Recruiting
Phase 1
Phase 2

ARO-INHBE & Tirzepatide

Sponsor:

Arrowhead Pharmaceuticals

Code:

NCT06700538

Conditions

Obesity

Eligibility Criteria

Sex: All

Age: 18 - 65

Healthy Volunteers: Not accepted

Interventions

ARO-INHBE

Placebo

Tirzepatide

Study Details

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

Study ID

NCT06700538

Start date

Dec 4, 2024

Status verified date

Sep, 2026

Completion date

Jan 17, 2028

Anticipated

Primary completion date

Sep 17, 2027

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18 - 65

Healthy Volunteers: Not accepted

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 Design

Enrollment

180 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Part 1: ARO-INHBE

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

placebo comparator: Part 1: Placebo

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

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

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

experimental: Part 3: ARO-INHBE

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

placebo comparator: Part 3: Placebo

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

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

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

Interventions

ARO-INHBE

Subcutaneous (SC) injection

Placebo

Calculated volume to match active treatment by SC injection

Tirzepatide

SC injection

Primary outcome measure

  • Number of Participants with Treatment-Emergent Adverse Events (TEAEs) [ Time Frame: Up to Day 365 ]

Central Contacts and Locations

Central contacts

Medical Monitor

626-304-3400AROINHBE@arrowheadpharma.com

Locations

Research Site

Recruiting

Chicoutimi, Canada, G7H 7K9

Research Site

Recruiting

Concord, Canada, L4K 4M2

Research Site

Recruiting

Toronto, Canada, M4G 3E8

More Information

Sponsor

Arrowhead Pharmaceuticals

Last update posted

Sep 25, 2026

Last verified

Sep, 2026

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-26. This information was provided to ClinicalTrials.gov by Arrowhead Pharmaceuticals on 2026-09-25. Recruitment status is synced daily from ClinicalTrials.gov and may not reflect the sponsor's current status. Confirm during your call.