Safety and Tolerability of WVE-120101 in Patients With Huntington's Disease

Phase 2TerminatedNCT03225833

Wave Life Sciences USA, Inc.61 enrolled

Overview

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).

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

Conditions

Huntington's Disease

Interventions

WVE-120101DRUG

WVE-120101 is a stereopure antisense oligonucleotide (ASO)

PlaceboDRUG

0.9% Sodium Chloride

Eligibility

Sex: ALLMin age: 25 YearsMax age: 65 Years

Medical Language ↔ Plain English

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

Locations (21)

Westmead Hospital

Sydney, New South Wales, Australia

Royal Brisbane & Women's Hospital

Outcomes

Primary Outcomes

Safety: Number of Patients With Treatment-emergent Adverse Events (TEAEs)

All TEAEs reported or observed during the study, including TEAEs resulting from concurrent illnesses, reactions to concurrent medications, or progression of disease states

Time frame: Day 1 to end of study (up to Day 182 [32 mg cohort]/ Day 210 [all other cohorts])

Safety: Severity of Adverse Events

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

Time frame: Day 1 to end of study (up to Day 182 [32 mg cohort]/ Day 210 [all other cohorts])

Safety: Number of Patients With Serious TEAEs

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.

Time frame: Day 1 to end of study (up to Day 182 [32 mg cohort]/ Day 210 [all other cohorts])

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 Outcomes

Pharmacokinetics (PK): Maximum Observed Concentration (Cmax)

Cmax of WVE-120101 in plasma

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.

PK: Time of Occurrence of Cmax (Tmax)

Data from ClinicalTrials.gov

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