- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01041222
Safety, Tolerability, and Activity Study of ISIS SOD1Rx to Treat Familial Amyotrophic Lateral Sclerosis (ALS) Caused by SOD1 Gene Mutations (SOD-1)
April 12, 2012 updated by: Ionis Pharmaceuticals, Inc.
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
This study will test the safety, tolerability and pharmacokinetics of single doses of ISIS 333611 administered into the spinal canal as 12 hour infusions.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Detailed Description
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 Type
Interventional
Enrollment (Actual)
33
Phase
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Maryland
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Baltimore, Maryland, United States, 21287
- Johns Hopkins University
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Massachusetts
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Charlestown, Massachusetts, United States, 02129
- Massachusetts General Hospital-East, Neurology Clinical Trials Unit
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Missouri
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St. Louis, Missouri, United States, 63110
- Washington University School of Medicine
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Texas
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Houston, Texas, United States, 77030
- Methodist Neurological Institute
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- 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.
Exclusion Criteria:
- 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:
- Drug abuse or alcoholism within one year of the Screening visit.
- Unstable cardiac, pulmonary, renal, hepatic, endocrine, hematologic function, or active infectious disease.
- Documented history of HIV infection.
- 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:
- History of structural spinal disease including tumors and hyperplasia.
- Presence of an implanted shunt for the drainage of CSF or an implanted CNS catheter.
- Clinically significant abnormalities in hematology or clinical chemistry parameters as assessed by the Site Investigator during the Screening visit.
- 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.
- ALT or AST >/= 3 x ULN, unless discussed with and approved by the Medical Monitor.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Arm 1
0.15 mg ISIS 333611 continuous intrathecal infusion over 12 hours
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5 arms of 12 hour infusion: Arm 1 0.15 mg, Arm 2 0.5 mg, Arm 3 1.5 mg, Arm 4 3.0 mg, matching volume of placebo
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Experimental: Arm 2
0.5 mg ISIS 333611 continuous intrathecal infusion over 12 hours
|
5 arms of 12 hour infusion: Arm 1 0.15 mg, Arm 2 0.5 mg, Arm 3 1.5 mg, Arm 4 3.0 mg, matching volume of placebo
|
Experimental: Arm 3
1.5 mg ISIS 333611 continuous intrathecal infusion over 12 hours
|
5 arms of 12 hour infusion: Arm 1 0.15 mg, Arm 2 0.5 mg, Arm 3 1.5 mg, Arm 4 3.0 mg, matching volume of placebo
|
Experimental: Arm 4
3.0 mg ISIS 333611 continuous intrathecal infusion over 12 hours
|
5 arms of 12 hour infusion: Arm 1 0.15 mg, Arm 2 0.5 mg, Arm 3 1.5 mg, Arm 4 3.0 mg, matching volume of placebo
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Placebo Comparator: Placebo (phosphate buffered saline)
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5 arms of 12 hour infusion: Arm 1 0.15 mg, Arm 2 0.5 mg, Arm 3 1.5 mg, Arm 4 3.0 mg, matching volume of placebo
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
To evaluate the safety, tolerability, and pharmacokinetics of four dose levels of ISIS 333611
Time Frame: Safety analysis for dose escalation after Study Day 8
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Safety analysis for dose escalation after Study Day 8
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- Study Chair: Merit Cudkowicz, MD, MSc, Massachusetts General Hospital
- Study Chair: Timothy Miller, MD, PhD, Washington University School of Medicine
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
January 1, 2010
Primary Completion (Actual)
December 1, 2011
Study Completion (Actual)
January 1, 2012
Study Registration Dates
First Submitted
December 30, 2009
First Submitted That Met QC Criteria
December 30, 2009
First Posted (Estimate)
December 31, 2009
Study Record Updates
Last Update Posted (Estimate)
April 13, 2012
Last Update Submitted That Met QC Criteria
April 12, 2012
Last Verified
April 1, 2012
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- ISIS 333611- CS1
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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