A Multicenter, Randomized, Double-blind, Placebo-controlled, Phase 1b/2a Study of WVE-003 Administered Intrathecally in Patients With Huntington’s Disease

• Register: EUCTR
• Last refreshed on: 24 February 2025
• Main ID: EUCTR2020-004556-15-NL
• Date of registration: 11/02/2022
• 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-003 Administered Intrathecally in Patients With Huntington’s Disease
• Scientific title: A Multicenter, Randomized, Double-blind, Placebo-controlled, Phase 1b/2a Study of WVE-003 Administered Intrathecally in Patients With Huntington’s Disease
• Date of first enrolment: 01/03/2022
• Target sample size: 36
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2020-004556-15
• 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, Italy, Netherlands, Poland, Spain, Switzerland, United Kingdom

Contacts

• Name: Adrian Haines
• Affiliation: PPD

• Name: Adrian Haines
• Affiliation: PPD

Key inclusion & exclusion criteria

Inclusion criteria:
1. Documented ability to understand the written study ICF(s) and consent, and has provided signed written informed consent prior to any study procedures.
2. Ambulatory male or female
3. Age =25 to =60 years old
4. Body mass index (BMI) =32 kg/m2
5. Documented CAG triplet repeats =36 in the HTT gene
6. Documented heterozygosity at SNP3
7. Documented presence of the A variant of SNP3 on the same allele as the pathogenic CAG triplet expansion
8. Clinical diagnostic motor features of HD, defined as UHDRS Diagnostic Confidence Score = 4
9. UHDRS Total Functional Capacity (TFC) scores =9 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 and for 5 months (i.e., 5 elimination half-lives) after the last dose of study drug, if patients or their partners are of childbearing potential. Non-childbearing potential and highly effective methods of contraception are defined in the protocol. In addition, willingness to forego sperm or ova (egg) donation for the duration of the study and 5 months after completion of the study.
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 36
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. Previously received tominersen.
6. Received prior treatment with viral or cellular-based gene therapy.
7. Received any other study drug, including an investigational oligonucleotide, within the past 1 year or 5 half-lives of the drug, whichever is longer, with the exception of the following:
a. Received WVE-120101 within the last 3 months (i.e., 5 half-lives); or
b. Received WVE-120102 within the last 3 months (i.e., 5 half-lives)
8. Implantable central nervous system device that may interfere with ability to administer study drug via lumbar puncture or undergo MRI scan.
9. History of substance abuse disorder (except nicotine) within 6 months prior to the Screening Visit.
10. Positive for opioids (unprescribed), cocaine, amphetamines, methadone, barbiturates, methamphetamine, or phencyclidine at the Screening Visit.
11. 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).
12. 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.
13. Clinically significant laboratory abnormality at Screening.
14. 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.
15. 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. Mental status, psychiatric medical history, and eligibility for the study must be documented in the screening questionnaire.
16. Bone, spine, bleeding, or other disorder that exposes the patient to risk of injury or unsuccessful lumbar puncture.
17. Inability to undergo brain MRI (with or without sedation).
18. Deemed to be at significant risk for suicidal behavior based on any of the following criteria:
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).
19. Involved directly or indirectly in the conduct and administration of this study as an Investigator, sub-investigator, study

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-003
Product Code: WVE-003
Pharmaceutical Form: Powder for solution for injection
INN or Proposed INN: WVE-003
Current Sponsor code: WVE-003
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 20-
Pharmaceutical form of the placebo: Solution for injection
Route of administration of the placebo: Intrathecal use

Primary Outcome(s)

Primary end point(s): Safety:
Adverse events, concomitant medications, physical examinations including detailed neurological examination, vital signs, weight, 12-lead ECGs, clinical laboratory evaluations (including clinical chemistry, hematology, and urinalysis), CSF safety evaluations, MRI of the brain, and C-SSRS.

Pharmacokinetics:
•Pharmacokinetic parameters of WVE-003 in plasma.
•Concentration of WVE-003 in CSF.

Main Objective: To evaluate the safety and tolerability of WVE-003 in patients with Huntington’s disease (HD).

Timepoint(s) of evaluation of this end point: Primary safety and PK endpoints will be assessed as the change from baseline parameters in UHDRS, cUHDRS, SDMT, PBA-s and MRIs after all patients in Period 1 cohort received study drug and completed 4 weeks of post-dose follow up.

Secondary Objective: • To characterize the pharmacokinetics (PK) of WVE-003 in plasma.
• To characterize the concentration of WVE-003 in cerebrospinal fluid (CSF).

Secondary Outcome(s)

Secondary end point(s): Pharmacodynamics
•Change from baseline in the level of mHTT protein in CSF
•Change from baseline in the level of wtHTT protein in CSF
•Change from baseline in the level of tHTT protein in CSF
•Change from baseline in the level of NfL in CSF

Clinical Effects:
• Change from baseline in the UHDRS TFC
• Change from baseline in UHDRS total motor score
• Change from baseline in the UHDRS independence scale
• Change from baseline in Symbol Digit Modalities Test
• Change from baseline in Stroop word reading test
• Change from baseline in the composite UHDRS
• Change from baseline in the PBA-s
• Changes from baseline in MRI of the brain

Timepoint(s) of evaluation of this end point: At study time points from baseline value to last measured time point

Secondary ID(s)

2020-004556-15-DE

WVE-003-001

Source(s) of Monetary Support

Wave Life Sciences UK Limited

Ethics review

Status: Approved
Approval date: 01/03/2022
Contact: