Study of WVE-003 in Patients With Huntington's Disease

Phase 1

Completed

• Conditions: Huntington Disease
• Interventions: Drug: WVE-003

• Registration Number: NCT05032196
• Lead Sponsor: Wave Life Sciences Ltd.

Brief Summary

This is a Phase 1b/2a multicenter, randomized, double-blind, placebo-controlled study to evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of WVE-003 in adult patients with early-manifest HD who carry the targeted single nucleotide polymorphism (SNP) - SNP3.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2021-08-18
• Study First Submitted QC: 2021-08-26
• Study First Posted: 2021-09-02
• Study Start: 2021-09-06
• Primary Completion: 2024-05-24
• Study Completion: 2024-05-24
• Results First Submitted: 2025-06-06
• Status Verified: 2025-07
• Results First Submitted QC: 2025-07-23
• Last Update Submitted: 2025-07-23
• Results First Posted: 2025-08-12
• Last Update Posted: 2025-08-12

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 47

Inclusion Criteria

1. Presence of the A variant of SNP3 on the same allele as the pathogenic CAG triplet expansion
2. Ambulatory, male or female patients aged ≥25 to ≤60 years
3. Clinical diagnostic motor features of HD, defined as Unified Huntington's Disease Rating Scale (UHDRS) Diagnostic Confidence Score = 4
4. UHDRS Total Functional Capacity Scores ≥9 and ≤13

Exclusion Criteria

1. Malignancy or received treatment for malignancy, other than treated basal cell or squamous cell carcinoma of the skin, within the previous 5 years

2. Received any other study drug, including an investigational oligonucleotide, within the past 1 year or 5 half-lives of the drug, whichever is longer, with the exception of the following:

   a. Received WVE-120101 or WVE-120102 within the last 3 months

3. Implantable CNS device that may interfere with ability to administer study drug via lumbar puncture or undergo MRI scan

4. Inability to undergo brain MRI (with or without sedation)

5. Bone, spine, bleeding, or other disorder that exposes the patient to risk of injury or unsuccessful lumbar puncture

6. Previously received tominersen

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
WVE-003 (Dose B) or placebo	WVE-003	-
WVE-003 (Dose A) or placebo	WVE-003	-
WVE-003 (Dose C) or placebo	WVE-003	-

Primary Outcome Measures

Name	Time	Method
Safety: Proportion of Patients With Treatment Emergent Adverse Events (TEAEs) Related to Study Drug	Day 1 through Week 24 (single ascending dose Period 1); Day 1 through Week 28 (multi dose Period 2)	The primary outcome for this study was safety and is reported as the proportion of patients with TEAEs related to study drug.

Secondary Outcome Measures

Name	Time	Method
Pharmacokinetics of WVE-003 in Plasma	Day 1 (single ascending dose Period 1); Day 1 and Day 113 (multi dose Period 2)	Parameter analyzed: Cmax = maximum observed concentration.
Concentration of WVE-003 in Cerebrospinal Fluid (CSF)	28 days post-dose during Period 1 (P1:Day29); 28 days post last dose during Period 2 (P2: Day141)	WVE-003 concentration in cerebrospinal fluid (CSF) is reported in ng/mL.

Trial Locations

Locations (23)

Westmead Hospital; 🇦🇺 Westmead, New South Wales, Australia

Monash Health; 🇦🇺 Clayton, Victoria, Australia

Royal Melbourne Hospital; 🇦🇺 Melbourne, Victoria, Australia

University of Alberta Hospital; 🇨🇦 Edmonton, Alberta, Canada

The Ottawa Hospital; 🇨🇦 Ottawa, Ontario, Canada

Centre Hospitalier de l-Universite de Montreal; 🇨🇦 Montréal, Quebec, Canada

Rigshospitalet; 🇩🇰 Copenhagen, Denmark

Hopital Henri Mondor - Hospital; 🇫🇷 Créteil, France

Institut du Cerveau et de la Moelle Epiniere; 🇫🇷 Paris, France

Katholisches Klinikum Bochum gGmbH; 🇩🇪 Bochum, Germany

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