Safety and Tolerability of WVE-120102 in Patients With Huntington's Disease
- Conditions
- Huntington's Disease
- Interventions
- Drug: WVE-120102Drug: Placebo
- Registration Number
- NCT03225846
- Lead Sponsor
- Wave Life Sciences Ltd.
- Brief Summary
PRECISION-HD2 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-120102 in adult patients with early manifest Huntington's disease (HD) who carry a targeted single nucleotide polymorphism (SNP) rs362331 (SNP2).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 88
- 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
- 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 halflives 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description WVE-120102 (16 mg) or placebo Placebo - WVE-120102 (2 mg) or placebo WVE-120102 - WVE-120102 (2 mg) or placebo Placebo - WVE-120102 (16 mg) or placebo WVE-120102 - WVE-120102 (4 mg) or placebo WVE-120102 - WVE-120102 (4 mg) or placebo Placebo - WVE-120102 (8 mg) or placebo WVE-120102 - WVE-120102 (8 mg) or placebo Placebo - WVE-120102 (32 mg ) or placebo WVE-120102 - WVE-120102 (32 mg ) or placebo Placebo -
- Primary Outcome Measures
Name Time Method Safety: Number of Patients With Serious TEAEs Time Frame: Day 1 to end of study (up to Day 182 [32 mg cohort]/ Day 210 [all other cohorts]) A serious TEAE is defined as any event that results in death, is immediately life threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, or is a congenital anomaly/birth defect not present at Prescreening.
Safety: Number of Patients With Treatment-emergent Adverse Events (TEAEs) Day 1 to end of study (up to Day 182 [32 mg cohort]/ Day 210 [all other cohorts]) All TEAEs reported or observed during the study, including TEAEs resulting from concurrent illnesses, reactions to concurrent medications, or progression of disease states
Safety: Number of Patients Who Experienced Severe TEAEs Time Frame: Day 1 to end of study (up to Day 182 [32 mg cohort]/ Day 210 [all other cohorts]) Number of patients who experienced a severe treatment-emergent adverse event. Severity was evaluated using the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0
Safety and Tolerability: Number of Patients Who Withdraw Due to TEAEs Time Frame: Day 1 to end of study (up to Day 182 [32 mg cohort]/ Day 210 [all other cohorts])
- Secondary Outcome Measures
Name Time Method PK: Time of Occurrence of Cmax (Tmax) 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. tmax of WVE-120102 in plasma
Clinical Effects: Total Functional Capacity (TFC) Day 1 Day 1 to last observation - up to Day 140 (32 mg cohort) or Day 196 (all other cohorts) Percentage change from baseline to the last measured time point in the Total Functional Capacity score, administered as part of the Unified Huntington's Disease Rating Scale (UHDRS). Total Functional Capacity is scored 13 (normal) to 0 (severe disability)
Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) 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. Cmax of WVE-120102 in plasma
PK: Area Under the Plasma Concentration-time Curve (AUC 0-t) 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. AUC 0-t from time zero to the last quantifiable concentration of WVE-120102 in plasma
PK: Terminal Elimination Half-life 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. Terminal elimination half life of WVE-120102 in plasma (t1/2)
Pharmacodynamics (PD): Percentage Change From Baseline in Mutant Huntingtin Protein Day 1 to last observation - up to Day 140 (32 mg cohort) or Day 196 (all other cohorts) Percentage change from baseline to last observation in mutant huntingtin protein
Trial Locations
- Locations (26)
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
University of California Davis Medical Center
🇺🇸Sacramento, California, United States
Westmead Hospital
🇦🇺Sidney, New South Wales, Australia
Royal Brisbane & Women's Hospital
🇦🇺Herston, Queensland, Australia
North Metropolitan Health Service
🇦🇺Perth, Western Australia, Australia
Centre For Movement Disorders
🇨🇦Toronto, Ontario, Canada
Hospital Henri Mondor
🇫🇷Créteil, France
Institut du Cerveau et de la Moelle Epinière
🇫🇷Paris, France
Szpital Sw. Wojciecha
🇵🇱Gdańsk, Poland
Queen Elizabeth University Hospital - PPDS
🇬🇧Glasgow, Glasgow City, United Kingdom
The Ohio State University
🇺🇸Columbus, Ohio, United States
Vanderbilt University Medical Center
🇺🇸Nashville, Tennessee, United States
Centre Hospitalier de l-Universite de Montreal
🇨🇦Montreal, Quebec, Canada
Instytut Psychiatrii i Neurologii
🇵🇱Warsaw, Poland
Royal Melbourne Hospital
🇦🇺Carlton, Victoria, Australia
Monash Health
🇦🇺Clayton, Victoria, Australia
Alfred Health
🇦🇺Melbourne, Victoria, Australia
Calvary Health Care Bethlehem
🇦🇺Parkdale, Victoria, Australia
University of Alberta
🇨🇦Edmonton, Alberta, Canada
University of California San Diego
🇺🇸La Jolla, California, United States
Royal Devon and Exeter Hospital NHS Trust
🇬🇧Exeter, Devon, United Kingdom
George-Huntington-Institut GmbH
🇩🇪Muenster, Germany
Aarhus Universitets Hospital
🇩🇰Aarhus N, Denmark
Rigshospitalet
🇩🇰Copenhagen, Denmark
Odense University Hospital and University of Southern Denmark
🇩🇰Odense, Denmark
Royal Liverpool University Hospital
🇬🇧Liverpool, United Kingdom