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Completed

NCT Number: NCT02519036

Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of ISIS 443139 in Participants 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.

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Key information

Conditions

Huntington's Disease Basal Ganglia Diseases Brain Diseases Central Nervous System Diseases Chorea Cognition Disorders Congenital, Hereditary, and Neonatal Diseases and Abnormalities Dementia Dyskinesias Genetic Diseases, Inborn Heredodegenerative Disorders, Nervous System Huntington Disease Mental Disorders Movement Disorders Nervous System Diseases Neurocognitive Disorders Neurodegenerative Diseases

Age range

25 year–65 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1 / Phase 2

Primary location

University of British Columbia, Vancouver, British Columbia, Canada

Loading trial locations.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

ISIS 443139 10 mg

Drug

ISIS 443139, 10 mg, was administered by intrathecal injection, on Study Days 1, 29, 57, and 85.

Other names: IONIS HTTRx

ISIS 443139 30 mg

Drug

ISIS 443139, 30 mg, was administered by intrathecal injection, on Study Days 1, 29, 57, and 85.

Other names: IONIS HTTRx

ISIS 443139 60 mg

Drug

ISIS 443139, 60 mg, was administered by intrathecal injection, on Study Days 1, 29, 57, and 85.

Other names: IONIS HTTRx

ISIS 443139 90 mg

Drug

ISIS 443139, 90 mg, was administered by intrathecal injection, on Study Days 1, 29, 57, and 85.

Other names: IONIS HTTRx

ISIS 443139 120 mg

Drug

ISIS 443139, 120 mg, was administered by intrathecal injection, on Study Days 1, 29, 57, and 85.

Other names: IONIS HTTRx

Placebo

Other

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

Primary outcomes

  1. Number of Participants With Treatment-related Adverse Events (TEAEs)

    Time frame: 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 outcomes

  1. Observed Cerebrospinal Fluid (CSF) Concentration for ISIS 443139

    Time frame: Days 1, 29, 57, 85, and 113 or 141

Other outcomes

  1. Maximum Plasma Concentration (Cmax) for ISIS 443139

    Time frame: Days 1 and 85

  2. Time to Maximum Plasma Concentration (Tmax) for ISIS 443139

    Time frame: Days 1 and 85

  3. Change From Baseline in CSF Mutant Huntingtin (fM) Protein Concentration

    Time frame: Baseline to Final Assessment (Day 85 or 113)

    Baseline was defined as the last non-missing measure prior to the first dose.

  4. Change From Baseline in CSF Neurofilament Light Chain Concentration

    Time frame: Baseline to Final Assessment (Day 85 or 113)

    Baseline was defined as the last non-missing measure prior to the first dose.

  5. Ventricular Volume as Assessed by Structural Magnetic Resonance Imaging (MRI)

    Time frame: Screening, Days 113, and 197

  6. Huntington's Disease (HD) Cognitive Assessment Battery Composite Score

    Time frame: Baseline to Days 84, 141, and 197

    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.

Sponsors and collaborators

Lead sponsor

Ionis Pharmaceuticals, Inc.

Industry

Registry information

Official study 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

Important dates

Study start
2015
Primary completion
2017
Study completion
2017
First posted
Aug 10, 2015
Registry last updated
May 31, 2019

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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