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

Официальное название

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

Обзор

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).

Вмешательства

• Препарат ARO-INHBE
  Subcutaneous (SC) injection
• Препарат Placebo
  Calculated volume to match active treatment by SC injection
• Препарат Tirzepatide
  SC injection

Первичные конечные точки

• Number of Participants with Treatment-Emergent Adverse Events (TEAEs) [Срок оценки: Up to Day 365]

Вторичные конечные точки (11)

• PK of ARO-INHBE: Maximum observed Plasma Concentration (Cmax) [Срок оценки: 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) [Срок оценки: 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 24 Hours (AUC0-24) [Срок оценки: 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) [Срок оценки: 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-∞) [Срок оценки: 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) [Срок оценки: 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) [Срок оценки: 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) [Срок оценки: 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) [Срок оценки: 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) [Срок оценки: 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) [Срок оценки: 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]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Четверное слепое

Основная цель

Лечение

Центры проведения

Новая Зеландия · 5 центров

• Research Site 1 — Grafton
• Research Site 5 — Auckland
• Research Site 3 — Auckland
• Research Site 2 — Christchurch
• Research Site 4 — Hamilton

Идентификаторы

NCT: NCT06700538 · AROINHBE-1001

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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