Study Purpose:This study will test the safety, tolerability and pharmacokinetics of single doses of ISIS 333611 administered into the spinal canal as 12 hour infusions.
Familial Amyotrophic Lateral Sclerosis
Type of Intervention:
Study Chair(s)/Principal Investigator(s):
Merit Cudkowicz, MD, MSc, Massachusetts General Hospital, Timothy Miller, MD, PhD, Washington University School of Medicine
Coordinating Center Contact Information
Massachusetts General Hospital
149 13th Street
Charlestown, Massachusetts, 02129 United States
Full Study Summary:
Ionis Pharmaceuticals, Inc.
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 Study Start Date:
12 / 31 / 2009
Estimated Study Completion Date:
01 / 01 / 2012
Posting Last Modified Date:
04 / 13 / 2012
Date Study Added to neals.org:
12 / 31 / 2009
Can participants use Riluzole?
- Clinical signs of weakness attributed to ALS.
- Familial ALS with a documented SOD1 gene mutation.
- Age 18 years or older.
- Capable of providing informed consent and willing to comply with trial procedures and time commitments.
- Vital capacity (VC) at least 50% predicted value for gender, height and age at screening and not using invasive respiratory support.
- 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.
- Medically able to undergo temporary insertion of intrathecal catheter.
- Normal test results for coagulation parameters.
- Treatment with another investigational drug for ALS (e.g. pyrimethamine, ceftriaxone, lithium, tamoxifen, arimoclomol, high dose creatine, biological agent, or device within 1-month of Screening or 5 half-lives of study agent, whichever is longer. No prior treatment with siRNA, cell transplant, or gene therapy is allowed.
- Dosing in ISIS 333611-CS1 in a previous dose cohort within 60 days of screening.
- Presence of any of the following clinical conditions:
1. Drug abuse or alcoholism within one year of the Screening visit.
2. Unstable cardiac, pulmonary, renal, hepatic, endocrine, hematologic function, or active infectious disease.
3. Documented history of HIV infection.
4. Unstable psychiatric illness defined as psychosis or untreated major depression within 90 days of the Screening Visit.
- Any condition that may impact intrathecal infusion including:
1. History of structural spinal disease including tumors and hyperplasia.
2. Presence of an implanted shunt for the drainage of CSF or an implanted CNS catheter.
3. Clinically significant abnormalities in hematology or clinical chemistry parameters as assessed by the Site Investigator during the Screening visit.
4. Ongoing medical condition that according to the Site Investigator would interfere with the conduct and assessments of the study. Examples are medical disability (e.g., severe degenerative arthritis, compromised nutritional state, peripheral neuropathy) that would interfere with the assessment of safety and efficacy of study material or device performance, or would compromise the ability of the patient to undergo study procedures.
5. ALT or AST >/= 3 x ULN, unless discussed with and approved by the Medical Monitor.
Johns Hopkins University
Massachusetts General Hospital-East, Neurology Clinical Trials Unit
Washington University School of Medicine
St. Louis, Missouri
Methodist Neurological Institute