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

A Multicenter, Randomized, Double-blind, Placebo Controlled, Phase 1b/2a Study of WVE-003 Administered Intrathecally in Patients With Huntington's Disease (SELECT-HD)

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.

Study Overview

• Status: Completed
• Conditions: Huntington Disease
• Intervention / Treatment: Drug: SAD: Pooled Placebo; Drug: SAD: 30mg WVE-003; Drug: SAD: 60mg WVE-003; Drug: SAD: 90mg WVE-003; Drug: MD: Placebo; Drug: MD: 30mg WVE-003

• Study Type: Interventional
• Enrollment (Actual): 47
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Westmead, New South Wales, Australia, 2145
      • Westmead Hospital
  • Victoria
    • Clayton, Victoria, Australia, 3168
      • Monash Health
    • Melbourne, Victoria, Australia, 3050
      • Royal Melbourne Hospital
• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 2G3
      • University of Alberta Hospital
  • Ontario
    • Ottawa, Ontario, Canada, K1H 8L6
      • The Ottawa Hospital
  • Quebec
    • Montréal, Quebec, Canada, H2X019
      • Centre Hospitalier de l-Universite de Montreal
• Denmark
  • Copenhagen, Denmark, 2100
    • Rigshospitalet
• France
  • Créteil, France, 94010
    • Hopital Henri Mondor - Hospital
  • Paris, France, 75646
    • Institut du Cerveau et de la Moelle Epinière
• Germany
  • Bochum, Germany, 44791
    • Katholisches Klinikum Bochum gGmbH
  • Muenster, Germany, 48149
    • George-Huntington-Institut GmbH
  • Taufkirchen, Germany, 84416
    • Kbo-Isar-Amper-Klinikum Taufkirchen (Vils)
• Italy
  • Verona, Italy
    • Centro Ricerche Cliniche di Verona
• Netherlands
  • Leiden, Netherlands, 2333 ZA
    • Leiden University Medical Center
  • Maastricht, Netherlands, 6229 HX
    • Maastricht University Medical Center
• Poland
  • Gdańsk, Poland, 80-462
    • Szpital Sw. Wojciecha
  • Warsaw, Poland, 02-957
    • Instytut Psychiatrii i Neurologii
• Spain
  • Barcelona, Spain, 08041
    • Hospital de la Sanata Creu i Sant Pau
  • Madrid, Spain, 28034
    • Hospital Universitario Ramon y Cajal
• United Kingdom
  • Liverpool, United Kingdom, L7 8XP
    • Royal Liverpool University Hospital
  • Devon
    • Exeter, Devon, United Kingdom, EX2 5DW
      • Royal Devon and Exeter Hospital NHS Trust
  • Glasgow City
    • Glasgow, Glasgow City, United Kingdom, G51 4TF
      • Royal Hospital for Children, Pharmacy Aseptic Unit
  • Wales
    • Cardiff, Wales, United Kingdom, CF14 4XW
      • Cardiff University, Schools of Medicine and Biosciences

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 25 years to 60 years (Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Double

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: SAD: Pooled Placebo; Placebo	Drug: SAD: Pooled Placebo; Single dose of placebo
Experimental: SAD: 30mg WVE-003; Single Ascending Dose - 30mg WVE-003	Drug: SAD: 30mg WVE-003; Single ascending dose of 30mg WVE-003, an allele-selective stereopure antisense oligonucleotide (ASO)
Experimental: SAD: 60mg WVE-003; Single Ascending Dose - 60mg WVE-003	Drug: SAD: 60mg WVE-003; Single ascending dose of 60mg WVE-003, an allele-selective stereopure antisense oligonucleotide (ASO)
Experimental: SAD: 90mg WVE-003; Single Ascending Dose - 90mg WVE-003	Drug: SAD: 90mg WVE-003; Single ascending dose of 90mg WVE-003, an allele-selective stereopure antisense oligonucleotide (ASO)
Placebo Comparator: MD: Placebo; Placebo	Drug: MD: Placebo; Three doses of placebo Q8WK
Experimental: MD: 30mg WVE-003; Multiple Dose - 30mg WVE-003	Drug: MD: 30mg WVE-003; Three doses of 30mg WVE-003 Q8WK an allele-selective stereopure, antisense oligonucleotide (ASO)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics of WVE-003 in Plasma	Parameter analyzed: AUC0-6 = area under the concentration-time curve from time 0 to 6 hrs	Day 1 (single ascending dose Period 1); Day 1 and Day 113 (multi dose Period 2)
Pharmacokinetics of WVE-003 in Plasma	Parameter analyzed: Cmax = maximum observed concentration.	Day 1 (single ascending dose Period 1); Day 1 and Day 113 (multi dose Period 2)
Concentration of WVE-003 in Cerebrospinal Fluid (CSF)	WVE-003 concentration in cerebrospinal fluid (CSF) is reported in ng/mL.	28 days post-dose during Period 1 (P1:Day29); 28 days post last dose during Period 2 (P2: Day141)

Collaborators and Investigators

• Sponsor: Wave Life Sciences Ltd.
• Investigators: Study Director: Medical Director, MD, Wave Life Sciences

Study record dates

Study Major Dates

• Study Start (Actual): September 6, 2021
• Primary Completion (Actual): May 24, 2024
• Study Completion (Actual): May 24, 2024

Study Registration Dates

• First Submitted: August 18, 2021
• First Submitted That Met QC Criteria: August 26, 2021
• First Posted (Actual): September 2, 2021

Study Record Updates

• Last Update Posted (Actual): August 12, 2025
• Last Update Submitted That Met QC Criteria: July 23, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Mental Disorders; Genetic Diseases, Inborn; Neurocognitive Disorders; Cognition Disorders; Dementia; Neurodegenerative Diseases; Movement Disorders; Heredodegenerative Disorders, Nervous System; Basal Ganglia Diseases; Dyskinesias; Chorea; Huntington Disease
• Other Study ID Numbers: WVE-003-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes