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

Huntington's Disease Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02519036
• Other study ID #: ISIS 443139-CS1
• Secondary ID: 2015-000381-66
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: August 6, 2015
• Est. completion date: November 8, 2017

Study information

• Verified date: May 2019
• Source: Ionis Pharmaceuticals, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 46
• Est. completion date: November 8, 2017
• Est. primary completion date: November 8, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 25 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Huntington Disease
• Huntington's Disease

Intervention

Drug:
• ISIS 443139 10 mg
ISIS 443139, 10 mg, was administered by intrathecal injection, on Study Days 1, 29, 57, and 85.
• ISIS 443139 30 mg
ISIS 443139, 30 mg, was administered by intrathecal injection, on Study Days 1, 29, 57, and 85.
• ISIS 443139 60 mg
ISIS 443139, 60 mg, was administered by intrathecal injection, on Study Days 1, 29, 57, and 85.
• ISIS 443139 90 mg
ISIS 443139, 90 mg, was administered by intrathecal injection, on Study Days 1, 29, 57, and 85.
• ISIS 443139 120 mg
ISIS 443139, 120 mg, was administered by intrathecal injection, on Study Days 1, 29, 57, and 85.

Other:
• Placebo
Placebo was administered by intrathecal injection, on Study Days 1, 29, 57, and 85.

Locations

Country	Name	City	State
Canada	University of British Columbia	Vancouver	British Columbia
Germany	Charite University Berlin	Berlin
Germany	Ruhr-University of Bochum	Bochum
Germany	Ulm University Hospital	Ulm
United Kingdom	University Hospitals Birmingham	Birmingham
United Kingdom	Cambridge University Hospital	Cambridge
United Kingdom	University Hospital of Wales	Cardiff
United Kingdom	University College London	London
United Kingdom	University of Manchester, St. Mary's Hospital	Manchester

Sponsors (1)

Lead Sponsor	Collaborator
Ionis Pharmaceuticals, Inc.

Countries where clinical trial is conducted

Canada,  Germany,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Maximum Plasma Concentration (Cmax) for ISIS 443139		Days 1 and 85
Other	Time to Maximum Plasma Concentration (Tmax) for ISIS 443139		Days 1 and 85
Other	Change From Baseline in CSF Mutant Huntingtin (fM) Protein Concentration	Baseline was defined as the last non-missing measure prior to the first dose.	Baseline to Final Assessment (Day 85 or 113)
Other	Change From Baseline in CSF Neurofilament Light Chain Concentration	Baseline was defined as the last non-missing measure prior to the first dose.	Baseline to Final Assessment (Day 85 or 113)
Other	Ventricular Volume as Assessed by Structural Magnetic Resonance Imaging (MRI)		Screening, Days 113, and 197
Other	Huntington's Disease (HD) Cognitive Assessment Battery Composite Score	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.	Baseline to Days 84, 141, and 197
Primary	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	Observed Cerebrospinal Fluid (CSF) Concentration for ISIS 443139		Days 1, 29, 57, 85, and 113 or 141

External Links

•   Ionis Pharmaceuticals, Inc. home page