Development and Validation of Models to Predict Functional Cure in Patients With CHB After Peg-IFN Based Therapy

Development and Validation of Logistic Regression Models to Predict Durable Functional Cure in Patients With Chronic Hepatitis B After Pegylated Interferon Alpha-2b Based Therapy

Hepatitis B virus (HBV) infection is prevalent across the world. Functional cure is the optimal endpoint of antiviral therapy for chronic hepatitis B virus (HBV) infection. Currently available anti-HBV therapy includes nucleoside analogs (NAs) and peginterferon-α (Peg-IFNα). Combination of Peg-IFNα and NAs, each with different mechanisms of action, is an attractive approach for treating chronic HBV infection. In this study, we aim to establish logistic regression models to predict durable functional cure in patients with CHB treated by combination of Peg-IFNα and NAs, which might be useful for clinical physicians to make personalized treatment decisions. These models will be constructed using baseline routine clinical laboratory indicators with high diagnostic accuracy. These models might be widely applicable to almost all medical institutions and will effectively promote the application of Peg IFN α plus NAs therapy in clinical work. The findings in this study might greatly improve the functional cure rate of CHB and reducing the incidence rate and mortality of HBV related end-stage liver diseases.

Study Overview

• Status: Recruiting
• Conditions: Hepatitis B, Chronic
• Intervention / Treatment: Drug: Peginterferon-α; Nucleoside analogs

• Study Type: Observational
• Enrollment (Estimated): 1000

Contacts and Locations

• Study Contact: Name: Shuai Gao, MD;PhD; Phone Number: +86-18560088213; Email: qilugaoshuai@sdu.edu.cn

Study Locations

• China
  • Shandong
    • Jinan, Shandong, China, 250012
      • Recruiting
      • Qilu Hospital of Shandong University
      • Contact: Shuai Gao, MD;PhD; Phone Number: +86-18560088213; Email: qilugaoshuai@sdu.edu.cn

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Probability Sample

Study Population

The participants were retrospectively enrolled from more than 10 hospitals in China.

Description

Inclusion Criteria:

• 1. Sign an informed consent form;
• 2. HBsAg (+), and the course of the disease exceeds six months;
• 3. Age range from 16 to 70 years old;
• 4. Female participants of childbearing age who had a negative pregnancy test before the trial and were able to take effective contraceptive measures;
• 5. During the treatment period, within six months after the end of treatment, the patients agrees to use contraception

Exclusion Criteria:

• 1. Patients with a known history of allergy to Peg-IFNα and NAs;
• 2. Co-infection with other virus such as HAV, HCV, HDV, HEV, HIV, etc;
• 3. Patients with liver cirrhosis or a Child Pugh score of 7 or above;
• 4. History or evidence of liver disease caused by other factors (such as autoimmune liver disease, alcoholic liver disease, non-alcoholic fatty liver disease, drug-induced hepatitis, hepatolenticular degeneration, etc.);
• 5. Pregnant or lactating women; Have a history of alcohol or drug abuse within the year prior to the trial enrollment screening;
• 6. Neutrophil count<1.5 × 109/L or hemoglobin<100g/L or platelet count<80 × 109/L; During the trial enrollment screening, serum creatinine was higher than the upper normal limit;
• 7. A history of severe diseases in important organs and tissues such as the heart, brain, kidneys, retina, and muscles;
• 8. Having a history of mental illness or a family history of mental illness, or a Hamilton Depression Scale score greater than 7 points;
• 9. History of endocrine system or autoimmune diseases, such as thyroid disease, diabetes, systemic lupus erythematosus, sarcoidosis, autoimmune thrombocytopenic purpura, etc;
• 10. History of malignant tumors;
• 11. During the trial enrollment screening, suspicious liver malignant tumors were detected by ultrasound, or AFP was greater than 100ng/mL or AFP cannot remain stable within 3 months prior to the experiment;
• 12. Has a history of important organ transplantation;
• 13. Other diseases that researchers believe are not suitable for inclusion.

Study Plan

How is the study designed?

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
"de novo" strategy-HBeAg positive; HBeAg positive patients treated with simultaneous administration of NA and Peg-IFN	Drug: Peginterferon-α; Nucleoside analogs; Patients with chronic hepatitis B were treated with the combination of peginterferon-α and nucleoside analogs
"de novo" strategy-HBeAg negative; HBeAg positive patients treated with simultaneous administration of NA and Peg-IFN	Drug: Peginterferon-α; Nucleoside analogs; Patients with chronic hepatitis B were treated with the combination of peginterferon-α and nucleoside analogs
"add-on" strategy-HBeAg positive; HBeAg positive patients treated with NA followed by addition of Peg-IFN.	Drug: Peginterferon-α; Nucleoside analogs; Patients with chronic hepatitis B were treated with the combination of peginterferon-α and nucleoside analogs
"add-on" strategy-HBeAg negative; HBeAg negative patients treated with NA followed by addition of Peg-IFN.	Drug: Peginterferon-α; Nucleoside analogs; Patients with chronic hepatitis B were treated with the combination of peginterferon-α and nucleoside analogs

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Functional cure of chronic hepatit B	The level of hepatitis B surface antigen (HBsAg) is below 0.05IU/ml.	48 weeks

Collaborators and Investigators

• Sponsor: Qilu Hospital of Shandong University

Study record dates

Study Major Dates

• Study Start (Actual): January 6, 2024
• Primary Completion (Estimated): July 31, 2024
• Study Completion (Estimated): December 31, 2025

Study Registration Dates

• First Submitted: December 25, 2023
• First Submitted That Met QC Criteria: December 25, 2023
• First Posted (Actual): January 9, 2024

Study Record Updates

• Last Update Posted (Actual): February 7, 2024
• Last Update Submitted That Met QC Criteria: February 5, 2024
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Disease Attributes; Liver Diseases; Hepatitis, Viral, Human; Hepadnaviridae Infections; DNA Virus Infections; Hepatitis, Chronic; Chronic Disease; Hepatitis B; Hepatitis; Hepatitis B, Chronic
• Other Study ID Numbers: KYLL-2023(ZM)-726

Drug and device information, study documents

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