| Study summary: |
|
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 or MGH 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 Emory or MGH 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). Participants who complete ths study will
be eligible to receive open-label Arimoclomol. |
| Criteria: |
|
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.
- Not taking riluzole, or on a stable dose for at least thirty days prior to the
baseline visit.
- 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:
1. Substance abuse within the past year
2. Unstable cardiac, pulmonary, renal, hepatic, endocrine, hematologic, or active
infectious disease
3. AIDS or AIDS-related complex
4. Unstable psychiatric illness defined as psychosis (hallucinations or delusions),
untreated major depression within 90 days of the screening visit.
5. Positive pregnancy test at screening visit
- Screening laboratory values:
1. Creatinine greater than 1.5
2. Alanine aminotransferase (ALT) or Aspartate aminotransferase (AST) greater
than 3.0 times the upper limit of normal
3. Total bilirubin greater than 2.0 times the upper limit of normal
4. White blood cell (WBC) count less than 3,500/mm3
5. Platelet concentration less than 100,000/ul
6. Hematocrit level less than 33 for female or less than 35 for male
- Female patients who are breast-feeding |