Huntington's DiseasePhase 1POINT-HDNCT07246941
A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of RG6496 in Huntington's Disease
A Phase 1 study testing RG6496 in people with Huntington's Disease, run by Hoffmann-La Roche at 7 sites in 5 countries.
Trial 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)]. Read more about this study
- Who is it for?
- Ages 25 to 65 years
- Conditions the study is for
- Huntington's Disease
- What is being tested?
- RG6496
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 3 participants
- Where
- 7 sitesin 5 countries
- Study dates
- 19 Nov 2025to 1 Dec 2026
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 25 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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
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- 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.
Trial locations and contacts
7 sites in 5 countries.
7 sites in 5 countries
Australia3 sites
Monash Health
Clayton, Victoria, 3168
Royal Melbourne Hospital
Parkville, Victoria, 3050
Westmead Hospital
Westmead, New South Wales, 2145
Argentina1 site
Hospital Britanico de Buenos Aires
Ciudad Autonoma Bs As, C1280AEB
Canada1 site
Montreal Neurological Institute Clinical Research Unit
Montral, Quebec, H3A 2B4
United Kingdom1 site
Cambridge Centre for Brain Repair
Cambridge, Cambridgeshire, CB2 0PY
About this study
Official title: A Phase I, 2-Part Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Single-ascending Doses of Intrathecally Administered RG6496 in a Randomized, Placebo-controlled, Investigator/Participant-blind Study With an Open-label Extension in Huntington's Disease Gene Expansion Carriers
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
- Being tested
- RG6496, Placebo
- Medical subject headings
- Huntington Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RG6496Drug
RG6496 will be administered as per the schedule specified in the respective arms.
PlaceboDrug
RG6496 matching placebo will be administered as per the schedule specified in placebo arm.
| Study group | Role | What they receive |
|---|---|---|
| Part 1: RG6496 | Experimental | Participants will receive single dose of RG6496. Participants will be enrolled in planned sequential cohorts associated with ascending dose levels. Receives: Drug: RG6496 |
| Part 1: Placebo | Placebo comparator | Participants will receive a single dose of RG6496 matching placebo. Receives: Drug: Placebo |
| Part 2: OLE | Experimental | All participants who have completed Part 1 and are eligible for Part 2 will receive one open-label dose of RG6496. Receives: Drug: RG6496 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Part 1: Number of Participants With Adverse Events (AEs)
Measured: Up to approximately 24 months
Part 1: Change From Baseline in Neurological Assessment
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.
Measured: Up to approximately 24 months
Part 1: Percentage of Participants With Suicidal Ideation or Behavior, as Assessed by Columbia-Suicide Severity Rating Scale (C-SSRS) Score
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.
Measured: Up to approximately 24 months
Part 1: Change from Baseline in Montreal Cognitive Assessment (MoCA)
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.
Measured: Up to approximately 24 months
Part 2: Number of Participants With AEs
Measured: Up to approximately 38 months
Part 2: Change From Baseline in Neurological Assessment
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.
Measured: Up to approximately 38 months
Part 2: Number of Participants With Suicidal Ideation or Behavior, as Assessed by C-SSRS Score
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.
Measured: Up to approximately 38 months
Part 2: Change from Baseline in MoCA
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.
Measured: Up to approximately 38 months
Secondary outcomes (3)
Part 1: Plasma Concentration of RG6496
Measured: Up to approximately 24 months
Part 1 and Part 2: Number of Participants With Anti-drug Antibody (ADA) in Plasma to RG6496
Measured: Part 1: Up to approximately 24 months; Part 2: Up to approximately 38 months
Part 1 and Part 2: Change From Baseline of Mutant Huntingtin Protein (mHTT) Concentrations in Cerebrospinal Fluid (CSF) Over Time
Measured: Part 1: Up to approximately 24 months; Part 2: Up to approximately 38 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Nov 2025
- Study start19 Nov 2025
- Primary completion1 Dec 2026 (estimated)
- Study completion1 Dec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Huntington's DiseaseStudies of the same condition, open and under way.
- More trials run by Hoffmann-La RocheThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 3 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hoffmann-La Roche
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Clinical Trials, Study director, Hoffmann-La Roche
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07246941
- Sponsor's protocol ID
- BP45378
- Other IDs
- 2025-520631-17-00, 2025
- Acronym
- POINT-HD
- Status last verified
- Sep 2026
- First submitted
- 19 Nov 2025
- Last updated
- 2 Sep 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 2 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I, 2-Part Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Single-ascending Doses of Intrathecally Administered RG6496 in a Randomized, Placebo-controlled, Investigator/Participant-blind Study With an Open-label Extension in Huntington's Disease Gene Expansion Carriers
- ClinicalTrials.gov ID
- NCT07246941
- Acronym / sponsor ID
- POINT-HD / BP45378
- Conditions
- Huntington's Disease
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 3 participants (actual)
- Lead sponsor
- Hoffmann-La RocheIndustry (pharma, biotech, devices)
- Study start
- 19 Nov 2025 (actual)
- Primary completion
- 1 Dec 2026 (estimated)
- Study completion
- 1 Dec 2026 (estimated)
- First posted
- 24 Nov 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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)].
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Part 1: RG6496 | Experimental | Drug: RG6496Participants will receive single dose of RG6496. Participants will be enrolled in planned sequential cohorts associated with ascending dose levels. |
| Part 1: Placebo | Placebo comparator | Drug: PlaceboParticipants will receive a single dose of RG6496 matching placebo. |
| Part 2: OLE | Experimental | Drug: RG6496All participants who have completed Part 1 and are eligible for Part 2 will receive one open-label dose of RG6496. |
Who may qualify
- Ages
- 25 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- 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.
Key exclusion criteria (16 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RG6496RG6496 will be administered as per the schedule specified in the respective arms. | Drug | Part 1: RG6496, Part 2: OLE |
| PlaceboRG6496 matching placebo will be administered as per the schedule specified in placebo arm. | Drug | Part 1: Placebo |
Primary outcome
Part 1: Number of Participants With Adverse Events (AEs)
Time frame: Up to approximately 24 months
Part 1: Change From Baseline in Neurological Assessment
Time frame: 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
Time frame: 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)
Time frame: 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
Time frame: Up to approximately 38 months
Part 2: Change From Baseline in Neurological Assessment
Time frame: 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
Time frame: 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
Time frame: 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.
3 secondary outcomes
Part 1: Plasma Concentration of RG6496
Time frame: Up to approximately 24 months
Part 1 and Part 2: Number of Participants With Anti-drug Antibody (ADA) in Plasma to RG6496
Time frame: Part 1: Up to approximately 24 months; Part 2: Up to approximately 38 months
Part 1 and Part 2: Change From Baseline of Mutant Huntingtin Protein (mHTT) Concentrations in Cerebrospinal Fluid (CSF) Over Time
Time frame: Part 1: Up to approximately 24 months; Part 2: Up to approximately 38 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Sep 2026.
- Please use this form to submit your questions for a faster response: https://www.gene.com/contact-us/submit-medical-inquiry. Do not include or attach any medical records when emailing or completing the form. A nurse will respond within 24 business hours.Link provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Clinical Trials study director
Hoffmann-La Roche
7 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing RG6496 in people with Huntington's Disease, run by Hoffmann-La Roche at 7 sites in 5 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 2 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in Australia, Argentina, Canada, New Zealand, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Part 1: Number of Participants With Adverse Events (AEs) (time frame: Up to approximately 24 months). The study lists 8 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Sep 2026.