Huntington DiseasePhase 1/2NCT05032196
Study of WVE-003 in Patients With Huntington's Disease
A Phase 1/2 study testing SAD: 30mg WVE-003, SAD: 60mg WVE-003 and SAD: 90mg WVE-003 in people with Huntington Disease, run by Wave Life Sciences USA, Inc. at 23 sites in 10 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 25 to 60 years
- Conditions the study is for
- Huntington Disease
- What is being tested?
- SAD: 30mg WVE-003, SAD: 60mg WVE-003 and SAD: 90mg WVE-003
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 47 participants
- Where
- 23 sitesin 10 countries
- Study dates
- 6 Sep 2021to 24 May 2024
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 25 to 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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
Who cannot join
- 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:
- 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
Trial locations and contacts
23 sites in 10 countries.
23 sites in 10 countries
United Kingdom4 sites
Cardiff University, Schools of Medicine and Biosciences
Cardiff, Wales, CF14 4XW
Royal Devon and Exeter Hospital NHS Trust
Exeter, Devon, EX2 5DW
Royal Hospital for Children, Pharmacy Aseptic Unit
Glasgow, Glasgow City, G51 4TF
Royal Liverpool University Hospital
Liverpool, L7 8XP
Australia3 sites
Monash Health
Clayton, Victoria, 3168
Royal Melbourne Hospital
Melbourne, Victoria, 3050
Westmead Hospital
Westmead, New South Wales, 2145
Canada3 sites
University of Alberta Hospital
Edmonton, Alberta, T6G 2G3
Centre Hospitalier de l-Universite de Montreal
Montreal, Quebec, H2X019
The Ottawa Hospital
Ottawa, Ontario, K1H 8L6
Germany3 sites
Katholisches Klinikum Bochum gGmbH
Bochum, 44791
George-Huntington-Institut GmbH
Münster, 48149
kbo-Isar-Amper-Klinikum Taufkirchen (Vils)
Taufkirchen, 84416
France2 sites
Hopital Henri Mondor - Hospital
Créteil, 94010
Institut du Cerveau et de la Moelle Epiniere
Paris, 75646
Netherlands2 sites
Leiden University Medical Center
Leiden, 2333 ZA
Maastricht University Medical Center
Maastricht, 6229 HX
Poland2 sites
Szpital Sw. Wojciecha
Gdansk, 80-462
Instytut Psychiatrii I Neurologii
Warsaw, 02-957
Spain2 sites
Hospital de la Sanata Creu i Sant Pau
Barcelona, 08041
Hospital Universitario Ramón y Cajal
Madrid, 28034
About this study
Official title: 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.
- Conditions
- Huntington Disease
- Being tested
- SAD: 30mg WVE-003, SAD: 60mg WVE-003, SAD: 90mg WVE-003, SAD: Pooled Placebo, MD: 30mg WVE-003
- Medical subject headings
- Huntington Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SAD: 30mg WVE-003Drug
Single ascending dose of 30mg WVE-003, an allele-selective stereopure antisense oligonucleotide (ASO)
SAD: 60mg WVE-003Drug
Single ascending dose of 60mg WVE-003, an allele-selective stereopure antisense oligonucleotide (ASO)
SAD: 90mg WVE-003Drug
Single ascending dose of 90mg WVE-003, an allele-selective stereopure antisense oligonucleotide (ASO)
SAD: Pooled PlaceboDrug
Single dose of placebo
MD: 30mg WVE-003Drug
Three doses of 30mg WVE-003 Q8WK an allele-selective stereopure, antisense oligonucleotide (ASO)
MD: PlaceboDrug
Three doses of placebo Q8WK
| Study group | Role | What they receive |
|---|---|---|
| SAD: Pooled Placebo | Placebo comparator | Placebo Receives: Drug: SAD: Pooled Placebo |
| SAD: 30mg WVE-003 | Experimental | Single Ascending Dose - 30mg WVE-003 Receives: Drug: SAD: 30mg WVE-003 |
| SAD: 60mg WVE-003 | Experimental | Single Ascending Dose - 60mg WVE-003 Receives: Drug: SAD: 60mg WVE-003 |
| SAD: 90mg WVE-003 | Experimental | Single Ascending Dose - 90mg WVE-003 Receives: Drug: SAD: 90mg WVE-003 |
| MD: Placebo | Placebo comparator | Placebo Receives: Drug: MD: Placebo |
| MD: 30mg WVE-003 | Experimental | Multiple Dose - 30mg WVE-003 Receives: Drug: MD: 30mg WVE-003 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
Parameter analyzed: AUC0-6 = area under the concentration-time curve from time 0 to 6 hrs
Measured: 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.
Measured: 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.
Measured: 28 days post-dose during Period 1 (P1:Day29); 28 days post last dose during Period 2 (P2: Day141)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Sep 2021
- Study start6 Sep 2021
- Primary completion24 May 2024
- Study completion24 May 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Huntington DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 47 participants (actual)
Sponsor and investigators
- Lead sponsor
- Wave Life Sciences USA, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Director, MD, Study director, Wave Life Sciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05032196
- Sponsor's protocol ID
- WVE-003-001
- Status last verified
- Jul 2025
- First submitted
- 18 Aug 2021
- Last updated
- 12 Aug 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 39027419Estevez-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.
PubMed 36463457
Study at a glance
From the registry record, last updated by the sponsor on 12 Aug 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicenter, Randomized, Double-blind, Placebo Controlled, Phase 1b/2a Study of WVE-003 Administered Intrathecally in Patients With Huntington's Disease (SELECT-HD)
- ClinicalTrials.gov ID
- NCT05032196
- Acronym / sponsor ID
- WVE-003-001
- Conditions
- Huntington Disease
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 47 participants (actual)
- Lead sponsor
- Wave Life Sciences USA, Inc.Industry (pharma, biotech, devices)
- Study start
- 6 Sep 2021 (actual)
- Primary completion
- 24 May 2024 (actual)
- Study completion
- 24 May 2024 (actual)
- First posted
- 2 Sep 2021 (actual)
- Results
- Posted 12 Aug 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Double blind (participant, investigator)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| SAD: Pooled Placebo | Placebo comparator | Drug: SAD: Pooled PlaceboPlacebo |
| SAD: 30mg WVE-003 | Experimental | Drug: SAD: 30mg WVE-003Single Ascending Dose - 30mg WVE-003 |
| SAD: 60mg WVE-003 | Experimental | Drug: SAD: 60mg WVE-003Single Ascending Dose - 60mg WVE-003 |
| SAD: 90mg WVE-003 | Experimental | Drug: SAD: 90mg WVE-003Single Ascending Dose - 90mg WVE-003 |
| MD: Placebo | Placebo comparator | Drug: MD: PlaceboPlacebo |
| MD: 30mg WVE-003 | Experimental | Drug: MD: 30mg WVE-003Multiple Dose - 30mg WVE-003 |
Who may qualify
- Ages
- 25 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (7 listed)
- 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:
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SAD: 30mg WVE-003Single ascending dose of 30mg WVE-003, an allele-selective stereopure antisense oligonucleotide (ASO) | Drug | SAD: 30mg WVE-003 |
| SAD: 60mg WVE-003Single ascending dose of 60mg WVE-003, an allele-selective stereopure antisense oligonucleotide (ASO) | Drug | SAD: 60mg WVE-003 |
| SAD: 90mg WVE-003Single ascending dose of 90mg WVE-003, an allele-selective stereopure antisense oligonucleotide (ASO) | Drug | SAD: 90mg WVE-003 |
| SAD: Pooled PlaceboSingle dose of placebo | Drug | SAD: Pooled Placebo |
| MD: 30mg WVE-003Three doses of 30mg WVE-003 Q8WK an allele-selective stereopure, antisense oligonucleotide (ASO) | Drug | MD: 30mg WVE-003 |
| MD: PlaceboThree doses of placebo Q8WK | Drug | MD: Placebo |
Primary outcome
Safety: Proportion of Patients With Treatment Emergent Adverse Events (TEAEs) Related to Study Drug
Time frame: 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.
3 secondary outcomes
Pharmacokinetics of WVE-003 in Plasma
Time frame: Day 1 (single ascending dose Period 1); Day 1 and Day 113 (multi dose Period 2)
Pharmacokinetics of WVE-003 in Plasma
Time frame: Day 1 (single ascending dose Period 1); Day 1 and Day 113 (multi dose Period 2)
Concentration of WVE-003 in Cerebrospinal Fluid (CSF)
Time frame: 28 days post-dose during Period 1 (P1:Day29); 28 days post last dose during Period 2 (P2: Day141)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Aug 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 39027419Iwamoto 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.
- Derived from this study: PubMed 36463457Estevez-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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Medical Director, MD study director
Wave Life Sciences
23 sites in 10 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing SAD: 30mg WVE-003, SAD: 60mg WVE-003 and SAD: 90mg WVE-003 in people with Huntington Disease, run by Wave Life Sciences USA, Inc. at 23 sites in 10 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 12 Aug 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 23 sites in United Kingdom, Australia, Canada, Germany, France and 5 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 12 Aug 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety: Proportion of Patients With Treatment Emergent Adverse Events (TEAEs) Related to Study Drug (time frame: Day 1 through Week 24 (single ascending dose Period 1); Day 1 through Week 28 (multi dose Period 2)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05032196, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Aug 2025.