A Multicenter, Randomized, Double-blind, Placebo-controlled, Phase 1b/2a Study of WVE-120101 Administered Intrathecally in Patients with Huntington’s Disease

• Register: EUCTR
• Last refreshed on: 14 June 2021
• Main ID: EUCTR2016-005095-10-DK
• Date of registration: 20/12/2018
• Prospective Registration: Yes
• Primary sponsor: Wave Life Sciences UK Limited
• Public title: A Multicenter, Randomized, Double-blind, Placebo-controlled, Phase 1b/2a Study of WVE-120101 Administered Intrathecally in Patients with Huntington’s Disease
• Scientific title: A Multicenter, Randomized, Double-blind, Placebo-controlled, Phase 1b/2a Study of WVE-120101 Administered Intrathecally in Patients with Huntington’s Disease
• Date of first enrolment: 26/02/2019
• Target sample size: 60
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2016-005095-10
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: no; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: yes; Other: no; Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): yes 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. Documented ability to understand the written study ICF(s), and has provided signed written informed consent prior to any study procedures.
2. Ambulatory male or female.
3. Age =25 to =65 years old.
4. Body mass index (BMI) =32 kg/m2
5. Documented CAG triplet repeats =36 in the Huntingtin gene.
6. Documented heterozygosity for SNP1.
7. Documented presence of the T variant of SNP1 on the same allele as the pathogenic CAG expansion
8. Has clinical diagnostic motor features of HD, defined as UHDRS Diagnostic Confidence Score = 4.
9. Stage I or Stage II HD, defined as UHDRS Total Functional Capacity scores =7 and =13.
10. In the opinion of the Investigator, the patient is able to tolerate all study procedures, and is willing to comply with all other protocol requirements.
11. Willingness to practice highly effective contraception for the duration of the study if patients or their partners are of childbearing potential. Non-childbearing potential and highly effective methods of contraception will be 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 60
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
1. Malignancy or received treatment for malignancy, other than treated basal cell or squamous cell carcinoma of the skin, within the previous 5 years.
2. Positive for Hepatitis B virus (HBV) or Hepatitis C virus (HCV).
3. Known to be positive for human immunodeficiency virus (HIV).
4. 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.
5. Received an investigational drug within the past 3 months, or an investigational oligonucleotide within the past 6 months.
6. Implantable central nervous system (CNS) device that may interfere with ability to administer study drug via lumbar puncture or undergo MRI scan.
7. 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) within 6 months prior to the Screening Visit.
8. Positive for opioids (unprescribed), cocaine, amphetamines, methadon, barbiturates, methamphetamine, or phencyclidine at the Screening Visit.
9. Started or changed dose for concomitant medication for the treatment of HD symptoms or psychiatric disorders within 30 days prior to the Screening Visit (concomitant medications that have been administered on a stable regimen for =30 days are permitted).
10. 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.
11. 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 as serum creatinine >1.8 mg/dL or creatinine clearance <40 mL/min.
12. Clinically significant abnormality at Screening electrocardiogram (ECG), including but not necessarily limited to a confirmed QT interval corrected for heart rate (QTc) =450 msec for males or =470 msec for females.
13. 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.
14. Bone, spine, bleeding, or other disorder that exposes the patient to risk of injury or unsuccessful lumbar puncture.
15. Inability to undergo brain MRI (with or without sedation).
16. Deemed to be at significant risk for suicidal behavior based on:
a The opinion of the Investigator; or
b Answers “yes” to Actual Suicide Attempts or Suicidal Behaviors in the Suicidal Behaviors section of the Columbia Suicide Severity Rating Scale (C-SSRS) with reference to a 2 year period prior to the Screening Visit; or
c Answers “yes” on any items in the Suicidal Ideation section of the C-SSRS with reference to a 6-month period prior to the Screening Visit; or
d Answers “yes” on any items in the Suicidal Ideation section of the C-SSRS at the Baseline Visit since the last visit (Screening Visit).
17. 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, sign

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-120101
Product Code: WVE-120101
Pharmaceutical Form: Powder for solution for injection
INN or Proposed INN: WVE-120101
Current Sponsor code: WVE-120101
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 8-
Pharmaceutical form of the placebo: Solution for injection
Route of administration of the placebo: Intrathecal use

Primary Outcome(s)

Secondary Objective: • Characterize the pharmacokinetics (PK) of WVE-120101 in plasma.
• Characterize the exposure of WVE-120101 in cerebrospinal fluid (CSF)
• Assess the pharmacodynamic (PD) effect of WVE-120101 on levels of mutant huntingtin protein (mHTT) in CSF.
• Assess the effect of WVE-120101 on signs and symptoms of HD, as measured by the Total Functional Capacity (TFC), administered as part of the Unified Huntington’s Disease Rating Scale (UHDRS).

Timepoint(s) of evaluation of this end point: Primary safety endpoints will be assessed as incidence of events from baseline through end of study.

Main Objective: Evaluate the safety and tolerability of WVE-120101 in patients with early manifest HD

Primary end point(s): The primary endpoint is the safety and tolerability of WVE 120101, as compared with placebo, as assessed by the number of patients with adverse events (AEs), severity of AEs, number of patients with serious AEs (SAEs), and the number of patients who withdraw due to AEs.

Secondary Outcome(s)

Secondary end point(s): Secondary endpoints include:
Pharmacokinetics
• PK parameters of WVE 120101 in plasma at predefined time points.
• Exposure of WVE 120101 in CSF at predefined time points.


Pharmacodynamics
• Concentration of mHTT protein in CSF predose (baseline value) and at the last measured time point

Clinical Effects
• Change from baseline (baseline value) to the last measured time point and difference from placebo in the TFC, administered as part of the UHDRS.

Timepoint(s) of evaluation of this end point: PK: At study time points from baseline to the last measured time point
PD: At study time points from to the last measured time point
Clinical effects: At study timepoints from baseline to the last measured time point

Secondary ID(s)

2016-005095-10-GB

WVE-HDSNP1-001

Source(s) of Monetary Support

Wave Life Science Ltd.

Ethics review

Status: Approved
Approval date: 26/02/2019
Contact: