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

NCT03225833 | Terminated Phase 1 Results DMC

• 1 other identifier: WVE-HDSNP1-001
• Study Type: interventional
• Target: 61
• Locations: 7 countries
• Sites: 21

Brief 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).

Conditions

Huntington's Disease

Outcome Measures

Primary Outcomes (4)

• 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: 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])

• 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])

• 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 Outcomes (6)

• Pharmacokinetics (PK): Maximum Observed Concentration (Cmax)

  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: Time of Occurrence of Cmax (Tmax)

  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 (AUClast)

  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

  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

  Day 1 to last observation - up to Day 140 (32 mg cohort) or Day 196 (all other cohorts)

Study Arms (5)

WVE-120101 (Dose A) or placebo

EXPERIMENTAL

Drug: WVE-120101; Drug: Placebo

WVE-120101 (Dose B) or placebo

EXPERIMENTAL

Drug: WVE-120101; Drug: Placebo

WVE-120101 (Dose C) or placebo

EXPERIMENTAL

Drug: WVE-120101; Drug: Placebo

WVE-120101 (Dose D) or placebo

EXPERIMENTAL

Drug: WVE-120101; Drug: Placebo

WVE-120101 (Dose E) or placebo

EXPERIMENTAL

Drug: WVE-120101; Drug: Placebo

Interventions

WVE-120101 DRUG

WVE-120101 is a stereopure antisense oligonucleotide (ASO)

WVE-120101 (Dose A) or placebo; WVE-120101 (Dose B) or placebo; WVE-120101 (Dose C) or placebo; WVE-120101 (Dose D) or placebo; WVE-120101 (Dose E) or placebo

Placebo DRUG

0.9% Sodium Chloride

WVE-120101 (Dose A) or placebo; WVE-120101 (Dose B) or placebo; WVE-120101 (Dose C) or placebo; WVE-120101 (Dose D) or placebo; WVE-120101 (Dose E) or placebo

Eligibility Criteria

• Age: 25 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Wave Life Sciences Ltd.: lead

Study Sites (21)

Westmead Hospital

Sydney, New South Wales, 2145, Australia

Location

Royal Brisbane & Women's Hospital

Herston, Queensland, QLD 4006, Australia

Location

Royal Melbourne Hospital

Carlton, Victoria, 3053, Australia

Location

Monash Health

Clayton, Victoria, 3168, Australia

Location

Alfred Health

Melbourne, Victoria, 3004, Australia

Location

Calvary Health Care Bethlehem

Parkdale, Victoria, 3195, Australia

Location

North Metropolitan Health Service

Perth, Western Australia, 6910, Australia

Location

University of Alberta

Edmonton, Alberta, T6G 2B7, Canada

Location

Centre For Movement Disorders

Toronto, Ontario, M3B 2S7, Canada

Location

Center Hospitalier de l'Universite de Montreal

Montreal, Quebec, H2X0A9, Canada

Location

Aarhus Universitets Hospital

Aarhus, 8200, Denmark

Location

Rigshospitalet

Copenhagen, 2100, Denmark

Location

Odense University Hospital and University of Southern Denmark

Odense, 5000, Denmark

Location

Hospital Henri Mondor

Créteil, 94010, France

Location

Institut du Cerveau et de la Moelle Epinière

Paris, 75646, France

Location

George-Huntington-Institut GmbH

Münster, 48149, Germany

Location

Szpital Sw. Wojciecha

Gdansk, 80-462, Poland

Location

Instytut Psychiatrii i Neurologii

Warsaw, 02-957, Poland

Location

Royal Devon and Exeter Hospital NHS Trust

Exeter, Devon, EX2 5DW, United Kingdom

Location

Queen Elizabeth University Hospital - PPDS

Glasgow, Glasgow City, G12 0XH, United Kingdom

Location

Royal Liverpool University Hospital

Liverpool, L7 8XP, United Kingdom

Location

Related Publications (2)

• 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.

  PMID: 32250312 DERIVED

• 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.

  PMID: 29480210 DERIVED

MeSH Terms

Conditions

Huntington Disease

Condition Hierarchy (Ancestors)

Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Dementia; Chorea; Dyskinesias; Movement Disorders; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Cognition Disorders; Neurocognitive Disorders; Mental Disorders

Results Point of Contact

• Title: Medical Director
• Organization: Wave Life Sciences

clinicaltrials@wavelifesci.com

855-215-4687

Study Officials

• Medical Director, MD

  Wave Life Sciences

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 17, 2017
• First Posted: July 21, 2017
• Study Start: July 17, 2017
• Primary Completion: May 11, 2021
• Study Completion: May 11, 2021
• Last Updated: February 10, 2022
• Results First Posted: February 10, 2022

Record last verified: 2022-02

Locations

PL (2); CA (3); GB (3); DK (3); FR (2); AU (7); DE (1)