NCT07246941 · Phase 1 · RECRUITING

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

This trial is testing RG6496, a new drug for Huntington's disease, in people who carry the genetic expansion that causes HD. It is a first-in-human Phase 1 study, meaning the primary goal is to check whether the drug is safe and how the body processes it, not yet to prove it works. Participants receive a single dose, then may continue into an open-label extension phase.

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.

The sponsor's own eligibility wording, lightly reformatted. The study team makes the final eligibility decision — worth discussing with your doctor.

Eligibility criteria as of 2026-06-02

View full record on ClinicalTrials.gov

All APOE4 clinical trials