Obese, Obesity
Conditions
Keywords
Obese, Obesity
Brief summary
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.
Detailed description
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.
Interventions
DRUGHM17321
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.
DRUGPlacebo 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.
Sponsors
Hanmi Pharmaceutical Company Limited
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Masking description
The study will be conducted in a double-blind manner. Participants, investigators, and outcome assessors will remain blinded to treatment assignments. Only designated unblinded personnel (e.g., pharmacist or site staff responsible for drug preparation) will have access to treatment allocation information, and they will not be involved in any other study assessments.
Intervention model description
Participants in each cohort will be randomly assigned to receive either HM17321 or placebo. Dose levels will be escalated sequentially in separate cohorts after review of safety data.
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
* 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.
Exclusion criteria
* 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Treatment-Emergent Adverse Events (TEAEs) Following Single and Multiple Subcutaneous Doses of HM17321 | Up to Day 29 (Part A); Up to Day 113 (Part B) | Number, type, and severity of treatment-emergent adverse events, including changes in vital signs, electrocardiograms, clinical laboratory tests, and immunogenicity assessments following administration of HM17321 or placebo |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Peak Plasma Concentration (Cmax) of HM17321 | Up to Day 29 (Part A); Up to Day 113 (Part B) | Maximum observed plasma concentration of HM17321 following single and multiple subcutaneous doses. |
| Time to Maximum Plasma Concentration (Tmax) of HM17321 | Up to Day 29 (Part A); Up to Day 113 (Part B) | Time to reach maximum observed plasma concentration following single and multiple subcutaneous doses. |
| Area Under Plasma Concentration-Time Curve (AUC) of HM17321 | Up to Day 29 (Part A); Up to Day 113 (Part B) | Area under the plasma concentration-time curve from time zero to the last measurable concentration following single and multiple subcutaneous doses. |
Countries
United States
Contacts
CONTACTJimin Han
Outcome results
None listed