A Multicenter, Open-label Extension Study to Evaluate the Safety, Pharmacodynamics, and Clinical Effects of WVE-120102 in Patients with Huntington’s Disease

• Register: EUCTR
• Last refreshed on: 13 September 2021
• Main ID: EUCTR2019-002178-30-PL
• Date of registration: 13/08/2019
• Prospective Registration: Yes
• Primary sponsor: Wave Life Sciences UK Limited
• Public title: A Multicenter, Open-label Extension Study to Evaluate the Safety, Pharmacodynamics, and Clinical Effects of WVE-120102 in Patients with Huntington’s Disease
• Scientific title: A Multicenter, Open-label Extension Study to Evaluate the Safety, Pharmacodynamics, and Clinical Effects of WVE-120102 in Patients with Huntington’s Disease
• Date of first enrolment: 29/10/2019
• Target sample size: 70
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2019-002178-30
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no; Randomised: no; Open: yes; Single blind: no; Double blind: no; Parallel group: yes; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: no; Other: no; Number of treatment arms in the trial: 3
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Australia, Canada, Denmark, France, Germany, Poland, United Kingdom

Contacts

• Name: Martina Novotna
• Affiliation: PPD

• Name: Martina Novotna
• Affiliation: PPD

Key inclusion & exclusion criteria

Inclusion criteria:
1.Patient has documented ability to understand the written study ICFs at the time of screening and has provided signed written informed consent prior to any study procedures.
2.Patient successfully completed Day 210 of hase 1b/2a study with WVE-120102, WVE-HDSNP2-001.
3.In the opinion of the Investigator, the patient is able to tolerate all study procedures, is willing to comply with all other protocol requirements, and tolerated study drug in the parent study
4.Patient is willing to practice highly effective contraception for the duration of the study if the patient or their partner are of childbearing potential. Non-childbearing potential and highly effective methods of contraception are defined in the protocol
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 70
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
1.Clinically significant medical finding on the physical examination other than HD that, in the judgment of the Investigator, will make the patient unsuitable for participation in and/or completion of the study procedures.
2.Received an investigational drug other than WVE-120102, including an investigational oligonucleotide, within the past 1 year or 5 half-lives of the drug, whichever is longer.
3.Implantable CNS device that may interfere with ability to administer study drug via lumbar puncture or undergo brain magnetic resonance imaging (MRI) scan.
4.Diagnostic and Statistical Manual of Mental Disorders 5th Edition (DSM-5) diagnosis at the Screening Visit of active alcohol, cannabinoid, or other substance use disorder (except nicotine).
5.Positive for opioids (unprescribed), cocaine, amphetamines, methadone, barbiturates, methamphetamine, or phencyclidine at the Screening Visit.
6.Pregnant (as determined by a serum pregnancy test) or breast feeding at the Screening Visit, or plans to become pregnant during the course of the study.
7.Clinically significant laboratory abnormality at Screening, including, but not limited to:
a.Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) values at Screening or Baseline >3 times the upper limit of normal (ULN).
b.Renal insufficiency, defined as either serum creatinine >1.8 mg/dL or creatinine clearance <40 mL/min.
8.Clinically significant abnormality at Screening electrocardiogram (ECG), including but not limited to a confirmed QT interval corrected for heart rate (QTc) =450 msec for males or =470 msec for females.
9.Clinically significant cardiovascular, endocrine, hepatic, renal, pulmonary, gastrointestinal, neurologic, malignant, metabolic, psychiatric, or other condition that, in the opinion of the Investigator, precludes the patient’s safe participation in the study or would interfere with the study assessments.
10.Bone, spine, bleeding, or other disorder that exposes the patient to risk of injury or unsuccessful lumbar puncture.
11.Inability to undergo brain MRI (with or without sedation).
12.In the opinion of the Investigator, deemed to be at significant risk for suicidal behavior.
13.Involved directly or indirectly in the conduct and administration of this study as an Investigator, sub-investigator, study coordinator, or other study staff member, or the patient is a first-degree family member, significant other, or relative residing with one of the above persons involved directly or indirectly in the study.
14. Anticipates using antiplatelet or anticoagulant therapy during the
course of the study. Patients who received antiplatelet or anticoagulant therapy must complete one of the following washout periods before the Screening Visit:
a. A 7-day washout period for antiplatelet therapy,
b. A 1-day washout period for anticoagulants (except warfarin), or
c. A 5-day washout period for warfarin.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Huntington’s Disease
MedDRA version: 20.0 Level: PT Classification code 10070668 Term: Huntington's disease System Organ Class: 10010331 - Congenital, familial and genetic disorders

Therapeutic area: Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]

Intervention(s)

Product Name: WVE-120102
Product Code: WVE-120102
Pharmaceutical Form: Powder for solution for injection
INN or Proposed INN: WVE-120102
Current Sponsor code: WVE-120102
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 8-

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: Every 4 weeks from week 1 to week 97

Secondary Objective: To evaluate the clinical and pharmacodynamic effects of WVE-120102 in patients with early manifest HD

Main Objective: To evaluate the safety and tolerability of long-term exposure to WVE-120102 in patients with early manifest HD.

Primary end point(s): The number of patients with adverse events (AEs), severity of AEs, number of patients with serious AEs (SAEs), clinically significant changes in laboratory values, and the number of patients who withdraw due to AEs.

Secondary Outcome(s)

Secondary end point(s): •Change from baseline in the Total Functional Capacity (TFC), administered as part of the Unified Huntington’s Disease Rating Scale (UHDRS).
•Change from baseline in the motor, cognitive, independence, and functional assessments administered as part of the UHDRS.
•Change from baseline in the composite UHDRS (cUHDRS).
•Change from baseline in the Short Problem Behaviors Assessment (PBA-s).

Timepoint(s) of evaluation of this end point: Every 12 weeks, from week 1 to week 97.

Secondary ID(s)

WVE-HDSNP2-002

Source(s) of Monetary Support

Wave Life Sciences UK Limited

Ethics review

Status: Approved
Approval date: 11/09/2019
Contact: