A Study to Evaluate ALN-4324 in Overweight to Obese Healthy Volunteers and in Overweight to Obese Patients With T2DM

A Phase 1/2, Randomized, Double-blind, Placebo-controlled 2-part Study of the Safety, Tolerability, Efficacy, Pharmacokinetics, and Pharmacodynamics of Single Dose ALN-4324 in Overweight to Obese Adult Healthy Volunteers and Multiple Dose ALN-4324 in Overweight to Obese Patients With Type 2 Diabetes Mellitus (T2DM)

The purpose of this study is to:

• evaluate the safety and tolerability of single ascending doses of ALN-4324 in healthy volunteers and to characterize the single-dose PK of ALN-4324
• evaluate the efficacy, safety, tolerability, and pharmacodynamics (PD) of multiple doses of ALN-4324 in adult overweight to obese patients with T2DM

Study Overview

• Status: Recruiting
• Conditions: Type 2 Diabetes Mellitus (T2DM); Obese or Overweight Healthy Volunteers
• Intervention / Treatment: Drug: Placebo; Drug: ALN-4324

• Study Type: Interventional
• Enrollment (Estimated): 144
• 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

• Argentina
  • Buenos Aires, Argentina, C1060
    • Recruiting
    • Clinical Trial Site
  • Buenos Aires, Argentina, C1061
    • Recruiting
    • Clinical Trial Site
  • Buenos Aires, Argentina, C1061AAE
    • Recruiting
    • Clinical Trial Site
  • San Miguel de Tucumán, Argentina, T4000IHE
    • Recruiting
    • Clinical Trial Site
• Canada
  • Concord, Canada, L4K 4M2
    • Recruiting
    • Clinical Trial Site
  • Mount Royal, Canada, H3P 3P1
    • Recruiting
    • Clinical Trial Site
  • Vancouver, Canada, V5Y 3W2
    • Not yet recruiting
    • Clinical Trial Site
• Chile
  • Santiago, Chile, 7770086
    • Not yet recruiting
    • Clinical Trial Site
  • Santiago, Chile, 8320000
    • Recruiting
    • Clinical Trial Site
  • Santiago, Chile, 7500710
    • Not yet recruiting
    • Clinical Trial Site
• Germany
  • Essen, Germany, 45355
    • Recruiting
    • Clinical Trial Site
• Poland
  • Gdansk, Poland, 80-546
    • Recruiting
    • Clinical Trial Site
  • Tarnów, Poland, 33-100
    • Not yet recruiting
    • Clinical Trial Site
  • Warsaw, Poland, 02-507
    • Recruiting
    • Clinical Trial Site
  • Wroclaw, Poland, 51-162
    • Recruiting
    • Clinical Trial Site
• United States
  • California
    • Montclair, California, United States, 91763
      • Recruiting
      • Clinical Trial Site
  • District of Columbia
    • Washington D.C., District of Columbia, United States, 20009
      • Not yet recruiting
      • Clinical Trial Site
  • Florida
    • Miami, Florida, United States, 33126
      • Recruiting
      • Clinical Trial Site
  • New Jersey
    • Marlton, New Jersey, United States, 08053
      • Recruiting
      • Clinical Trial Site
  • North Carolina
    • Monroe, North Carolina, United States, 28112
      • Recruiting
      • Clinical Trial Site
  • Texas
    • Dallas, Texas, United States, 75230
      • Recruiting
      • Clinical Trial Site
    • Dallas, Texas, United States, 75246
      • Recruiting
      • Clinical Trial Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

Part A:

• Has a body mass index (BMI) of ≥27 kg/m^2 and <40 kg/m^2

Part B:

• Is an adult patient with a confirmed diagnosis of T2DM
• Has a hemoglobin A1c (HbA1c) ≥7% to <10.5%
• Has a BMI of ≥25 kg/m^2 and <45 kg/m^2
• Is on a stable dose of either metformin or metformin and a sodium-glucose cotransporter 2 inhibitor (SGLT2i)

Exclusion Criteria:

Part A:

• Has known human immunodeficiency virus (HIV) infection; or known current or chronic hepatitis C virus or hepatitis B virus infection

Part B:

• Receiving therapies for chronic weight management or antidiabetic medications other than metformin and SGLT2i

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

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Part A: Placebo; Participants will be administered a single dose of placebo.	Drug: Placebo; Placebo will be administered SC
Experimental: Part A: ALN-4324; Participants will be administered a single dose of ALN-4324.	Drug: ALN-4324; ALN-4324 will be administered subcutaneously (SC)
Experimental: Part B: ALN-4324; Participants will be administered multiple doses of ALN-4324	Drug: ALN-4324; ALN-4324 will be administered subcutaneously (SC)
Placebo Comparator: Part B: Placebo; Participants will be administered multiple doses of placebo	Drug: Placebo; Placebo 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 9 months
Part B: Frequency of Adverse Events	Up to 12 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Part A: Area Under the Plasma Concentration-time Curve (AUC) of ALN-4324 in Plasma	Predose and up to 3 days postdose
Part A: Maximum Observed Plasma Concentration (Cmax) of ALN-4324 in Plasma	Predose and up to 3 days postdose
Part A: Time to Maximum Plasma Concentration (Tmax) of ALN-4324 in Plasma	Predose and up to 3 days postdose
Part A: Fraction of ALN-4324 excreted in urine	Predose and up to 24 hours postdose (fe)
Part B: Change from Baseline in HbA1c	Baseline up to 6 months
Part B: Response to Glucose Tolerance Test	Predose and up to 2 hours postdose
Part B: Concentrations of ALN-4324 in Plasma	Predose and up to 4 hours postdose

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): March 3, 2025
• Primary Completion (Estimated): August 31, 2027
• Study Completion (Estimated): August 31, 2027

Study Registration Dates

• First Submitted: February 20, 2025
• First Submitted That Met QC Criteria: February 20, 2025
• First Posted (Actual): February 25, 2025

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: Endocrine System Diseases; Nutrition Disorders; Metabolic Diseases; Overnutrition; Body Weight; Glucose Metabolism Disorders; Diabetes Mellitus; Overweight; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Signs and Symptoms; Obesity; Diabetes Mellitus, Type 2
• Other Study ID Numbers: ALN-4324-001; 2024-519005-35-00 (Ctis)

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: Yes
• Studies a U.S. FDA-regulated device product: No