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

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.