A Study of HRS-9057 in Patients With Heart Failure and Volume Overload

An Open Label, Tolvaptan-controlled Phase I Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of Multiple Ascending Dose of HRS-9057 in Heart Failure With Volume Overload

The study is an open-label, Tolvaptan-controlled Phase I study to evaluate the safety, tolerability, PK/PD profile and efficacy of HRS-9057 in the treatment of heart failure with volume overload. A total of 24 subjects who experience volume overload due to heart failure despite diuretic treatment will be enrolled in the study and receive HRS-9057 injection or Tolvaptan tablets.

Study Overview

• Status: Completed
• Conditions: Heart Failure With Volume Overload
• Intervention / Treatment: Drug: HRS-9057; Drug: HRS-9057; Drug: Tolvaptan

• Study Type: Interventional
• Enrollment (Actual): 25
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510285
      • The second Affiliated Hospital of Guangzhou Medical University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Male or female, age 18-75 years at the time of signing informed consent.
2. Diagnosed as chronic heart failure at least 1 month prior to screening.
3. Patients with CHF in whom lower limb edema, pulmonary congestion, jugular venous distension or hepatomegaly due to volume overload is present despite diuretics treatment.

Exclusion Criteria:

1. Medical history of myocardial infarction, acute decompensated heart failure, stroke, or transient ischemic attack within 30 days prior to or at screening;
2. Hypovolemic hyponatremia.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment group A: HRS-9057/ Tolvaptan	Drug: HRS-9057; HRS-9057 injection dose 1; Drug: HRS-9057; HRS-9057 injection dose 2; Drug: Tolvaptan; Tolvaptan tablets
Experimental: Treatment group B: HRS-9057/ Tolvaptan	Drug: HRS-9057; HRS-9057 injection dose 1; Drug: HRS-9057; HRS-9057 injection dose 2; Drug: Tolvaptan; Tolvaptan tablets

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The incidence and severity of any adverse events (AEs)	baseline up to Day 14

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tmax for HRS-9057		Predose on Day 1 through Day 6
Cmax for HRS-9057		Predose on Day 1 through Day 6
Daily urine volume		Predose on Day 1 through Day 7
Daily fluid balance	Daily fluid balance is calculated by subtracting daily urine volume from daily fluid intake.	Predose on Day 1 through Day 7
Serum sodium concentration		Predose on Day 1 through Day 6
Serum osmolality		Predose on Day 1 through Day 6
Urine osmolality		Predose on Day 1 through Day 7
Body weight		baseline to Day 8
Lower limb edema change from baseline	The severity of edema in the subject's tibial border or dorsum of the foot will be assessed in the sitting position using a 4-point scale (0-absent, 1-mild, 2-moderate and 3-severe) by the investigator. The percentage of subjects in whom the lower limb edema was improved or worsening at Day 8 will be evaluated.	baseline to Day 8
Jugular venous distension change from baseline	Whether or not the subject has jugular venous distension will be documented. If distension is observed, the vertical height (in centimeters) from the sternal angle to the highest point of pulsation of the internal jugular vein will be documented and the change from baseline to Day 8 will be evaluated.	baseline to Day 8
Pulmonary congestion change from baseline	The investigator will perform chest X-ray at baseline and Day 8 to assess the severity of pulmonary congestion using a 4-point scale (0-absent, 1-mild, 2-moderate and 3-severe). The percentage of subjects in whom pulmonary congestion was improved or worsening at Day 8 will be evaluated.	baseline to Day 8
New York Heart Association (NYHA) classification change from baseline		baseline to Day 8

Collaborators and Investigators

• Sponsor: Fujian Shengdi Pharmaceutical Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): August 16, 2024
• Primary Completion (Actual): October 29, 2025
• Study Completion (Actual): October 29, 2025

Study Registration Dates

• First Submitted: June 28, 2024
• First Submitted That Met QC Criteria: July 16, 2024
• First Posted (Actual): July 18, 2024

Study Record Updates

• Last Update Posted (Actual): November 17, 2025
• Last Update Submitted That Met QC Criteria: November 14, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Failure; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Benzazepines; Tolvaptan
• Other Study ID Numbers: HRS-9057-103

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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