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Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of IONIS-HTTRx in Patients With Early Manifest Huntington's Disease
This study is ongoing, but not recruiting participants.
Sponsor:
Ionis Pharmaceuticals, Inc.
Information provided by (Responsible Party):
Ionis Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier:
NCT02519036
First received: August 1, 2015
Last updated: June 22, 2017
Last verified: June 2017
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Purpose
This study will test the safety, tolerability, pharmacokinetics and pharmacodynamics of multiple ascending doses of IONIS-HTTRx administered intrathecally to adult patients with early manifest Huntington's Disease.
| Condition | Intervention | Phase |
|---|---|---|
| Huntington's Disease | Drug: IONIS HTTRx Drug: Placebo | Phase 1 Phase 2 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Intervention Model: Parallel Assignment Masking: Participant, Investigator Primary Purpose: Treatment |
| Official Title: | 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 |
Resource links provided by NLM:
Further study details as provided by Ionis Pharmaceuticals, Inc.:
Primary Outcome Measures:
- Safety (The number of participants with adverse events) [ Time Frame: Participants will be followed for the duration of the study; an expected 29 weeks ]The number of participants with adverse events
- Tolerability (The number of participants with adverse events) [ Time Frame: Participants will be followed for the duration of the study; an expected 29 weeks ]The number of participants with adverse events
Secondary Outcome Measures:
- CSF Pharmacokinetics (The observed CSF drug concentration) [ Time Frame: Day 1, Day 29, Day 57, Day 85, and Day 113 or Day 141 ]
Other Outcome Measures:
- Peak ISIS 443139 plasma concentration, Cmax (ug/mL) [ Time Frame: Day 1 and Day 85 ]
- Time to peak ISIS 443139 plasma concentration, Tmax (hours) [ Time Frame: Day 1 and Day 85 ]
- CSF huntingtin protein concentration (fM) [ Time Frame: Day 1, Day 29, Day 57, Day 85, and Day 113 or Day 141 ]
- CSF neurofilament light chain (pg/mL) [ Time Frame: Day 1, Day 29, Day 57, Day 85, and Day 113 or Day 141 ]
- Ventricular volume (mL) [ Time Frame: Screening, Day 113, and Day 197 ]
- Huntington's disease cognitive assessment battery composite score (unitless) [ Time Frame: Screening, Day -1, Day 84, Day 141, and Day 197 ]
| Enrollment: | 46 |
| Actual Study Start Date: | August 31, 2015 |
| Estimated Study Completion Date: | November 30, 2017 |
| Estimated Primary Completion Date: | July 31, 2017 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: IONIS HTTRx
IONIS HTTRx is administered intrathecally at 4 week intervals over the course of a 13 week treatment period for dose levels A, B, C, D and E.
|
Drug: IONIS HTTRx
Other Name: ISIS 443139
|
|
Placebo Comparator: Placebo
A placebo is administered intrathecally at 4 week intervals over the course of 13 weeks.
|
Drug: Placebo |
Eligibility| Ages Eligible for Study: | 25 Years to 65 Years (Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
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 patient 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 patient unsuitable for inclusion or could interfere with the patient participating in or completing the study
- Recent treatment with another investigational drug, biological agent, or device
- Prior treatment with an antisense oligonucleotide (including siRNA)
- Any history of gene therapy or cell transplantation or any other experimental brain surgery
- Presence of an implanted shunt for the drainage of CSF or an implanted 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
Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study.
To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.
Please refer to this study by its ClinicalTrials.gov identifier: NCT02519036
Please refer to this study by its ClinicalTrials.gov identifier: NCT02519036
Locations
| Canada, British Columbia | |
| University of British Columbia | |
| Vancouver, British Columbia, Canada, V6T 2B5 | |
| Germany | |
| Charite University Berlin | |
| Berlin, Germany, 10117 | |
| Ruhr-University of Bochum | |
| Bochum, Germany, 44791 | |
| Ulm University Hospital | |
| Ulm, Germany, 89081 | |
| United Kingdom | |
| University Hospitals Birmingham | |
| Birmingham, United Kingdom, B15 2TH | |
| Cambridge University Hospital | |
| Cambridge, United Kingdom, CB2 0PY | |
| University Hospital of Wales | |
| Cardiff, United Kingdom, CF14 4XN | |
| University College London | |
| London, United Kingdom, WC1N 3BG | |
| University of Manchester, St. Mary's Hospital | |
| Manchester, United Kingdom, M13 9WL | |
Sponsors and Collaborators
Ionis Pharmaceuticals, Inc.
More Information
Additional Information:
| Responsible Party: | Ionis Pharmaceuticals, Inc. |
| ClinicalTrials.gov Identifier: | NCT02519036 History of Changes |
| Other Study ID Numbers: |
ISIS 443139-CS1 |
| Study First Received: | August 1, 2015 |
| Last Updated: | June 22, 2017 |
Keywords provided by Ionis Pharmaceuticals, Inc.:
|
Huntington's Disease HTTRx Early Manifest Huntington's Disease |
Additional relevant MeSH terms:
|
Huntington Disease Basal Ganglia Diseases Brain Diseases Central Nervous System Diseases Nervous System Diseases Dementia Chorea Dyskinesias |
Movement Disorders Heredodegenerative Disorders, Nervous System Neurodegenerative Diseases Genetic Diseases, Inborn Cognition Disorders Neurocognitive Disorders Mental Disorders |
ClinicalTrials.gov processed this record on July 07, 2017