Safety, Tolerability, and Activity Study of ISIS SOD1Rx to Treat Familial Amyotrophic Lateral Sclerosis (ALS) Caused by SOD1 Gene Mutations (SOD-1)
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ClinicalTrials.gov Identifier: NCT01041222 |
Recruitment Status :
Completed
First Posted : December 31, 2009
Last Update Posted : April 13, 2012
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Condition or disease | Intervention/treatment | Phase |
---|---|---|
Familial Amyotrophic Lateral Sclerosis | Drug: ISIS 333611 | Phase 1 |
Study Type : | Interventional (Clinical Trial) |
Actual Enrollment : | 33 participants |
Allocation: | Randomized |
Intervention Model: | Parallel Assignment |
Masking: | Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) |
Primary Purpose: | Treatment |
Official Title: | 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 |
Study Start Date : | January 2010 |
Actual Primary Completion Date : | December 2011 |
Actual Study Completion Date : | January 2012 |

Arm | Intervention/treatment |
---|---|
Experimental: Arm 1
0.15 mg ISIS 333611 continuous intrathecal infusion over 12 hours
|
Drug: ISIS 333611
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 2
0.5 mg ISIS 333611 continuous intrathecal infusion over 12 hours
|
Drug: ISIS 333611
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
|
Drug: ISIS 333611
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
|
Drug: ISIS 333611
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 |
Placebo Comparator: Placebo (phosphate buffered saline) |
Drug: ISIS 333611
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 |
- 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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Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
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.
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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.
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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.

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01041222
United States, Maryland | |
Johns Hopkins University | |
Baltimore, Maryland, United States, 21287 | |
United States, Massachusetts | |
Massachusetts General Hospital-East, Neurology Clinical Trials Unit | |
Charlestown, Massachusetts, United States, 02129 | |
United States, Missouri | |
Washington University School of Medicine | |
St. Louis, Missouri, United States, 63110 | |
United States, Texas | |
Methodist Neurological Institute | |
Houston, Texas, United States, 77030 |
Study Chair: | Merit Cudkowicz, MD, MSc | Massachusetts General Hospital | |
Study Chair: | Timothy Miller, MD, PhD | Washington University School of Medicine |
Responsible Party: | Ionis Pharmaceuticals, Inc. |
ClinicalTrials.gov Identifier: | NCT01041222 |
Other Study ID Numbers: |
ISIS 333611- CS1 |
First Posted: | December 31, 2009 Key Record Dates |
Last Update Posted: | April 13, 2012 |
Last Verified: | April 2012 |
Familial ALS ALS SOD1 Protein ISIS 333611 SOD1Rx |
Motor Neuron Disease Amyotrophic Lateral Sclerosis Sclerosis Pathologic Processes Neurodegenerative Diseases Nervous System Diseases |
Neuromuscular Diseases Spinal Cord Diseases Central Nervous System Diseases TDP-43 Proteinopathies Proteostasis Deficiencies Metabolic Diseases |