ALS CLINICAL RESEARCH TRIAL - ARIMOCLOMOL

Study hypotheses: Arimoclomol, taken at a dose of 200 mg three times daily will reduce by at least 30% the rate of progression of disease. In addition, it will be safe and well tolerated in subjects with SOD1 positive familial ALS.

Primary Outcome Measures:
Rate of decline of ALSFRS-R (ALS functional rating scale-revised) over a period of 12 months will be the primary outcome measure.

Secondary Outcome Measures:
Disease progression as measured by the rate of decline of FEV6 and MUNE.

Time to death, tracheostomy or permanent assisted ventilation will be the secondary endpoint.

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.

Detailed Description: Using a seamless, adaptive, phase II/III design, we 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 to Emory, MGH, or UC Irvine for final eligibility determination, baseline evaluation and will then be randomized 1:1 to receive either placebo or arimoclomol at a dose of 100mg t.i.d.

Participants will then be evaluated again in person at Emory, MGH, or UC Irvine 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. An Emory study coordinator will perform an in-person visit at Month-12. A final evaluation will be performed via telephone at Month -13 (30 days after the last dose of study medication).

We now have approval for the off-label extension of Arimoclomol for participants who complete the 12 months of the study.

Eligibility: