A Single and Multiple Ascending Dose Study of HM17321 in Healthy and Obese Participants

Официальное название

A Randomized, Double-Blind, Placebo-Controlled, Single and Multiple Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of HM17321 in Healthy and Obese Participants

Обзор

This is a Phase 1 study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of HM17321 after single and multiple ascending doses in healthy and obese participants.

Подробное описание

This is a Phase 1, randomized, double-blind, placebo-controlled, single and multiple ascending dose study designed to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of HM17321, a urocortine 2 (UCN2) analog, administered by subcutaneous (SC) injection in healthy and obese participants.

The study consists of two parts: Part A (Single Ascending Dose) and Part B (Multiple Ascending Dose), with approximately 90 participants to be enrolled in total.

In Part A, approximately 40 healthy participants with a body mass index (BMI) of ≥20 kg/m² and ≤27 kg/m² will be enrolled across 5 sequential dose cohorts. Each cohort will consist of approximately 8 participants randomized in a 6:2 ratio to receive a single SC dose of HM17321 or placebo. A sentinel dosing strategy will be applied in each cohort to ensure participant safety, with initial safety data reviewed prior to dosing the remainder of the cohort. Dose escalation decisions will be made by a Safety Review Committee (SRC) based on safety, tolerability, and available PK data. Part A will include a screening period of up to 28 days, a 5-day inpatient stay with single SC dosing, and an outpatient follow-up period through Day 29, with an overall study duration of approximately 8 weeks per participant.

In Part B, approximately 50 healthy obese participants with a BMI of ≥30 kg/m² and ≤45 kg/m² will be enrolled across 5 sequential dose cohorts. Each cohort will consist of approximately 10 participants randomized in an 8:2 ratio to receive once-weekly SC doses of HM17321 or placebo over a 12-week treatment period. Dose escalation will be guided by SRC review of safety, tolerability, and PK data at predefined time points. Part B will include a screening period of up to 45 days, a 12-week treatment period with once-weekly SC dosing, and a 4-week follow-up period through Day 113, with an overall study duration of approximately 22 weeks per participant.

Вмешательства

• Препарат HM17321
  Participants will receive a single or multiple subcutaneous injections of HM17321 at the assigned dose level. HM17321 is provided as a sterile solution in prefilled syringes.
• Препарат Placebo of HM17321
  Participants will receive a single or multiple subcutaneous injections of a matching placebo solution in prefilled syringes. The placebo does not contain any active ingredients.

Первичные конечные точки

• Incidence of Treatment-Emergent Adverse Events (TEAEs) Following Single and Multiple Subcutaneous Doses of HM17321 [Срок оценки: Up to Day 29 (Part A); Up to Day 113 (Part B)]

Вторичные конечные точки (3)

• Peak Plasma Concentration (Cmax) of HM17321 [Срок оценки: Up to Day 29 (Part A); Up to Day 113 (Part B)]
• Time to Maximum Plasma Concentration (Tmax) of HM17321 [Срок оценки: Up to Day 29 (Part A); Up to Day 113 (Part B)]
• Area Under Plasma Concentration-Time Curve (AUC) of HM17321 [Срок оценки: Up to Day 29 (Part A); Up to Day 113 (Part B)]

Критерии участия

Критерии включения

• Adults aged 18-65 years.
• Part A: Healthy participants with BMI ≥20 kg/m² and ≤27 kg/m² at screening.
• Part B: Healthy obese participants with BMI ≥30 kg/m² and ≤45 kg/m² at screening.
• Stable body weight (<5% change) in the past 3 months.
• Able and willing to provide written informed consent.
• Male participants must use contraception or remain abstinent from women of childbearing potential.
• Female participants must not be pregnant or breastfeeding and use highly effective contraception if of childbearing potential.

Критерии исключения

• History of any bariatric procedure.
• Uncontrolled thyroid disease (TSH >6.0 or <0.4 mIU/L).
• Abnormal liver function or clinically significant liver disease

• Part A: ALT or AST ≥ ULN, or total bilirubin ≥ ULN
• Part B: ALT or AST >2× ULN, or total bilirubin >1.5× ULN
• Abnormal pancreatic function

• Part A: amylase or lipase ≥ ULN
• Part B: amylase or lipase >3× ULN
• Clinically significant cardiovascular disorders (e.g., myocardial infarction, congestive heart failure, long QT syndrome).
• Abnormal renal function (eGFR <60 mL/min/1.73 m²).
• Positive test for hepatitis B, hepatitis C, or HIV at screening.
• Women who are pregnant, planning to become pregnant, or breastfeeding.
• History of drug or alcohol abuse within defined timeframes (e.g., alcohol >14 standard units/week in past year, or positive drug screen).
• Use of any investigational product within 30 days or 5 half-lives (whichever is longer) prior to screening.
• Additional Exclusion Criteria for Part B

• HbA1c ≥6.5% or a history of diabetes mellitus (type 1 or type 2).
• Obesity induced by other endocrine disorders (e.g., Cushing syndrome).
• Use of weight control treatments (e.g., GLP-1 receptor agonists or other anti-obesity medications) and antihypertensive medications within 3 months prior to screening.
• Use of any lipid-lowering medications, unless on a stable dose for at least 3 months prior to screening.

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

Здоровые добровольцы: Да

Дизайн исследования

Распределение

Рандомизированное

Модель

Последовательный дизайн

Маскирование

Тройное слепое

Основная цель

Лечение

Центры проведения

США · 1 центр

• Medpace Clinical Pharmacology Unit — Cincinnati

Идентификаторы

NCT: NCT07219589 · HM-UCN2-101

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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