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

Study Overview
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Brief Summary
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This is a Phase 1b/2a multicenter, randomized, double-blind, placebo-controlled study to evaluate the safety, tolerability, PK, and PD of WVE-003 in adult patients with early-manifest HD who carry the targeted single nucleotide polymorphism (SNP) - SNP3.

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

Conditions
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Huntington Disease

Intervention / Treatment
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* Drug: WVE-003


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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 Exclusion Criteria: 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

Ages Eligible for Study
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Minimum Age: 25 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: WVE-003 (Dose A) or placebo<br> | Drug: WVE-003<br>* WVE-003 is a stereopure antisense oligonucleotide (ASO)<br>|
| Experimental: WVE-003 (Dose B) or placebo<br> | Drug: WVE-003<br>* WVE-003 is a stereopure antisense oligonucleotide (ASO)<br>|
| Experimental: WVE-003 (Dose C) or placebo<br> | Drug: WVE-003<br>* WVE-003 is a stereopure antisense oligonucleotide (ASO)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety: Proportion of patients with adverse events (AEs) |  | Day 1 through end of study (minimum of 36 weeks) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum concentration (Cmax) of WVE-003 in plasma |  | Day 1 through end of study (minimum of 36 weeks) | 
| Area under the plasma concentration time curve for WVE-003 from time 0 to last quantifiable concentration (AUC0-t) |  | Day 1 through end of study (minimum of 36 weeks) | 
| Terminal half-life (t1/2) of WVE-003 in cerebrospinal fluid (CSF) |  | Day 1 through end of study (minimum of 36 weeks) |