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

NCT06700538 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: AROINHBE-1001
• Study Type: interventional
• Target: 180
• Locations: 1 country
• Sites: 3

Brief Summary

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).

Conditions

Obesity

Outcome Measures

Primary Outcomes (1)

• Number of Participants with Treatment-Emergent Adverse Events (TEAEs)

  Up to Day 365

Secondary Outcomes (11)

• 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

Study Arms (8)

Part 1: ARO-INHBE

EXPERIMENTAL

ARO-INHBE in single (Day 1) or multiple (Days 1 and 29) ascending doses

Drug: ARO-INHBE

Part 1: Placebo

PLACEBO COMPARATOR

Placebo in single (Day 1) or multiple (Days 1 and 29) matching doses

Drug: Placebo

Part 2: ARO-INHBE + Tirzepatide

EXPERIMENTAL

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: ARO-INHBE; Drug: Tirzepatide

Part 2: Placebo + Tirzepatide

PLACEBO COMPARATOR

Placebo dose on Days 1 and 29 plus weekly doses of tirzepatide (2.5 to 5 mg) starting Day 15 through Day 169

Drug: Placebo; Drug: Tirzepatide

Part 3: ARO-INHBE

EXPERIMENTAL

ARO-INHBE on Days 1, 85, 169, and 253

Drug: ARO-INHBE

Part 3: Placebo

PLACEBO COMPARATOR

Placebo doses on Days 1, 85, 169, and 253

Drug: Placebo

Part 3: ARO-INHBE + Tirzepatide

EXPERIMENTAL

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: ARO-INHBE; Drug: Tirzepatide

Part 3: Placebo + Tirzepatide

PLACEBO COMPARATOR

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: Placebo; Drug: Tirzepatide

Interventions

ARO-INHBE DRUG

Subcutaneous (SC) injection

Part 1: ARO-INHBE; Part 2: ARO-INHBE + Tirzepatide; Part 3: ARO-INHBE; Part 3: ARO-INHBE + Tirzepatide

Placebo DRUG

Calculated volume to match active treatment by SC injection

Part 1: Placebo; Part 2: Placebo + Tirzepatide; Part 3: Placebo; Part 3: Placebo + Tirzepatide

Tirzepatide DRUG

SC injection

Part 2: ARO-INHBE + Tirzepatide; Part 2: Placebo + Tirzepatide; Part 3: ARO-INHBE + Tirzepatide; Part 3: Placebo + Tirzepatide

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Arrowhead Pharmaceuticals: lead

Study Sites (3)

Research Site 1

Grafton, Auckland, 1010, New Zealand

RECRUITING

Research Site 3

Auckland, 2025, New Zealand

RECRUITING

Research Site 2

Christchurch, 8011, New Zealand

RECRUITING

MeSH Terms

Conditions

Obesity

Interventions

Tirzepatide

Condition Hierarchy (Ancestors)

Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Glucagon-Like Peptide-1 Receptor; Glucagon-Like Peptide Receptors; Receptors, G-Protein-Coupled; Receptors, Cell Surface; Membrane Proteins; Proteins; Amino Acids, Peptides, and Proteins; Receptors, Gastrointestinal Hormone; Receptors, Peptide

Central Study Contacts

Medical Monitor

CONTACT

626-304-3400; AROINHBE@arrowheadpharma.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 20, 2024
• First Posted: November 22, 2024
• Study Start: December 4, 2024
• Primary Completion (Estimated): September 17, 2027
• Study Completion (Estimated): January 17, 2028
• Last Updated: April 24, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

NZ (3)