NCT06700538招募中1 期
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
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 180
- 试验地点
- 10
- 主要终点
- Number of Participants with Treatment-Emergent Adverse Events (TEAEs)
研究概览
简要总结
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 (in Part 1), the safety, tolerability, PK, and PD of multiple doses of ARO-INHBE either as monotherapy, or in combination with tirzepatide, in adult participants with obesity with and without type 2 diabetes mellitus (in Part 2 and Part 3).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Obesity, defined as Body Mass Index (BMI) between 30 to 50 kilograms (kg)/square meter (m^2) at Screening
- •At least one self-reported, unsuccessful attempt at weight loss with lifestyle modification
- •Type 2 diabetes mellitus for at least 6 months prior to Screening, with glycated hemoglobin (HgbA1c) between 6.0% (42 millimole [mmol]/mole [mol]) and 9.5% (80 mmol/mol) at Screening, on a stable diabetes medication regimen for at least 3 months (select Part 2 and Part 3 cohorts only)
- •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 participant safety 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 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.
排除标准
- •Self-reported (or documented) weight gain or loss >5% within 3 months prior to Screening
- •Use of glucagon-like protein 1 receptor (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, monogenic, or endocrinologic disorders (other than polycystic ovary syndrome)
- •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 milli-international units (mIU)/liter (L) at Screening
- •Evidence of clinically significant end-organ disease
- •Note: Other Inclusion/Exclusion criteria may apply per protocol
研究组 & 干预措施
Part 3: ARO-INHBE + Tirzepatide
Experimental
ARO-INHBE at ascending doses on Days 1, 85, 169, and 253 plus weekly doses of tirzepatide (2.5 to 15 mg [or the maximally tolerated dose]) starting Day 15 through Day 365
干预措施: Tirzepatide (Drug)
Part 1: Placebo
Placebo Comparator
Placebo in single (Day 1) or multiple (Days 1 and 29) matching doses
干预措施: Placebo (Drug)
Part 1: ARO-INHBE
Experimental
ARO-INHBE in single (Day 1) or multiple (Days 1 and 29) ascending doses
干预措施: ARO-INHBE (Drug)
Part 2: ARO-INHBE + Tirzepatide
Experimental
ARO-INHBE at ascending doses on Days 1 and 29 plus weekly doses of tirzepatide (2.5 to 5 milligrams [mg]) starting Day 15 through Day 169
干预措施: ARO-INHBE (Drug)
Part 3: Placebo + Tirzepatide
Placebo Comparator
Placebo doses on Days 1, 85, 169, and 253 plus weekly doses of tirzepatide (2.5 to 15 mg [or the maximally tolerated dose]) starting Day 15 through Day 365
干预措施: Tirzepatide (Drug)
Part 2: Placebo + Tirzepatide
Placebo Comparator
Placebo dose on Days 1 and 29 plus weekly doses of tirzepatide (2.5 to 5 mg) starting Day 15 through Day 169
干预措施: Placebo (Drug)
Part 2: Placebo + Tirzepatide
Placebo Comparator
Placebo dose on Days 1 and 29 plus weekly doses of tirzepatide (2.5 to 5 mg) starting Day 15 through Day 169
干预措施: Tirzepatide (Drug)
Part 3: Placebo
Placebo Comparator
Placebo doses on Days 1, 85, 169, and 253
干预措施: Placebo (Drug)
Part 2: ARO-INHBE + Tirzepatide
Experimental
ARO-INHBE at ascending doses on Days 1 and 29 plus weekly doses of tirzepatide (2.5 to 5 milligrams [mg]) starting Day 15 through Day 169
干预措施: Tirzepatide (Drug)
Part 3: ARO-INHBE
Experimental
ARO-INHBE on Days 1, 85, 169, and 253
干预措施: ARO-INHBE (Drug)
Part 3: ARO-INHBE + Tirzepatide
Experimental
ARO-INHBE at ascending doses on Days 1, 85, 169, and 253 plus weekly doses of tirzepatide (2.5 to 15 mg [or the maximally tolerated dose]) starting Day 15 through Day 365
干预措施: ARO-INHBE (Drug)
Part 3: Placebo + Tirzepatide
Placebo Comparator
Placebo doses on Days 1, 85, 169, and 253 plus weekly doses of tirzepatide (2.5 to 15 mg [or the maximally tolerated dose]) starting Day 15 through Day 365
干预措施: Placebo (Drug)
结局指标
主要结局
Number of Participants with Treatment-Emergent Adverse Events (TEAEs)
时间窗: 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)
Number of Participants with Treatment-Emergent Adverse Events (TEAEs)
时间窗: Up to Day 365
次要结局
- Pharmacokinetics (PK) of ARO-INHBE: Maximum observed Plasma Concentration (Cmax)(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)
- PK of ARO-INHBE: Time to Maximum Observed Plasma Concentration (Tmax)(Part 1: single dose (Day 1): Through 48 hours post-dose; Part 1: multiple dose (Day 1, Day 29))
- PK of ARO-INHBE: Area Under the Plasma Concentration Versus Time Curve from Zero to 24 Hours (AUC0-24)(Part 1: single dose (Day 1): Through 48 hours post-dose; Part 1: multiple dose (Day 1, Day 29))
- PK of ARO-INHBE: Area Under the Plasma Concentration Versus Time Curve from Zero to the Last Quantifiable Plasma Concentration (AUC0-t)(Part 1: single dose (Day 1): Through 48 hours post-dose; Part 1: multiple dose (Day 1, Day 29))
- PK of ARO-INHBE: Area Under the Plasma Concentration Versus Time Curve from Zero to Infinity (AUC0-∞)(Part 1: single dose (Day 1): Through 48 hours post-dose; Part 1: multiple dose (Day 1, Day 29))
- PK of ARO-INHBE: Terminal Half-life (t1/2)(Part 1: single dose (Day 1): Through 48 hours post-dose; Part 1: multiple dose (Day 1, Day 29))
- PK of ARO-INHBE: Apparent Systemic Clearance (CL/F)(Part 1: single dose (Day 1): Through 48 hours post-dose; Part 1: multiple dose (Day 1, Day 29))
- PK of ARO-INHBE: Apparent Terminal-phase Volume of Distribution (Vz/F)(Part 1: single dose (Day 1): Through 48 hours post-dose; Part 1: multiple dose (Day 1, Day 29))
- PK of ARO-INHBE: Recovery of Unchanged Drug in Urine from Time 0 to 24 Hours after dosing (amount excreted: Ae)(Part 1: single dose (Day 1): Through 48 hours post-dose; Part 1: multiple dose (Day 1, Day 29))
- PK of ARO-INHBE: Fraction or Percentage of Administered Drug Excreted in Urine from Time 0 to 24 Hours after Dosing (Fe)(Part 1: single dose (Day 1): Through 48 hours post-dose; Part 1: multiple dose (Day 1, Day 29))
- PK of ARO-INHBE: Renal Clearance (CLr)(Part 1: single dose (Day 1): Through 48 hours post-dose; Part 1: multiple dose (Day 1, Day 29))
- PK of ARO-INHBE: Area Under the Plasma Concentration Versus Time Curve from Zero to 24 Hours (AUC0-24)(Part 1: single dose (Day 1): Through 48 hours post-dose; Part 1: multiple dose (Day 1, Day 29); Part 3: multiple dose (Day 1, Day 85): Through 48 hours post first and second dose)
- PK of ARO-INHBE: Maximum observed Plasma Concentration (Cmax)(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; Part 3: multiple dose (Day 1, Day 85): Through 48 hours post first and second dose)
- PK of ARO-INHBE: Time to Maximum Observed Plasma Concentration (Tmax)(Part 1: single dose (Day 1): Through 48 hours post-dose; Part 1: multiple dose (Day 1, Day 29); Part 3: multiple dose (Day 1, Day 85): Through 48 hours post first and second dose)
- PK of ARO-INHBE: Area Under the Plasma Concentration Versus Time Curve from Zero to the Last Quantifiable Plasma Concentration (AUC0-t)(Part 1: single dose (Day 1): Through 48 hours post-dose; Part 1: multiple dose (Day 1, Day 29); Part 3: multiple dose (Day 1, Day 85): Through 48 hours post first and second dose)
- PK of ARO-INHBE: Area Under the Plasma Concentration Versus Time Curve from Zero to Infinity (AUC0-∞)(Part 1: single dose (Day 1): Through 48 hours post-dose; Part 1: multiple dose (Day 1, Day 29); Part 3: multiple dose (Day 1, Day 85): Through 48 hours post first and second dose)
- PK of ARO-INHBE: Terminal Half-life (t1/2)(Part 1: single dose (Day 1): Through 48 hours post-dose; Part 1: multiple dose (Day 1, Day 29); Part 3: multiple dose (Day 1, Day 85): Through 48 hours post first and second dose)
- PK of ARO-INHBE: Apparent Systemic Clearance (CL/F)(Part 1: single dose (Day 1): Through 48 hours post-dose; Part 1: multiple dose (Day 1, Day 29); Part 3: multiple dose (Day 1, Day 85): Through 48 hours post first and second dose)
- PK of ARO-INHBE: Apparent Terminal-phase Volume of Distribution (Vz/F)(Part 1: single dose (Day 1): Through 48 hours post-dose; Part 1: multiple dose (Day 1, Day 29); Part 3: multiple dose (Day 1, Day 85): Through 48 hours post first and second dose)
- PK of ARO-INHBE: Recovery of Unchanged Drug in Urine from Time 0 to 24 Hours after dosing (amount excreted: Ae)(Part 1: single dose (Day 1): Through 48 hours post-dose; Part 1: multiple dose (Day 1, Day 29); Part 3: multiple dose (Day 1, Day 85): Through 48 hours post first and second dose)
- PK of ARO-INHBE: Fraction or Percentage of Administered Drug Excreted in Urine from Time 0 to 24 Hours after Dosing (Fe)(Part 1: single dose (Day 1): Through 48 hours post-dose; Part 1: multiple dose (Day 1, Day 29); Part 3: multiple dose (Day 1, Day 85): Through 48 hours post first and second dose)
- PK of ARO-INHBE: Renal Clearance (CLr)(Part 1: single dose (Day 1): Through 48 hours post-dose; Part 1: multiple dose (Day 1, Day 29); Part 3: multiple dose (Day 1, Day 85): Through 48 hours post first and second dose)
研究者
研究点 (10)
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