A First-In-Human Study of ARO-ALK7 in Adults With Obesity With and Without Type 2 Diabetes Mellitus

Arrowhead Pharmaceuticals

Status and phase: Enrolling; Phase 2; Phase 1

Conditions: Obesity; Diabetes Mellitus, Type 2

Treatments: Drug: ARO-ALK7; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT06937203

AROALK7-1001

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-ALK7 in adult participants with obesity without Type 2 Diabetes Mellitus (T2DM) (Part 1), and the safety, tolerability and PD of multiple doses of ARO-ALK7 in adult participants with obesity with and without T2DM, either as monotherapy or in combination with tirzepatide (Part 2).

Enrollment: 138 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 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 in the Investigator's opinion to medication use, monogenic or endocrinologic disorders (other than polycystic ovary syndrome)
• 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

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138 participants in 4 patient groups, including a placebo group

Part 1 and Part 2 (optional cohort): ARO-ALK7

Experimental group

Description:

ARO-ALK7 in single (Day 1) or multiple (Days 1 and 85) ascending doses

Treatment:

Drug: ARO-ALK7

Part 1 and Part 2 (optional cohort): Placebo

Placebo Comparator group

Description:

Placebo in single (Day 1) or multiple (Days 1 and 85) matching doses

Treatment:

Drug: Placebo

Part:2: ARO-ALK7 + Tirzepatide

Experimental group

Description:

ARO-ALK7 at ascending doses on Days 1 and 85 plus weekly doses of tirzepatide initiated at D15 through D253

Treatment:

Drug: ARO-ALK7

Part 2: Placebo + Tirzepatide

Placebo Comparator group

Description:

Placebo dose on Days 1 and 85 plus weekly doses of tirzepatide initiated at D15 through D253

Treatment:

Drug: Placebo