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Safety and Tolerability of WVE-120101 in Patients With Huntington's Disease (PRECISION-HD1)

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ClinicalTrials.gov Identifier: NCT03225833
Recruitment Status : Recruiting
First Posted : July 21, 2017
Last Update Posted : March 27, 2018
Sponsor:
Information provided by (Responsible Party):
Wave Life Sciences Ltd.

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).

Condition or disease Intervention/treatment Phase
Huntington's Disease Drug: WVE-120101 Drug: Placebo Phase 1 Phase 2

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 48 participants
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: A Multicenter, Randomized, Double-blind, Placebo-controlled, Phase 1b/2a Study of WVE-120101 Administered Intrathecally in Patients With Huntington's Disease
Actual Study Start Date : July 17, 2017
Estimated Primary Completion Date : September 2019
Estimated Study Completion Date : September 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: WVE-120101 (Dose A) or placebo Drug: WVE-120101
WVE-120101 is a stereopure antisense oligonucleotide (ASO)

Drug: Placebo
0.9% Sodium Chloride

Experimental: WVE-120101 (Dose B) or placebo Drug: WVE-120101
WVE-120101 is a stereopure antisense oligonucleotide (ASO)

Drug: Placebo
0.9% Sodium Chloride

Experimental: WVE-120101 (Dose C) or placebo Drug: WVE-120101
WVE-120101 is a stereopure antisense oligonucleotide (ASO)

Drug: Placebo
0.9% Sodium Chloride

Experimental: WVE-120101 (Dose D) or placebo Drug: WVE-120101
WVE-120101 is a stereopure antisense oligonucleotide (ASO)

Drug: Placebo
0.9% Sodium Chloride




Primary Outcome Measures :
  1. Safety: Number of patients with adverse events (AEs) [ Time Frame: Day 1 to Day 210 (end of study) ]
    All AEs reported or observed during the study, including AEs resulting from concurrent illnesses, reactions to concurrent medications, or progression of disease states

  2. Safety: Severity of AEs [ Time Frame: Day 1 to Day 210 (end of study) ]
    Severity will be evaluated using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0

  3. Safety: Number of patients with serious AEs (SAEs) [ Time Frame: Day 1 to Day 210 (end of study) ]
    An SAE 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.

  4. Safety and Tolerability: Number of patients who withdraw due to AEs [ Time Frame: Day 1 to Day 210 (end of study) ]

Secondary Outcome Measures :
  1. Pharmacokinetics (PK): Maximum observed concentration (Cmax) [ Time Frame: Day 1 to Day 196 ]
    Cmax of WVE-120101 in plasma

  2. PK: Time of occurrence of Cmax (tmax) [ Time Frame: Day 1 to Day 196 ]
    tmax of WVE-120101 in plasma

  3. PK: Area under the plasma concentration-time curve (AUC 0-t) [ Time Frame: Day 1 to Day 196 ]
    AUC 0-t from time zero to the last quantifiable concentration of WVE-120101 in plasma

  4. PK: Terminal elimination rate constant [ Time Frame: Day 1 to Day 196 ]
    Elimination rate of WVE-120101 from plasma

  5. Pharmacodynamics (PD) [ Time Frame: Day 1 to Day 196 ]
    Concentration of mutant huntingtin (mHTT) protein in CSF

  6. Clinical Effects: Total Functional Capacity (TFC) [ Time Frame: Day 1 to Day 140 ]
    Change from baseline to the last measured time point (Day 140) and difference from placebo in the TFC, administered as part of the Unified Huntington's Disease Rating Scale (UHDRS).


Other Outcome Measures:
  1. UHDRS [ Time Frame: Day 1 to Day 140 ]
    Change from baseline to the last measured time point (Day 140) and difference from placebo in the UHDRS

  2. Short Problems Behavior Assessment (PBA-s) [ Time Frame: Day 1 to Day 140 ]
    Change from baseline to the last measured time point (Day 140) and difference from placebo in the PBA-s

  3. Magnetic Resonance Imaging [ Time Frame: Screening to Day 140 ]
    Changes from baseline MRI of the brain.



Information from the National Library of Medicine

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Ages Eligible for Study:   25 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03225833


Contacts
Contact: Clinical Operations 855-215-4687 clinicaltrials@wavelifesci.com

Locations
Canada, Ontario
Centre For Movement Disorders Recruiting
Toronto, Ontario, Canada, M3B 2S7
Principal Investigator: Mark Guttman, MD         
Poland
Szpital Sw. Wojciecha Recruiting
Gdańsk, Poland, 80-462
Principal Investigator: Jaroslaw Slawek, MD         
Instytut Psychiatrii i Neurologii Recruiting
Warsaw, Poland, 02-957
Principal Investigator: Grzegorz Witkowski, MD         
Sponsors and Collaborators
Wave Life Sciences Ltd.
Investigators
Study Director: Serena Hung, MD Wave Life Sciences

Responsible Party: Wave Life Sciences Ltd.
ClinicalTrials.gov Identifier: NCT03225833     History of Changes
Other Study ID Numbers: WVE-HDSNP1-001
First Posted: July 21, 2017    Key Record Dates
Last Update Posted: March 27, 2018
Last Verified: March 2018

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Huntington Disease
Basal Ganglia Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Movement Disorders
Heredodegenerative Disorders, Nervous System
Neurodegenerative Diseases
Genetic Diseases, Inborn
Cognition Disorders
Neurocognitive Disorders
Mental Disorders
Dementia
Chorea
Dyskinesias