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

NCT ID: NCT05032196

Last Updated: 2025-08-12

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

47 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-09-06

Study Completion Date

2024-05-24

Brief Summary

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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

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Conditions

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Huntington Disease

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

SEQUENTIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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SAD: Pooled Placebo

Placebo

Group Type PLACEBO_COMPARATOR

SAD: Pooled Placebo

Intervention Type DRUG

Single dose of placebo

SAD: 30mg WVE-003

Single Ascending Dose - 30mg WVE-003

Group Type EXPERIMENTAL

SAD: 30mg WVE-003

Intervention Type DRUG

Single ascending dose of 30mg WVE-003, an allele-selective stereopure antisense oligonucleotide (ASO)

SAD: 60mg WVE-003

Single Ascending Dose - 60mg WVE-003

Group Type EXPERIMENTAL

SAD: 60mg WVE-003

Intervention Type DRUG

Single ascending dose of 60mg WVE-003, an allele-selective stereopure antisense oligonucleotide (ASO)

SAD: 90mg WVE-003

Single Ascending Dose - 90mg WVE-003

Group Type EXPERIMENTAL

SAD: 90mg WVE-003

Intervention Type DRUG

Single ascending dose of 90mg WVE-003, an allele-selective stereopure antisense oligonucleotide (ASO)

MD: Placebo

Placebo

Group Type PLACEBO_COMPARATOR

MD: Placebo

Intervention Type DRUG

Three doses of placebo Q8WK

MD: 30mg WVE-003

Multiple Dose - 30mg WVE-003

Group Type EXPERIMENTAL

MD: 30mg WVE-003

Intervention Type DRUG

Three doses of 30mg WVE-003 Q8WK an allele-selective stereopure, antisense oligonucleotide (ASO)

Interventions

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SAD: 30mg WVE-003

Single ascending dose of 30mg WVE-003, an allele-selective stereopure antisense oligonucleotide (ASO)

Intervention Type DRUG

SAD: 60mg WVE-003

Single ascending dose of 60mg WVE-003, an allele-selective stereopure antisense oligonucleotide (ASO)

Intervention Type DRUG

SAD: 90mg WVE-003

Single ascending dose of 90mg WVE-003, an allele-selective stereopure antisense oligonucleotide (ASO)

Intervention Type DRUG

SAD: Pooled Placebo

Single dose of placebo

Intervention Type DRUG

MD: 30mg WVE-003

Three doses of 30mg WVE-003 Q8WK an allele-selective stereopure, antisense oligonucleotide (ASO)

Intervention Type DRUG

MD: Placebo

Three doses of placebo Q8WK

Intervention Type DRUG

Eligibility Criteria

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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
Minimum Eligible Age

25 Years

Maximum Eligible Age

60 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Wave Life Sciences Ltd.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Medical Director, MD

Role: STUDY_DIRECTOR

Wave Life Sciences

Locations

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Westmead Hospital

Westmead, New South Wales, Australia

Site Status

Monash Health

Clayton, Victoria, Australia

Site Status

Royal Melbourne Hospital

Melbourne, Victoria, Australia

Site Status

University of Alberta Hospital

Edmonton, Alberta, Canada

Site Status

The Ottawa Hospital

Ottawa, Ontario, Canada

Site Status

Centre Hospitalier de l-Universite de Montreal

Montreal, Quebec, Canada

Site Status

Rigshospitalet

Copenhagen, , Denmark

Site Status

Hopital Henri Mondor - Hospital

Créteil, , France

Site Status

Institut du Cerveau et de la Moelle Epiniere

Paris, , France

Site Status

Katholisches Klinikum Bochum gGmbH

Bochum, , Germany

Site Status

George-Huntington-Institut GmbH

Münster, , Germany

Site Status

kbo-Isar-Amper-Klinikum Taufkirchen (Vils)

Taufkirchen, , Germany

Site Status

Centro Ricerche Cliniche Di Verona

Verona, , Italy

Site Status

Leiden University Medical Center

Leiden, , Netherlands

Site Status

Maastricht University Medical Center

Maastricht, , Netherlands

Site Status

Szpital Sw. Wojciecha

Gdansk, , Poland

Site Status

Instytut Psychiatrii I Neurologii

Warsaw, , Poland

Site Status

Hospital de la Sanata Creu i Sant Pau

Barcelona, , Spain

Site Status

Hospital Universitario Ramón y Cajal

Madrid, , Spain

Site Status

Royal Devon and Exeter Hospital NHS Trust

Exeter, Devon, United Kingdom

Site Status

Royal Hospital for Children, Pharmacy Aseptic Unit

Glasgow, Glasgow City, United Kingdom

Site Status

Cardiff University, Schools of Medicine and Biosciences

Cardiff, Wales, United Kingdom

Site Status

Royal Liverpool University Hospital

Liverpool, , United Kingdom

Site Status

Countries

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Australia Canada Denmark France Germany Italy Netherlands Poland Spain United Kingdom

References

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Iwamoto N, Liu Y, Frank-Kamenetsky M, Maguire A, Tseng WC, Taborn K, Kothari N, Akhtar A, Bowman K, Shelke JD, Lamattina A, Hu XS, Jang HG, Kandasamy P, Liu F, Longo K, Looby R, Meena, Metterville J, Pan Q, Purcell-Estabrook E, Shimizu M, Prakasha PS, Standley S, Upadhyay H, Yang H, Yin Y, Zhao A, Francis C, Byrne M, Dale E, Verdine GL, Vargeese C. Preclinical evaluation of stereopure antisense oligonucleotides for allele-selective lowering of mutant HTT. Mol Ther Nucleic Acids. 2024 Jun 11;35(3):102246. doi: 10.1016/j.omtn.2024.102246. eCollection 2024 Sep 10.

Reference Type DERIVED
PMID: 39027419 (View on PubMed)

Estevez-Fraga C, Tabrizi SJ, Wild EJ. Huntington's Disease Clinical Trials Corner: November 2022. J Huntingtons Dis. 2022;11(4):351-367. doi: 10.3233/JHD-229006.

Reference Type DERIVED
PMID: 36463457 (View on PubMed)

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

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WVE-003-001

Identifier Type: -

Identifier Source: org_study_id

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