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

A Phase 1/2A Dose-Escalating Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of ARO-ALK7 in Adult Volunteers With Obesity With and Without Type 2 Diabetes Mellitus

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).

Study Overview

• Status: Recruiting
• Conditions: Obesity; Diabetes Mellitus, Type 2
• Intervention / Treatment: Drug: Placebo; Drug: ARO-ALK7

• Study Type: Interventional
• Enrollment (Estimated): 150
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Medical Monitor; Phone Number: 626-304-3400; Email: AROALK71001@arrowheadpharma.com

Study Locations

• Australia
  • QLC
    • Morayfield, QLC, Australia, 4506
      • Recruiting
      • Research Site 8
      • Principal Investigator: Principle Investigator
  • Western Australia
    • Nedlands, Western Australia, Australia, 6009
      • Not yet recruiting
      • Research Site 7
      • Principal Investigator: Principle Investigator
• New Zealand
  • Auckland, New Zealand, 1010
    • Recruiting
    • Research Site 1
    • Principal Investigator: Principle Investigator
  • Christchurch, New Zealand, 8011
    • Recruiting
    • Research Site 2
    • Principal Investigator: Principle Investigator
  • Rotorua, New Zealand, 3010
    • Recruiting
    • Research Site 4
    • Principal Investigator: Principle Principle Investigator
  • Auckland
    • Grafton, Auckland, New Zealand, 1010
      • Recruiting
      • Research Site 5
      • Principal Investigator: Principle Investigator
    • Papatoetoe, Auckland, New Zealand, 2025
      • Recruiting
      • Research Site 6
      • Principal Investigator: Principle Investigator
    • Takapuna, Auckland, New Zealand, 0622
      • Recruiting
      • Research Site 3
      • Principal Investigator: Principle Investigator

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Obesity, defined as body mass index (BMI) between 30-50 kilograms (kg)/square meter (m^2), inclusive, with weight at Screening not to exceed 159 kg (350 pounds [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
• Female participants of childbearing potential must agree to use highly effective contraception and male participants with female partners of childbearing potential must agree to use 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 glucagon-like peptide-1 receptor agonist (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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1 and Part 2 (optional cohort): ARO-ALK7; ARO-ALK7 in single (Day 1) or multiple (Days 1 and 85) ascending doses	Drug: ARO-ALK7; Subcutaneous (SC) injection
Placebo Comparator: Part 1 and Part 2 (optional cohort): Placebo; Placebo in single (Day 1) or multiple (Days 1 and 85) matching doses	Drug: Placebo; calculated volume to match active treatment by SC injection; Other Names: 0.9% sodium chloride
Experimental: Part:2: ARO-ALK7 + Tirzepatide; ARO-ALK7 at ascending doses on Days 1 and 85 plus weekly doses of tirzepatide initiated at Day 15 through Day 253	Drug: ARO-ALK7; Subcutaneous (SC) injection
Placebo Comparator: Part 2: Placebo + Tirzepatide; Placebo dose on Days 1 and 85 plus weekly doses of tirzepatide initiated at Day 15 through Day 253	Drug: Placebo; calculated volume to match active treatment by SC injection; Other Names: 0.9% sodium chloride

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of Participants with Treatment-Emergent Adverse Events (TEAEs)	Up to Day 253 End of Study (EOS)

Secondary Outcome Measures

Outcome Measure	Time Frame
Pharmacokinetics (PK) of ARO-ALK7 (Part 1 Only): Maximum Observed Plasma Concentration (Cmax)	Through 48 hours post-dose
PK of ARO-ALK7 (Part 1 Only): Time to Maximum Observed Plasma Concentration (Tmax)	Through 48 hours post-dose
PK of ARO-ALK7 (Part 1 Only): Area Under the Plasma Concentration Versus Time Curve from Zero to 24 Hours (AUC0-24)	Through 48 hours post-dose
PK of ARO-ALK7 (Part 1 Only): Area Under the Plasma Concentration Versus Time Curve from Zero to the Last Quantifiable Plasma Concentration (AUC0-t)	Through 48 hours post-dose
PK of ARO-ALK7 (Part 1 Only): Area Under the Plasma Concentration Versus Time Curve from Zero to Infinity (AUC0-∞)	Through 48 hours post-dose
PK of ARO-ALK7 (Part 1 Only): Terminal Elimination Half-life (t1/2)	Through 48 hours post-dose
PK of ARO-ALK7 (Part 1 Only): Apparent Systemic Clearance (CL/F)	Through 48 hours post-dose
PK of ARO-ALK7 (Part 1 Only): Apparent Terminal-phase Volume of Distribution (Vz/F)	Through 48 hours post-dose
PK of ARO-ALK7 (Part 1 Only): Recovery of Unchanged Drug in Urine from Time 0 to 24 Hours after Dosing (Amount excreted: Ae)	Through 24 hours post-dose
PK of ARO-ALK7 (Part 1 Only): Fraction or Percentage of Administered Drug Excreted in Urine from Time 0 to 24 Hours after Dosing (Fe)	Through 24 hours post-dose
PK of ARO-ALK7: Renal Clearance (CLr)	Through 24 hours post-dose

Collaborators and Investigators

• Sponsor: Arrowhead Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): May 9, 2025
• Primary Completion (Estimated): February 1, 2027
• Study Completion (Estimated): February 1, 2027

Study Registration Dates

• First Submitted: April 15, 2025
• First Submitted That Met QC Criteria: April 15, 2025
• First Posted (Actual): April 22, 2025

Study Record Updates

• Last Update Posted (Actual): July 8, 2026
• Last Update Submitted That Met QC Criteria: July 6, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Endocrine System Diseases; Nutrition Disorders; Metabolic Diseases; Overnutrition; Body Weight; Glucose Metabolism Disorders; Diabetes Mellitus; Overweight; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Signs and Symptoms; Obesity; Diabetes Mellitus, Type 2; Inorganic Chemicals; Chlorine Compounds; Sodium Compounds; Chlorides; Hydrochloric Acid; Sodium Chloride
• Other Study ID Numbers: AROALK7-1001

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes