Study of ARO-ALK7 in Adult Volunteers With Obesity With and Without Type 2 Diabetes Mellitus
- Conditions
- ObesityDiabetes Mellitus, Type 2
- Interventions
- Registration Number
- NCT06937203
- Lead Sponsor
- Arrowhead Pharmaceuticals
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- All
- Target Recruitment
- 90
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Part1: ARO-ALK7 ARO-ALK7 ARO-ALK7 in single (Day 1) or multiple (Days 1 and 29) ascending doses Part 1: Placebo Placebo Placebo in single (Day 1) or multiple (Days 1 and 29) matching doses Part:2: ARO-ALK7 + Tirzepetide ARO-ALK7 ARO-ALK7 at selected dose on Days 1 and 29 plus weekly doses of tirzepetide up to Day 253 Part:2: ARO-ALK7 + Tirzepetide Tirzepetide ARO-ALK7 at selected dose on Days 1 and 29 plus weekly doses of tirzepetide up to Day 253 Part 2: Placebo + Tirzepetide Placebo Placebo dose on Days 1 and 29 plus weekly doses of tirzepetide up to Day 253 Part 2: Placebo + Tirzepetide Tirzepetide Placebo dose on Days 1 and 29 plus weekly doses of tirzepetide up to Day 253 Part 2: Tirzepetide Tirzepetide Tirzepetide in weekly doses up to Day 253
- Primary Outcome Measures
Name Time Method Number of Participants with Treatment-Emergent Adverse Events (TEAEs) Up to Day 253 End of Study (EOS)
- Secondary Outcome Measures
Name Time Method 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