FindTrial
Sign In

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)

Status
Completed
Phases
Phase 1Phase 2
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT05032196
Enrollment
47
Registered
2021-09-02
Start date
2021-09-06
Completion date
2024-05-24
Last updated
2025-08-12

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Huntington Disease

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.

Interventions

DRUGSAD: 30mg WVE-003

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

DRUGSAD: 60mg WVE-003

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

DRUGSAD: 90mg WVE-003

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

DRUGSAD: Pooled Placebo

Single dose of placebo

DRUGMD: 30mg WVE-003

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

DRUGMD: Placebo

Three doses of placebo Q8WK

Sponsors

Wave Life Sciences Ltd.
Lead SponsorINDUSTRY

Study design

Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)

Eligibility

Sex/Gender
ALL
Age
25 Years to 60 Years
Healthy volunteers
No

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

Design outcomes

Primary

MeasureTime frameDescription
Safety: Proportion of Patients With Treatment Emergent Adverse Events (TEAEs) Related to Study DrugDay 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

MeasureTime frameDescription
Pharmacokinetics of WVE-003 in PlasmaDay 1 (single ascending dose Period 1); Day 1 and Day 113 (multi dose Period 2)Parameter analyzed: AUC0-6 = area under the concentration-time curve from time 0 to 6 hrs
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.

Countries

Australia, Canada, Denmark, France, Germany, Italy, Netherlands, Poland, Spain, United Kingdom

Participant flow

Participants by arm

ArmCount
SAD: Pooled Placebo
Placebo SAD: Pooled Placebo: Single dose of placebo
16
SAD: 30mg WVE-003
Single Ascending Dose - 30mg WVE-003 SAD: 30mg WVE-003: Single ascending dose of 30mg WVE-003, an allele-selective stereopure antisense oligonucleotide (ASO)
13
SAD: 60mg WVE-003
Single Ascending Dose - 60mg WVE-003 SAD: 60mg WVE-003: Single ascending dose of 60mg WVE-003, an allele-selective stereopure antisense oligonucleotide (ASO)
10
SAD: 90mg WVE-003
Single Ascending Dose - 90mg WVE-003 SAD: 90mg WVE-003: Single ascending dose of 90mg WVE-003, an allele-selective stereopure antisense oligonucleotide (ASO)
8
MD: Placebo
Placebo MD: Placebo: Three doses of placebo Q8WK
7
MD: 30mg WVE-003
Multiple Dose - 30mg WVE-003 MD: 30mg WVE-003: Three doses of 30mg WVE-003 Q8WK an allele-selective stereopure antisense oligonucleotide (ASO
16
Total70

Withdrawals & dropouts

PeriodReasonFG000FG001FG002FG003FG004FG005
Period 1 (Single Ascending Dose)Adverse Event000100
Period 1 (Single Ascending Dose)Withdrawal by Subject010000
Period 2 (Multidose)Physician Decision000010

Baseline characteristics

CharacteristicSAD: Pooled PlaceboSAD: 30mg WVE-003SAD: 60mg WVE-003SAD: 90mg WVE-003TotalMD: PlaceboMD: 30mg WVE-003
Age, Continuous
Period 1
45.5 years
STANDARD_DEVIATION 7.4
47.8 years
STANDARD_DEVIATION 9.2
43.9 years
STANDARD_DEVIATION 8.6
49.6 years
STANDARD_DEVIATION 5.3
46.5 years
STANDARD_DEVIATION 7.9
——
Age, Continuous
Period 2
————47.1 years
STANDARD_DEVIATION 8.2
45.6 years
STANDARD_DEVIATION 8.3
47.8 years
STANDARD_DEVIATION 8.3
Ethnicity (NIH/OMB)
Period 1
Hispanic or Latino
1 Participants0 Participants0 Participants0 Participants1 Participants——
Ethnicity (NIH/OMB)
Period 1
Not Hispanic or Latino
15 Participants13 Participants10 Participants8 Participants46 Participants——
Ethnicity (NIH/OMB)
Period 1
Unknown or Not Reported
0 Participants0 Participants0 Participants0 Participants0 Participants——
Ethnicity (NIH/OMB)
Period 2
Hispanic or Latino
————1 Participants1 Participants0 Participants
Ethnicity (NIH/OMB)
Period 2
Not Hispanic or Latino
————22 Participants6 Participants16 Participants
Ethnicity (NIH/OMB)
Period 2
Unknown or Not Reported
————0 Participants0 Participants0 Participants
Race (NIH/OMB)
Period 1
American Indian or Alaska Native
0 Participants0 Participants0 Participants0 Participants0 Participants——
Race (NIH/OMB)
Period 1
Asian
0 Participants0 Participants0 Participants0 Participants0 Participants——
Race (NIH/OMB)
Period 1
Black or African American
0 Participants0 Participants0 Participants0 Participants0 Participants——
Race (NIH/OMB)
Period 1
More than one race
0 Participants0 Participants0 Participants0 Participants0 Participants——
Race (NIH/OMB)
Period 1
Native Hawaiian or Other Pacific Islander
0 Participants0 Participants0 Participants0 Participants0 Participants——
Race (NIH/OMB)
Period 1
Unknown or Not Reported
0 Participants0 Participants0 Participants0 Participants0 Participants——
Race (NIH/OMB)
Period 1
White
16 Participants13 Participants10 Participants8 Participants47 Participants——
Race (NIH/OMB)
Period 2
American Indian or Alaska Native
————0 Participants0 Participants0 Participants
Race (NIH/OMB)
Period 2
Asian
————0 Participants0 Participants0 Participants
Race (NIH/OMB)
Period 2
Black or African American
————23 Participants7 Participants16 Participants
Race (NIH/OMB)
Period 2
More than one race
————0 Participants0 Participants0 Participants
Race (NIH/OMB)
Period 2
Native Hawaiian or Other Pacific Islander
————0 Participants0 Participants0 Participants
Race (NIH/OMB)
Period 2
Unknown or Not Reported
————0 Participants0 Participants0 Participants
Race (NIH/OMB)
Period 2
White
————0 Participants0 Participants0 Participants
Sex: Female, Male
Period 1
Female
6 Participants6 Participants3 Participants3 Participants18 Participants——
Sex: Female, Male
Period 1
Male
10 Participants7 Participants7 Participants5 Participants29 Participants——
Sex: Female, Male
Period 2
Female
————7 Participants2 Participants5 Participants
Sex: Female, Male
Period 2
Male
————16 Participants5 Participants11 Participants

Adverse events

Event typeEG000
affected / at risk
EG001
affected / at risk
EG002
affected / at risk
EG003
affected / at risk
EG004
affected / at risk
EG005
affected / at risk
deaths
Total, all-cause mortality
0 / 160 / 130 / 100 / 80 / 70 / 16
other
Total, other adverse events
13 / 169 / 138 / 108 / 87 / 713 / 16
serious
Total, serious adverse events
1 / 160 / 131 / 100 / 80 / 70 / 16

Outcome results

Primary

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.

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

ArmMeasureValue (COUNT_OF_PARTICIPANTS)
SAD: Pooled PlaceboSafety: Proportion of Patients With Treatment Emergent Adverse Events (TEAEs) Related to Study Drug2 Participants
SAD: 30mg WVE-003Safety: Proportion of Patients With Treatment Emergent Adverse Events (TEAEs) Related to Study Drug1 Participants
SAD: 60mg WVE-003Safety: Proportion of Patients With Treatment Emergent Adverse Events (TEAEs) Related to Study Drug3 Participants
SAD: 90mg WVE-003Safety: Proportion of Patients With Treatment Emergent Adverse Events (TEAEs) Related to Study Drug3 Participants
MD: PlaceboSafety: Proportion of Patients With Treatment Emergent Adverse Events (TEAEs) Related to Study Drug0 Participants
MD: 30mg WVE-003Safety: Proportion of Patients With Treatment Emergent Adverse Events (TEAEs) Related to Study Drug8 Participants
Secondary

Concentration of WVE-003 in Cerebrospinal Fluid (CSF)

WVE-003 concentration in cerebrospinal fluid (CSF) is reported in ng/mL.

Time frame: 28 days post-dose during Period 1 (P1:Day29); 28 days post last dose during Period 2 (P2: Day141)

Population: Please note that the PK analysis only includes participants treated with WVE-003 (all placebo participants have been set as '0').

ArmMeasureValue (MEAN)Dispersion
SAD: Pooled PlaceboConcentration of WVE-003 in Cerebrospinal Fluid (CSF)3.6405 ng/mLStandard Deviation 1.6133
SAD: 30mg WVE-003Concentration of WVE-003 in Cerebrospinal Fluid (CSF)5.5346 ng/mLStandard Deviation 2.8402
SAD: 60mg WVE-003Concentration of WVE-003 in Cerebrospinal Fluid (CSF)7.0983 ng/mLStandard Deviation 3.1335
SAD: 90mg WVE-003Concentration of WVE-003 in Cerebrospinal Fluid (CSF)4.2903 ng/mLStandard Deviation 1.9722
Secondary

Pharmacokinetics of WVE-003 in Plasma

Parameter analyzed: AUC0-6 = area under the concentration-time curve from time 0 to 6 hrs

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

Population: Please note that the PK analysis only includes participants treated with WVE-003 (all placebo participants have been set as '0').

ArmMeasureGroupValue (MEAN)Dispersion
SAD: Pooled PlaceboPharmacokinetics of WVE-003 in PlasmaD1: AUC 0-6 (hr*ng/mL)1000 AUC 0-6 (hr*ng/mL)Standard Deviation 702
SAD: 30mg WVE-003Pharmacokinetics of WVE-003 in PlasmaD1: AUC 0-6 (hr*ng/mL)2310 AUC 0-6 (hr*ng/mL)Standard Deviation 3090
SAD: 60mg WVE-003Pharmacokinetics of WVE-003 in PlasmaD1: AUC 0-6 (hr*ng/mL)3890 AUC 0-6 (hr*ng/mL)Standard Deviation 2900
SAD: 90mg WVE-003Pharmacokinetics of WVE-003 in PlasmaD1: AUC 0-6 (hr*ng/mL)822 AUC 0-6 (hr*ng/mL)Standard Deviation 409
SAD: 90mg WVE-003Pharmacokinetics of WVE-003 in PlasmaD113: AUC 0-6 (hr*ng/mL)698 AUC 0-6 (hr*ng/mL)Standard Deviation 432
Secondary

Pharmacokinetics of WVE-003 in Plasma

Parameter analyzed: Cmax = maximum observed concentration.

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

Population: Please note that the PK analysis only includes participants treated with WVE-003 (all placebo participants have been set as '0').

ArmMeasureGroupValue (MEAN)Dispersion
SAD: Pooled PlaceboPharmacokinetics of WVE-003 in PlasmaD1: Cmax (ng/mL)240 Cmax (ng/mL)Standard Deviation 168
SAD: 30mg WVE-003Pharmacokinetics of WVE-003 in PlasmaD1: Cmax (ng/mL)601 Cmax (ng/mL)Standard Deviation 774
SAD: 60mg WVE-003Pharmacokinetics of WVE-003 in PlasmaD1: Cmax (ng/mL)1061 Cmax (ng/mL)Standard Deviation 942
SAD: 90mg WVE-003Pharmacokinetics of WVE-003 in PlasmaD1: Cmax (ng/mL)186 Cmax (ng/mL)Standard Deviation 106
SAD: 90mg WVE-003Pharmacokinetics of WVE-003 in PlasmaD113: Cmax (ng/mL)157 Cmax (ng/mL)Standard Deviation 97.3

Source: ClinicalTrials.gov · Data processed: Feb 6, 2026