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Safety and Tolerability of WVE-120102 in Patients With Huntington's Disease (PRECISION-HD2)

Primary Purpose

Huntington's Disease

Status
Terminated
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
WVE-120102
Placebo
Sponsored by
Wave Life Sciences Ltd.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Huntington's Disease

Eligibility Criteria

25 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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 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

Sites / Locations

  • University of California San Diego
  • University of California Davis Medical Center
  • Massachusetts General Hospital
  • The Ohio State University
  • Vanderbilt University Medical Center
  • Westmead Hospital
  • Royal Brisbane & Women's Hospital
  • Royal Melbourne Hospital
  • Monash Health
  • Alfred Health
  • Calvary Health Care Bethlehem
  • North Metropolitan Health Service
  • University of Alberta
  • Centre For Movement Disorders
  • Centre Hospitalier de l-Universite de Montreal
  • Aarhus Universitets Hospital
  • Rigshospitalet
  • Odense University Hospital and University of Southern Denmark
  • Hospital Henri Mondor
  • Institut du Cerveau et de la Moelle Epinière
  • George-Huntington-Institut GmbH
  • Szpital Sw. Wojciecha
  • Instytut Psychiatrii i Neurologii
  • Royal Devon and Exeter Hospital NHS Trust
  • Queen Elizabeth University Hospital - PPDS
  • Royal Liverpool University Hospital

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm Type

Experimental

Experimental

Experimental

Experimental

Experimental

Arm Label

WVE-120102 (2 mg) or placebo

WVE-120102 (4 mg) or placebo

WVE-120102 (8 mg) or placebo

WVE-120102 (16 mg) or placebo

WVE-120102 (32 mg ) or placebo

Arm Description

Outcomes

Primary Outcome Measures

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
Safety: Number of Patients Who Experienced Severe TEAEs
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: 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.
Safety and Tolerability: Number of Patients Who Withdraw Due to TEAEs

Secondary Outcome Measures

Pharmacokinetics (PK): Maximum Observed Concentration (Cmax)
Cmax of WVE-120102 in plasma
PK: Time of Occurrence of Cmax (Tmax)
tmax of WVE-120102 in plasma
PK: Area Under the Plasma Concentration-time Curve (AUC 0-t)
AUC 0-t from time zero to the last quantifiable concentration of WVE-120102 in plasma
PK: Terminal Elimination Half-life
Terminal elimination half life of WVE-120102 in plasma (t1/2)
Pharmacodynamics (PD): Percentage Change From Baseline in Mutant Huntingtin Protein
Percentage change from baseline to last observation in mutant huntingtin protein
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)

Full Information

First Posted
July 17, 2017
Last Updated
March 28, 2022
Sponsor
Wave Life Sciences Ltd.
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1. Study Identification

Unique Protocol Identification Number
NCT03225846
Brief Title
Safety and Tolerability of WVE-120102 in Patients With Huntington's Disease
Acronym
PRECISION-HD2
Official Title
A Multicenter, Randomized, Double-blind, Placebo-controlled, Phase 1b/2a Study of WVE-120102 Administered Intrathecally in Patients With Huntington's Disease
Study Type
Interventional

2. Study Status

Record Verification Date
January 2022
Overall Recruitment Status
Terminated
Why Stopped
Lack of efficacy
Study Start Date
July 17, 2017 (Actual)
Primary Completion Date
May 10, 2021 (Actual)
Study Completion Date
May 10, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Wave Life Sciences Ltd.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Huntington's Disease

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Sequential Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
88 (Actual)

8. Arms, Groups, and Interventions

Arm Title
WVE-120102 (2 mg) or placebo
Arm Type
Experimental
Arm Title
WVE-120102 (4 mg) or placebo
Arm Type
Experimental
Arm Title
WVE-120102 (8 mg) or placebo
Arm Type
Experimental
Arm Title
WVE-120102 (16 mg) or placebo
Arm Type
Experimental
Arm Title
WVE-120102 (32 mg ) or placebo
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
WVE-120102
Intervention Description
WVE-120102 is a stereopure antisense oligonucleotide (ASO)
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
0.9% Sodium Chloride
Primary Outcome Measure Information:
Title
Safety: Number of Patients With Treatment-emergent Adverse Events (TEAEs)
Description
All TEAEs reported or observed during the study, including TEAEs resulting from concurrent illnesses, reactions to concurrent medications, or progression of disease states
Time Frame
Day 1 to end of study (up to Day 182 [32 mg cohort]/ Day 210 [all other cohorts])
Title
Safety: Number of Patients Who Experienced Severe TEAEs
Description
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
Time Frame
Time Frame: Day 1 to end of study (up to Day 182 [32 mg cohort]/ Day 210 [all other cohorts])
Title
Safety: Number of Patients With Serious TEAEs
Description
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.
Time Frame
Time Frame: Day 1 to end of study (up to Day 182 [32 mg cohort]/ Day 210 [all other cohorts])
Title
Safety and Tolerability: Number of Patients Who Withdraw Due to TEAEs
Time Frame
Time Frame: Day 1 to end of study (up to Day 182 [32 mg cohort]/ Day 210 [all other cohorts])
Secondary Outcome Measure Information:
Title
Pharmacokinetics (PK): Maximum Observed Concentration (Cmax)
Description
Cmax of WVE-120102 in plasma
Time Frame
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.
Title
PK: Time of Occurrence of Cmax (Tmax)
Description
tmax of WVE-120102 in plasma
Time Frame
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.
Title
PK: Area Under the Plasma Concentration-time Curve (AUC 0-t)
Description
AUC 0-t from time zero to the last quantifiable concentration of WVE-120102 in plasma
Time Frame
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.
Title
PK: Terminal Elimination Half-life
Description
Terminal elimination half life of WVE-120102 in plasma (t1/2)
Time Frame
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.
Title
Pharmacodynamics (PD): Percentage Change From Baseline in Mutant Huntingtin Protein
Description
Percentage change from baseline to last observation in mutant huntingtin protein
Time Frame
Day 1 to last observation - up to Day 140 (32 mg cohort) or Day 196 (all other cohorts)
Title
Clinical Effects: Total Functional Capacity (TFC)
Description
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)
Time Frame
Day 1 Day 1 to last observation - up to Day 140 (32 mg cohort) or Day 196 (all other cohorts)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
25 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
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 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Director, MD
Organizational Affiliation
Wave Life Sciences
Official's Role
Study Director
Facility Information:
Facility Name
University of California San Diego
City
La Jolla
State/Province
California
ZIP/Postal Code
92037-0949
Country
United States
Facility Name
University of California Davis Medical Center
City
Sacramento
State/Province
California
ZIP/Postal Code
95817
Country
United States
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02129
Country
United States
Facility Name
The Ohio State University
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43210
Country
United States
Facility Name
Vanderbilt University Medical Center
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37232
Country
United States
Facility Name
Westmead Hospital
City
Sidney
State/Province
New South Wales
ZIP/Postal Code
2145
Country
Australia
Facility Name
Royal Brisbane & Women's Hospital
City
Herston
State/Province
Queensland
ZIP/Postal Code
QLD 4006
Country
Australia
Facility Name
Royal Melbourne Hospital
City
Carlton
State/Province
Victoria
ZIP/Postal Code
3053
Country
Australia
Facility Name
Monash Health
City
Clayton
State/Province
Victoria
ZIP/Postal Code
3168
Country
Australia
Facility Name
Alfred Health
City
Melbourne
State/Province
Victoria
ZIP/Postal Code
3004
Country
Australia
Facility Name
Calvary Health Care Bethlehem
City
Parkdale
State/Province
Victoria
ZIP/Postal Code
3195
Country
Australia
Facility Name
North Metropolitan Health Service
City
Perth
State/Province
Western Australia
ZIP/Postal Code
6910
Country
Australia
Facility Name
University of Alberta
City
Edmonton
State/Province
Alberta
ZIP/Postal Code
T6G 2B7
Country
Canada
Facility Name
Centre For Movement Disorders
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M3B 2S7
Country
Canada
Facility Name
Centre Hospitalier de l-Universite de Montreal
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H2X019
Country
Canada
Facility Name
Aarhus Universitets Hospital
City
Aarhus N
ZIP/Postal Code
8200
Country
Denmark
Facility Name
Rigshospitalet
City
Copenhagen
ZIP/Postal Code
2100
Country
Denmark
Facility Name
Odense University Hospital and University of Southern Denmark
City
Odense
ZIP/Postal Code
5000
Country
Denmark
Facility Name
Hospital Henri Mondor
City
Créteil
ZIP/Postal Code
94010
Country
France
Facility Name
Institut du Cerveau et de la Moelle Epinière
City
Paris
ZIP/Postal Code
75646
Country
France
Facility Name
George-Huntington-Institut GmbH
City
Muenster
ZIP/Postal Code
48149
Country
Germany
Facility Name
Szpital Sw. Wojciecha
City
Gdańsk
ZIP/Postal Code
80-462
Country
Poland
Facility Name
Instytut Psychiatrii i Neurologii
City
Warsaw
ZIP/Postal Code
02-957
Country
Poland
Facility Name
Royal Devon and Exeter Hospital NHS Trust
City
Exeter
State/Province
Devon
ZIP/Postal Code
EX2 5DW
Country
United Kingdom
Facility Name
Queen Elizabeth University Hospital - PPDS
City
Glasgow
State/Province
Glasgow City
ZIP/Postal Code
G12 0XH
Country
United Kingdom
Facility Name
Royal Liverpool University Hospital
City
Liverpool
ZIP/Postal Code
L7 8XP
Country
United Kingdom

12. IPD Sharing Statement

Citations:
PubMed Identifier
32250312
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.
Results Reference
derived
PubMed Identifier
29480210
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.
Results Reference
derived

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Safety and Tolerability of WVE-120102 in Patients With Huntington's Disease

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