A Study to Evaluate ALN-2232 in Participants With Obesity

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

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 Overview

• Status: Recruiting
• Conditions: Obesity
• Intervention / Treatment: Drug: Placebo; Drug: ALN-2232; Drug: Tirzepatide

• Study Type: Interventional
• Enrollment (Estimated): 156
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Alnylam Clinical Trial Information Line; Phone Number: 1-877-ALNYLAM; Email: clinicaltrials@alnylam.com
• Study Contact Backup: Name: Alnylam Clinical Trial Information Line; Phone Number: 1-877-256-9526; Email: clinicaltrials@alnylam.com

Study Locations

• Canada
  • Mount Royal, Canada, H3P 3P1
    • Recruiting
    • Clinical Trial Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

All Parts:

• 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:

All Parts:

• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

7

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Part B: Placebo; Participants will be administered multiple doses of placebo	Drug: Placebo; Placebo will be administered SC
Experimental: Part A: ALN-2232; Participants will be administered a single dose of ALN-2232	Drug: ALN-2232; ALN-2232 will be administered subcutaneously (SC)
Placebo Comparator: Part A: Placebo; Participants will be administered a single dose of placebo	Drug: Placebo; Placebo will be administered SC
Experimental: Part B: ALN-2232; Participants will be administered multiple doses of ALN-2232	Drug: ALN-2232; ALN-2232 will be administered subcutaneously (SC)
Experimental: Part C: ALN-2232; Participants will be administered multiple doses of ALN-2232	Drug: ALN-2232; ALN-2232 will be administered subcutaneously (SC); Drug: Tirzepatide; Tirzepatide will be administered SC
Placebo Comparator: Part C: Placebo; Participants will be administered multiple doses of placebo	Drug: Placebo; Placebo will be administered SC
Other: Part C: Tirzepatide; Participants will be administered multiple doses of tirzepatide once weekly	Drug: Tirzepatide; Tirzepatide will be administered SC

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Part A: Frequency of Adverse Events (AEs)	Up to 12 months
Part B: Percent Change from Baseline in Body Weight	Baseline up to Month 6
Part C: Percent Change from Baseline in Body Weight	Baseline up to Month 6

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	Measured by dual x-ray absorptiometry (DXA)	Baseline up to Month 12

Collaborators and Investigators

• Sponsor: Alnylam Pharmaceuticals
• Investigators: Study Director: Medical Director, Alnylam Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): March 2, 2026
• Primary Completion (Estimated): April 27, 2027
• Study Completion (Estimated): March 2, 2028

Study Registration Dates

• First Submitted: March 6, 2026
• First Submitted That Met QC Criteria: March 6, 2026
• First Posted (Actual): March 11, 2026

Study Record Updates

• Last Update Posted (Actual): May 14, 2026
• Last Update Submitted That Met QC Criteria: May 12, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: siRNA, RNAi therepeutic
• Additional Relevant MeSH Terms: Nutrition Disorders; Overnutrition; Body Weight; Overweight; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Signs and Symptoms; Obesity; Amino Acids, Peptides, and Proteins; Proteins; Glucagon-Like Peptide-1 Receptor; Glucagon-Like Peptide Receptors; Receptors, G-Protein-Coupled; Receptors, Cell Surface; Membrane Proteins; Receptors, Gastrointestinal Hormone; Receptors, Peptide; Tirzepatide
• Other Study ID Numbers: ALN-2232-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Access to Anonymized individual participant data that support these results is made available 12 months after study completion and not less than 12 months after the product and indication have been approved in the US and/or the EU.

Access to data may be declined where there is likelihood a patient could be identified or other feasibility issue, where there is a potential conflict of interest, planned business activities or an actual or potential competitive risk. Data will be provided contingent upon the approval of a research proposal and the execution of a data sharing agreement. Timeframes for data access may vary and can take up to 6 months or more.

Requests for access to data can be submitted via the website www.vivli.org. Questions can also be directed to datasharing@alnylam.com.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes