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

Wave Life Sciences

Status and phase: Completed; Phase 2; Phase 1

Conditions: Huntington Disease

Treatments: Drug: SAD: 60mg WVE-003; Drug: SAD: 30mg WVE-003; Drug: MD: Placebo; Drug: SAD: Pooled Placebo; Drug: MD: 30mg WVE-003; Drug: SAD: 90mg WVE-003

Study type: Interventional

Funder types: Industry

Identifiers

NCT05032196

WVE-003-001

Details and patient eligibility

About

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.

Enrollment: 47 patients

Sex: All

Ages: 25 to 60 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Sequential Assignment

Masking: Double Blind

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47 participants in 6 patient groups, including a placebo group

SAD: Pooled Placebo

Placebo Comparator group

Description:

Placebo

Treatment:

Drug: SAD: Pooled Placebo

SAD: 30mg WVE-003

Experimental group

Description:

Single Ascending Dose - 30mg WVE-003

Treatment:

Drug: SAD: 30mg WVE-003

SAD: 60mg WVE-003

Experimental group

Description:

Single Ascending Dose - 60mg WVE-003

Treatment:

Drug: SAD: 60mg WVE-003

SAD: 90mg WVE-003

Experimental group

Description:

Single Ascending Dose - 90mg WVE-003

Treatment:

Drug: SAD: 90mg WVE-003

MD: Placebo

Placebo Comparator group

Description:

Placebo

Treatment:

Drug: MD: Placebo

MD: 30mg WVE-003

Experimental group

Description:

Multiple Dose - 30mg WVE-003

Treatment:

Drug: MD: 30mg WVE-003