A Phase 1, Double-Blind, Placebo-Controlled, Dose Escalation Study of the Safety, Tolerability, and Pharmacokinetics of ISIS 333611 Administered Intrathecally to Patients with Familial Amyotrophic Lateral Sclerosis Due to Superoxide Dismutase 1 Gene Mutations
Recruitment Status: Recruiting
Expression of mutant SOD1 in mice and rats causes death of motor neurons and an ALS-like phenotype. ISIS SOD1 Rx has been shown to decrease levels of mutant SOD1 in rodents and may be therapeutic. This Phase I study will evaluate the safety, tolerability, and pharmacokinetics of a new investigational drug, antisense oligonucleotide ISIS 333611, also known as SOD1 Rx . The drug will be administered intrathecally (using an external pump and a temporary catheter to deliver drug into the spinal fluid) during a single, 12-hour infusion. Four dosage cohorts will each include eight participants: six participants will be randomly assigned to receive SOD1 Rx and two participants will receive placebo. A total of 32 eligible persons with familial amyotrophic lateral sclerosis (ALS) due to mutations in superoxide dismutase 1 (SOD1) gene will be enrolled in this multi-center research study.
Sponsor and Collaborators:
Isis Pharmaceuticals, Inc.
MDA
ALS Association
Massachusetts General Hospital
Washington University
NEALS Consortium
Purpose: The purpose of the study is to evaluate the safety, tolerability, and pharmacokinetics of escalating doses of SOD1 Rx in patients with familial ALS caused by mutations in the SOD1 gene.
Primary Outcome Measures:
Safety measures
Pharmacokinetic analyses
Secondary Outcome Measures:
Vital capacity
ALSFRS-R
Estimated Enrollment: 32
Study Start Date: January 2010
Detailed Description:
Each participant will be in the study for approximately 50 days, which includes four visits to the site facility and phone assessments. After the initial screening to determine eligibility, participants will be admitted to a research unit for approximately 48 hours. During this time, an intrathecal catheter (a tube inserted into the space surrounding the spinal cord) will be temporarily placed and the participant will undergo a 12 hour infusion of study drug or placebo. Safety, tolerability, and pharmacokinetic measures will be performed at regular intervals and at follow-up visits to determine the safety and tolerability of the drug.
Eligibility:
Ages Eligible for Study: 18 Years and older
Genders Eligible for Study: Both
Accepts Healthy Volunteers: No
Locations & Contact Information: Patients: Please Click HERE for a complete list of participating sites.
Patients may contact individual study coordinators at the participating sites directly.
Coordination Center Contact Information:
Pat Andres, Project Manager
617-724-8995
pandres1@partners.org
Kate Jackson, Assistant Project Manager
617-724-3871
KJackson13@partners.org
Clinical Trials Information Line
1-877-458-0631
For more information on this trial please visit:
http://clinicaltrials.gov/ct2/show/NCT01041222?term=ALS&recr=Open&type=Intr&phase=0&ran
