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Trial record 1 of 9 for:    Huntington isis
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Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of IONIS-HTTRx in Patients With Early Manifest Huntington's Disease

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2017 by Ionis Pharmaceuticals, Inc.
Information provided by (Responsible Party):
Ionis Pharmaceuticals, Inc. Identifier:
First received: August 1, 2015
Last updated: March 7, 2017
Last verified: March 2017
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: 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 ]

Estimated Enrollment: 44
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.
Other Name: ISIS 443139
Placebo Comparator: Placebo
A placebo is administered intrathecally at 4 week intervals over the course of 13 weeks.
Drug: Placebo


Ages Eligible for Study:   25 Years to 65 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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 identifier: NCT02519036

Contact: Ionis Pharmaceuticals 800-679-4747

Canada, British Columbia
University of British Columbia Recruiting
Vancouver, British Columbia, Canada, V6T 2B5
Charite University Berlin Recruiting
Berlin, Germany, 10117
Ruhr-University of Bochum Recruiting
Bochum, Germany, 44791
Ulm University Hospital Recruiting
Ulm, Germany, 89081
United Kingdom
University Hospitals Birmingham Recruiting
Birmingham, United Kingdom, B15 2TH
Cambridge University Hospital Recruiting
Cambridge, United Kingdom, CB2 0PY
University Hospital of Wales Not yet recruiting
Cardiff, United Kingdom, CF14 4XN
University College London Recruiting
London, United Kingdom, WC1N 3BG
University of Manchester, St. Mary's Hospital Recruiting
Manchester, United Kingdom, M13 9WL
Sponsors and Collaborators
Ionis Pharmaceuticals, Inc.
  More Information

Additional Information:
Responsible Party: Ionis Pharmaceuticals, Inc. Identifier: NCT02519036     History of Changes
Other Study ID Numbers: ISIS 443139-CS1
Study First Received: August 1, 2015
Last Updated: March 7, 2017

Keywords provided by Ionis Pharmaceuticals, Inc.:
Huntington's Disease
Early Manifest Huntington's Disease

Additional relevant MeSH terms:
Huntington Disease
Basal Ganglia Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Movement Disorders
Heredodegenerative Disorders, Nervous System
Neurodegenerative Diseases
Genetic Diseases, Inborn
Cognition Disorders
Neurocognitive Disorders
Mental Disorders processed this record on May 22, 2017