A Phase 1, Double-Blind, Placebo-Controlled, Dose-Escalation Study of the Safety, Tolerability, & Pharmacokinetics of ISIS333611 Administered Intrathecally to Patients w Familial Amyotrophic Lateral Sclerosis Due to Superoxide Dismutase 1 Gene Mutation
Study Purpose:This study will test the safety, tolerability, and pharmacokinetics of single doses of ISIS 333611 administered as 12-hour intrathecal infusions.
Disease:Amyotrophic Lateral Sclerosis (ALS), Familial ALS
Study Type:Interventional Trial
Study Category:Drug Trial
Study Status:Not enrolling
Study Chair(s)/Principal Investigator(s):Merit Cudkowicz MD, MSc, (Massachusetts General Hospital)
Timothy Miller MD, PhD, (Washington University)
Clinicaltrials.gov ID (11 digit #):NCT01041222
Coordinating Center Contact InformationMassachusetts General Hospital
Charlestown, Massachusetts 02129 United States
Full Study Summary:This study will test the safety, tolerability, and pharmacokinetics of single doses of ISIS 333611 administered as 12-hour intrathecal infusions. Four dose levels (0.15, 0.5, 1.5 and 3 mg) will be evaluated sequentially. The volume of the infusion is 0.25 mL/12 hours. Each dose level will be studied in a cohort of 8 patients where 6 are randomized to active treatment with ISIS 333611 and 2 are randomized to placebo.
Study Sponsor:Isis Pharmaceuticals, Inc.
Participant Duration:Total enrollment time for this study is about 8 weeks. The screening visit will last approximately 2-4 hours. During the treatment phase of the study, you will be admitted to the hospital for the temporary intrathecal infusion procedure for about two days. After the treatment phase, there is a 4 week follow up period with two in-clinic visits (each visit is about 2-3 hours) and one telephone contact/visit (about 30 minutes).
Estimated Enrollment:4 cohorts of 8 patients each, total 32 patients
Estimated Study Start Date:12/31/2009
Estimated Study Completion Date:11/30/2011
Posting Last Modified Date:11/30/2011
Date Study Added to alsconsortium.org:11/01/2011
Time since Symptom Onset:N/A
Time since Diagnosis:N/A
Can participants use Riluzole?Yes
If taking riluzole, patients must be on stable dosage for at least 30 days prior to starting the study and expect to remain at that dosage until the end of the study.
Site Contact Information
Center for Neurologic Study
La Jolla, California 92037
Johns Hopkins University
Baltimore, Maryland 21287
Massachusetts General Hospital
Charlestown, Massachusetts 02129
Washington University School of Medicine
St Louis, Missouri 63110
Methodist Hospital Research Institute
Houston, Texas 77030
A total of 32 doses were given to 21 individuals with SOD1 ALS (7 subjects were dosed 2 times and 2 subjects were dosed 3 times). Results indicate that ISIS 333611 was well tolerated. No safety or tolerability concerns related to ISIS 333611 were identified. Drug levels in the spinal fluid and blood corresponded well with the predicted levels based on preclinical testing.
Read more here: http://www.ncbi.n...icles/PMC3712285/