POINT-HD
Not Yet Recruiting
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 trial testing a new experimental drug called RG6496 in people who carry the HD gene. It is a randomized, double-blind, placebo-controlled trial, testing safety and how the drug behaves in the body, using careful dose increases.
There are 2 parts to the trial
Part 1 – Single-ascending doses: Participants will receive single dose of RG6496
Part 2 – Open label-OLE. All participants who have completed Part 1 and are eligible for Part 2 will receive one open-label dose of RG6496.
The drug or placebo will be delivered by lumbar puncture(injected into the spine). It will aim to lower only the mutant(mHTT) allele using a SNP directed aprroach. Only particpants with this specific SNP will be included in the trial
Phase: 1a/b
Subtype: Interventional Therapeutic
Primary Purpose: Treatment
Intervention Type: nucleic acid therapy
Primary Intervention: Drug: RG6496
Mode of Action: mHTT Lowering, ASO, SNP directed
Duration: 58 weeks
Ages Eligible
for Study:
25 Years to 65 Years
Sexes Eligible
for Study:
All
Accepts Healthy Volunteers:
No
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.
LOCATIONS
To be confirmed
