Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of ISIS 443139 in Participants With Early Manifest Huntington's Disease
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
2 other identifiers
interventional
46
3 countries
9
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_1
Started Aug 2015
Typical duration for phase_1
9 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
August 1, 2015
CompletedStudy Start
First participant enrolled
August 6, 2015
CompletedFirst Posted
Study publicly available on registry
August 10, 2015
CompletedPrimary Completion
Last participant's last visit for primary outcome
November 8, 2017
CompletedStudy Completion
Last participant's last visit for all outcomes
November 8, 2017
CompletedResults Posted
Study results publicly available
May 31, 2019
CompletedMay 31, 2019
May 1, 2019
2.3 years
August 1, 2015
May 6, 2019
May 30, 2019
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Number of Participants With Treatment-related Adverse Events (TEAEs)
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.
Up to approximately 28 weeks
Secondary Outcomes (1)
Observed Cerebrospinal Fluid (CSF) Concentration for ISIS 443139
Days 1, 29, 57, 85, and 113 or 141
Other Outcomes (6)
Maximum Plasma Concentration (Cmax) for ISIS 443139
Days 1 and 85
Time to Maximum Plasma Concentration (Tmax) for ISIS 443139
Days 1 and 85
Change From Baseline in CSF Mutant Huntingtin (fM) Protein Concentration
Baseline to Final Assessment (Day 85 or 113)
- +3 more other outcomes
Study Arms (6)
ISIS 443139 10 mg
EXPERIMENTALParticipants received ISIS 443139, 10 milligrams (mg), by intrathecal injection, on Study Days 1, 29, 57, and 85.
ISIS 443139 30 mg
EXPERIMENTALParticipants received ISIS 443139, 30 mg, by intrathecal injection, on Study Days 1, 29, 57, and 85.
ISIS 443139 60 mg
EXPERIMENTALParticipants received ISIS 443139, 60 mg, by intrathecal injection, on Study Days 1, 29, 57, and 85.
ISIS 443139 90 mg
EXPERIMENTALParticipants received ISIS 443139, 90 mg, by intrathecal injection, on Study Days 1, 29, 57, and 85.
ISIS 443139 120 mg
EXPERIMENTALParticipants received ISIS 443139, 120 mg, by intrathecal injection, on Study Days 1, 29, 57, and 85.
Placebo
PLACEBO COMPARATORParticipants received placebo, by intrathecal injection, on Study Days 1, 29, 57, and 85.
Interventions
ISIS 443139, 10 mg, was administered by intrathecal injection, on Study Days 1, 29, 57, and 85.
ISIS 443139, 30 mg, was administered by intrathecal injection, on Study Days 1, 29, 57, and 85.
ISIS 443139, 60 mg, was administered by intrathecal injection, on Study Days 1, 29, 57, and 85.
ISIS 443139, 90 mg, was administered by intrathecal injection, on Study Days 1, 29, 57, and 85.
ISIS 443139, 120 mg, was administered by intrathecal injection, on Study Days 1, 29, 57, and 85.
Placebo was administered by intrathecal injection, on Study Days 1, 29, 57, and 85.
Eligibility Criteria
You may qualify if:
- 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
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (9)
University of British Columbia
Vancouver, British Columbia, V6T 2B5, Canada
Charite University Berlin
Berlin, 10117, Germany
Ruhr-University of Bochum
Bochum, 44791, Germany
Ulm University Hospital
Ulm, 89081, Germany
University Hospitals Birmingham
Birmingham, B15 2TH, United Kingdom
Cambridge University Hospital
Cambridge, CB2 0PY, United Kingdom
University Hospital of Wales
Cardiff, CF14 4XN, United Kingdom
University College London
London, WC1N 3BG, United Kingdom
University of Manchester, St. Mary's Hospital
Manchester, M13 9WL, United Kingdom
Related Publications (3)
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.
PMID: 31381524DERIVEDTabrizi 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.
PMID: 31059641DERIVEDRodrigues FB, Wild EJ. Huntington's Disease Clinical Trials Corner: February 2018. J Huntingtons Dis. 2018;7(1):89-98. doi: 10.3233/JHD-189001.
PMID: 29480210DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Limitations and Caveats
There are no limitations or caveats for this study.
Results Point of Contact
- Title
- Ionis Pharmaceuticals, Inc.
- Organization
- Ionis Pharmaceuticals, Inc.
Publication Agreements
- PI is Sponsor Employee
- No
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
August 1, 2015
First Posted
August 10, 2015
Study Start
August 6, 2015
Primary Completion
November 8, 2017
Study Completion
November 8, 2017
Last Updated
May 31, 2019
Results First Posted
May 31, 2019
Record last verified: 2019-05