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History of Changes for Study: NCT02519036
Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of ISIS-HTTRx in Patients With Early Manifest Huntington's Disease
Latest version (submitted May 30, 2019) on ClinicalTrials.gov
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Study Record Versions
Version A B Submitted Date Changes
1 August 5, 2015 None (earliest Version on record)
2 August 10, 2015 Recruitment Status, Study Status, Contacts/Locations, Outcome Measures and Study Identification
3 August 20, 2015 Contacts/Locations and Study Status
4 March 2, 2016 Arms and Interventions, Contacts/Locations, References, Study Status, Study Identification and Study Description
5 March 7, 2017 Study Status, Contacts/Locations, Arms and Interventions and Study Design
6 June 22, 2017 Recruitment Status, Study Status, Contacts/Locations and Study Design
7 May 14, 2018 Recruitment Status and Study Status
8 June 29, 2018 Oversight and Study Status
9 August 15, 2018 Study Status
10 October 3, 2018 Study Status
11 May 30, 2019 Arms and Interventions, Study Status, Outcome Measures, More Information, Study Design, Study Identification, Document Section, Adverse Events, Baseline Characteristics, Participant Flow, Eligibility and Study Description
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Study NCT02519036
Submitted Date:  August 5, 2015 (v1)

Open or close this module Study Identification
Unique Protocol ID: ISIS 443139-CS1
Brief Title: Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of ISIS-HTTRx in Patients With Early Manifest Huntington's Disease
Official Title: A Randomized, Double-blind, Placebo-controlled Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Multiple Ascending Doses of Intrathecally Adminstered ISIS 443139 in Patients With Early Manifest Huntington's Disease
Secondary IDs:
Open or close this module Study Status
Record Verification: August 2015
Overall Status: Not yet recruiting
Study Start: August 2015
Primary Completion: March 2017 [Anticipated]
Study Completion: September 2017 [Anticipated]
First Submitted: August 1, 2015
First Submitted that
Met QC Criteria:
August 5, 2015
First Posted: August 10, 2015 [Estimate]
Last Update Submitted that
Met QC Criteria:
August 5, 2015
Last Update Posted: August 10, 2015 [Estimate]
Open or close this module Sponsor/Collaborators
Sponsor: Ionis Pharmaceuticals, Inc.
Responsible Party: Sponsor
Collaborators:
Open or close this module Oversight
U.S. FDA-regulated Drug:
U.S. FDA-regulated Device:
Data Monitoring: Yes
Open or close this module Study Description
Brief Summary: This study will test the safety, tolerability, pharmacokinetics and pharmacodynamics of multiple ascending doses of ISIS-HTTRx administered intrathecally to adult patients with early manifest Huntington's Disease.
Detailed Description:
Open or close this module Conditions
Conditions: Huntington's Disease
Keywords: Huntington's Disease
HTTRx
Early Manifest Huntington's Disease
Open or close this module Study Design
Study Type: Interventional
Primary Purpose: Treatment
Study Phase: Phase 1/Phase 2
Interventional Study Model: Parallel Assignment
Number of Arms: 2
Masking: Double (Participant, Investigator)
Allocation: Randomized
Enrollment: 36 [Anticipated]
Open or close this module Arms and Interventions
Arms Assigned Interventions
Experimental: ISIS HTTRx
ISIS HTTRx is administered intrathecally at 4 week intervals over the course of a 13 week treatment period for dose levels A, B, C, and D.
Drug: ISIS HTTRx
Other Names:
  • ISIS 443139
Placebo Comparator: Placebo
A placebo is administered intrathecally at 4 week intervals over the course of 13 weeks.
Drug: Placebo
Open or close this module Outcome Measures
Primary Outcome Measures:
1. 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
2. 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:
1. 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
Other Outcome Measures:
1. Peak ISIS 443139 plasma concentration, Cmax (ug/mL)
[ Time Frame: Day 1 and Day 85 ]

2. Time to peak ISIS 443139 plasma concentration, Tmax (hours)
[ Time Frame: Day 1 and Day 85 ]

3. CSF huntingtin protein concentration (fM)
[ Time Frame: Day 1, Day 29, Day 57, Day 85, and Day 113 or Day 141 ]

4. CSF neurofilament light chain (pg/mL)
[ Time Frame: Day 1, Day 29, Day 57, Day 85, and Day 113 or Day 141 ]

5. Ventricular volume (mL)
[ Time Frame: Screening, Day 113, and Day 197 ]

6. Huntington's disease cognitive assessment battery composite score (unitless)
[ Time Frame: Screening, Day -1, Day 84, Day 141, and Day 197 ]

Open or close this module Eligibility
Minimum Age: 25 Years
Maximum Age: 65 Years
Sex: All
Gender Based:
Accepts Healthy Volunteers: No
Criteria:

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
Open or close this module Contacts/Locations
Central Contact Person: Isis Pharmaceuticals
Telephone: 800-679-4747
Email: patients@isisph.com
Locations: Canada, British Columbia
University of British Columbia
Vancouver, British Columbia, Canada, V6T 2B5
Germany
Ruhr-University of Bochum
Bochum, Germany, 44791
Ulm University Hospital
Ulm, Germany, 89081
United Kingdom
Cambridge University Hospital
Cambridge, United Kingdom, CB2 0PY
University College London
London, United Kingdom, WC1N 3BG
University of Manchester, St. Mary's Hospital
Manchester, United Kingdom, M13 9WL
Open or close this module IPDSharing
Plan to Share IPD:
Open or close this module References
Links: Description: Isis Pharmaceuticals, Inc. home page
Available IPD/Information:

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