Safety and Tolerability of WVE-120101 in Patients With Huntington's Disease

Huntington's Disease Clinical Trial

— PRECISION-HD1  

Official title:

A Multicenter, Randomized, Double-blind, Placebo-controlled, Phase 1b/2a Study of WVE-120101 Administered Intrathecally in Patients With Huntington's Disease

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03225833
• Other study ID #: WVE-HDSNP1-001
• Status: Terminated
• Phase: Phase 1/Phase 2
• Start date: July 17, 2017
• Est. completion date: May 11, 2021

Study information

• Verified date: February 2022
• Source: Wave Life Sciences Ltd.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 61
• Est. completion date: May 11, 2021
• Est. primary completion date: May 11, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 25 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Huntington Disease
• Huntington's Disease

Intervention

Drug:
• WVE-120101
WVE-120101 is a stereopure antisense oligonucleotide (ASO)
• Placebo
0.9% Sodium Chloride

Locations

Country	Name	City	State
Australia	Royal Melbourne Hospital	Carlton	Victoria
Australia	Monash Health	Clayton	Victoria
Australia	Royal Brisbane & Women's Hospital	Herston	Queensland
Australia	Alfred Health	Melbourne	Victoria
Australia	Calvary Health Care Bethlehem	Parkdale	Victoria
Australia	North Metropolitan Health Service	Perth	Western Australia
Australia	Westmead Hospital	Sidney	New South Wales
Canada	University of Alberta	Edmonton	Alberta
Canada	Center Hospitalier de l'Universite de Montreal	Montreal	Quebec
Canada	Centre For Movement Disorders	Toronto	Ontario
Denmark	Aarhus Universitets Hospital	Aarhus
Denmark	Rigshospitalet	Copenhagen
Denmark	Odense University Hospital and University of Southern Denmark	Odense
France	Hospital Henri Mondor	Créteil
France	Institut du Cerveau et de la Moelle Epinière	Paris
Germany	George-Huntington-Institut GmbH	Muenster
Poland	Szpital Sw. Wojciecha	Gdansk
Poland	Instytut Psychiatrii i Neurologii	Warsaw
United Kingdom	Royal Devon and Exeter Hospital NHS Trust	Exeter	Devon
United Kingdom	Queen Elizabeth University Hospital - PPDS	Glasgow	Glasgow City
United Kingdom	Royal Liverpool University Hospital	Liverpool

Sponsors (1)

Lead Sponsor	Collaborator
Wave Life Sciences Ltd.

Countries where clinical trial is conducted

Australia,  Canada,  Denmark,  France,  Germany,  Poland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety: Number of Patients With Treatment-emergent Adverse Events (TEAEs)	All TEAEs reported or observed during the study, including TEAEs resulting from concurrent illnesses, reactions to concurrent medications, or progression of disease states	Day 1 to end of study (up to Day 182 [32 mg cohort]/ Day 210 [all other cohorts])
Primary	Safety: Severity of Adverse Events	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	Day 1 to end of study (up to Day 182 [32 mg cohort]/ Day 210 [all other cohorts])
Primary	Safety: Number of Patients With Serious TEAEs	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.	Day 1 to end of study (up to Day 182 [32 mg cohort]/ Day 210 [all other cohorts])
Primary	Safety and Tolerability: Number of Patients Who Withdraw Due to TEAEs		Day 1 to end of study (up to Day 182 [32 mg cohort]/ Day 210 [all other cohorts])
Secondary	Pharmacokinetics (PK): Maximum Observed Concentration (Cmax)	Cmax of WVE-120101 in plasma	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.
Secondary	PK: Time of Occurrence of Cmax (Tmax)	tmax of WVE-120101 in plasma	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.
Secondary	PK: Area Under the Plasma Concentration-time Curve (AUClast)	AUClast from time 0 to the last quantifiable concentration of WVE-120101 in plasma	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.
Secondary	PK: Terminal Elimination Half Life	Terminal elimination half life of WVE-120101 in plasma (t1/2)	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.
Secondary	Pharmacodynamics	Percentage change from baseline in concentration of mutant huntingtin (mHTT) protein in CSF	Day 1 to last observation - up to Day 140 (32 mg cohort) or Day 196 (all other cohorts)
Secondary	Clinical Effects: Total Functional Capacity (TFC)	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).	Day 1 to last observation - up to Day 140 (32 mg cohort) or Day 196 (all other cohorts)