Clinical trial NCT03225833: Safety and Tolerability of WVE-120101 in Patients With Huntington's Disease
Official title: A Multicenter, Randomized, Double-blind, Placebo-controlled, Phase 1b/2a Study of WVE-120101 Administered Intrathecally in Patients With Huntington's Disease
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Huntington's Disease
Lead sponsor: Wave Life Sciences Ltd.
Sponsor class: INDUSTRY
First posted: 2017-07-21
Enrollment: 61
Sex: ALL
Minimum age (years): 25
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: PRECISION-HD1 is a Phase 1b/2a multicenter, randomized, double-blind, placebo-controlled study to evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of single and multiple doses of WVE-120101 in adult patients with early manifest Huntington's disease (HD) who carry a targeted single nucleotide polymorphism (SNP) rs362307 (SNP1).


Eligibility criteria: Key Inclusion Criteria:

* Prescreened with targeted SNP on the same allele as the pathogenic CAG expansion
* Ambulatory, male or female patients aged ≥25 - ≤65 years
* Clinical diagnostic motor features of HD, defined as Unified Huntington's Disease Rating Scale (UHDRS) Diagnostic Confidence Score = 4
* Early manifest HD, Stage I or Stage II based on UHDRS Total Functional Capacity Scores ≥7 and ≤13

Key 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 investigational drug or implantable device in prior 3 months or investigational oligonucleotide in prior 6 months or 5 half-lives of the oligonucleotide, whichever is longer
* Clinically significant medical condition, unstable psychiatric symptoms, substance abuse, or pregnancy
* Inability to undergo brain MRI
* Bone, spine, bleeding, or other disorder that exposes the patient to risk of injury or unsuccessful lumbar puncture

Primary outcomes:
measure: Safety: Number of Patients With Treatment-emergent Adverse Events (TEAEs)
timeFrame: Day 1 to end of study (up to Day 182 [32 mg cohort]/ Day 210 [all other cohorts])
measure: Safety: Severity of Adverse Events
timeFrame: Day 1 to end of study (up to Day 182 [32 mg cohort]/ Day 210 [all other cohorts])
measure: Safety: Number of Patients With Serious TEAEs
timeFrame: Day 1 to end of study (up to Day 182 [32 mg cohort]/ Day 210 [all other cohorts])
measure: Safety and Tolerability: Number of Patients Who Withdraw Due to TEAEs
timeFrame: Day 1 to end of study (up to Day 182 [32 mg cohort]/ Day 210 [all other cohorts])
Secondary outcomes:
measure: Pharmacokinetics (PK): Maximum Observed Concentration (Cmax)
timeFrame: Patients participating in Period 1 (SAD) had PK samples collected on Day 1 predose through 24-48 hours postdose. Patients participating in Period 2 (MAD) had PK samples collected predose on Day 112 and through 4 hours postdose.
measure: PK: Time of Occurrence of Cmax (Tmax)
timeFrame: Patients participating in Period 1 (SAD) had PK samples collected on Day 1 predose through 24-48 hours postdose. Patients participating in Period 2 (MAD) had PK samples collected predose on Day 112 and through 4 hours postdose.
measure: PK: Area Under the Plasma Concentration-time Curve (AUClast)
timeFrame: Patients participating in Period 1 (SAD) had PK samples collected on Day 1 predose through 24-48 hours postdose. Patients participating in Period 2 (MAD) had PK samples collected predose on Day 112 and through 4 hours postdose.
measure: PK: Terminal Elimination Half Life
timeFrame: Patients participating in Period 1 (SAD) had PK samples collected on Day 1 predose through 24-48 hours postdose. Patients participating in Period 2 (MAD) had PK samples collected predose on Day 112 and through 4 hours postdose.
measure: Pharmacodynamics
timeFrame: Day 1 to last observation - up to Day 140 (32 mg cohort) or Day 196 (all other cohorts)
measure: Clinical Effects: Total Functional Capacity (TFC)
timeFrame: Day 1 to last observation - up to Day 140 (32 mg cohort) or Day 196 (all other cohorts)
Other outcomes:
Locations:
city: Sidney
country: Australia
facility: Westmead Hospital
state: New South Wales
city: Herston
country: Australia
facility: Royal Brisbane & Women's Hospital
state: Queensland
city: Carlton
country: Australia
facility: Royal Melbourne Hospital
state: Victoria
city: Clayton
country: Australia
facility: Monash Health
state: Victoria
city: Melbourne
country: Australia
facility: Alfred Health
state: Victoria
city: Parkdale
country: Australia
facility: Calvary Health Care Bethlehem
state: Victoria
city: Perth
country: Australia
facility: North Metropolitan Health Service
state: Western Australia
city: Edmonton
country: Canada
facility: University of Alberta
state: Alberta
city: Toronto
country: Canada
facility: Centre For Movement Disorders
state: Ontario
city: Montreal
country: Canada
facility: Center Hospitalier de l'Universite de Montreal
state: Quebec
city: Aarhus
country: Denmark
facility: Aarhus Universitets Hospital
city: Copenhagen
country: Denmark
facility: Rigshospitalet
city: Odense
country: Denmark
facility: Odense University Hospital and University of Southern Denmark
city: Créteil
country: France
facility: Hospital Henri Mondor
city: Paris
country: France
facility: Institut du Cerveau et de la Moelle Epinière
city: Muenster
country: Germany
facility: George-Huntington-Institut GmbH
city: Gdańsk
country: Poland
facility: Szpital Sw. Wojciecha
city: Warsaw
country: Poland
facility: Instytut Psychiatrii i Neurologii
city: Exeter
country: United Kingdom
facility: Royal Devon and Exeter Hospital NHS Trust
state: Devon
city: Glasgow
country: United Kingdom
facility: Queen Elizabeth University Hospital - PPDS
state: Glasgow City
city: Liverpool
country: United Kingdom
facility: Royal Liverpool University Hospital
Study officials:
affiliation: Wave Life Sciences
name: Medical Director, MD
role: STUDY_DIRECTOR
References:
citation: Rodrigues FB, Wild EJ. Huntington's Disease Clinical Trials Corner: April 2020. J Huntingtons Dis. 2020;9(2):185-197. doi: 10.3233/JHD-200002.
citation: Rodrigues FB, Wild EJ. Huntington's Disease Clinical Trials Corner: February 2018. J Huntingtons Dis. 2018;7(1):89-98. doi: 10.3233/JHD-189001.