 10.1212/WNL.0000000000004960. Epub 2018 Jan 24.

  PMID: 29367439 DERIVED

MeSH Terms

Conditions

Amyotrophic Lateral Sclerosis; Motor Neuron Disease; Neuromuscular Diseases

Interventions

arimoclomol

Condition Hierarchy (Ancestors)

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

Study Officials

• Michael Benatar, MBChB, DPhil

  University of Miami

  PRINCIPAL INVESTIGATOR

• Merit Cudkowicz, MD, MSc

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor, Department of Neurology

Study Record Dates

• First Submitted: June 24, 2008
• First Posted: June 27, 2008
• Study Start: January 1, 2009
• Primary Completion: December 1, 2014
• Study Completion: November 1, 2016
• Last Updated: January 11, 2019

Record last verified: 2019-01

Locations

US (2)