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

Phase:

Phase I

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

Neals Affiliated?

Yes

Coordinating Center Contact Information

Massachusetts General Hospital
Katy Mahoney / .(JavaScript must be enabled to view this email address) / 617-643-7434
.(JavaScript must be enabled to view this email address) 149 13th Street
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

Eligibility Criteria

Gender:
Female, Male
Minimum Age:
18
Maximum Age:
N/A
Min Vital Capacity (% predicted normal):
50

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
Lucie Barbie / .(JavaScript must be enabled to view this email address) / 858-455-5463
La Jolla, California 92037
United States

Johns Hopkins University
Richard Kimball / .(JavaScript must be enabled to view this email address) / 410-955-8511
Baltimore, Maryland 21287
United States

Massachusetts General Hospital
Melanie Majkut / .(JavaScript must be enabled to view this email address) / 617-643-5581
Charlestown, Massachusetts 02129
United States

Washington University School of Medicine
Charlie Wulf / .(JavaScript must be enabled to view this email address) / 314-362-6980
St Louis, Missouri 63110
United States

Methodist Hospital Research Institute
Sharon L. Halton / .(JavaScript must be enabled to view this email address) / 713-441-3420
Houston, Texas 77030
United States
Study Results
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/