Actively Recruiting
A Phase I, Randomized, Placebo-controlled Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Single-ascending Doses of Intrathecal RG6496 with Open-label Extension in Huntington's Disease Gene Expansion Carriers
Led by Hoffmann-La Roche · Updated on 2026-06-02
40
Participants Needed
4
Research Sites
64 weeks
Total Duration
On this page
AI-Summary
What this Trial Is About
Researchers are evaluating the safety and tolerability of RG6496, a drug given in single ascending doses, in people who carry the gene expansion for Huntington's Disease. This first-in-human study is divided into two parts: Part 1 tests different dose levels in a randomized, placebo-controlled, double-blind design, followed by Part 2, an open-label extension where all eligible participants receive RG6496. In Part 1, participants receive either a single dose of RG6496 or a matching placebo, with dosing increasing in planned groups. Those who complete Part 1 and meet criteria may enter Part 2, where they receive one open-label dose of RG6496. The drug is administered intrathecally (into the spinal canal) under careful monitoring. Participants will be monitored up to approximately 24 months in Part 1 and up to 38 months in Part 2. Assessments include tracking adverse events, neurological function, cognitive testing with the Montreal Cognitive Assessment (MoCA), and suicidal ideation using the Columbia-Suicide Severity Rating Scale (C-SSRS). Blood and cerebrospinal fluid samples will be collected to measure drug levels, immune response, and mutant huntingtin protein concentrations. Safety and tolerability will be closely observed throughout the study.
CONDITIONS
Brief Title
A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of RG6496 in Huntington's Disease
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Confirmed Huntington's Disease gene expansion carrier status with a CAG repeat greater than 39
- Confirmation of specific SNP carrier status related to the study
- Independence Scale score of 70 or higher, total functional capacity at least 10, total motor score greater than 6
- Ability to read certain words and be fluent in the language used for consent and tests
- Ability to walk unassisted
- Body weight over 40 kilograms and BMI between 18 and 32 kg/m² inclusive at baseline
- Ability to undergo and tolerate MRI scans
- Completion of Part 1 safety follow-up for entry into Part 2
- Investigator's opinion that health status allows safe continued participation in Part 2
You will not qualify if you...
- Participation in any interventional clinical study or use of huntingtin-lowering therapies within 90 days or 5 drug half-lives before screening
- Pregnant, breastfeeding, or planning pregnancy during the study or contraception period
- History of malignancy within 5 years prior to screening
- Planned brain surgery during the study
- Positive tests for HIV or hepatitis B at screening
- Active psychosis, confusion, or violent behavior within 12 weeks prior to screening
- Current or past primary independent psychotic disorder
- Scoliosis, spinal deformity, or surgery preventing intrathecal injection in an outpatient setting
- History of suicide attempts or active suicidal ideation requiring hospital visit or care change within 12 months prior to screening
- Premature discontinuation from Part 1 (for Part 2 eligibility)
- Receipt of investigational treatments other than RG6496 during or after Part 1
- Confirmed dose-limiting adverse event in Part 1
AI-Screening
AI-Powered Screening
Complete this quick 3-step screening to check your eligibility
Your Study Journey
Duration - 2 to 4 weeks
Participants are screened for eligibility to participate in the trial.
1 visit (in-person)
Duration - Up to approximately 24 months
Participants receive a single dose of RG6496 or matching placebo in planned sequential cohorts with ascending dose levels.
1 dosing visit and multiple follow-up visits over 24 months
Duration - Up to approximately 38 months
Participants who completed initial treatment and are eligible receive one open-label dose of RG6496.
1 open-label dosing visit and follow-up visits over 38 months
Trial Site Locations
Total: 4 locations
1
Hospital Britanico de Buenos Aires
Ciudad Autonoma Bs As, Argentina, C1280AEB
Actively Recruiting
2
Westmead Hospital
Westmead, New South Wales, Australia, 2145
Actively Recruiting
3
Royal Melbourne Hospital
Parkville, Victoria, Australia, 3050
Actively Recruiting
4
New Zealand Brain Research Institute
Christchurch, New Zealand, 8011
Actively Recruiting
Research Team
R
Reference Study ID Number: BP45378 https://forpatients.roche.com/
F
Fastest response: use the inquiry form. No email attachments. https://www.gene.com/contact-us/submit-medical-inquiry
How is the study designed?
Study Type
INTERVENTIONAL
Masking
DOUBLE
Allocation
RANDOMIZED
Model
PARALLEL
Primary Purpose
TREATMENT
Number of Arms
3
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