A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of RG6496 in Huntington's Disease

NCT ID: NCT07246941

Last Updated: 2025-12-30

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-11-19
• Study Completion Date: 2029-03-05

Brief Summary

This is a first-in-human (FIH) study of RG6496 that will assess the safety and tolerability of single-ascending doses of RG6496 administered to huntington's disease gene expansion carriers (HDGECs). The study consists of two parts: Part 1 [single-ascending dose] followed by Part 2 [open-label extension (OLE)].

Conditions

Huntington's Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Part 1: RG6496

Participants will receive single dose of RG6496. Participants will be enrolled in planned sequential cohorts associated with ascending dose levels.

Group Type: EXPERIMENTAL

RG6496

Intervention Type: DRUG

RG6496 will be administered as per the schedule specified in the respective arms.

Part 1: Placebo

Participants will receive a single dose of RG6496 matching placebo.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

RG6496 matching placebo will be administered as per the schedule specified in placebo arm.

Part 2: OLE

All participants who have completed Part 1 and are eligible for Part 2 will receive one open-label dose of RG6496.

Group Type: EXPERIMENTAL

RG6496

Intervention Type: DRUG

RG6496 will be administered as per the schedule specified in the respective arms.

Interventions

RG6496

RG6496 will be administered as per the schedule specified in the respective arms.

Intervention Type: DRUG

Placebo

RG6496 matching placebo will be administered as per the schedule specified in placebo arm.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

Part 1

• Confirmation of HDGEC status with cytosine-adenine-guanine (CAG) expansion > 39.
• Confirmation of SNP carrier status of the target SNP
• Independence Scale (IS) score of ≥70, total functional capacity (TFC) ≥10, total motor score (TMS) >6.
• Ability to read the words "red," "blue," and "green" and be fluent in the language of the informed consent form (ICF) and the tests used at the study site.
• Ability to walk unassisted.
• Total body weight > 40 kilogram (kg) and body mass index (BMI) within the range 18-32 kilogram per square meter (kg/m^2) (inclusive) at baseline.
• Ability to undergo and tolerate MRI scans.

Part 2

• Completed the post-dose safety follow-up period in the Part 1 of the study.
• In the opinion of the Investigator, the participant has not experienced a worsening in health that precludes their safe continued participation in the study.

Exclusion Criteria

Part 1

• Concurrent or planned participation in any interventional clinical study, including current use of an ASO or any HTT-lowering therapy or treatment with investigational therapy within 90 days or 5 drug-elimination half-lives, whichever is longer prior to screening
• Pregnant or breastfeeding, or with the intention of becoming pregnant during the study or within the timeframe in which contraception is required
• Malignancy within 5 years prior to screening
• Planned brain surgery during the study
• Positive HIV test, hepatitis B surface antigen and hepatitis B surface antigen at screening
• Active psychosis, confusional state, or violent behavior, including aggression that could cause harm to self or others, over the 12 weeks prior to screening.
• Current or previous history of a primary independent psychotic disorder.
• Scoliosis or spinal deformity or surgery making IT injection not feasible in an outpatient setting
• History of attempted suicide or suicidal ideation with plan (i.e., active suicidal ideation) that required hospital visit and/or change in level of care within 12 months prior to screening.

Part 2

• Prematurely discontinued from Part 1 for any reason (i.e., before the completion of the postdose safety follow-up period of Part 1).
• Pregnant or breastfeeding, or with the intention of becoming pregnant during the study or within the timeframe in which contraception is required.
• Concurrent or planned participation in any interventional clinical study, including current use of an ASO or any HTT-lowering therapy
• Received any active investigational treatment other than RG6496 during or since completion of Part 1 of the study.
• Had confirmed Dose-Limiting Adverse Event (DLAE)(s) in Part 1 of the study.

• Minimum Eligible Age: 25 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hoffmann-La Roche

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Trials

Role: STUDY_DIRECTOR

Hoffmann-La Roche

Locations

Westmead Hospital

Westmead, New South Wales, Australia

Site Status: RECRUITING

New Zealand Brain Research Institute

Christchurch, , New Zealand

Site Status: RECRUITING

Countries

Australia; New Zealand

Central Contacts

Reference Study ID Number: BP45378 https://forpatients.roche.com/

Role: CONTACT

Phone: 888-662-6728 (U.S. Only)

Email: global-roche-genentech-trials@gene.com

Other Identifiers

2025-520631-17-00

Identifier Type: CTIS

Identifier Source: secondary_id

BP45378

Identifier Type: -

Identifier Source: org_study_id