Phase 1 Study of PK and Safety of HM15912 (Sonefpeglutide) in Subjects With Normal and Severe Kidney Function

An Open-label, Single-dose Study to Evaluate the Pharmacokinetics, Safety and Tolerability of HM15912(Sonefpeglutide) in Subjects With Renal Impairment and Matched Control Subjects With Normal Renal Function

An Open-label, Single-dose Study to Evaluate the Pharmacokinetics, Safety and Tolerability of HM15912 in Subjects with Renal Impairment and Matched Control Subjects with Normal Renal Function

Study Overview

• Status: Completed
• Conditions: Renal Impairment
• Intervention / Treatment: Drug: HM15912

Detailed Description

A single-dose, open-label, Phase 1 study (HM-GLP2-102) was conducted to evaluate the impact of renal impairment (RI) on the pharmacokinetics (PK) of HM15912. This study aimed to assess the safety and PK profile of HM15912 at a minimum effective dose of 0.5 mg/kg, which was determined based on findings from a previous clinical study (HM-GLP2-101).

The study was initially designed to be conducted in two parts.

Part 1: An open-label, single-dose, parallel-group study to investigate the effect of RI on the PK, safety, and tolerability of HM15912 in subjects with severe RI and subjects with normal renal function as a control group.

Part 2 (if applicable): An open-label, single-dose, parallel-group study to investigate the effect of RI on the PK, safety, and tolerability of HM15912 in subjects with moderate and mild RI.

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Tustin, California, United States, 92780
      • Orange County Research Center
  • Florida
    • Miami, Florida, United States, 33014
      • Clinical Pharmacology of Miami
    • Miami Lakes, Florida, United States, 33014
      • Panax Clinical Research
  • Tennessee
    • Knoxville, Tennessee, United States, 37920
      • AMR Knoxville

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

All Subjects

• Subjects voluntarily agreed to participate in this study and sign an institutional review board (IRB)-approved informed consent form prior to performing any of the S1 procedures.
• Males and females ≥ 18 and ≤ 80 years of age at S1.
• Body mass index (BMI) of ≥ 17.5 to ≤ 40.0 kg/m^2.

Subjects with Normal Renal Function

• No clinically relevant abnormalities identified by detailed medical history, full physical examination, including blood pressure (BP) and heart rate (HR) measurements, 12-lead ECG, and clinical laboratory tests.
• Normal renal function (eGFR ≥ 90 mL/min/1.73m^2) at screening based on the chronic kidney disease-epidemiology collaboration (CKD-EPI) equation.
• Demographically comparable to the group of subjects with impaired renal function.

Subjects with Impaired Renal Function

• Met the following eGFR criteria during the screening period based on the CKD-EPI equation:

  1. Severe renal impairment: eGFR < 30 mL/min/1.73m^2, but not requiring hemodialysis.
  2. Moderate renal impairment: 30 mL/min/1.73m^2 ≤ eGFR < 60 mL/min/1.73m^2
  3. Mild renal impairment: 60 mL/min/1.73m^2 ≤ eGFR < 90 mL/min/1.73m^2

Exclusion Criteria:

All Subjects:

• Renal transplant recipients or subjects requiring hemodialysis and peritoneal dialysis.
• Subject with a history or presence of any psychiatric disorder that, in the opinion of the Investigator, might have confounded the results of the study or posed additional risk in administering the IP to the subject.
• Had participated in an interventional clinical trial (investigational or marketed product) within 1 month of screening or 5 half-lives of the drug under investigation (whichever came first), or planned to participate in another clinical trial.
• Subject with a history of any SAEs, hypersensitivity reactions, or intolerance to IP components.

Additional Exclusion Criteria for Subjects with Normal Renal Function

• Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal (GI), cardiovascular, hepatic, psychiatric, neurological, or allergic disease (including drug allergies, but excluding treatment not required, asymptomatic, seasonal allergies at the time of dosing).
• Subject who had a mean BP ≥ 140 mmHg (systolic) or ≥ 90 mmHg (diastolic). After at least 5 minutes of supine rest, measurements were taken 2 consecutive times at least 2 minutes apart. If the mean of the 2 BP was ≥ 140mmHg (systolic) or ≥ 90 mmHg (diastolic), the BP should have been repeated 1 more time and the average of the 3 BP values should have been used to determine the subject's eligibility.
• Subject who had a baseline corrected QT using the Fridericia correction formula (QTcF) > 450 msec in males or QTcF > 470 msec in females.

Additional Exclusion Criteria for Subjects with Impaired Renal Function

• Subject with clinically significant active diseases that may have affected the safety of the subject or that may have affected the PK of HM15912 (including drug allergies, but excluding treatment not required, asymptomatic, seasonal allergies at time of dosing). Subjects with any significant hepatic, cardiac, or pulmonary disease or subjects who were clinically nephrotic. Hypertension, diabetes mellitus, hyperparathyroidism, ischemic heart disease, etc. were not causes for exclusion as long as the subject was medically stable and any drugs that were administered for these conditions were not expected to interfere with the PK of HM15912.
• Subject who had a mean BP ≥ 180 mm Hg (systolic) or ≥ 120 mm Hg (diastolic). After at least 5 minutes of supine rest, measurements were taken 2 consecutive times at least 2 minutes apart. If the mean of the 2 BP was ≥ 180 mm Hg (systolic) or ≥ 120 mmHg (diastolic), the BP should have been repeated 1 more time and the average of the 3 BP values should have been used to determine the subject's eligibility.
• Subject who had a baseline QTcF > 480 msec.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Severe renal impairment; Subjects with eGFR < 30mL/min/1.73m^2, but not requiring hemodialysis	Drug: HM15912; Singe subcutaneous administration of HM15912 0.5 mg/kg; Other Names: Sonefpeglutide
Experimental: Normal renal function; Subjects with eGFR ≥ 90 mL/min/1.73m^2	Drug: HM15912; Singe subcutaneous administration of HM15912 0.5 mg/kg; Other Names: Sonefpeglutide
Experimental: Moderate renal impairment; Subjects with 30 mL/min/1.73m^2 ≤ eGFR < 60 mL/min/1.73m^2	Drug: HM15912; Singe subcutaneous administration of HM15912 0.5 mg/kg; Other Names: Sonefpeglutide
Experimental: Mild renal impairment; Subjects with 60 mL/min/1.73m^2 ≤ eGFR < 90 mL/min/1.73m^2	Drug: HM15912; Singe subcutaneous administration of HM15912 0.5 mg/kg; Other Names: Sonefpeglutide

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Serum Concentration (Cmax) of HM15912	Pharmacokinetic (PK) samples were collected for measurement of serum concentrations of HM15912 and analyzed using a fully validated method.	Day 1 to 29 (Total duration: 29 days)
Area Under the Concentration-time Curve From Extrapolated to Infinity (AUC 0-infinity) of HM15912	PK samples were collected for measurement of serum concentrations of HM15912 and analyzed using a fully validated method.	Day 1 to 29 (Total duration: 29 days)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Summary of Treatment-emergent Adverse Events (TEAEs)	The number and percentages of subjects with TEAEs were to be summarized by cohort. A TEAE was defined as any AE that began, or worsened in severity, on or after the date of the first IP administration until the last follow-up visit.	Day 1 up to Day 29

Collaborators and Investigators

• Sponsor: Hanmi Pharmaceutical Company Limited

Study record dates

Study Major Dates

• Study Start (Actual): December 2, 2022
• Primary Completion (Actual): August 15, 2023
• Study Completion (Actual): August 15, 2023

Study Registration Dates

• First Submitted: November 8, 2022
• First Submitted That Met QC Criteria: January 25, 2023
• First Posted (Actual): February 3, 2023

Study Record Updates

• Last Update Posted (Actual): April 4, 2025
• Last Update Submitted That Met QC Criteria: March 20, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Renal Insufficiency
• Other Study ID Numbers: HM-GLP2-102

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No