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

This study is currently recruiting participants.
See Contacts and Locations
Verified July 2017 by Wave Life Sciences Ltd.
Sponsor:
Information provided by (Responsible Party):
Wave Life Sciences Ltd.
ClinicalTrials.gov Identifier:
NCT03225833
First received: July 17, 2017
Last updated: July 20, 2017
Last verified: July 2017
  Purpose
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 Intervention Phase
Huntington's Disease Drug: WVE-120101 Drug: Placebo Phase 1 Phase 2

Study Type: Interventional
Study Design: 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

Resource links provided by NLM:


Further study details as provided by Wave Life Sciences Ltd.:

Primary Outcome Measures:
  • Safety: Number of patients with adverse events (AEs) [ Time Frame: Day 1 to Day 210 (end of study) ]
    All AEs reported or observed during the study, including AEs resulting from concurrent illnesses, reactions to concurrent medications, or progression of disease states

  • Safety: Severity of AEs [ Time Frame: Day 1 to Day 210 (end of study) ]
    Severity will be evaluated using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0

  • Safety: Number of patients with serious AEs (SAEs) [ Time Frame: Day 1 to Day 210 (end of study) ]
    An SAE 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.

  • Safety and Tolerability: Number of patients who withdraw due to AEs [ Time Frame: Day 1 to Day 210 (end of study) ]

Secondary Outcome Measures:
  • Pharmacokinetics (PK): Maximum observed concentration (Cmax) [ Time Frame: Day 1 to Day 196 ]
    Cmax of WVE-120101 in plasma and CSF

  • PK: Time of occurrence of Cmax (tmax) [ Time Frame: Day 1 to Day 196 ]
    tmax of WVE-120101 in plasma and CSF

  • PK: Area under the plasma concentration-time curve (AUC 0-t) [ Time Frame: Day 1 to Day 196 ]
    AUC 0-t from time zero to the last quantifiable concentration of WVE-120101 in plasma and CSF

  • PK: Terminal elimination rate constant [ Time Frame: Day 1 to Day 196 ]
    Elimination rate of WVE-120101 from plasma and CSF

  • Pharmacodynamics (PD) [ Time Frame: Day 1 to Day 196 ]
    Concentration of mutant huntingtin (mHTT) protein in CSF

  • Clinical Effects: Total Functional Capacity (TFC) [ Time Frame: Day 1 to Day 140 ]
    Change from baseline to the last measured time point (Day 140) and difference from placebo in the TFC, administered as part of the Unified Huntington's Disease Rating Scale (UHDRS).


Other Outcome Measures:
  • UHDRS [ Time Frame: Day 1 to Day 140 ]
    Change from baseline to the last measured time point (Day 140) and difference from placebo in the UHDRS

  • Short Problems Behavior Assessment (PBA-s) [ Time Frame: Day 1 to Day 140 ]
    Change from baseline to the last measured time point (Day 140) and difference from placebo in the PBA-s

  • Magnetic Resonance Imaging [ Time Frame: Screening to Day 140 ]
    Changes from baseline MRI of the brain.


Estimated Enrollment: 48
Actual Study Start Date: July 17, 2017
Estimated Study Completion Date: September 2019
Estimated Primary Completion Date: September 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   25 Years to 65 Years   (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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT03225833

Contacts
Contact: Clinical Operations 855-215-4687 clinicaltrials@wavelifesci.com

Locations
Canada, Ontario
Centre For Movement Disorders Recruiting
Toronto, Ontario, Canada, M3B 2S7
Principal Investigator: Mark Guttman, MD         
Sponsors and Collaborators
Wave Life Sciences Ltd.
Investigators
Study Director: Serena Hung, MD Wave Life Sciences
  More Information

Responsible Party: Wave Life Sciences Ltd.
ClinicalTrials.gov Identifier: NCT03225833     History of Changes
Other Study ID Numbers: WVE-HDSNP1-001
Study First Received: July 17, 2017
Last Updated: July 20, 2017

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
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

ClinicalTrials.gov processed this record on September 21, 2017