- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02519036
Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of ISIS 443139 in Participants With Early Manifest Huntington's Disease
May 30, 2019 updated by: Ionis Pharmaceuticals, Inc.
A Randomized, Double-blind, Placebo-controlled Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Multiple Ascending Doses of Intrathecally Administered ISIS 443139 in Patients With Early Manifest Huntington's Disease
This study tested the safety, tolerability, pharmacokinetics and pharmacodynamics of multiple ascending doses of ISIS 443139 administered intrathecally to adult participants with early manifest Huntington's Disease.
Study Overview
Status
Completed
Conditions
Study Type
Interventional
Enrollment (Actual)
46
Phase
- Phase 2
- 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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British Columbia
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Vancouver, British Columbia, Canada, V6T 2B5
- University of British Columbia
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Berlin, Germany, 10117
- Charite University Berlin
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Bochum, Germany, 44791
- Ruhr-University of Bochum
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Ulm, Germany, 89081
- Ulm University Hospital
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Birmingham, United Kingdom, B15 2TH
- University Hospitals Birmingham
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Cambridge, United Kingdom, CB2 0PY
- Cambridge University Hospital
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Cardiff, United Kingdom, CF14 4XN
- University Hospital of Wales
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London, United Kingdom, WC1N 3BG
- University College London
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Manchester, United Kingdom, M13 9WL
- University of Manchester, St. Mary's Hospital
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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
23 years to 63 years (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Key Inclusion Criteria:
- Diagnosed with early manifest Huntington's disease
- Male or female, aged 25 to 65 years, inclusive, at the time of informed consent
- Able and willing to meet all study requirements, including travel to Study Center and participation in all procedures and measurements at study visits
- Have a trial partner who is reliable, competent and at least 18 years of age, is willing to accompany the participant to select trial visits and to be available to the Study Center by phone if needed
- Able to tolerate MRI scans, blood draws and lumbar punctures
- Reside within 4 hours travel of the Study Center
Key Exclusion Criteria:
- Clinically significant medical condition, such as severe chorea, active suicidal ideation or any other conditions which would make the participant unsuitable for inclusion or could interfere with the participant participating in or completing the study
- Recent treatment with another investigational drug, biological agent, or device
- Prior treatment with an antisense oligonucleotide [including small interfering ribonucleic acid (siRNA)]
- Any history of gene therapy or cell transplantation or any other experimental brain surgery
- Presence of an implanted shunt for the drainage of cerebrospinal fluid (CSF) or an implanted central nervous system (CNS) catheter
- History of post-lumbar-puncture headache of moderate or severe intensity and/or blood patch
- Malignancy within 5 years of Screening, except for basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix that has been successfully treated
- Hospitalization for any major medical or surgical procedure involving general anesthesia within 12 weeks of Screening or planned during the study
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: ISIS 443139 10 mg
Participants received ISIS 443139, 10 milligrams (mg), by intrathecal injection, on Study Days 1, 29, 57, and 85.
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ISIS 443139, 10 mg, was administered by intrathecal injection, on Study Days 1, 29, 57, and 85.
Other Names:
|
Experimental: ISIS 443139 30 mg
Participants received ISIS 443139, 30 mg, by intrathecal injection, on Study Days 1, 29, 57, and 85.
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ISIS 443139, 30 mg, was administered by intrathecal injection, on Study Days 1, 29, 57, and 85.
Other Names:
|
Experimental: ISIS 443139 60 mg
Participants received ISIS 443139, 60 mg, by intrathecal injection, on Study Days 1, 29, 57, and 85.
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ISIS 443139, 60 mg, was administered by intrathecal injection, on Study Days 1, 29, 57, and 85.
Other Names:
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Experimental: ISIS 443139 90 mg
Participants received ISIS 443139, 90 mg, by intrathecal injection, on Study Days 1, 29, 57, and 85.
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ISIS 443139, 90 mg, was administered by intrathecal injection, on Study Days 1, 29, 57, and 85.
Other Names:
|
Experimental: ISIS 443139 120 mg
Participants received ISIS 443139, 120 mg, by intrathecal injection, on Study Days 1, 29, 57, and 85.
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ISIS 443139, 120 mg, was administered by intrathecal injection, on Study Days 1, 29, 57, and 85.
Other Names:
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Placebo Comparator: Placebo
Participants received placebo, by intrathecal injection, on Study Days 1, 29, 57, and 85.
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Placebo was administered by intrathecal injection, on Study Days 1, 29, 57, and 85.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of Participants With Treatment-related Adverse Events (TEAEs)
Time Frame: Up to approximately 28 weeks
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An adverse event (AE) was any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the study or use of investigational drug product, whether or not the AE was considered related to the investigational drug product.
An AE was to be regarded as a TEAE if it was present prior to receiving the first dose of Study Drug and subsequently worsened or was not present prior to receiving the first dose of Study Drug but subsequently appeared.
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Up to approximately 28 weeks
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Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Observed Cerebrospinal Fluid (CSF) Concentration for ISIS 443139
Time Frame: Days 1, 29, 57, 85, and 113 or 141
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Days 1, 29, 57, 85, and 113 or 141
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Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Maximum Plasma Concentration (Cmax) for ISIS 443139
Time Frame: Days 1 and 85
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Days 1 and 85
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Time to Maximum Plasma Concentration (Tmax) for ISIS 443139
Time Frame: Days 1 and 85
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Days 1 and 85
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Change From Baseline in CSF Mutant Huntingtin (fM) Protein Concentration
Time Frame: Baseline to Final Assessment (Day 85 or 113)
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Baseline was defined as the last non-missing measure prior to the first dose.
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Baseline to Final Assessment (Day 85 or 113)
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Change From Baseline in CSF Neurofilament Light Chain Concentration
Time Frame: Baseline to Final Assessment (Day 85 or 113)
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Baseline was defined as the last non-missing measure prior to the first dose.
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Baseline to Final Assessment (Day 85 or 113)
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Ventricular Volume as Assessed by Structural Magnetic Resonance Imaging (MRI)
Time Frame: Screening, Days 113, and 197
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Screening, Days 113, and 197
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Huntington's Disease (HD) Cognitive Assessment Battery Composite Score
Time Frame: Baseline to Days 84, 141, and 197
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The HD Cognitive Battery was developed as a means of measuring cognitive dysfunction in late premanifest and early manifest HD patients.
The 6 tests that comprise the battery were selected based on test sensitivity, practice effects, reliability, domain coverage, feasibility for use in clinical trials, and tolerability.
A composite cognitive score was calculated by the average z-score of the 6 individual tests.
A positive change from baseline indicated improvement in cognitive function; a negative change indicated worsening.
Baseline was defined as the last non-missing measure prior to the first dose.
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Baseline to Days 84, 141, and 197
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
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.
General Publications
- Rodrigues FB, Ferreira JJ, Wild EJ. Huntington's Disease Clinical Trials Corner: June 2019. J Huntingtons Dis. 2019;8(3):363-371. doi: 10.3233/JHD-199003.
- Tabrizi SJ, Leavitt BR, Landwehrmeyer GB, Wild EJ, Saft C, Barker RA, Blair NF, Craufurd D, Priller J, Rickards H, Rosser A, Kordasiewicz HB, Czech C, Swayze EE, Norris DA, Baumann T, Gerlach I, Schobel SA, Paz E, Smith AV, Bennett CF, Lane RM; Phase 1-2a IONIS-HTTRx Study Site Teams. Targeting Huntingtin Expression in Patients with Huntington's Disease. N Engl J Med. 2019 Jun 13;380(24):2307-2316. doi: 10.1056/NEJMoa1900907. Epub 2019 May 6. Erratum In: N Engl J Med. 2019 Oct 3;381(14):1398.
- Rodrigues FB, Wild EJ. Huntington's Disease Clinical Trials Corner: February 2018. J Huntingtons Dis. 2018;7(1):89-98. doi: 10.3233/JHD-189001.
Helpful Links
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 (Actual)
August 6, 2015
Primary Completion (Actual)
November 8, 2017
Study Completion (Actual)
November 8, 2017
Study Registration Dates
First Submitted
August 1, 2015
First Submitted That Met QC Criteria
August 5, 2015
First Posted (Estimate)
August 10, 2015
Study Record Updates
Last Update Posted (Actual)
May 31, 2019
Last Update Submitted That Met QC Criteria
May 30, 2019
Last Verified
May 1, 2019
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Mental Disorders
- Brain Diseases
- Central Nervous System Diseases
- Nervous System Diseases
- Neurocognitive Disorders
- Genetic Diseases, Inborn
- Basal Ganglia Diseases
- Movement Disorders
- Neurodegenerative Diseases
- Dyskinesias
- Heredodegenerative Disorders, Nervous System
- Dementia
- Cognition Disorders
- Chorea
- Huntington Disease
Other Study ID Numbers
- ISIS 443139-CS1
- 2015-000381-66 (EudraCT Number)
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Yes
product manufactured in and exported from the U.S.
Yes
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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