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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03225846




Registration number
NCT03225846
Ethics application status
Date submitted
17/07/2017
Date registered
21/07/2017
Date last updated
25/04/2022

Titles & IDs
Public title
Safety and Tolerability of WVE-120102 in Patients With Huntington's Disease
Scientific title
A Multicenter, Randomized, Double-blind, Placebo-controlled, Phase 1b/2a Study of WVE-120102 Administered Intrathecally in Patients With Huntington's Disease
Secondary ID [1] 0 0
WVE-HDSNP2-001
Universal Trial Number (UTN)
Trial acronym
PRECISION-HD2
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Huntington's Disease 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - WVE-120102
Treatment: Drugs - Placebo

Experimental: WVE-120102 (2 mg) or placebo -

Experimental: WVE-120102 (4 mg) or placebo -

Experimental: WVE-120102 (8 mg) or placebo -

Experimental: WVE-120102 (16 mg) or placebo -

Experimental: WVE-120102 (32 mg ) or placebo -


Treatment: Drugs: WVE-120102
WVE-120102 is a stereopure antisense oligonucleotide (ASO)

Treatment: Drugs: Placebo
0.9% Sodium Chloride
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Safety: Number of Patients With Treatment-emergent Adverse Events (TEAEs)
Timepoint [1] 0 0
Day 1 to end of study (up to Day 182 [32 mg cohort]/ Day 210 [all other cohorts])
Primary outcome [2] 0 0
Safety: Number of Patients Who Experienced Severe TEAEs
Timepoint [2] 0 0
Time Frame: Day 1 to end of study (up to Day 182 [32 mg cohort]/ Day 210 [all other cohorts])
Primary outcome [3] 0 0
Safety: Number of Patients With Serious TEAEs
Timepoint [3] 0 0
Time Frame: Day 1 to end of study (up to Day 182 [32 mg cohort]/ Day 210 [all other cohorts])
Primary outcome [4] 0 0
Safety and Tolerability: Number of Patients Who Withdraw Due to TEAEs
Timepoint [4] 0 0
Time Frame: Day 1 to end of study (up to Day 182 [32 mg cohort]/ Day 210 [all other cohorts])
Secondary outcome [1] 0 0
Pharmacokinetics (PK): Maximum Observed Concentration (Cmax)
Timepoint [1] 0 0
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 outcome [2] 0 0
PK: Time of Occurrence of Cmax (Tmax)
Timepoint [2] 0 0
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 outcome [3] 0 0
PK: Area Under the Plasma Concentration-time Curve (AUC 0-t)
Timepoint [3] 0 0
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 outcome [4] 0 0
PK: Terminal Elimination Half-life
Timepoint [4] 0 0
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 outcome [5] 0 0
Pharmacodynamics (PD): Percentage Change From Baseline in Mutant Huntingtin Protein
Timepoint [5] 0 0
Day 1 to last observation - up to Day 140 (32 mg cohort) or Day 196 (all other cohorts)
Secondary outcome [6] 0 0
Clinical Effects: Total Functional Capacity (TFC)
Timepoint [6] 0 0
Day 1 Day 1 to last observation - up to Day 140 (32 mg cohort) or Day 196 (all other cohorts)

Eligibility
Key inclusion criteria
Key

* 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
Minimum age
25 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
No
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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Other
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
17/07/2017
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
10/05/2021
Sample size
Target
Accrual to date
Final
88
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC,WA
Recruitment hospital [1] 0 0
Westmead Hospital - Sidney
Recruitment hospital [2] 0 0
Royal Brisbane & Women's Hospital - Herston
Recruitment hospital [3] 0 0
Royal Melbourne Hospital - Carlton
Recruitment hospital [4] 0 0
Monash Health - Clayton
Recruitment hospital [5] 0 0
Alfred Health - Melbourne
Recruitment hospital [6] 0 0
Calvary Health Care Bethlehem - Parkdale
Recruitment hospital [7] 0 0
North Metropolitan Health Service - Perth
Recruitment postcode(s) [1] 0 0
2145 - Sidney
Recruitment postcode(s) [2] 0 0
QLD 4006 - Herston
Recruitment postcode(s) [3] 0 0
3053 - Carlton
Recruitment postcode(s) [4] 0 0
3168 - Clayton
Recruitment postcode(s) [5] 0 0
3004 - Melbourne
Recruitment postcode(s) [6] 0 0
3195 - Parkdale
Recruitment postcode(s) [7] 0 0
6910 - Perth
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Massachusetts
Country [3] 0 0
United States of America
State/province [3] 0 0
Ohio
Country [4] 0 0
United States of America
State/province [4] 0 0
Tennessee
Country [5] 0 0
Canada
State/province [5] 0 0
Alberta
Country [6] 0 0
Canada
State/province [6] 0 0
Ontario
Country [7] 0 0
Canada
State/province [7] 0 0
Quebec
Country [8] 0 0
Denmark
State/province [8] 0 0
Aarhus N
Country [9] 0 0
Denmark
State/province [9] 0 0
Copenhagen
Country [10] 0 0
Denmark
State/province [10] 0 0
Odense
Country [11] 0 0
France
State/province [11] 0 0
Créteil
Country [12] 0 0
France
State/province [12] 0 0
Paris
Country [13] 0 0
Germany
State/province [13] 0 0
Muenster
Country [14] 0 0
Poland
State/province [14] 0 0
Gdansk
Country [15] 0 0
Poland
State/province [15] 0 0
Warsaw
Country [16] 0 0
United Kingdom
State/province [16] 0 0
Devon
Country [17] 0 0
United Kingdom
State/province [17] 0 0
Glasgow City
Country [18] 0 0
United Kingdom
State/province [18] 0 0
Liverpool

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Wave Life Sciences Ltd.
Address
Country

Ethics approval
Ethics application status

Summary
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).
Trial website
https://clinicaltrials.gov/study/NCT03225846
Trial related presentations / publications
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.
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.
Public notes

Contacts
Principal investigator
Name 0 0
Medical Director, MD
Address 0 0
Wave Life Sciences
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT03225846