A First-In-Human Study of ARO-INHBE in Adults With Obesity With and Without Type 2 Diabetes Mellitus

A Phase 1/2a Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of ARO-INHBE in Adult Volunteers With Obesity With and Without Diabetes Mellitus

This is a Phase 1/2a double-blind dose-escalating study to evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of single and multiple doses of ARO-INHBE in adult participants with obesity (in Part 1), the safety, tolerability, PK, and PD of multiple doses of ARO-INHBE either as monotherapy, or in combination with tirzepatide, in adult participants with obesity with and without type 2 diabetes mellitus (in Part 2 and Part 3).

Study Overview

• Status: Recruiting
• Conditions: Obesity
• Intervention / Treatment: Drug: Tirzepatide; Drug: Placebo; Drug: ARO-INHBE

• Study Type: Interventional
• Enrollment (Estimated): 180
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Medical Monitor; Phone Number: 626-304-3400; Email: AROINHBE@arrowheadpharma.com

Study Locations

• New Zealand
  • Auckland, New Zealand, 2025
    • Recruiting
    • Research Site 3
  • Christchurch, New Zealand, 8011
    • Recruiting
    • Research Site 2
  • Auckland
    • Grafton, Auckland, New Zealand, 1010
      • Recruiting
      • Research Site 1

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Obesity, defined as Body Mass Index (BMI) between 30 to 50 kilograms (kg)/square meter (m^2) at Screening
• At least one self-reported, unsuccessful attempt at weight loss with lifestyle modification
• Type 2 diabetes mellitus for at least 6 months prior to Screening, with glycated hemoglobin (HgbA1c) between 6.0% (42 millimole [mmol]/mole [mol]) and 9.5% (80 mmol/mol) at Screening, on a stable diabetes medication regimen for at least 3 months (select Part 2 and Part 3 cohorts only)
• Willing, able and motivated to comply with all study assessments and adhere to the protocol schedule, including adherence to a stable diet and exercise routine for the duration of the study
• No abnormal finding of clinical relevance at Screening that, in the opinion of investigator, could adversely impact participant safety or adversely impact study results
• Participants of childbearing potential must agree to use highly effective contraception during the study and for at least 90 days following the end of the study or last dose of study medication, whichever is later. Participants must not donate sperm or eggs during the study and for at least 90 days following the end of the study or last dose of study medication, whichever is later.

Exclusion Criteria:

• Self-reported (or documented) weight gain or loss >5% within 3 months prior to Screening
• Use of glucagon-like protein 1 receptor (GLP1R) agonists (liraglutide, semaglutide, etc.) for any indication within 6 months prior to Screening
• Use of non-GLP1R medications for weight loss within 3 months prior to Screening, including but not limited to naltrexone/bupropion, orlistat, phentermine/topiramate, and other prescription or over-the-counter medication or supplements taken for weight loss
• Obesity attributable, in the investigator's opinion, to medication use, monogenic, or endocrinologic disorders (other than polycystic ovary syndrome)
• History or prior surgical or device-based therapy for obesity
• Use of medications strongly associated with weight gain within 3 months prior to Screening
• Type 1 diabetes mellitus
• History of hyperthyroidism or thyroid-stimulating hormone (TSH) levels <0.4 or >6.0 milli-international units (mIU)/liter (L) at Screening
• Evidence of clinically significant end-organ disease

Note: Other Inclusion/Exclusion criteria may apply per protocol

Study Plan

How is the study designed?

Design Details

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

Number of Arms

8

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1: ARO-INHBE; ARO-INHBE in single (Day 1) or multiple (Days 1 and 29) ascending doses	Drug: ARO-INHBE; Subcutaneous (SC) injection
Placebo Comparator: Part 1: Placebo; Placebo in single (Day 1) or multiple (Days 1 and 29) matching doses	Drug: Placebo; Calculated volume to match active treatment by SC injection
Placebo Comparator: Part 2: Placebo + Tirzepatide; Placebo dose on Days 1 and 29 plus weekly doses of tirzepatide (2.5 to 5 mg) starting Day 15 through Day 169	Drug: Tirzepatide; SC injection; Drug: Placebo; Calculated volume to match active treatment by SC injection
Experimental: Part 2: ARO-INHBE + Tirzepatide; ARO-INHBE at ascending doses on Days 1 and 29 plus weekly doses of tirzepatide (2.5 to 5 milligrams [mg]) starting Day 15 through Day 169	Drug: Tirzepatide; SC injection; Drug: ARO-INHBE; Subcutaneous (SC) injection
Experimental: Part 3: ARO-INHBE; ARO-INHBE on Days 1, 85, 169, and 253	Drug: ARO-INHBE; Subcutaneous (SC) injection
Placebo Comparator: Part 3: Placebo; Placebo doses on Days 1, 85, 169, and 253	Drug: Placebo; Calculated volume to match active treatment by SC injection
Experimental: Part 3: ARO-INHBE + Tirzepatide; ARO-INHBE at ascending doses on Days 1, 85, 169, and 253 plus weekly doses of tirzepatide (2.5 to 15 mg [or the maximally tolerated dose]) starting Day 15 through Day 365	Drug: Tirzepatide; SC injection; Drug: ARO-INHBE; Subcutaneous (SC) injection
Placebo Comparator: Part 3: Placebo + Tirzepatide; Placebo doses on Days 1, 85, 169, and 253 plus weekly doses of tirzepatide (2.5 to 15 mg [or the maximally tolerated dose]) starting Day 15 through Day 365	Drug: Tirzepatide; SC injection; Drug: Placebo; Calculated volume to match active treatment by SC injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of Participants with Treatment-Emergent Adverse Events (TEAEs)	Up to Day 365

Secondary Outcome Measures

Outcome Measure	Time Frame
PK of ARO-INHBE: Maximum observed Plasma Concentration (Cmax)	Part 1: single dose (Day 1): Through 48 hours post-dose; Part 1: multiple dose (Day 1, Day 29): Through 48 hours post first and second dose; Part 3: multiple dose (Day 1, Day 85): Through 48 hours post first and second dose
PK of ARO-INHBE: Time to Maximum Observed Plasma Concentration (Tmax)	Part 1: single dose (Day 1): Through 48 hours post-dose; Part 1: multiple dose (Day 1, Day 29); Part 3: multiple dose (Day 1, Day 85): Through 48 hours post first and second dose
PK of ARO-INHBE: Area Under the Plasma Concentration Versus Time Curve from Zero to 24 Hours (AUC0-24)	Part 1: single dose (Day 1): Through 48 hours post-dose; Part 1: multiple dose (Day 1, Day 29); Part 3: multiple dose (Day 1, Day 85): Through 48 hours post first and second dose
PK of ARO-INHBE: Area Under the Plasma Concentration Versus Time Curve from Zero to the Last Quantifiable Plasma Concentration (AUC0-t)	Part 1: single dose (Day 1): Through 48 hours post-dose; Part 1: multiple dose (Day 1, Day 29); Part 3: multiple dose (Day 1, Day 85): Through 48 hours post first and second dose
PK of ARO-INHBE: Area Under the Plasma Concentration Versus Time Curve from Zero to Infinity (AUC0-∞)	Part 1: single dose (Day 1): Through 48 hours post-dose; Part 1: multiple dose (Day 1, Day 29); Part 3: multiple dose (Day 1, Day 85): Through 48 hours post first and second dose
PK of ARO-INHBE: Terminal Half-life (t1/2)	Part 1: single dose (Day 1): Through 48 hours post-dose; Part 1: multiple dose (Day 1, Day 29); Part 3: multiple dose (Day 1, Day 85): Through 48 hours post first and second dose
PK of ARO-INHBE: Apparent Systemic Clearance (CL/F)	Part 1: single dose (Day 1): Through 48 hours post-dose; Part 1: multiple dose (Day 1, Day 29); Part 3: multiple dose (Day 1, Day 85): Through 48 hours post first and second dose
PK of ARO-INHBE: Apparent Terminal-phase Volume of Distribution (Vz/F)	Part 1: single dose (Day 1): Through 48 hours post-dose; Part 1: multiple dose (Day 1, Day 29); Part 3: multiple dose (Day 1, Day 85): Through 48 hours post first and second dose
PK of ARO-INHBE: Recovery of Unchanged Drug in Urine from Time 0 to 24 Hours after dosing (amount excreted: Ae)	Part 1: single dose (Day 1): Through 48 hours post-dose; Part 1: multiple dose (Day 1, Day 29); Part 3: multiple dose (Day 1, Day 85): Through 48 hours post first and second dose
PK of ARO-INHBE: Fraction or Percentage of Administered Drug Excreted in Urine from Time 0 to 24 Hours after Dosing (Fe)	Part 1: single dose (Day 1): Through 48 hours post-dose; Part 1: multiple dose (Day 1, Day 29); Part 3: multiple dose (Day 1, Day 85): Through 48 hours post first and second dose
PK of ARO-INHBE: Renal Clearance (CLr)	Part 1: single dose (Day 1): Through 48 hours post-dose; Part 1: multiple dose (Day 1, Day 29); Part 3: multiple dose (Day 1, Day 85): Through 48 hours post first and second dose

Collaborators and Investigators

• Sponsor: Arrowhead Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): December 4, 2024
• Primary Completion (Estimated): September 17, 2027
• Study Completion (Estimated): January 17, 2028

Study Registration Dates

• First Submitted: November 20, 2024
• First Submitted That Met QC Criteria: November 20, 2024
• First Posted (Actual): November 22, 2024

Study Record Updates

• Last Update Posted (Actual): April 24, 2026
• Last Update Submitted That Met QC Criteria: April 21, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• 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: AROINHBE-1001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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