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

NCT ID: NCT02519036

Last Updated: 2019-05-31

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

46 participants

Study Classification

INTERVENTIONAL

Study Start Date

2015-08-06

Study Completion Date

2017-11-08

Brief Summary

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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.

Detailed Description

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Conditions

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Huntington's Disease

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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ISIS 443139 10 mg

Participants received ISIS 443139, 10 milligrams (mg), by intrathecal injection, on Study Days 1, 29, 57, and 85.

Group Type EXPERIMENTAL

ISIS 443139 10 mg

Intervention Type DRUG

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

ISIS 443139 30 mg

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

Group Type EXPERIMENTAL

ISIS 443139 30 mg

Intervention Type DRUG

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

ISIS 443139 60 mg

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

Group Type EXPERIMENTAL

ISIS 443139 60 mg

Intervention Type DRUG

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

ISIS 443139 90 mg

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

Group Type EXPERIMENTAL

ISIS 443139 90 mg

Intervention Type DRUG

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

ISIS 443139 120 mg

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

Group Type EXPERIMENTAL

ISIS 443139 120 mg

Intervention Type DRUG

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

Placebo

Participants received placebo, by intrathecal injection, on Study Days 1, 29, 57, and 85.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type OTHER

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

Interventions

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ISIS 443139 10 mg

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

Intervention Type DRUG

ISIS 443139 30 mg

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

Intervention Type DRUG

ISIS 443139 60 mg

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

Intervention Type DRUG

ISIS 443139 90 mg

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

Intervention Type DRUG

ISIS 443139 120 mg

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

Intervention Type DRUG

Placebo

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

Intervention Type OTHER

Other Intervention Names

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IONIS HTTRx IONIS HTTRx IONIS HTTRx IONIS HTTRx IONIS HTTRx

Eligibility Criteria

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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

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
Minimum Eligible Age

25 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Ionis Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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University of British Columbia

Vancouver, British Columbia, Canada

Site Status

Charite University Berlin

Berlin, , Germany

Site Status

Ruhr-University of Bochum

Bochum, , Germany

Site Status

Ulm University Hospital

Ulm, , Germany

Site Status

University Hospitals Birmingham

Birmingham, , United Kingdom

Site Status

Cambridge University Hospital

Cambridge, , United Kingdom

Site Status

University Hospital of Wales

Cardiff, , United Kingdom

Site Status

University College London

London, , United Kingdom

Site Status

University of Manchester, St. Mary's Hospital

Manchester, , United Kingdom

Site Status

Countries

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Canada Germany United Kingdom

References

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Rodrigues FB, Ferreira JJ, Wild EJ. Huntington's Disease Clinical Trials Corner: June 2019. J Huntingtons Dis. 2019;8(3):363-371. doi: 10.3233/JHD-199003.

Reference Type DERIVED
PMID: 31381524 (View on PubMed)

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; Phase 1-2a IONIS-HTTRx Study Site Teams. Targeting Huntingtin Expression in Patients with Huntington's Disease. N Engl J Med. 2019 Jun 13;380(24):2307-2316. doi: 10.1056/NEJMoa1900907. Epub 2019 May 6.

Reference Type DERIVED
PMID: 31059641 (View on PubMed)

Rodrigues FB, Wild EJ. Huntington's Disease Clinical Trials Corner: February 2018. J Huntingtons Dis. 2018;7(1):89-98. doi: 10.3233/JHD-189001.

Reference Type DERIVED
PMID: 29480210 (View on PubMed)

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Related Links

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http://www.ionispharma.com

Ionis Pharmaceuticals, Inc. home page

Other Identifiers

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2015-000381-66

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

ISIS 443139-CS1

Identifier Type: -

Identifier Source: org_study_id

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