Safety and Tolerability of WVE-120102 in Patients With Huntington’s Disease

Overview

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).

Full Title of Study: “A Multicenter, Randomized, Double-blind, Placebo-controlled, Phase 1b/2a Study of WVE-120102 Administered Intrathecally in Patients With Huntington’s Disease”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Sequential Assignment
    • Primary Purpose: Treatment
    • Masking: Double (Participant, Investigator)
  • Study Primary Completion Date: May 10, 2021

Interventions

  • Drug: WVE-120102
    • WVE-120102 is a stereopure antisense oligonucleotide (ASO)
  • Drug: Placebo
    • 0.9% Sodium Chloride

Arms, Groups and Cohorts

  • Experimental: WVE-120102 (2 mg) or placebo
  • Experimental: WVE-120102 (4 mg) or placebo
  • Experimental: WVE-120102 (8 mg) or placebo
  • Experimental: WVE-120102 (16 mg) or placebo
  • Experimental: WVE-120102 (32 mg ) or placebo

Clinical Trial Outcome Measures

Primary Measures

  • 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
  • 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])
    • 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
  • 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])
    • 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.
  • 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])

Secondary Measures

  • 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-120102 in plasma
  • 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-120102 in plasma
  • 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.
    • AUC 0-t from time zero to the last quantifiable concentration of WVE-120102 in plasma
  • 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-120102 in plasma (t1/2)
  • 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)
    • Percentage change from baseline to last observation in mutant huntingtin protein
  • 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)
    • 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)

Participating in This Clinical Trial

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

Gender Eligibility: All

Minimum Age: 25 Years

Maximum Age: 65 Years

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Wave Life Sciences Ltd.
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Medical Director, MD, Study Director, Wave Life Sciences

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