Study of ARO-ALK7 in Adult Volunteers With Obesity With and Without Type 2 Diabetes Mellitus

Arrowhead Pharmaceuticals

Status and phase: Begins enrollment this month; Phase 2; Phase 1

Conditions: Obesity; Diabetes Mellitus, Type 2

Treatments: Drug: ARO-ALK7; Drug: Placebo; Drug: Tirzepetide

Study type: Interventional

Funder types: Industry

Identifiers

NCT06937203

AROALK7-1001

Details and patient eligibility

About

This study will evaluate the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics of single and multiple doses of ARO-ALK7 in adult volunteers with obesity (Part 1) and the safety, tolerability, and PD of multiple doses of ARO-ALK7 in adult volunteers with obesity with and without Type 2 Diabetes Mellitus (T2DM) receiving tirzepatide (Part 2). In Part 1A eligible participants with obesity will be randomized to receive a single dose of ARO-ALK7 or placebo (PBO) administered on Day 1. In Part 1B, eligible participants with obesity will be randomized to receive two doses of ARO-ALK7 or PBO administered on Day 1 and Day 29. In Part 2, eligible subjects with and without diabetes will randomized to combined therapy with tirzepatide and ARO-ALK7 or PBO (intervention arm) or tirzepatide monotherapy (control arm). Tirzepatide will be initiated on Day 1 and administered by subcutaneous injection (sc) weekly. ARO-ALK7 or PBO will be administered by sc injection on Day 1 and Day 29. All subjects in Part 2 will undergo adipose aspiration at Screening and Days 57, 113, 169 and 253.

Enrollment: 90 estimated patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Obesity, defined as BMI between 30-50 kg/m2, inclusive, with weight at Screening not to exceed 159 kg (350 lbs)
• At least one self-reported, unsuccessful attempt at weight loss with lifestyle modification
• No abnormal finding of clinical relevance at Screening that could adversely impact participant safety during the study or adversely impact study results
• Participants of childbearing potential must agree to use highly effective contraception in addition to a condom during the study and for at least 90 days following the end of the study or last dose of study drug, whichever is later. Participants must not donate sperm or eggs during the study for at least 90 days following the end of the study or last dose of study drug, whichever is later

Exclusion criteria

• Self-reported (or documented) weight gain or loss >5% within 3 months prior to Screening
• Use of GLP-1RAs (liraglutide, semaglutide, etc.) for any indication within 6 months prior to Screening
• Use of non-GLP-1R 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 supplement taken for weight loss purposes
• Obesity attributable primarily to medication use, endocrinologic or monogenic disorders
• History of prior surgical or device-based therapy for obesity (including endoscopic bariatric procedures)
• Use of medications or therapies strongly associated with weight gain, alterations in body composition, or increase in muscle mass, within 3 months prior to Screening
• Type 1 diabetes mellitus

Note: Additional inclusion/exclusion criteria may apply per protocol

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

---

90 participants in 5 patient groups, including a placebo group

Part1: ARO-ALK7

Experimental group

Description:

ARO-ALK7 in single (Day 1) or multiple (Days 1 and 29) ascending doses

Treatment:

Drug: ARO-ALK7

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-ALK7 + Tirzepetide

Experimental group

Description:

ARO-ALK7 at selected dose on Days 1 and 29 plus weekly doses of tirzepetide up to Day 253

Treatment:

Drug: Tirzepetide

Drug: ARO-ALK7

Part 2: Placebo + Tirzepetide

Placebo Comparator group

Description:

Placebo dose on Days 1 and 29 plus weekly doses of tirzepetide up to Day 253

Treatment:

Drug: Tirzepetide

Drug: Placebo

Part 2: Tirzepetide

Experimental group

Description:

Tirzepetide in weekly doses up to Day 253

Treatment:

Drug: Tirzepetide