- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03225846
Safety and Tolerability of WVE-120102 in Patients With Huntington's Disease (PRECISION-HD2)
March 28, 2022 updated by: Wave Life Sciences Ltd.
A Multicenter, Randomized, Double-blind, Placebo-controlled, Phase 1b/2a Study of WVE-120102 Administered Intrathecally in Patients With Huntington's Disease
PRECISION-HD2 is a Phase 1b/2a multicenter, randomized, double-blind, placebo-controlled study to evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of single and multiple doses of WVE-120102 in adult patients with early manifest Huntington's disease (HD) who carry a targeted single nucleotide polymorphism (SNP) rs362331 (SNP2).
Study Overview
Status
Terminated
Conditions
Intervention / Treatment
Study Type
Interventional
Enrollment (Actual)
88
Phase
- Phase 2
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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New South Wales
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Sidney, New South Wales, Australia, 2145
- Westmead Hospital
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Queensland
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Herston, Queensland, Australia, QLD 4006
- Royal Brisbane & Women's Hospital
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Victoria
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Carlton, Victoria, Australia, 3053
- Royal Melbourne Hospital
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Clayton, Victoria, Australia, 3168
- Monash Health
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Melbourne, Victoria, Australia, 3004
- Alfred Health
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Parkdale, Victoria, Australia, 3195
- Calvary Health Care Bethlehem
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Western Australia
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Perth, Western Australia, Australia, 6910
- North Metropolitan Health Service
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Alberta
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Edmonton, Alberta, Canada, T6G 2B7
- University of Alberta
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Ontario
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Toronto, Ontario, Canada, M3B 2S7
- Centre for Movement Disorders
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Quebec
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Montreal, Quebec, Canada, H2X019
- Centre Hospitalier de l-Universite de Montreal
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Aarhus N, Denmark, 8200
- Aarhus Universitets Hospital
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Copenhagen, Denmark, 2100
- Rigshospitalet
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Odense, Denmark, 5000
- Odense University Hospital and University of Southern Denmark
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Créteil, France, 94010
- Hospital Henri Mondor
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Paris, France, 75646
- Institut du Cerveau et de la Moelle Epinière
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Muenster, Germany, 48149
- George-Huntington-Institut GmbH
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Gdańsk, Poland, 80-462
- Szpital Sw. Wojciecha
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Warsaw, Poland, 02-957
- Instytut Psychiatrii i Neurologii
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Liverpool, United Kingdom, L7 8XP
- Royal Liverpool University Hospital
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Devon
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Exeter, Devon, United Kingdom, EX2 5DW
- Royal Devon and Exeter Hospital NHS Trust
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Glasgow City
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Glasgow, Glasgow City, United Kingdom, G12 0XH
- Queen Elizabeth University Hospital - PPDS
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California
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La Jolla, California, United States, 92037-0949
- University of California San Diego
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Sacramento, California, United States, 95817
- University of California Davis Medical Center
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Massachusetts
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Boston, Massachusetts, United States, 02129
- Massachusetts General Hospital
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Ohio
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Columbus, Ohio, United States, 43210
- The Ohio State University
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Tennessee
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Nashville, Tennessee, United States, 37232
- Vanderbilt University Medical Center
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
25 years to 65 years (ADULT, OLDER_ADULT)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Key Inclusion Criteria:
- Prescreened with targeted SNP on the same allele as the pathogenic CAG expansion
- Ambulatory, male or female patients aged ≥25 - ≤65 years
- Clinical diagnostic motor features of HD, defined as Unified Huntington's Disease Rating Scale (UHDRS) Diagnostic Confidence Score = 4
- Early manifest HD, Stage I or Stage II based on UHDRS Total Functional Capacity Scores ≥7 and ≤13
Key Exclusion Criteria:
- Malignancy or received treatment for malignancy, other than treated basal cell or squamous cell carcinoma of the skin, within the previous 5 years
- Received investigational drug or implantable device in prior 3 months or investigational oligonucleotide in prior 6 months or 5 halflives of the oligonucleotide, whichever is longer
- Clinically significant medical condition, unstable psychiatric symptoms, substance abuse, or pregnancy
- Inability to undergo brain MRI
- Bone, spine, bleeding, or other disorder that exposes the patient to risk of injury or unsuccessful lumbar puncture
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: RANDOMIZED
- Interventional Model: SEQUENTIAL
- Masking: DOUBLE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
EXPERIMENTAL: WVE-120102 (2 mg) or placebo
|
0.9% Sodium Chloride
WVE-120102 is a stereopure antisense oligonucleotide (ASO)
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EXPERIMENTAL: WVE-120102 (4 mg) or placebo
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0.9% Sodium Chloride
WVE-120102 is a stereopure antisense oligonucleotide (ASO)
|
EXPERIMENTAL: WVE-120102 (8 mg) or placebo
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0.9% Sodium Chloride
WVE-120102 is a stereopure antisense oligonucleotide (ASO)
|
EXPERIMENTAL: WVE-120102 (16 mg) or placebo
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0.9% Sodium Chloride
WVE-120102 is a stereopure antisense oligonucleotide (ASO)
|
EXPERIMENTAL: WVE-120102 (32 mg ) or placebo
|
0.9% Sodium Chloride
WVE-120102 is a stereopure antisense oligonucleotide (ASO)
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Safety: Number of Patients With Treatment-emergent Adverse Events (TEAEs)
Time Frame: Day 1 to end of study (up to Day 182 [32 mg cohort]/ Day 210 [all other cohorts])
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All TEAEs reported or observed during the study, including TEAEs resulting from concurrent illnesses, reactions to concurrent medications, or progression of disease states
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Day 1 to end of study (up to Day 182 [32 mg cohort]/ Day 210 [all other cohorts])
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Safety: Number of Patients Who Experienced Severe TEAEs
Time Frame: Time Frame: Day 1 to end of study (up to Day 182 [32 mg cohort]/ Day 210 [all other cohorts])
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Number of patients who experienced a severe treatment-emergent adverse event.
Severity was evaluated using the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0
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Time Frame: Day 1 to end of study (up to Day 182 [32 mg cohort]/ Day 210 [all other cohorts])
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Safety: Number of Patients With Serious TEAEs
Time Frame: Time Frame: Day 1 to end of study (up to Day 182 [32 mg cohort]/ Day 210 [all other cohorts])
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A serious TEAE is defined as any event that results in death, is immediately life threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, or is a congenital anomaly/birth defect not present at Prescreening.
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Time Frame: Day 1 to end of study (up to Day 182 [32 mg cohort]/ Day 210 [all other cohorts])
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Safety and Tolerability: Number of Patients Who Withdraw Due to TEAEs
Time Frame: Time Frame: Day 1 to end of study (up to Day 182 [32 mg cohort]/ Day 210 [all other cohorts])
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Time Frame: Day 1 to end of study (up to Day 182 [32 mg cohort]/ Day 210 [all other cohorts])
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Pharmacokinetics (PK): Maximum Observed Concentration (Cmax)
Time Frame: Patients participating in Period 1 (SAD) had PK samples collected on Day 1 predose through 24-48 hours postdose. Patients participating in Period 2 (MAD) had PK samples collected predose on Day 112 and through 4 hours postdose.
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Cmax of WVE-120102 in plasma
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Patients participating in Period 1 (SAD) had PK samples collected on Day 1 predose through 24-48 hours postdose. Patients participating in Period 2 (MAD) had PK samples collected predose on Day 112 and through 4 hours postdose.
|
PK: Time of Occurrence of Cmax (Tmax)
Time Frame: Patients participating in Period 1 (SAD) had PK samples collected on Day 1 predose through 24-48 hours postdose. Patients participating in Period 2 (MAD) had PK samples collected predose on Day 112 and through 4 hours postdose.
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tmax of WVE-120102 in plasma
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Patients participating in Period 1 (SAD) had PK samples collected on Day 1 predose through 24-48 hours postdose. Patients participating in Period 2 (MAD) had PK samples collected predose on Day 112 and through 4 hours postdose.
|
PK: Area Under the Plasma Concentration-time Curve (AUC 0-t)
Time Frame: Patients participating in Period 1 (SAD) had PK samples collected on Day 1 predose through 24-48 hours postdose. Patients participating in Period 2 (MAD) had PK samples collected predose on Day 112 and through 4 hours postdose.
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AUC 0-t from time zero to the last quantifiable concentration of WVE-120102 in plasma
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Patients participating in Period 1 (SAD) had PK samples collected on Day 1 predose through 24-48 hours postdose. Patients participating in Period 2 (MAD) had PK samples collected predose on Day 112 and through 4 hours postdose.
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PK: Terminal Elimination Half-life
Time Frame: Patients participating in Period 1 (SAD) had PK samples collected on Day 1 predose through 24-48 hours postdose. Patients participating in Period 2 (MAD) had PK samples collected predose on Day 112 and through 4 hours postdose.
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Terminal elimination half life of WVE-120102 in plasma (t1/2)
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Patients participating in Period 1 (SAD) had PK samples collected on Day 1 predose through 24-48 hours postdose. Patients participating in Period 2 (MAD) had PK samples collected predose on Day 112 and through 4 hours postdose.
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Pharmacodynamics (PD): Percentage Change From Baseline in Mutant Huntingtin Protein
Time Frame: Day 1 to last observation - up to Day 140 (32 mg cohort) or Day 196 (all other cohorts)
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Percentage change from baseline to last observation in mutant huntingtin protein
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Day 1 to last observation - up to Day 140 (32 mg cohort) or Day 196 (all other cohorts)
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Clinical Effects: Total Functional Capacity (TFC)
Time Frame: Day 1 Day 1 to last observation - up to Day 140 (32 mg cohort) or Day 196 (all other cohorts)
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Percentage change from baseline to the last measured time point in the Total Functional Capacity score, administered as part of the Unified Huntington's Disease Rating Scale (UHDRS).
Total Functional Capacity is scored 13 (normal) to 0 (severe disability)
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Day 1 Day 1 to last observation - up to Day 140 (32 mg cohort) or Day 196 (all other cohorts)
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
General Publications
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (ACTUAL)
July 17, 2017
Primary Completion (ACTUAL)
May 10, 2021
Study Completion (ACTUAL)
May 10, 2021
Study Registration Dates
First Submitted
July 17, 2017
First Submitted That Met QC Criteria
July 19, 2017
First Posted (ACTUAL)
July 21, 2017
Study Record Updates
Last Update Posted (ACTUAL)
April 25, 2022
Last Update Submitted That Met QC Criteria
March 28, 2022
Last Verified
January 1, 2022
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Mental Disorders
- Brain Diseases
- Central Nervous System Diseases
- Nervous System Diseases
- Neurocognitive Disorders
- Genetic Diseases, Inborn
- Basal Ganglia Diseases
- Movement Disorders
- Neurodegenerative Diseases
- Dyskinesias
- Heredodegenerative Disorders, Nervous System
- Dementia
- Cognition Disorders
- Chorea
- Huntington Disease
Other Study ID Numbers
- WVE-HDSNP2-001
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Yes
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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