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

NCT05032196 | Completed Phase 1 Results DMC FDA Drug

• 1 other identifier: WVE-003-001
• Study Type: interventional
• Target: 47
• Locations: 10 countries
• Sites: 23

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.

Conditions

Huntington Disease

Outcome Measures

Primary Outcomes (1)

• Safety: Proportion of Patients With Treatment Emergent Adverse Events (TEAEs) Related to Study Drug

  The primary outcome for this study was safety and is reported as the proportion of patients with TEAEs related to study drug.

  Day 1 through Week 24 (single ascending dose Period 1); Day 1 through Week 28 (multi dose Period 2)

Secondary Outcomes (3)

• Pharmacokinetics of WVE-003 in Plasma

  Day 1 (single ascending dose Period 1); Day 1 and Day 113 (multi dose Period 2)

• Pharmacokinetics of WVE-003 in Plasma

  Day 1 (single ascending dose Period 1); Day 1 and Day 113 (multi dose Period 2)

• 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)

Study Arms (6)

SAD: Pooled Placebo

PLACEBO COMPARATOR

Placebo

Drug: SAD: Pooled Placebo

SAD: 30mg WVE-003

EXPERIMENTAL

Single Ascending Dose - 30mg WVE-003

Drug: SAD: 30mg WVE-003

SAD: 60mg WVE-003

EXPERIMENTAL

Single Ascending Dose - 60mg WVE-003

Drug: SAD: 60mg WVE-003

SAD: 90mg WVE-003

EXPERIMENTAL

Single Ascending Dose - 90mg WVE-003

Drug: SAD: 90mg WVE-003

MD: Placebo

PLACEBO COMPARATOR

Placebo

Drug: MD: Placebo

MD: 30mg WVE-003

EXPERIMENTAL

Multiple Dose - 30mg WVE-003

Drug: MD: 30mg WVE-003

Interventions

SAD: 30mg WVE-003 DRUG

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

SAD: 30mg WVE-003

SAD: 60mg WVE-003 DRUG

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

SAD: 60mg WVE-003

SAD: 90mg WVE-003 DRUG

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

SAD: 90mg WVE-003

SAD: Pooled Placebo DRUG

Single dose of placebo

SAD: Pooled Placebo

MD: 30mg WVE-003 DRUG

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

MD: 30mg WVE-003

MD: Placebo DRUG

Three doses of placebo Q8WK

MD: Placebo

Eligibility Criteria

• Age: 25 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

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

You may not qualify if:

• Malignancy or received treatment for malignancy, other than treated basal cell or squamous cell carcinoma of the skin, within the previous 5 years
• 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
• Implantable CNS device that may interfere with ability to administer study drug via lumbar puncture or undergo MRI scan
• Inability to undergo brain MRI (with or without sedation)
• Bone, spine, bleeding, or other disorder that exposes the patient to risk of injury or unsuccessful lumbar puncture
• Previously received tominersen

Sponsors & Collaborators

• Wave Life Sciences Ltd.: lead

Study Sites (23)

Westmead Hospital

Westmead, New South Wales, 2145, Australia

Location

Monash Health

Clayton, Victoria, 3168, Australia

Location

Royal Melbourne Hospital

Melbourne, Victoria, 3050, Australia

Location

University of Alberta Hospital

Edmonton, Alberta, T6G 2G3, Canada

Location

The Ottawa Hospital

Ottawa, Ontario, K1H 8L6, Canada

Location

Centre Hospitalier de l-Universite de Montreal

Montreal, Quebec, H2X019, Canada

Location

Rigshospitalet

Copenhagen, 2100, Denmark

Location

Hopital Henri Mondor - Hospital

Créteil, 94010, France

Location

Institut du Cerveau et de la Moelle Epiniere

Paris, 75646, France

Location

Katholisches Klinikum Bochum gGmbH

Bochum, 44791, Germany

Location

George-Huntington-Institut GmbH

Münster, 48149, Germany

Location

kbo-Isar-Amper-Klinikum Taufkirchen (Vils)

Taufkirchen, 84416, Germany

Location

Centro Ricerche Cliniche Di Verona

Verona, Italy

Location

Leiden University Medical Center

Leiden, 2333 ZA, Netherlands

Location

Maastricht University Medical Center

Maastricht, 6229 HX, Netherlands

Location

Szpital Sw. Wojciecha

Gdansk, 80-462, Poland

Location

Instytut Psychiatrii I Neurologii

Warsaw, 02-957, Poland

Location

Hospital de la Sanata Creu i Sant Pau

Barcelona, 08041, Spain

Location

Hospital Universitario Ramón y Cajal

Madrid, 28034, Spain

Location

Royal Devon and Exeter Hospital NHS Trust

Exeter, Devon, EX2 5DW, United Kingdom

Location

Royal Hospital for Children, Pharmacy Aseptic Unit

Glasgow, Glasgow City, G51 4TF, United Kingdom

Location

Cardiff University, Schools of Medicine and Biosciences

Cardiff, Wales, CF14 4XW, United Kingdom

Location

Royal Liverpool University Hospital

Liverpool, L7 8XP, United Kingdom

Location

Related Publications (2)

• 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.

  PMID: 39027419 DERIVED

• 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.

  PMID: 36463457 DERIVED

MeSH Terms

Conditions

Huntington Disease

Interventions

Sagittal Abdominal Diameter

Condition Hierarchy (Ancestors)

Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Dementia; Chorea; Dyskinesias; Movement Disorders; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Cognition Disorders; Neurocognitive Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Body Size; Body Weights and Measures; Body Constitution; Physical Examination; Diagnostic Techniques and Procedures; Diagnosis; Anthropometry; Investigative Techniques; Physiological Phenomena

Results Point of Contact

• Title: Medical Director, MD
• Organization: Wave Life Sciences USA, Inc

info@wavelifesci.com

+1 617-949-2900

Study Officials

• Medical Director, MD

  Wave Life Sciences

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 18, 2021
• First Posted: September 2, 2021
• Study Start: September 6, 2021
• Primary Completion: May 24, 2024
• Study Completion: May 24, 2024
• Last Updated: August 12, 2025
• Results First Posted: August 12, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

CA (3); PL (2); AU (3); NL (2); DK (1); FR (2); IT (1); DE (3); GB (4); ES (2)