Phase III Study of HRS-5635 in Nucleos(t)Ide Analogue-suppressed HBeAg-negative Patients With Chronic Hepatitis B

A Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel-designed Phase III Clinical Study to Evaluate the Efficacy and Safety of HRS-5635 Injection in Nucleos(t)Ide Analogue-suppressed HBeAg-negative Patients With Chronic Hepatitis B

This study is intended to confirm the efficacy, safety, pharmacokinetic (PK) profile, and immunogenicity of HRS-5635 injection as compared to the placebo arm in nucleos(t)ide analogue-suppressed HBeAg-negative patients with chronic hepatitis B. The total duration of the study, including screening (up to 4 weeks), the double-blind treatment stage (60 weeks) and the off-treatment follow-up (24 weeks), is up to approximately 88 weeks at maximum for each participant.

Study Overview

• Status: Not yet recruiting
• Conditions: Nucleos(t)Ide Analogue-suppressed HBeAg-negative Patients With Chronic Hepatitis B
• Intervention / Treatment: Drug: HRS-5635 Injection; Drug: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 540
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Guangchao Dong; Phone Number: 0518-82342973; Email: guangchao.dong.gd1@hengrui.com

Study Locations

• China
  • Guangzhou
    • Guangzhou, Guangzhou, China, 510515
      • Nanfang Hospital, Southern Medical University
      • Principal Investigator: Jinlin Hou

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Chronic hepatitis B defined as HBV infection documented for at least 6 months prior to screening;
2. Virologically suppressed on nucleoside or nucleotide analogues treatment with HBV DNA below the lower limit of quantitation;
3. HBeAg negative at screening;
4. On commercially available NAs monotherapy for at least 24 weeks before randomization, and the dosing regimen remained unchanged for at least 4 weeks before randomization;
5. Need to take effective contraceptive measures；
6. Volunteer to sign an informed consent.

Exclusion Criteria:

1. History of cirrhosis or clinical evidence of hepatic decompensation, confirmed or suspected liver cancer, with other liver diseases other than chronic hepatitis B that may affect the evaluation of the study;
2. With autoimmune disease;
3. History of solid organ transplantation or hematopoietic stem cell transplantation;
4. Clinically significant and unstable or uncontrolled severe cardiovascular and cerebrovascular diseases;
5. Malignant tumors were diagnosed within 5 years prior to randomization；
6. Major trauma or major surgery within the 12 weeks prior to randomization, or surgical plans or other treatment during the study period which the investigators determined may influence the evaluation of the study results;
7. Laboratory tests during the screening period were obviously abnormal;
8. Prolonged ECG QTcF or other clinically significant abnormal results that may pose a significant safety risk to the subject during the screening period;
9. History of drug use, alcohol or drug abuse in the 12 months prior to randomization;
10. Participated in clinical study of other drugs (received experimental drugs);
11. Pregnant or nursing women;
12. Allergic to a drug ingredient or component;
13. Other reasons for ineligibility as judged by the investigators.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; Placebo, administered by subcutaneous injection.
Experimental: HRS-5635 Injection	Drug: HRS-5635 Injection; HRS-5635 Injection, administered by subcutaneous injection;

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Percentage of participants with sustained HBV DNA suppression and HBsAg loss within 24 weeks after discontinuation of all HBV therapy	24 weeks after discontinuation of all CHB treatment

Secondary Outcome Measures

Outcome Measure	Time Frame
Percentage of participants with sustained HBV DNA suppression and HBsAg < 100 IU/mL	Pre-specified time points up to 24 weeks after discontinuation of all CHB treatment
Percentage of participants with sustained HBV DNA suppression and HBsAg < 10 IU/mL	Pre-specified time points up to 24 weeks after discontinuation of all CHB treatment
Percentage of participants with sustained HBV DNA suppression	Pre-specified time points up to 24 weeks after discontinuation of all CHB treatment
Percentage of participants with HBsAg < 100 IU/mL	Pre-specified time points up to 24 weeks after discontinuation of all CHB treatment
Percentage of participants with HBsAg < 10 IU/mL	Pre-specified time points up to 24 weeks after discontinuation of all CHB treatment
Changes from baseline in mean log10 HBsAg levels	Pre-specified time points up to 24 weeks after discontinuation of all CHB treatment
Percentage of participants with HBsAg loss	Pre-specified time points up to 24 weeks after discontinuation of all CHB treatment
Percentage of participants with HBsAg seroconversion	Pre-specified time points up to 24 weeks after discontinuation of all CHB treatment
Percentage of participants with HBeAb positive	Pre-specified time points up to 24 weeks after discontinuation of all CHB treatment
Percentage of participants with virologic breakthrough	Pre-specified time points up to 24 weeks after discontinuation of all CHB treatment
Percentage of participants with drug resistance	Pre-specified time points up to 24 weeks after discontinuation of all CHB treatment
Percentage of participants who meet the criteria for stopping nucleos(t)ide analogue	Week 48、Week 60 and Week 84
Relapse rate after discontinuation of NAs therapy	Up to 24 weeks after discontinuation of NAs treatment
Treatment-emergent adverse events	Up to 24 weeks after discontinuation of NAs treatment
Percentage of participants with detectable anti-drug antibodies	Pre-specified time points up to 24 weeks after discontinuation of all CHB treatment

Collaborators and Investigators

• Sponsor: Fujian Shengdi Pharmaceutical Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): June 1, 2028
• Study Completion (Estimated): June 1, 2028

Study Registration Dates

• First Submitted: May 19, 2026
• First Submitted That Met QC Criteria: May 19, 2026
• First Posted (Actual): May 26, 2026

Study Record Updates

• Last Update Posted (Actual): May 26, 2026
• Last Update Submitted That Met QC Criteria: May 19, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Other Study ID Numbers: HRS-5635-301

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