A Phase 1/2, Randomized, Double-blind, Placebo-controlled, Study of the Safety, Tolerability, Efficacy, Pharmacokinetics, and Pharmacodynamics of ALN-2232 as Monotherapy and Co-initiated With Tirzepatide in Adult Participants With Obesity
Overview
- Phase
- Phase 1
- Status
- Recruiting
- Sponsor
- Alnylam Pharmaceuticals
- Enrollment
- 156
- Locations
- 1
- Primary Endpoint
- Part A: Frequency of Adverse Events (AEs)
Overview
Brief Summary
The purpose of this study is to:
- evaluate the safety, tolerability, efficacy, pharmacokinetics (PK), and pharmacodynamics (PD) of single ascending doses of ALN-2232 in patients with obesity
- evaluate the safety, tolerability, efficacy, PK, and PD of multiple doses of ALN-2232 in patients with obesity
- evaluate the safety, tolerability, efficacy, PK, and PD of multiple doses of ALN-2232 co-initiated with tirzepatide in patients with obesity
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Triple (Participant, Care Provider, Investigator)
Eligibility Criteria
- Ages
- 18 Years to 65 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Has a body mass index (BMI) of ≥30 kg/m\^2 and \<40 kg/m\^2
- •Has a hemoglobin A1c (HbA1c) \<6.5%
Exclusion Criteria
- •Has any clinically significant concomitant disease, medical condition, or abnormal laboratory finding that could compromise participant safety or confound interpretation of study results
- •Receiving therapies for chronic weight management or antidiabetic medications
- •Note: other protocol defined inclusion/exclusion criteria apply
Arms & Interventions
Part B: ALN-2232
Participants will be administered multiple doses of ALN-2232
Intervention: ALN-2232 (Drug)
Part B: Placebo
Participants will be administered multiple doses of placebo
Intervention: Placebo (Drug)
Part C: ALN-2232
Participants will be administered multiple doses of ALN-2232
Intervention: ALN-2232 (Drug)
Part A: Placebo
Participants will be administered a single dose of placebo
Intervention: Placebo (Drug)
Part A: ALN-2232
Participants will be administered a single dose of ALN-2232
Intervention: ALN-2232 (Drug)
Part C: ALN-2232
Participants will be administered multiple doses of ALN-2232
Intervention: Tirzepatide (Drug)
Part C: Placebo
Participants will be administered multiple doses of placebo
Intervention: Placebo (Drug)
Part C: Tirzepatide
Participants will be administered multiple doses of tirzepatide once weekly
Intervention: Tirzepatide (Drug)
Outcomes
Primary Outcomes
Part A: Frequency of Adverse Events (AEs)
Time Frame: Up to 12 months
Part B: Percent Change from Baseline in Body Weight
Time Frame: Baseline up to Month 6
Part C: Percent Change from Baseline in Body Weight
Time Frame: Baseline up to Month 6
Secondary Outcomes
- Part A: Change from Baseline in Proteins in Adipose Tissue(Baseline up to Month 12)
- Part A: Area Under the Plasma Concentration-time Curve (AUC) of ALN-2232 in Plasma(Predose and up to 15 days postdose)
- Part A: Maximum Observed Plasma Concentration (Cmax) of ALN-2232 in Plasma(Predose and up to 15 days postdose)
- Part A: Time to Maximum Plasma Concentration (Tmax) of ALN-2232 in Plasma(Predose and up to 15 days postdose)
- Part A: Fraction of ALN-2232 excreted in urine(Predose and up to 8 days postdose (fe))
- Part A: Percent Change from Baseline in Body Weight(Baseline up to Month 12)
- Part B and Part C: Concentrations of ALN-2232 in Plasma(Predose and up to 6 months postdose)
- Part B and Part C: Percent Change from Baseline in Body Weight(Baseline up to Month 12)
- Part B and Part C: Change from Baseline in Body Fat Mass and Lean Mass(Baseline up to Month 12)