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Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of IONIS-HTTRx in Patients With Early Manifest Huntington's Disease

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ClinicalTrials.gov Identifier: NCT02519036
Recruitment Status : Completed
First Posted : August 10, 2015
Last Update Posted : October 5, 2018
Sponsor:
Information provided by (Responsible Party):
Ionis Pharmaceuticals, Inc.

Tracking Information
First Submitted Date  ICMJE August 1, 2015
First Posted Date  ICMJE August 10, 2015
Last Update Posted Date October 5, 2018
Actual Study Start Date  ICMJE August 6, 2015
Actual Primary Completion Date November 1, 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 5, 2015)
  • 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
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT02519036 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: August 10, 2015)
CSF Pharmacokinetics (The observed CSF drug concentration) [ Time Frame: Day 1, Day 29, Day 57, Day 85, and Day 113 or Day 141 ]
Original Secondary Outcome Measures  ICMJE
 (submitted: August 5, 2015)
CSF Pharmacokinetics (The observed CSF drug concentration) [ Time Frame: Day 1, Day 29, Day 57, Day 85, and Day 113 or Day 141 ]
The observed CSF drug concentration
Current Other Pre-specified Outcome Measures
 (submitted: August 5, 2015)
  • 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 ]
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title  ICMJE Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of IONIS-HTTRx in Patients With Early Manifest Huntington's Disease
Official Title  ICMJE 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
Brief Summary 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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Huntington's Disease
Intervention  ICMJE
  • Drug: IONIS HTTRx
    Other Name: ISIS 443139
  • Drug: Placebo
Study Arms  ICMJE
  • 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.
    Intervention: Drug: IONIS HTTRx
  • Placebo Comparator: Placebo
    A placebo is administered intrathecally at 4 week intervals over the course of 13 weeks.
    Intervention: Drug: Placebo
Publications * Tabrizi 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. Targeting Huntingtin Expression in Patients with Huntington's Disease. N Engl J Med. 2019 May 6. doi: 10.1056/NEJMoa1900907. [Epub ahead of print]

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: June 22, 2017)
46
Original Estimated Enrollment  ICMJE
 (submitted: August 5, 2015)
36
Actual Study Completion Date  ICMJE November 1, 2017
Actual Primary Completion Date November 1, 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 25 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Canada,   Germany,   United Kingdom
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02519036
Other Study ID Numbers  ICMJE ISIS 443139-CS1
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Product Manufactured in and Exported from the U.S.: Yes
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Ionis Pharmaceuticals, Inc.
Study Sponsor  ICMJE Ionis Pharmaceuticals, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Ionis Pharmaceuticals, Inc.
Verification Date October 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP