Clinical Trials in the UK / NCT07246941
Active, not recruiting
Phase 1
A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of RG6496 in Huntington's Disease
NCT07246941 · tracked via the Priya Life Science UK tracker
Condition(s) studied
Huntington's Disease
Investigational drug(s) / intervention(s)
RG6496Placebo
RG6496: RG6496 will be administered as per the schedule specified in the respective arms.
Placebo: RG6496 matching placebo will be administered as per the schedule specified in placebo arm.
Study 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 \[open-label extension (OLE)\].
Eligibility
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.
Primary outcome measure(s)
- Part 1: Number of Participants With Adverse Events (AEs) — Up to approximately 24 months
- Part 1: Change From Baseline in Neurological Assessment — Up to approximately 24 months
A neurologic examination including fundoscopy, will be performed by a neurologist or an ophthalmologist depending on local practice. A neurologic examination will include an assessment of mental status, level of consciousness, cranial nerve function, motor function, sensory function, reflexes, gait, and coordination. - Part 1: Percentage of Participants With Suicidal Ideation or Behavior, as Assessed by Columbia-Suicide Severity Rating Scale (C-SSRS) Score — Up to approximately 24 months
C-SSRS measures 4 constructs as follows: severity of ideation, intensity of ideation, behavior, and lethality of actual suicide attempts. Binary (yes/no) data are collected for 10 categories. Numeric ratings are provided for intensity of ideation (if present), from 1 to 5, with 1 being the least severe and 5 being the most severe. - Part 1: Change from Baseline in Montreal Cognitive Assessment (MoCA) — Up to approximately 24 months
MoCA is a rater-administered, participant completed assessment (PerfO instrument) used to detect cognitive impairment. It contains a series of basic assessments, including attention and visuospatial tasks. The total score ranges from 0 to 30, where lower scores indicate greater impairment. - Part 2: Number of Participants With AEs — Up to approximately 38 months
- Part 2: Change From Baseline in Neurological Assessment — Up to approximately 38 months
A neurologic examination including fundoscopy, will be performed by a neurologist or an ophthalmologist depending on local practice. A neurologic examination will include an assessment of mental status, level of consciousness, cranial nerve function, motor function, sensory function, reflexes, gait, and coordination. - Part 2: Number of Participants With Suicidal Ideation or Behavior, as Assessed by C-SSRS Score — Up to approximately 38 months
C-SSRS measures 4 constructs as follows: severity of ideation, intensity of ideation, behavior, and lethality of actual suicide attempts. Binary (yes/no) data are collected for 10 categories. Numeric ratings are provided for intensity of ideation (if present), from 1 to 5, with 1 being the least severe and 5 being the most severe. - Part 2: Change from Baseline in MoCA — Up to approximately 38 months
MoCA is a rater-administered, participant completed assessment (PerfO instrument) used to detect cognitive impairment. It contains a series of basic assessments, including attention and visuospatial tasks. The total score ranges from 0 to 30, where lower scores indicate greater impairment.
Trial sites (7)
| Facility | City | Region | Status |
|---|---|---|---|
| Hospital Britanico de Buenos Aires | Ciudad Autonoma Bs As | Argentina | |
| Westmead Hospital | Westmead | New South Wales | |
| Monash Health | Clayton | Victoria | |
| Royal Melbourne Hospital | Parkville | Victoria | |
| Montreal Neurological Institute Clinical Research Unit | Montral | Quebec | |
| New Zealand Brain Research Institute | Christchurch | New Zealand | |
| Cambridge Centre for Brain Repair | Cambridge | Cambridgeshire |
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Official registry record
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
View NCT07246941 on ClinicalTrials.gov ↗ ← All trials in the UK