Safety and Tolerability of WVE-120102 in Patients With Hu... | NCT03225846 | Trialant
NCT03225846
Sponsor
Wave Life Sciences USA, Inc.
Status
Terminated
Last Update Posted
Apr 25, 2022Actual
Enrollment
88Actual
Phase
Phase 1Phase 2
Conditions
Huntington's Disease
Interventions
WVE-120102
Placebo
Countries
United States
Australia
Canada
Denmark
France
Germany
Poland
United Kingdom
Protocol Section
Identification Module
NCT ID
NCT03225846
Obsolete or Duplicate NCT IDs
Not provided
Organization Study
WVE-HDSNP2-001
Secondary IDs
Not provided
Brief Title
Safety and Tolerability of WVE-120102 in Patients With Huntington's Disease
Official Title
A Multicenter, Randomized, Double-blind, Placebo-controlled, Phase 1b/2a Study of WVE-120102 Administered Intrathecally in Patients With Huntington's Disease
Acronym
PRECISION-HD2
Organization
Wave Life Sciences USA, Inc.INDUSTRY
Status Module
Record Verification Date
Jan 2022
Overall Recruitment Status or Expanded Access Status
Terminated
Last Known Status
Not provided
Delayed Posting
Not provided
Why Stopped
Lack of efficacy
Expanded Access Info
No
Start Date
Jul 17, 2017Actual
Primary Completion Date
May 10, 2021Actual
Completion Date
May 10, 2021Actual
First Submitted Date
Jul 17, 2017
First Submission Date that Met QC Criteria
Jul 19, 2017
First Posted Date
Jul 21, 2017Actual
Results Waived
Not provided
Results First Submitted Date
Dec 17, 2021
Results First Submitted that Met QC Criteria
Mar 28, 2022
Results First Posted Date
Apr 25, 2022Actual
Certification/Extension (aka Delayed Results) First Submitted Date
Not provided
Certification/Extension First Submitted that Passed QC Review
Not provided
Certification/Extension First Posted Date
Not provided
Last Update Submitted Date
Mar 28, 2022
Last Update Posted Date
Apr 25, 2022Actual
Sponsor/Collaborators Module
Responsible Party, by Official Title
Sponsor
Lead Sponsor
Wave Life Sciences USA, Inc.INDUSTRY
Collaborators
Not provided
Oversight Module
Has Data Monitoring Committee (DMC)
Yes
Is FDA Regulated Drug
Yes
Is FDA Regulated Device
No
Is Unapproved Device
Not provided
Pediatric Postmarket Surveillance of a Device Product
Not provided
Product Exported from US
Not provided
FDAAA801 Violation
Not provided
Description Module
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 provided
Conditions Module
Conditions
Huntington's Disease
Keywords
Not provided
Design Module
Study Type
Interventional
Number of References to an Expanded Access Study
Not provided
Expanded Access Types
Not provided
Patient Registry
Not provided
Target Follow-Up Duration
Not provided
Phases
Phase 1Phase 2
Interventional Study Design
Allocation
Biospecimen
No data available
No data is available for this block.
Enrollment
88Actual
Arms/Interventions Module
Arm Groups
Label
Type
Description
Intervention Names
WVE-120102 (2 mg) or placebo
Experimental
Drug: WVE-120102
Drug: Placebo
WVE-120102 (4 mg) or placebo
Experimental
Drug: WVE-120102
Drug: Placebo
WVE-120102 (8 mg) or placebo
Experimental
Drug: WVE-120102
Drug: Placebo
WVE-120102 (16 mg) or placebo
Experimental
Drug: WVE-120102
Drug: Placebo
WVE-120102 (32 mg ) or placebo
Experimental
Drug: WVE-120102
Drug: Placebo
Interventions
Name
Type
Description
Arm Group Labels
Other Names
WVE-120102
Drug
WVE-120102 is a stereopure antisense oligonucleotide (ASO)
WVE-120102 (16 mg) or placebo
WVE-120102 (2 mg) or placebo
WVE-120102 (32 mg ) or placebo
Outcomes Module
Primary Outcomes
Measure
Description
Time Frame
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])
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
Time Frame: Day 1 to end of study (up to Day 182 [32 mg cohort]/ Day 210 [all other cohorts])
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.
Time Frame: Day 1 to end of study (up to Day 182 [32 mg cohort]/ Day 210 [all other cohorts])
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 Outcomes
Measure
Description
Time Frame
Pharmacokinetics (PK): Maximum Observed Concentration (Cmax)
Cmax of WVE-120102 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.
Other Outcomes
Not provided
Eligibility Module
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
WVE-120102: WVE-120102 is a stereopure antisense oligonucleotide (ASO)
Periods
Title
Milestones
Reasons Not Completed
Overall Study
Type
Comment
Milestone Data
STARTED
Baseline Characteristics Module
Baseline Analysis Population Description
Not provided
Outcome Measures Module
Outcome Measures
Adverse Events Module
Frequency Threshold
5
More Info Module
Limitations and Caveats
Not provided
Annotation Section
No data available
No data is available for this block.
Document Section
Large Document Module
Document Has No Statistical Analysis Plan (SAP)
Not provided
Uploaded Document Information
Type
Includes Protocol
Includes SAP
Includes ICF
Document Label
Document Date
Document Uploaded Date
Document File Name
Prot_SAP
Yes
Yes
No
Study Protocol and Statistical Analysis Plan
Sep 17, 2019
Derived Section
Miscellaneous Info Module
Version Holder
Jul 10, 2026
Removed Countries
Not provided
Submission Tracking
Estimated Results First Submitted Date
Not provided
Condition Browse Module
MeSH Terms
Intervention Browse Module
No data available
No data is available for this block.
Randomized
Intervention Model
Sequential Assignment
Intervention Model Description
Not provided
Primary Purpose
Treatment
Observational Model
Not provided
Time Perspective
Not provided
Masking Info
Masking
Double
Masking Description
Not provided
Who Masked
ParticipantInvestigator
WVE-120102 (4 mg) or placebo
WVE-120102 (8 mg) or placebo
Placebo
Drug
0.9% Sodium Chloride
WVE-120102 (16 mg) or placebo
WVE-120102 (2 mg) or placebo
WVE-120102 (32 mg ) or placebo
WVE-120102 (4 mg) or placebo
WVE-120102 (8 mg) or placebo
PK: Time of Occurrence of Cmax (Tmax)
tmax of WVE-120102 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.
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
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.
PK: Terminal Elimination Half-life
Terminal elimination half life of WVE-120102 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.
Pharmacodynamics (PD): Percentage Change From Baseline in Mutant Huntingtin Protein
Percentage change from baseline to last observation in mutant huntingtin protein
Day 1 to last observation - up to Day 140 (32 mg cohort) or Day 196 (all other cohorts)
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 Day 1 to last observation - up to Day 140 (32 mg cohort) or Day 196 (all other cohorts)
Sacramento
California
95817
United States
Massachusetts General Hospital
Boston
Massachusetts
02129
United States
The Ohio State University
Columbus
Ohio
43210
United States
Vanderbilt University Medical Center
Nashville
Tennessee
37232
United States
Westmead Hospital
Sydney
New South Wales
2145
Australia
Royal Brisbane & Women's Hospital
Herston
Queensland
QLD 4006
Australia
Royal Melbourne Hospital
Carlton
Victoria
3053
Australia
Monash Health
Clayton
Victoria
3168
Australia
Alfred Health
Melbourne
Victoria
3004
Australia
Calvary Health Care Bethlehem
Parkdale
Victoria
3195
Australia
North Metropolitan Health Service
Perth
Western Australia
6910
Australia
University of Alberta
Edmonton
Alberta
T6G 2B7
Canada
Centre For Movement Disorders
Toronto
Ontario
M3B 2S7
Canada
Centre Hospitalier de l-Universite de Montreal
Montreal
Quebec
H2X019
Canada
Aarhus Universitets Hospital
Aarhus N
8200
Denmark
Rigshospitalet
Copenhagen
2100
Denmark
Odense University Hospital and University of Southern Denmark
Odense
5000
Denmark
Hospital Henri Mondor
Créteil
94010
France
Institut du Cerveau et de la Moelle Epinière
Paris
75646
France
George-Huntington-Institut GmbH
Münster
48149
Germany
Szpital Sw. Wojciecha
Gdansk
80-462
Poland
Instytut Psychiatrii i Neurologii
Warsaw
02-957
Poland
Royal Devon and Exeter Hospital NHS Trust
Exeter
Devon
EX2 5DW
United Kingdom
Queen Elizabeth University Hospital - PPDS
Glasgow
Glasgow City
G12 0XH
United Kingdom
Royal Liverpool University Hospital
Liverpool
L7 8XP
United Kingdom
FG002
WVE-120102 (4 mg)
WVE-120102: WVE-120102 is a stereopure antisense oligonucleotide (ASO)
FG003
WVE-120102 (8 mg)
WVE-120102: WVE-120102 is a stereopure antisense oligonucleotide (ASO)
FG004
WVE-120102 (12 mg)
WVE-120102: WVE-120102 is a stereopure antisense oligonucleotide (ASO)
FG005
WVE-120102 (16 mg)
WVE-120102: WVE-120102 is a stereopure antisense oligonucleotide (ASO)
FG006
WVE-120102 (32 mg )
WVE-120102: WVE-120102 is a stereopure antisense oligonucleotide (ASO)
FG00022 subjects
FG0019 subjects
FG00212 subjects
FG00315 subjects
FG0048 subjects
FG0059 subjects
FG00613 subjects
Single Dose Period Only
FG0006 subjects
FG0013 subjects
FG0024 subjects
FG0037 subjects
FG0048 subjects
FG0050 subjects
FG0064 subjects
Multiple Dose Period Only
FG0003 subjects
FG0010 subjects
FG0023 subjects
FG0036 subjects
FG0040 subjects
FG0050 subjects
FG0064 subjects
Single Dose and Multiple Dose
FG00013 subjects
FG0016 subjects
FG0025 subjects
FG0032 subjects
FG0040 subjects
FG0059 subjects
FG0065 subjects
COMPLETED
FG00022 subjects
FG0017 subjects
FG00211 subjects
FG00315 subjects
FG0048 subjects
FG0059 subjects
FG0066 subjects
NOT COMPLETED
FG0000 subjects
FG0012 subjects
FG0021 subjects
FG0030 subjects
FG0040 subjects
FG0050 subjects
FG0067 subjects
Type
Comment
Reasons
Adverse Event
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG0040 subjects
FG0050 subjects
FG0066 subjects
Withdrawal by Subject
FG0000 subjects
FG0011 subjects
FG0020 subjects
FG0030 subjects
FG004
Death
FG0000 subjects
FG0011 subjects
FG0020 subjects
FG0030 subjects
FG004
Patient did not wish to comply with IC/EC
FG0000 subjects
FG0010 subjects
FG0021 subjects
FG0030 subjects
FG004
Patient decision
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
BG000
Pooled Placebo
Placebo: 0.9% Sodium Chloride
BG001
WVE-120102 (2 mg)
WVE-120102: WVE-120102 is a stereopure antisense oligonucleotide (ASO)
BG002
WVE-120102 (4 mg)
WVE-120102: WVE-120102 is a stereopure antisense oligonucleotide (ASO)
BG003
WVE-120102 (8 mg)
WVE-120102: WVE-120102 is a stereopure antisense oligonucleotide (ASO)
BG004
WVE-120102 (12 mg)
WVE-120102: WVE-120102 is a stereopure antisense oligonucleotide (ASO)
BG005
WVE-120102 (16 mg)
WVE-120102: WVE-120102 is a stereopure antisense oligonucleotide (ASO)
BG006
WVE-120102 (32 mg )
WVE-120102: WVE-120102 is a stereopure antisense oligonucleotide (ASO)
BG007
Total
Total of all reporting groups
Denominators
Units
Counts
Participants
BG00022
BG0019
BG00212
BG00315
BG0048
BG0059
BG00613
BG00788
Baseline Measures
Title
Description
Population Description
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Denominator Units Selected
Denominators
Classes
Age, Continuous
Mean
Standard Deviation
Years
Title
Denominators
Categories
Title
Measurements
BG00046.8± 10.16
BG00152.4± 11.59
BG00246± 10.63
BG003
Sex: Female, Male
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Female
BG0008
BG0015
BG002
Ethnicity (NIH/OMB)
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Hispanic or Latino
BG0001
BG0010
BG002
Race (NIH/OMB)
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
American Indian or Alaska Native
BG0000
BG0010
BG002
Region of Enrollment
Number
participants
Title
Denominators
Categories
Canada
Title
Measurements
BG0009
BG0018
BG002
Time since initial diagnosis
Mean
Standard Deviation
Years
Title
Denominators
Categories
Title
Measurements
BG0006.1± 5.95
BG0019.9± 8.80
BG002
Age at disease onset
Mean
Standard Deviation
Years
Title
Denominators
Categories
Title
Measurements
BG00040.18± 10.527
BG00142.00± 16.363
BG002
Diagnosis stage
Stage of disease, as defined by United Huntington's Disease Rating Scale, Total Functional Capacity Score. Stage 1 (least severe) = scores of 11 to 13. Stage 2 = scores of 7 to 10. Stages go up to Stage 5 = score of 0.
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Stage 1
BG0009
BG001
Type
Title
Description
Population Description
Reporting Status
Anticipated Posting Date
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Time Frame
Units Analyzed
Denominator Units Selected
Arm/Group Information
Denominators
Classes
Analyses
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
No statistical analysis has been performed on these safety results
Posted
Count of Participants
Participants
Day 1 to end of study (up to Day 182 [32 mg cohort]/ Day 210 [all other cohorts])
ID
Title
Description
OG000
Pooled Placebo
Placebo: 0.9% Sodium Chloride
OG001
WVE-120102 (2 mg)
WVE-120102: WVE-120102 is a stereopure antisense oligonucleotide (ASO)
OG002
WVE-120102 (4 mg)
WVE-120102: WVE-120102 is a stereopure antisense oligonucleotide (ASO)
OG003
WVE-120102 (8 mg)
WVE-120102: WVE-120102 is a stereopure antisense oligonucleotide (ASO)
OG004
WVE-120102 (12 mg)
WVE-120102: WVE-120102 is a stereopure antisense oligonucleotide (ASO)
OG005
WVE-120102 (16 mg)
WVE-120102: WVE-120102 is a stereopure antisense oligonucleotide (ASO)
OG006
WVE-120102 (32 mg )
WVE-120102: WVE-120102 is a stereopure antisense oligonucleotide (ASO)
Units
Counts
Participants
OG00022
OG0019
OG00212
OG003
Title
Denominators
Categories
Title
Measurements
OG00020
OG0018
OG0029
OG003
Primary
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
No statistical analysis has been performed on these safety results
Posted
Count of Participants
Participants
Time Frame: Day 1 to end of study (up to Day 182 [32 mg cohort]/ Day 210 [all other cohorts])
ID
Title
Description
OG000
Pooled Placebo
Placebo: 0.9% Sodium Chloride
OG001
WVE-120102 (2 mg)
WVE-120102: WVE-120102 is a stereopure antisense oligonucleotide (ASO)
OG002
WVE-120102 (4 mg)
WVE-120102: WVE-120102 is a stereopure antisense oligonucleotide (ASO)
OG003
WVE-120102 (8 mg)
WVE-120102: WVE-120102 is a stereopure antisense oligonucleotide (ASO)
OG004
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.
No statistical analysis has been performed on these safety results
Posted
Count of Participants
Participants
Time Frame: Day 1 to end of study (up to Day 182 [32 mg cohort]/ Day 210 [all other cohorts])
ID
Title
Description
OG000
Pooled Placebo
Placebo: 0.9% Sodium Chloride
OG001
WVE-120102 (2 mg)
WVE-120102: WVE-120102 is a stereopure antisense oligonucleotide (ASO)
OG002
WVE-120102 (4 mg)
WVE-120102: WVE-120102 is a stereopure antisense oligonucleotide (ASO)
OG003
WVE-120102 (8 mg)
WVE-120102: WVE-120102 is a stereopure antisense oligonucleotide (ASO)
Primary
Safety and Tolerability: Number of Patients Who Withdraw Due to TEAEs
No statistical analysis has been performed on these safety results
Posted
Count of Participants
Participants
Time Frame: Day 1 to end of study (up to Day 182 [32 mg cohort]/ Day 210 [all other cohorts])
ID
Title
Description
OG000
Pooled Placebo
Placebo: 0.9% Sodium Chloride
OG001
WVE-120102 (2 mg)
WVE-120102: WVE-120102 is a stereopure antisense oligonucleotide (ASO)
OG002
WVE-120102 (4 mg)
WVE-120102: WVE-120102 is a stereopure antisense oligonucleotide (ASO)
OG003
WVE-120102 (8 mg)
WVE-120102: WVE-120102 is a stereopure antisense oligonucleotide (ASO)
OG004
WVE-120102 (12 mg)
WVE-120102: WVE-120102 is a stereopure antisense oligonucleotide (ASO)
Secondary
Pharmacokinetics (PK): Maximum Observed Concentration (Cmax)
Cmax of WVE-120102 in plasma
Overall number of participants analyzed represents patients with at least 1 postdose plasma or CSF measurement at Day 1. The overall number for Day 112 was different and represents patients with at least 1 postdose plasma or CSF measurement at Day 112. Specimen samples collected following administration of 12 mg dose were not analyzed or tested, and therefore no data are available to be reported for this Arm/Group.
Posted
Mean
Standard Deviation
ng/mL
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.
ID
Title
Description
OG000
WVE-120102 (2 mg)
WVE-120102: WVE-120102 is a stereopure antisense oligonucleotide (ASO)
OG001
WVE-120102 (4 mg)
WVE-120102: WVE-120102 is a stereopure antisense oligonucleotide (ASO)
OG002
WVE-120102 (8 mg)
WVE-120102: WVE-120102 is a stereopure antisense oligonucleotide (ASO)
OG003
Secondary
PK: Time of Occurrence of Cmax (Tmax)
tmax of WVE-120102 in plasma
Overall number of participants analyzed represents patients with at least 1 postdose plasma or CSF measurement at Day 1. The overall number for Day 112 was different and represents patients with at least 1 postdose plasma or CSF measurement at Day 112. Specimen samples collected following administration of 12 mg dose were not analyzed or tested, and therefore no data are available to be reported for this Arm/Group.
Posted
Mean
Standard Deviation
hour
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.
ID
Title
Description
OG000
WVE-120102 (2 mg)
WVE-120102: WVE-120102 is a stereopure antisense oligonucleotide (ASO)
OG001
WVE-120102 (4 mg)
WVE-120102: WVE-120102 is a stereopure antisense oligonucleotide (ASO)
OG002
WVE-120102 (8 mg)
WVE-120102: WVE-120102 is a stereopure antisense oligonucleotide (ASO)
OG003
Secondary
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
Overall number of participants analyzed represents patients with at least 1 postdose plasma or CSF measurement at Day 1. The overall number for Day 112 was different and represents patients with at least 1 postdose plasma or CSF measurement at Day 112. Specimen samples collected following administration of 12 mg dose were not analyzed or tested, and therefore no data are available to be reported for this Arm/Group.
Posted
Mean
Standard Deviation
hr*ng/mL
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.
ID
Title
Description
OG000
WVE-120102 (2 mg)
WVE-120102: WVE-120102 is a stereopure antisense oligonucleotide (ASO)
OG001
WVE-120102 (4 mg)
WVE-120102: WVE-120102 is a stereopure antisense oligonucleotide (ASO)
OG002
WVE-120102 (8 mg)
WVE-120102: WVE-120102 is a stereopure antisense oligonucleotide (ASO)
Secondary
PK: Terminal Elimination Half-life
Terminal elimination half life of WVE-120102 in plasma (t1/2)
The t1/2 value was calculated using data from patients who had at least 3 postdose concentration values in the terminal phase. No patients had sufficient postdose samples at Day 112 to calculate t1/2 values. Specimen samples collected following administration of 12 mg dose were not analyzed or tested, and therefore no data are available to be reported for this Arm/Group.
Posted
Mean
Standard Deviation
hour
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.
ID
Title
Description
OG000
WVE-120102 (2 mg)
WVE-120102: WVE-120102 is a stereopure antisense oligonucleotide (ASO)
OG001
WVE-120102 (4 mg)
WVE-120102: WVE-120102 is a stereopure antisense oligonucleotide (ASO)
OG002
WVE-120102 (8 mg)
WVE-120102: WVE-120102 is a stereopure antisense oligonucleotide (ASO)
OG003
Secondary
Pharmacodynamics (PD): Percentage Change From Baseline in Mutant Huntingtin Protein
Percentage change from baseline to last observation in mutant huntingtin protein
The 12 mg dose group was not included in this analysis as these patients only received a single dose and did not attend the Day 140/Day 196 visit.
Posted
Median
Inter-Quartile Range
Percent change from baseline
Day 1 to last observation - up to Day 140 (32 mg cohort) or Day 196 (all other cohorts)
ID
Title
Description
OG000
Pooled Placebo
Placebo: 0.9% Sodium Chloride
OG001
WVE-120102 (2 mg)
WVE-120102: WVE-120102 is a stereopure antisense oligonucleotide (ASO)
OG002
WVE-120102 (4 mg)
WVE-120102: WVE-120102 is a stereopure antisense oligonucleotide (ASO)
OG003
WVE-120102 (8 mg)
WVE-120102: WVE-120102 is a stereopure antisense oligonucleotide (ASO)
OG004
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)
The 12 mg dose group was not included in this analysis as these patients only received a single dose and did not attend the Day 140/Day 196 visit.
Posted
Median
Inter-Quartile Range
Percent change from baseline
Day 1 Day 1 to last observation - up to Day 140 (32 mg cohort) or Day 196 (all other cohorts)
ID
Title
Description
OG000
Pooled Placebo
Placebo: 0.9% Sodium Chloride
OG001
WVE-120102 (2 mg)
WVE-120102: WVE-120102 is a stereopure antisense oligonucleotide (ASO)
OG002
WVE-120102 (4 mg)
WVE-120102: WVE-120102 is a stereopure antisense oligonucleotide (ASO)
OG003
WVE-120102 (8 mg)
WVE-120102: WVE-120102 is a stereopure antisense oligonucleotide (ASO)
Time Frame
Day 1 to end of study (Day 196 [32 mg cohort] or Day 210 [all other cohorts])
Description
Not provided
All-Cause Mortality Comment
Not provided
Arm/Groups
ID
Title
Description
Deaths (Affected)
Deaths (At Risk)
Serious Events (Affected)
Serious Events (At Risk)
Other Events (Affected)
Other Events (At Risk)
EG000
Pooled Placebo
Placebo: 0.9% Sodium Chloride
0
22
0
22
22
22
EG001
WVE-120102 (2 mg)
WVE-120102: WVE-120102 is a stereopure antisense oligonucleotide (ASO)
1
9
1
9
9
9
EG002
WVE-120102 (4 mg)
WVE-120102: WVE-120102 is a stereopure antisense oligonucleotide (ASO)
0
12
2
12
12
12
EG003
WVE-120102 (8 mg)
WVE-120102: WVE-120102 is a stereopure antisense oligonucleotide (ASO)
1
15
2
15
15
15
EG004
WVE-120102 (12 mg)
WVE-120102: WVE-120102 is a stereopure antisense oligonucleotide (ASO)
0
8
0
8
8
8
EG005
WVE-120102 (16 mg)
WVE-120102: WVE-120102 is a stereopure antisense oligonucleotide (ASO)
0
9
0
9
9
9
EG006
WVE-120102 (32 mg )
WVE-120102: WVE-120102 is a stereopure antisense oligonucleotide (ASO)