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)

Status

Active, not recruiting

Phases

Phase 1Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT06845202

Enrollment

105

Registered

2025-02-25

Start date

2025-03-03

Completion date

2027-08-31

Last updated

2026-09-16

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Obese or Overweight Healthy Volunteers, Type 2 Diabetes Mellitus (T2DM)

Keywords

siRNA, RNAi therepeutic

Brief summary

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, PK, and pharmacodynamics (PD) of multiple doses of ALN-4324 in adult overweight to obese patients with T2DM

Interventions

DRUGALN-4324

ALN-4324 will be administered subcutaneously (SC)

DRUGPlacebo

Placebo will be administered SC

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

TRIPLE (Subject, Caregiver, Investigator)

Eligibility

Sex/Gender

ALL

Age

18 Years to 75 Years

Healthy volunteers

Yes

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/

Design outcomes

Primary

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

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

Countries

Argentina, Canada, Chile, Germany, Poland, United States

Contacts

STUDY_DIRECTORMedical Director

Alnylam Pharmaceuticals

Outcome results

None listed

Source: ClinicalTrials.gov · Data processed: Sep 17, 2026