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

Arrowhead Pharmaceuticals

Status and phase: Enrolling; Phase 2; Phase 1

Conditions: Obesity

Treatments: Drug: Placebo; Drug: ARO-INHBE; Drug: Tirzepatide

Study type: Interventional

Funder types: Industry

Identifiers

NCT06700538

AROINHBE-1001

Details and patient eligibility

About

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).

Enrollment: 180 estimated patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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180 participants in 8 patient groups, including a placebo group

Part 1: ARO-INHBE

Experimental group

Description:

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

Treatment:

Drug: ARO-INHBE

Part 1: Placebo

Placebo Comparator group

Description:

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

Treatment:

Drug: Placebo

Part 2: ARO-INHBE + Tirzepatide

Experimental group

Description:

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

Treatment:

Drug: Tirzepatide

Drug: ARO-INHBE

Part 2: Placebo + Tirzepatide

Placebo Comparator group

Description:

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

Treatment:

Drug: Tirzepatide

Drug: Placebo

Part 3: ARO-INHBE

Experimental group

Description:

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

Treatment:

Drug: ARO-INHBE

Part 3: Placebo

Placebo Comparator group

Description:

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

Treatment:

Drug: Placebo

Part 3: ARO-INHBE + Tirzepatide

Experimental group

Description:

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

Treatment:

Drug: Tirzepatide

Drug: ARO-INHBE

Part 3: Placebo + Tirzepatide

Placebo Comparator group

Description:

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

Treatment:

Drug: Tirzepatide

Drug: Placebo