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Safety and Tolerability of WVE-120101 in Patients With Huntington's Disease (PRECISION-HD1)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03225833
Recruitment Status : Terminated (Lack of Efficacy)
First Posted : July 21, 2017
Results First Posted : February 10, 2022
Last Update Posted : February 10, 2022
Sponsor:
Information provided by (Responsible Party):
Wave Life Sciences Ltd.

Study Description
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Brief Summary:
PRECISION-HD1 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-120101 in adult patients with early manifest Huntington's disease (HD) who carry a targeted single nucleotide polymorphism (SNP) rs362307 (SNP1).

Condition or disease Intervention/treatment Phase
Huntington's Disease Drug: WVE-120101 Drug: Placebo Phase 1 Phase 2

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 61 participants
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: A Multicenter, Randomized, Double-blind, Placebo-controlled, Phase 1b/2a Study of WVE-120101 Administered Intrathecally in Patients With Huntington's Disease
Actual Study Start Date : July 17, 2017
Actual Primary Completion Date : May 11, 2021
Actual Study Completion Date : May 11, 2021

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: WVE-120101 (Dose A) or placebo Drug: WVE-120101
WVE-120101 is a stereopure antisense oligonucleotide (ASO)

Drug: Placebo
0.9% Sodium Chloride
Experimental: WVE-120101 (Dose B) or placebo Drug: WVE-120101
WVE-120101 is a stereopure antisense oligonucleotide (ASO)

Drug: Placebo
0.9% Sodium Chloride
Experimental: WVE-120101 (Dose C) or placebo Drug: WVE-120101
WVE-120101 is a stereopure antisense oligonucleotide (ASO)

Drug: Placebo
0.9% Sodium Chloride
Experimental: WVE-120101 (Dose D) or placebo Drug: WVE-120101
WVE-120101 is a stereopure antisense oligonucleotide (ASO)

Drug: Placebo
0.9% Sodium Chloride
Experimental: WVE-120101 (Dose E) or placebo Drug: WVE-120101
WVE-120101 is a stereopure antisense oligonucleotide (ASO)

Drug: Placebo
0.9% Sodium Chloride


Outcome Measures
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Primary Outcome Measures :
  1. 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]) ]
    All TEAEs reported or observed during the study, including TEAEs resulting from concurrent illnesses, reactions to concurrent medications, or progression of disease states

  2. Safety: Severity of Adverse Events [ Time Frame: Day 1 to end of study (up to Day 182 [32 mg cohort]/ Day 210 [all other cohorts]) ]
    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

  3. Safety: Number of Patients With Serious TEAEs [ Time Frame: Day 1 to end of study (up to Day 182 [32 mg cohort]/ Day 210 [all other cohorts]) ]
    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.

  4. Safety and Tolerability: Number of Patients Who Withdraw Due to TEAEs [ Time Frame: Day 1 to end of study (up to Day 182 [32 mg cohort]/ Day 210 [all other cohorts]) ]

Secondary Outcome Measures :
  1. 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. ]
    Cmax of WVE-120101 in plasma

  2. 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. ]
    tmax of WVE-120101 in plasma

  3. PK: Area Under the Plasma Concentration-time Curve (AUClast) [ 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. ]
    AUClast from time 0 to the last quantifiable concentration of WVE-120101 in plasma

  4. 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. ]
    Terminal elimination half life of WVE-120101 in plasma (t1/2)

  5. Pharmacodynamics [ Time Frame: Day 1 to last observation - up to Day 140 (32 mg cohort) or Day 196 (all other cohorts) ]
    Percentage change from baseline in concentration of mutant huntingtin (mHTT) protein in CSF

  6. Clinical Effects: Total Functional Capacity (TFC) [ Time Frame: Day 1 to last observation - up to Day 140 (32 mg cohort) or Day 196 (all other cohorts) ]
    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).


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

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 half-lives 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
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03225833


Locations
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Sponsors and Collaborators
Wave Life Sciences Ltd.
Investigators
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Study Director: Medical Director, MD Wave Life Sciences
  Study Documents (Full-Text)

Documents provided by Wave Life Sciences Ltd.:
Study Protocol and Statistical Analysis Plan  [PDF] January 21, 2020

More Information
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Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: Wave Life Sciences Ltd.
ClinicalTrials.gov Identifier: NCT03225833    
Other Study ID Numbers: WVE-HDSNP1-001
First Posted: July 21, 2017    Key Record Dates
Results First Posted: February 10, 2022
Last Update Posted: February 10, 2022
Last Verified: February 2022

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Huntington Disease
Basal Ganglia Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Dementia
Chorea
Dyskinesias
 Movement Disorders
Heredodegenerative Disorders, Nervous System
Neurodegenerative Diseases
Genetic Diseases, Inborn
Cognition Disorders
Neurocognitive Disorders
Mental Disorders