Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of ISIS 443139 in Participants With Early Manifest Huntington's Disease

Phase 1

Completed

• Conditions: Huntington's Disease
• Interventions: Drug: ISIS 443139 10 mg; Drug: ISIS 443139 30 mg; Drug: ISIS 443139 60 mg; Drug: ISIS 443139 90 mg; Drug: ISIS 443139 120 mg; Other: Placebo

• Registration Number: NCT02519036
• Lead Sponsor: Ionis Pharmaceuticals, Inc.

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2015-08-01
• Study First Submitted QC: 2015-08-05
• Study Start: 2015-08-06
• Study First Posted: 2015-08-10
• Primary Completion: 2017-11-08
• Study Completion: 2017-11-08
• Disposition First Submitted: 2018-10-03
• Disposition First Submitted QC: 2018-10-03
• Disposition First Posted: 2018-10-05
• Status Verified: 2019-05
• Results First Submitted: 2019-05-06
• Results First Submitted QC: 2019-05-30
• Last Update Submitted: 2019-05-30
• Results First Posted: 2019-05-31
• Last Update Posted: 2019-05-31

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 46

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
ISIS 443139 10 mg	ISIS 443139 10 mg	Participants received ISIS 443139, 10 milligrams (mg), by intrathecal injection, on Study Days 1, 29, 57, and 85.
ISIS 443139 30 mg	ISIS 443139 30 mg	Participants received ISIS 443139, 30 mg, by intrathecal injection, on Study Days 1, 29, 57, and 85.
ISIS 443139 60 mg	ISIS 443139 60 mg	Participants received ISIS 443139, 60 mg, by intrathecal injection, on Study Days 1, 29, 57, and 85.
ISIS 443139 90 mg	ISIS 443139 90 mg	Participants received ISIS 443139, 90 mg, by intrathecal injection, on Study Days 1, 29, 57, and 85.
ISIS 443139 120 mg	ISIS 443139 120 mg	Participants received ISIS 443139, 120 mg, by intrathecal injection, on Study Days 1, 29, 57, and 85.
Placebo	Placebo	Participants received placebo, by intrathecal injection, on Study Days 1, 29, 57, and 85.

Primary Outcome Measures

Name	Time	Method
Number of Participants With Treatment-related Adverse Events (TEAEs)	Up to approximately 28 weeks	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.

Secondary Outcome Measures

Name	Time	Method
Observed Cerebrospinal Fluid (CSF) Concentration for ISIS 443139	Days 1, 29, 57, 85, and 113 or 141

Trial Locations

Locations (9)

University College London; 🇬🇧 London, United Kingdom

Ulm University Hospital; 🇩🇪 Ulm, Germany

Cambridge University Hospital; 🇬🇧 Cambridge, United Kingdom

University Hospitals Birmingham; 🇬🇧 Birmingham, United Kingdom

Charite University Berlin; 🇩🇪 Berlin, Germany

University Hospital of Wales; 🇬🇧 Cardiff, United Kingdom

Ruhr-University of Bochum; 🇩🇪 Bochum, Germany

University of British Columbia; 🇨🇦 Vancouver, British Columbia, Canada

University of Manchester, St. Mary's Hospital; 🇬🇧 Manchester, United Kingdom