Familial Amyotrophic Lateral SclerosisPhase 1SOD-1NCT01041222
Safety, Tolerability, and Activity Study of ISIS SOD1Rx to Treat Familial Amyotrophic Lateral Sclerosis (ALS) Caused by SOD1 Gene Mutations
A Phase 1 study testing ISIS 333611 in people with Familial Amyotrophic Lateral Sclerosis, run by Ionis Pharmaceuticals, Inc. at 4 sites in United States.
Trial summary
This study will test the safety, tolerability and pharmacokinetics of single doses of ISIS 333611 administered into the spinal canal as 12 hour infusions. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Familial Amyotrophic Lateral Sclerosis
- What is being tested?
- ISIS 333611
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 33 participants
- Where
- 4 sitesUnited States
- Study dates
- Jan 2010to Jan 2012
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
4 sites in 1 country.
United States4 sites
Johns Hopkins University
Baltimore, Maryland, 21287
Massachusetts General Hospital-East, Neurology Clinical Trials Unit
Charlestown, Massachusetts, 02129
Methodist Neurological Institute
Houston, Texas, 77030
Washington University School of Medicine
St Louis, Missouri, 63110
About this study
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
This study will test the safety, tolerability and pharmacokinetics of single doses of ISIS 333611 administered into the spinal canal as 12 hour infusions.
Read the 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.
- Conditions
- Familial Amyotrophic Lateral Sclerosis
- Being tested
- ISIS 333611
- Keywords
- Familial ALS, ALS, SOD1 Protein, ISIS 333611, SOD1Rx
- Medical subject headings
- Amyotrophic Lateral Sclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ISIS 333611Drug
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
| Study group | Role | What they receive |
|---|---|---|
| Arm 1 | Experimental | 0.15 mg ISIS 333611 continuous intrathecal infusion over 12 hours Receives: Drug: ISIS 333611 |
| Arm 2 | Experimental | 0.5 mg ISIS 333611 continuous intrathecal infusion over 12 hours Receives: Drug: ISIS 333611 |
| Arm 3 | Experimental | 1.5 mg ISIS 333611 continuous intrathecal infusion over 12 hours Receives: Drug: ISIS 333611 |
| Arm 4 | Experimental | 3.0 mg ISIS 333611 continuous intrathecal infusion over 12 hours Receives: Drug: ISIS 333611 |
| Placebo (phosphate buffered saline) | Placebo comparator | Not described Receives: Drug: ISIS 333611 |
What is being measured
The primary outcome is the main question the study is designed to answer.
To evaluate the safety, tolerability, and pharmacokinetics of four dose levels of ISIS 333611
Measured: Safety analysis for dose escalation after Study Day 8
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Dec 2009 (estimated)
- Study startJan 2010
- Primary completionDec 2011
- Study completionJan 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Familial Amyotrophic Lateral SclerosisStudies of the same condition, open and under way.
- More trials run by Ionis Pharmaceuticals, Inc.The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 33 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ionis Pharmaceuticals, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Muscular Dystrophy Association, ALS Association
- Responsible party
- Sponsor
- Investigators
- Merit Cudkowicz, MD, MSc, Study chair, Massachusetts General HospitalTimothy Miller, MD, PhD, Study chair, Washington University School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01041222
- Sponsor's protocol ID
- ISIS 333611- CS1
- Acronym
- SOD-1
- Status last verified
- Apr 2012
- First submitted
- 30 Dec 2009
- Last updated
- 13 Apr 2012
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Miller TM, Pestronk A, David W, Rothstein J, Simpson E, Appel SH, Andres PL, Mahoney K, Allred P, Alexander K, Ostrow LW, Schoenfeld D, Macklin EA, Norris DA, Manousakis G, Crisp M, Smith R, Bennett CF, Bishop KM, Cudkowicz ME. An antisense oligonucleotide against SOD1 delivered intrathecally for patients with SOD1 familial amyotrophic lateral sclerosis: a phase 1, randomised, first-in-man study. Lancet Neurol. 2013 May;12(5):435-42. doi: 10.1016/S1474-4422(13)70061-9. Epub 2013 Mar 29.
PubMed 23541756
Study at a glance
From the registry record, last updated by the sponsor on 13 Apr 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01041222
- Acronym / sponsor ID
- SOD-1 / ISIS 333611- CS1
- Conditions
- Familial Amyotrophic Lateral Sclerosis
- Keywords
- Familial ALS, ALS, SOD1 Protein, ISIS 333611, SOD1Rx
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 33 participants (actual)
- Lead sponsor
- Ionis Pharmaceuticals, Inc.Industry (pharma, biotech, devices)
- Collaborators
- Muscular Dystrophy Association, ALS Association
- Study start
- Jan 2010
- Primary completion
- Dec 2011 (actual)
- Study completion
- Jan 2012 (actual)
- First posted
- 31 Dec 2009 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will test the safety, tolerability and pharmacokinetics of single doses of ISIS 333611 administered into the spinal canal as 12 hour infusions.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| Arm 1 | Experimental | Drug: ISIS 3336110.15 mg ISIS 333611 continuous intrathecal infusion over 12 hours |
| Arm 2 | Experimental | Drug: ISIS 3336110.5 mg ISIS 333611 continuous intrathecal infusion over 12 hours |
| Arm 3 | Experimental | Drug: ISIS 3336111.5 mg ISIS 333611 continuous intrathecal infusion over 12 hours |
| Arm 4 | Experimental | Drug: ISIS 3336113.0 mg ISIS 333611 continuous intrathecal infusion over 12 hours |
| Placebo (phosphate buffered saline) | Placebo comparator | Drug: ISIS 333611 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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.
Key exclusion criteria (13 listed)
- 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:
- Any condition that may impact intrathecal infusion including:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ISIS 3336115 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 | Drug | Arm 1, Arm 2, Arm 3, Arm 4, Placebo (phosphate buffered saline) |
Primary outcome
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Apr 2012.
- Derived from this study: PubMed 23541756Miller TM, Pestronk A, David W, Rothstein J, Simpson E, Appel SH, Andres PL, Mahoney K, Allred P, Alexander K, Ostrow LW, Schoenfeld D, Macklin EA, Norris DA, Manousakis G, Crisp M, Smith R, Bennett CF, Bishop KM, Cudkowicz ME. An antisense oligonucleotide against SOD1 delivered intrathecally for patients with SOD1 familial amyotrophic lateral sclerosis: a phase 1, randomised, first-in-man study. Lancet Neurol. 2013 May;12(5):435-42. doi: 10.1016/S1474-4422(13)70061-9. Epub 2013 Mar 29.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Merit Cudkowicz, MD, MSc study chair
Massachusetts General Hospital
Timothy Miller, MD, PhD study chair
Washington University School of Medicine
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing ISIS 333611 in people with Familial Amyotrophic Lateral Sclerosis, run by Ionis Pharmaceuticals, Inc. at 4 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 13 Apr 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01041222, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Apr 2012.