Clinical trial NCT06937203: Study of ARO-ALK7 in Adult Volunteers With Obesity With and Without Type 2 Diabetes Mellitus
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Obesity
Diabetes Mellitus, Type 2
Lead sponsor: Arrowhead Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2025-04-22
Enrollment: 126
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study will evaluate the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of single and multiple doses of ARO-ALK7 in adult volunteers with obesity without Type 2 Diabetes Mellitus (T2DM) (Part 1) and the safety, tolerability, and PD of multiple doses of ARO-ALK7 in adult volunteers with obesity with and without (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 85. In Part 2, eligible subjects with obesity with and without (T2DM) will randomized to combined therapy with tirzepatide and ARO-ALK7 (intervention arm) or tirzepatide and PBO (control arm). Tirzepatide will be initiated on Day 15 and administered by subcutaneous (SC) injection weekly. ARO-ALK7 or PBO will be administered by SC injection on Day 1 and Day 85. Subjects in both Part 1 and Part 2 will undergo adipose aspiration pre and post dose.


Eligibility criteria: 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

Primary outcomes:
measure: Number of Participants with Treatment-Emergent Adverse Events (TEAEs)
timeFrame: Up to Day 253 End of Study (EOS)
Secondary outcomes:
measure: Pharmacokinetics (PK) of ARO-ALK7 (Part 1 Only): Maximum Observed Plasma Concentration (Cmax)
timeFrame: Through 48 hours post-dose
measure: PK of ARO-ALK7 (Part 1 Only): Time to Maximum Observed Plasma Concentration (Tmax)
timeFrame: Through 48 hours post-dose
measure: PK of ARO-ALK7 (Part 1 Only): Area Under the Plasma Concentration Versus Time Curve from Zero to 24 Hours (AUC0-24)
timeFrame: Through 48 hours post-dose
measure: 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)
timeFrame: Through 48 hours post-dose
measure: PK of ARO-ALK7 (Part 1 Only): Area Under the Plasma Concentration Versus Time Curve from Zero to Infinity (AUC0-∞)
timeFrame: Through 48 hours post-dose
measure: PK of ARO-ALK7 (Part 1 Only): Terminal Elimination Half-life (t1/2)
timeFrame: Through 48 hours post-dose
measure: PK of ARO-ALK7 (Part 1 Only): Apparent Systemic Clearance (CL/F)
timeFrame: Through 48 hours post-dose
measure: PK of ARO-ALK7 (Part 1 Only): Apparent Terminal-phase Volume of Distribution (Vz/F)
timeFrame: Through 48 hours post-dose
measure: PK of ARO-ALK7 (Part 1 Only): Recovery of Unchanged Drug in Urine from Time 0 to 24 Hours after Dosing (Amount excreted: Ae)
timeFrame: Through 24 hours post-dose
measure: 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)
timeFrame: Through 24 hours post-dose
measure: PK of ARO-ALK7: Renal Clearance (CLr)
timeFrame: Through 24 hours post-dose
Other outcomes:
Locations:
city: Auckland
country: New Zealand
facility: Research Site
Study officials:
References: