Title
Safety and Tolerability of WVE-120101 in Patients With Huntington's Disease
A Multicenter, Randomized, Double-blind, Placebo-controlled, Phase 1b/2a Study of WVE-120101 Administered Intrathecally in Patients With Huntington's Disease
Phase
Phase 1/Phase 2Lead Sponsor
Wave Life SciencesStudy Type
InterventionalStatus
Terminated Results PostedIndication/Condition
Huntington's DiseaseIntervention/Treatment
WVE-120101 ...Study Participants
61PRECISION-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).
WVE-120101 is a stereopure antisense oligonucleotide (ASO)
0.9% Sodium Chloride
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
| Event Type | Organ System | Event Term | Pooled Placebo | WVE-120101 (2 mg) | WVE-120101 (4 mg) | WVE-120101 (8 mg) | WVE-120101 (16 mg) | WVE-120101 (32 mg) |
|---|
All TEAEs reported or observed during the study, including TEAEs resulting from concurrent illnesses, reactions to concurrent medications, or progression of disease states
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
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.
Cmax of WVE-120101 in plasma
tmax of WVE-120101 in plasma
AUClast from time 0 to the last quantifiable concentration of WVE-120101 in plasma
Terminal elimination half life of WVE-120101 in plasma (t1/2)
Percentage change from baseline in concentration of mutant huntingtin (mHTT) protein in CSF
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).
