Clinical trial NCT05032196: Study of WVE-003 in Patients With Huntington's Disease
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Huntington Disease
Lead sponsor: Wave Life Sciences Ltd.
Sponsor class: INDUSTRY
First posted: 2021-09-02
Enrollment: 47
Sex: ALL
Minimum age (years): 25
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Safety: Proportion of patients with adverse events (AEs)
timeFrame: Day 1 through end of study (minimum of 36 weeks)
Secondary outcomes:
measure: Maximum concentration (Cmax) of WVE-003 in plasma
timeFrame: Day 1 through end of study (minimum of 36 weeks)
measure: Area under the plasma concentration time curve for WVE-003 from time 0 to last quantifiable concentration (AUC0-t)
timeFrame: Day 1 through end of study (minimum of 36 weeks)
measure: Terminal half-life (t1/2) of WVE-003 in cerebrospinal fluid (CSF)
timeFrame: Day 1 through end of study (minimum of 36 weeks)
Other outcomes:
Locations:
city: Westmead
country: Australia
facility: Westmead Hospital
state: New South Wales
city: Clayton
country: Australia
facility: Monash Health
state: Victoria
city: Melbourne
country: Australia
facility: Royal Melbourne Hospital
state: Victoria
city: Edmonton
country: Canada
facility: University of Alberta Hospital
state: Alberta
city: Ottawa
country: Canada
facility: The Ottawa Hospital
state: Ontario
city: Montréal
country: Canada
facility: Centre Hospitalier de l-Universite de Montreal
state: Quebec
city: Copenhagen
country: Denmark
facility: Rigshospitalet
city: Créteil
country: France
facility: Hopital Henri Mondor - Hospital
city: Paris
country: France
facility: Institut du Cerveau et de la Moelle Epiniere
city: Bochum
country: Germany
facility: Katholisches Klinikum Bochum gGmbH
city: Muenster
country: Germany
facility: George-Huntington-Institut GmbH
city: Taufkirchen
country: Germany
facility: kbo-Isar-Amper-Klinikum Taufkirchen (Vils)
city: Verona
country: Italy
facility: Centro Ricerche Cliniche Di Verona
city: Leiden
country: Netherlands
facility: Leiden University Medical Center
city: Maastricht
country: Netherlands
facility: Maastricht University Medical Center
city: Gdańsk
country: Poland
facility: Szpital Sw. Wojciecha
city: Warsaw
country: Poland
facility: Instytut Psychiatrii I Neurologii
city: Barcelona
country: Spain
facility: Hospital de la Sanata Creu i Sant Pau
city: Madrid
country: Spain
facility: Hospital Universitario Ramón y Cajal
city: Exeter
country: United Kingdom
facility: Royal Devon and Exeter Hospital NHS Trust
state: Devon
city: Glasgow
country: United Kingdom
facility: Royal Hospital for Children, Pharmacy Aseptic Unit
state: Glasgow City
city: Cardiff
country: United Kingdom
facility: Cardiff University, Schools of Medicine and Biosciences
state: Wales
city: Liverpool
country: United Kingdom
facility: Royal Liverpool University Hospital
Study officials:
affiliation: Wave Life Sciences
name: Medical Director, MD
role: STUDY_DIRECTOR
References: