A Randomized, Double-blind, Placebo-controlled Study, to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Intrathecally Administered Single Ascending Doses of ALN-HTT02 in Adult Patients With Huntington's Disease
Trial Snapshot
- Phase
- Phase 1
- Status
- Recruiting
- Sponsor
- Enrollment
- 66
- Locations
- 20
- Primary Endpoint
- Frequency of Adverse Events (AEs) in the Double-blind Part of the Study
Study Overview
Brief Summary
The purpose of this study is to evaluate the safety, tolerability, pharmacodynamics (PD) and pharmacokinetics (PK) of single or repeat doses of ALN-HTT02.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Triple (Participant, Care Provider, Investigator)
Eligibility Criteria
- Ages
- 25 Years to 70 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Has stage 2 or early Stage 3 Huntington's disease (HD), per the Huntington's Disease Integrated Staging System (HD-ISS)
Exclusion Criteria
- •Has significant structural or degenerative neurologic disease other than Huntington's Disease (HD) at screening
- •Has primary or secondary immune compromise at screening due to infections, medical conditions, or chronic therapies
- •Has alanine aminotransferase or aspartate aminotransferase >2× upper limit of normal (ULN)
- •Has an estimated glomerular filtration rate (eGFR) of <60 mL/min/1.73m^2 at screening
- •Has received an investigational agent within the last 1 year or 5 half-lives (if known)
- •Note: other protocol defined inclusion / exclusion criteria apply
Arms & Interventions
Placebo + ALN-HTT02
Participants will be administered a single dose of placebo during the Double-blind Part of the study. Participants will have the option to receive a single dose of ALN-HTT02 during the Open-label Part of the study. Participants have the option to receive repeat doses of ALN-HTT02 in the OLE Part of the study.
Intervention: ALN-HTT02 (Drug)
Placebo + ALN-HTT02
Participants will be administered a single dose of placebo during the Double-blind Part of the study. Participants will have the option to receive a single dose of ALN-HTT02 during the Open-label Part of the study. Participants have the option to receive repeat doses of ALN-HTT02 in the OLE Part of the study.
Intervention: Placebo (Drug)
ALN-HTT02
Participants will be administered a single dose of ALN-HTT02 during the Double-blind Part of the study. Participants who received ALN-HTT02 in the Double-blind part of the study will not receive an additional dose during the Open-label Part of the study. Participants have the option to receive repeat doses of ALN-HTT02 in the Open-label Extension (OLE) Part of the study.
Intervention: ALN-HTT02 (Drug)
Outcomes
Primary Outcomes
Frequency of Adverse Events (AEs) in the Double-blind Part of the Study
Time Frame: Up to 12 months
Frequency of AEs in the Open-label Part of the Study
Time Frame: Up to 12 months
Frequency of AEs in the OLE Part of the Study
Time Frame: Up to 36 months
Secondary Outcomes
- Change from Baseline in Levels of Mutant Huntingtin (mHTT) in Cerebrospinal Fluid (CSF)(Baseline up to Month 12 in the Double-blind Part of the study; Baseline up to Month 12 in the Open-label Part of the study)
- Concentrations of ALN-HTT02 in Plasma(Up to Month 12 in the Double-blind Part of the study; Up to Month 12 in the Open-label Part of the study)
- Concentrations of ALN-HTT02 in Cerebrospinal Fluid (CSF)(Up to Month 12 in the Double-blind Part of the study; Up to Month 12 in the Open-label Part of the study)
- Concentrations of ALN-HTT02 in Urine(Up to Month 12 in the Double-blind Part of the study; Up to Month 12 in the Open-label Part of the study)
- Change from Baseline in Levels of Mutant Huntingtin (mHTT) in Cerebrospinal Fluid (CSF)(Baseline up to Month 12 in the Double-blind Part of the study; Baseline up to Month 12 in the Open-label Part of the study ; Baseline up to Month 36 in the OLE Part of the study)
- Concentrations of ALN-HTT02 in Plasma(Up to Month 12 in the Double-blind Part of the study; Up to Month 12 in the Open-label Part of the study; Up to Month 36 in the OLE Part of the study)
- Concentrations of ALN-HTT02 in Urine(Up to Month 12 in the Double-blind Part of the study; Up to Month 12 in the Open-label Part of the study; Up to Month 36 in the OLE Part of the study)
- Concentrations of ALN-HTT02 in Cerebrospinal Fluid (CSF)(Up to Month 12 in the Double-blind Part of the study; Up to Month 12 in the Open-label Part of the study ; Up to Month 36 in the OLE Part of the study)