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Safety and Tolerability of WVE-120102 in Patients With Huntington's Disease (PRECISION-HD2)

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ClinicalTrials.gov Identifier: NCT03225846
Recruitment Status : Recruiting
First Posted : July 21, 2017
Last Update Posted : July 10, 2019
Sponsor:
Information provided by (Responsible Party):
Wave Life Sciences Ltd.

Tracking Information
First Submitted Date  ICMJE July 17, 2017
First Posted Date  ICMJE July 21, 2017
Last Update Posted Date July 10, 2019
Actual Study Start Date  ICMJE July 17, 2017
Estimated Primary Completion Date March 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 19, 2017)
  • 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) ]
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03225846 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: October 23, 2017)
  • Pharmacokinetics (PK): Maximum observed concentration (Cmax) [ Time Frame: Day 1 to Day 196 ]
    Cmax of WVE-120102 in plasma
  • PK: Time of occurrence of Cmax (tmax) [ Time Frame: Day 1 to Day 196 ]
    tmax of WVE-120102 in plasma
  • 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-120102 in plasma
  • PK: Terminal elimination rate constant [ Time Frame: Day 1 to Day 196 ]
    Elimination rate of WVE-120102 from plasma
  • 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).
Original Secondary Outcome Measures  ICMJE
 (submitted: July 19, 2017)
  • Pharmacokinetics (PK): Maximum observed concentration (Cmax) [ Time Frame: Day 1 to Day 196 ]
    Cmax of WVE-120102 in plasma and CSF
  • PK: Time of occurrence of Cmax (tmax) [ Time Frame: Day 1 to Day 196 ]
    tmax of WVE-120102 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-120102 in plasma and CSF
  • PK: Terminal elimination rate constant [ Time Frame: Day 1 to Day 196 ]
    Elimination rate of WVE-120102 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).
Current Other Pre-specified Outcome Measures
 (submitted: July 19, 2017)
  • 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.
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title  ICMJE Safety and Tolerability of WVE-120102 in Patients With Huntington's Disease
Official Title  ICMJE A Multicenter, Randomized, Double-blind, Placebo-controlled, Phase 1b/2a Study of WVE-120102 Administered Intrathecally in Patients With Huntington's Disease
Brief Summary 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).
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Huntington's Disease
Intervention  ICMJE
  • Drug: WVE-120102
    WVE-120102 is a stereopure antisense oligonucleotide (ASO)
  • Drug: Placebo
    0.9% Sodium Chloride
Study Arms  ICMJE
  • Experimental: WVE-120102 (Dose A) or placebo
    Interventions:
    • Drug: WVE-120102
    • Drug: Placebo
  • Experimental: WVE-120102 (Dose B) or placebo
    Interventions:
    • Drug: WVE-120102
    • Drug: Placebo
  • Experimental: WVE-120102 (Dose C) or placebo
    Interventions:
    • Drug: WVE-120102
    • Drug: Placebo
  • Experimental: WVE-120102 (Dose D) or placebo
    Interventions:
    • Drug: WVE-120102
    • Drug: Placebo
Publications * 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: July 19, 2017)
48
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE March 2020
Estimated Primary Completion Date March 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 25 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Clinical Operations 855-215-4687 clinicaltrials@wavelifesci.com
Listed Location Countries  ICMJE Australia,   Canada,   Denmark,   Poland,   United Kingdom
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03225846
Other Study ID Numbers  ICMJE WVE-HDSNP2-001
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Wave Life Sciences Ltd.
Study Sponsor  ICMJE Wave Life Sciences Ltd.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Serena Hung, MD Wave Life Sciences
PRS Account Wave Life Sciences Ltd.
Verification Date July 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP