Phase II/III Randomized, Placebo-controlled Trial of Arimoclomol in SOD1 Positive Familial Amyotrophic Lateral Sclerosis
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).
Disease:Amyotrophic Lateral Sclerosis (ALS), Familial ALS
Study Type:Interventional Trial
Study Category:Drug Trial
Study Chair(s)/Principal Investigator(s):
Michael Benatar MBChB, DPhil, (University of Miami)
Merit Cudkowicz MD, MSc, (Massachusetts General Hospital)
Clinicaltrials.gov ID (11 digit #):NCT00706147
Coordinating Center Contact InformationUniversity of Miami
Miami, Florida 33136 United States
Full Study Summary:
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. 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. Subsequent telephonic evaluations at Month-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, -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).
Study Sponsor:FDA, ALSA
Estimated Study Start Date:12/31/2008
Estimated Study Completion Date:12/31/2014
Posting Last Modified Date:09/30/2011
Date Study Added to alsconsortium.org:10/12/2011
Estimated Study Completion Date: December 2016
Time since Symptom Onset:
Time since Diagnosis:<12 months
Can participants use Riluzole?Yes
If taking Riluzole, must be on a stable dose for at least thirty days prior to the baseline visit.
• 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 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).
• 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.
• Identifiable local medical doctor to assist with urgent care of any medical complications that may arise.
Site Contact Information
University of Miami
1120 NW 14th Street
Miami, Florida 33136
Massachusetts General Hospital
149 13th Street
Charlestown, Massachusetts 02129