Phase 1/2a Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Effect on Body Weight of RN3161 as Monotherapy and in Combination With Tirzepatide in Adults With Overweight and Obesity

A Randomized, Double-Blind, Placebo-Controlled Phase 1/2a Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Effect on Body Weight of RN3161 as Monotherapy and in Combination With Tirzepatide in Adults With Overweight and Obesity

Study to assess the safety, pharmacokinetics (the amount of study drug or any of its breakdown products in your body) and pharmacodynamics (how the study drug affects your body) of RN3161 alone (healthy volunteers) and RN3161 with tirzepatide (overweight and obese subjects)

Study Overview

• Status: Recruiting
• Conditions: Obesity &Amp; Overweight
• Intervention / Treatment: Drug: RN3161; Drug: Placebo Control; Drug: Tirzepatide

• Study Type: Interventional
• Enrollment (Estimated): 104
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Australia
  • Victoria
    • Melbourne, Victoria, Australia, 3004
      • Recruiting
      • Nucleus Network Pty Ltd
      • Contact: Philip Ryan, MD; Phone Number: 03 85939801; Email: p.ryan@nucleusnetwork.com.au

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• BMI:

Obesity: BMI ≥ 30 kg/m² for participants with no Asian ancestry and ≥ 27.5 kg/m² for participants with Asian ancestry that has been stable (± 5%) for the previous 3 months (based on participant self-report or available medical records), with or without a weight-related comorbidity (excluding diabetes)

Overweight: BMI 27 to <30 kg/m² for participants with no Asian ancestry and 23.0 to <27.5 kg/m² for participants with Asian ancestry that has been stable (± 5%) for the previous 3 months (based on participant self-report or available medical records), with at least 1 weight-related comorbidity (excluding diabetes)

Weight-related comorbidities include a diagnosis of the following:

• Hypertension: seated BP ≤ 140/90 mm Hg; receiving ≤ 2 stable (≥ 4 weeks) agents limited to ACE inhibitors, angiotensin receptor blockers, calcium channel blockers, or thiazide ≤ 25 mg, or untreated
• Dyslipidemia: stable use of lipid-lowering agents for dyslipidemia (LDL-C < 150 mg/dL, triglycerides < 300 mg/dL)
• Osteoarthritis

Exclusion Criteria:

• self-reported or documented weight gain or loss >5% within 3 months prior to screening
• use of GLP1R agonists within 6 months of screening
• intolerance to GLP-1 medications in the past
• use of non-GLP1R medications for weight loss within 3 months of screening
• HbA1c >6.5%
• diagnosis of significant liver disease
• history of malignancy or anaphylaxis
• use of any siRNA agent in the prior 12 months

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: RN3161; Investigational Product	Drug: RN3161; Investigational Product
Placebo Comparator: Placebo Control; placebo control	Drug: Placebo Control; 0.9% normal saline SC injection
Experimental: RN3161 and tirzepatide; In Part 3, RN3161 co-administered with tirezepatide	Drug: RN3161; Investigational Product; Drug: Tirzepatide; In Part 3; randomized to either RN3161 + tirzepatide or placebo + tirzepatide
Active Comparator: Placebo and tirzepatide; In Part 3; Placebo co-administered with tirzepatide	Drug: Placebo Control; 0.9% normal saline SC injection; Drug: Tirzepatide; In Part 3; randomized to either RN3161 + tirzepatide or placebo + tirzepatide

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Blood Pressure	Number of participants with blood pressure changes measured in mmHg	180 Days
ECG PR interval	Number of participants with change in PR interval measured as milliseconds	180 days
Physical Examination	Number of participants with changes seen by physical examination of skin, lymph nodes, eyes, ears, throat, chest, abdomen, musculoskeletal system and nervous system	180 days
Blood Chemistry Laboratory	Number of participants with changes in blood levels of sodium, potassium, chloride, calcium magnesium, creatinine, bilirubin, phosphate, AST, ALT, alkaline phosphatase, glucose, albumin, urea in standard units	180 days
Adverse Events	Incidence of adverse events reported	180 days
Heart Rate	Number of participants with change in heart rate measured in beats per minute	180 days
ECG QRS Complex	Number of participants with changes in QRS complex measured in milliseconds	180 days
ECG QT interval	Number of participants with change in QT interval measured by Frederica method in milliseconds	180 days
Blood Hematology Laboratory	Number of participants with changes in blood hemoglobin, hematocrit, platelets, neutrophils and leukocytes measured in standard units	180 days
Blood Coagulation Laboratory	Number of participants with changes in plasma prothrombin time, activated partial thromboplastin time, and international normalized ratio measured in standard units	180 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma and Urine Pharmacokinetics	plasma and urine levels of RN3161	180 Days
Presence of ADA	incidence of anti-drug antibodies in the plasma	180 days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Effect of RN3161 on plasma insulin	assess plasma insulin uU/mL	180 days
Assess RN3161 effect on plasma LDL	LDL-C in mg/dL	180 days
Effect of RN3161 on plasma HDL	HDL in mg/dL	180 days
Effect of RN3161 on plasma total cholesterol	total cholesterol in mg/dL	180 days
Effect of RN3161 on plasma triglycerides	triglycerides in mg/dL	180 days

Collaborators and Investigators

• Sponsor: Ikaria Bioscience Pty Ltd
• Collaborators: Shanghai Rona Therapeutics Co., Ltd.
• Investigators: Principal Investigator: Philip Ryan, MD, Nucleus Network Pty Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): November 4, 2025
• Primary Completion (Estimated): February 15, 2027
• Study Completion (Estimated): August 15, 2027

Study Registration Dates

• First Submitted: September 20, 2025
• First Submitted That Met QC Criteria: November 17, 2025
• First Posted (Actual): November 24, 2025

Study Record Updates

• Last Update Posted (Actual): November 24, 2025
• Last Update Submitted That Met QC Criteria: November 17, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: obesity; overweight; healthy volunteers
• Additional Relevant MeSH Terms: Nutrition Disorders; Overnutrition; Body Weight; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Signs and Symptoms; Overweight; 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: RN3161-101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The plan will be developed during study conduct.

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.: No