Clinical trial NCT06700538: Study of ARO-INHBE in Adults With Obesity With and Without Diabetes Mellitus
Official title: A Phase 1/2a Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of ARO-INHBE in Adult Volunteers With Obesity With and Without Diabetes Mellitus
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Obesity
Lead sponsor: Arrowhead Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2024-11-22
Enrollment: 120
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 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-INHBE in adult participants with obesity (Part 1), and the safety, tolerability and PD of multiple doses of ARO-INHBE in adult participants with obesity with and without type 2 diabetes mellitus receiving tirzepatide (Part 2).


Eligibility criteria: Inclusion Criteria:

* Obesity, defined as Body Mass Index (BMI) between 30 to 50 kg/m2 at Screening
* At least one self-reported, unsuccessful attempt at weight loss with lifestyle modification
* Willing, able and motivated to comply with all study assessments and adhere to the protocol schedule, including adherence to a stable diet and exercise routine for the duration of the study
* No abnormal finding of clinical relevance at Screening that, in the opinion of investigator, could adversely impact subject safety 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 endo of the study or last dose of study medication, whichever is later. Participants must not donate sperm or eggs during the study and for at least 90 days following the end of the study or last dose of study medication, whichever is later.

Exclusion Criteria:

* Self-reported (or documented) weight gain or loss \>5% within 3 months prior to Screening
* Use of GLP1R agonists (liraglutide, semaglutide, etc.) for any indication within 6 months prior to Screening
* Use of non-GLP1R 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 supplements taken for weight loss
* Obesity attributable, in the investigator's opinion, to medication use, endocrinologic or monogenic disorders
* History or prior surgical or device-based therapy for obesity
* Use of medications strongly associated with weight gain within 3 months prior to Screening
* Type 1 diabetes mellitus
* History of hyperthyroidism or thyroid-stimulating hormone (TSH) levels \<0.4 or \>6.0 mIU/L at Screening
* Evidence of clinically significant end-organ disease

Note: Other Inclusion/Exclusion criteria may apply per protocol

Primary outcomes:
measure: Number of Participants with Treatment-Emergent Adverse Events (TEAEs)
timeFrame: Part 1 single dose: up to Day 113 End of Study (EOS), Part 1 multiple doses: up to Day 169 (EOS), Part 2: up to Day 169 (EOS)
Secondary outcomes:
measure: Pharmacokinetics (PK) of ARO-INHBE: Maximum observed Plasma Concentration (Cmax)
timeFrame: Part 1: single dose (Day 1): Through 48 hours post-dose; Part 1: multiple dose (Day 1, Day 29): Through 48 hours post first and second dose
measure: PK of ARO-INHBE: Time to Maximum Observed Plasma Concentration (Tmax)
timeFrame: Part 1: single dose (Day 1): Through 48 hours post-dose; Part 1: multiple dose (Day 1, Day 29)
measure: PK of ARO-INHBE: Area Under the Plasma Concentration Versus Time Curve from Zero to 24 Hours (AUC0-24)
timeFrame: Part 1: single dose (Day 1): Through 48 hours post-dose; Part 1: multiple dose (Day 1, Day 29)
measure: PK of ARO-INHBE: Area Under the Plasma Concentration Versus Time Curve from Zero to the Last Quantifiable Plasma Concentration (AUC0-t)
timeFrame: Part 1: single dose (Day 1): Through 48 hours post-dose; Part 1: multiple dose (Day 1, Day 29)
measure: PK of ARO-INHBE: Area Under the Plasma Concentration Versus Time Curve from Zero to Infinity (AUC0-∞)
timeFrame: Part 1: single dose (Day 1): Through 48 hours post-dose; Part 1: multiple dose (Day 1, Day 29)
measure: PK of ARO-INHBE: Terminal Half-life (t1/2)
timeFrame: Part 1: single dose (Day 1): Through 48 hours post-dose; Part 1: multiple dose (Day 1, Day 29)
measure: PK of ARO-INHBE: Apparent Systemic Clearance (CL/F)
timeFrame: Part 1: single dose (Day 1): Through 48 hours post-dose; Part 1: multiple dose (Day 1, Day 29)
measure: PK of ARO-INHBE: Apparent Terminal-phase Volume of Distribution (Vz/F)
timeFrame: Part 1: single dose (Day 1): Through 48 hours post-dose; Part 1: multiple dose (Day 1, Day 29)
measure: PK of ARO-INHBE: Recovery of Unchanged Drug in Urine from Time 0 to 24 Hours after dosing (amount excreted: Ae)
timeFrame: Part 1: single dose (Day 1): Through 48 hours post-dose; Part 1: multiple dose (Day 1, Day 29)
measure: PK of ARO-INHBE: Fraction or Percentage of Administered Drug Excreted in Urine from Time 0 to 24 Hours after Dosing (Fe)
timeFrame: Part 1: single dose (Day 1): Through 48 hours post-dose; Part 1: multiple dose (Day 1, Day 29)
measure: PK of ARO-INHBE: Renal Clearance (CLr)
timeFrame: Part 1: single dose (Day 1): Through 48 hours post-dose; Part 1: multiple dose (Day 1, Day 29)
Other outcomes:
Locations:
city: Grafton
country: New Zealand
facility: Research Site
state: Auckland
Study officials:
References: