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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00706147
Recruitment Status : Completed
First Posted : June 27, 2008
Last Update Posted : January 11, 2019
Massachusetts General Hospital
Information provided by (Responsible Party):
Michael Benatar, University of Miami

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

Condition or disease Intervention/treatment Phase
Amyotrophic Lateral Sclerosis Drug: Arimoclomol Drug: Placebo Phase 2 Phase 3

Detailed Description:
Using a seamless, adaptive, phase II/III design, the investigators will determine the safety and efficacy of arimoclomol in patients with SOD1 positive familial ALS. Both stage-1 and stage-2 are randomized, double-blind and placebo-controlled in a population of patients with rapidly progressive SOD1 positive familial ALS. Patients with ALS, a history of a relative affected with ALS (i.e. familial ALS) and the presence of a demonstrable mutation in the SOD1 gene that is known to be associated with rapidly progressive disease, will be eligible for inclusion in this study. Potentially eligible subjects will undergo screening via telephone and, if necessary, review of outside medical records. The intervention will continue for up to 12 months. In the event that a participant reaches a study endpoint (e.g. tracheostomy or permanently assisted ventilation) study drug will be terminated. Subjects who meet all eligibility criteria will travel a study site for final eligibility determination, baseline evaluation and will then be randomized 1:1 to receive either placebo or arimoclomol at a dose of 200 mg t.i.d. Participants will then be evaluated again in person at a study site at Month-2. Telephonic evaluations at Month-1, 3, 4, 5, 6, 8, and 10 will be performed in participants' homes. Safety and tolerability evaluations will be performed at each of these visits. Collection of blood samples for safety laboratory analyses and measurement of blood pressure, heart rate, respiratory rate, temperature and weight will be performed at Months-1, 3, 4, 5, 6, 8, and 10 in the participant's home by a representative of a medical monitoring company. A study coordinator may perform an in-person visit at Month-12, or this visit may occur telephonically. A final evaluation will be performed via telephone at Month-13 (30 days after the last dose of study medication).

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 38 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: Phase II/III Randomized, Placebo-Controlled Trial of Arimoclomol in SOD1 Positive Familial Amyotrophic Lateral Sclerosis (ALS)
Study Start Date : January 2009
Actual Primary Completion Date : December 2014
Actual Study Completion Date : November 2016

Arm Intervention/treatment
Placebo Comparator: 1 Drug: Placebo
Drug: Placebo capsules given three times per day

Active Comparator: 2 Drug: Arimoclomol
Drug: Arimoclomol capsules given three times per day
Other Name: Arimoclomol (BRX-345)

Primary Outcome Measures :
  1. Time to death, tracheostomy or permanent assisted ventilation will be the primary outcome measure. [ Time Frame: 12 months ]

Secondary Outcome Measures :
  1. Rate of decline of ALSFRS-R (ALS functional rating scale-revised) over a period of up to 12 months. [ Time Frame: 12 months ]
  2. Disease progression as measured by the rate of decline of FEV6. [ Time Frame: 12 months ]
  3. 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. [ Time Frame: 12 months ]

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • 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.
  • Absence of any of the exclusion criteria.

Exclusion Criteria:

  • 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.
  • Female patients who are breast-feeding.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00706147

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United States, Florida
University of Miami Miller School of Medicine
Miami, Florida, United States, 33136
United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
Sponsors and Collaborators
University of Miami
Massachusetts General Hospital
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Principal Investigator: Michael Benatar, MBChB, DPhil University of Miami
Principal Investigator: Merit Cudkowicz, MD, MSc Massachusetts General Hospital
Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: Michael Benatar, Professor, Department of Neurology, University of Miami Identifier: NCT00706147    
Other Study ID Numbers: 20100758
3517 ( Other Grant/Funding Number: OOPD )
First Posted: June 27, 2008    Key Record Dates
Last Update Posted: January 11, 2019
Last Verified: January 2019
Keywords provided by Michael Benatar, University of Miami:
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
Additional relevant MeSH terms:
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Motor Neuron Disease
Amyotrophic Lateral Sclerosis
Pathologic Processes
Neurodegenerative Diseases
Nervous System Diseases
Neuromuscular Diseases
Spinal Cord Diseases
Central Nervous System Diseases
TDP-43 Proteinopathies
Proteostasis Deficiencies
Metabolic Diseases