Comparison of HBV Reactivation Between Patients With High HBV-DNA and Low HBV-DNA Loads Undergoing ICI and Concurrent Antiviral Prophylaxis: a Prospective Observational Study

August 1, 2023 updated by: Shi Ming, Sun Yat-sen University

Comparison of Hepatitis B Virus Reactivation Between Patients With High HBV-DNA and Low HBV-DNA Loads Undergoing Immune Checkpoint Inhibitor and Concurrent Antiviral Prophylaxis: a Prospective Observational Study

Immune checkpoint inhibitor (ICI), including programmed cell death protein-1 (PD-1) inhibitor or programmed cell death-Ligand 1 (PD-L1) inhibitor , is recommended to treat advanced hepatocellular carcinoma (HCC). However, the safety of ICI in patients with a high HBV-DNA load is unknown because of the potential risk of hepatitis B virus (HBV) reactivation. This study was to compare the HBV reactivation between patients with low HBV-DNA loads and high HBV-DNA loads undergoing antiviral prophylaxis and ICI.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Observational

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
800

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • China
      • Zhongshan, China
        • Recruiting
        • ZhongShan People 's Hospital
        • Contact:
    • Guangdong
      • Guangzhou, Guangdong, China, 510060
        • Recruiting
        • Cancer Center Sun Yat-sen University
        • Contact:
      • Guangzhou, Guangdong, China, 510620
        • Recruiting
        • Guangzhou Twelfth People 's Hospital
        • Contact:
        • Principal Investigator:
          • Jinghua Chen, MD
      • Kaiping, Guangdong, China, 529300
        • Recruiting
        • Kaiping Central Hospital
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

N/A

Sampling Method

Non-Probability Sample

Study Population

Eligible patients were divided into low HBV-DNA group (low group, ≤500 IU/ml) and high HBV-DNA group (high group, >500 IU/ml) according to baseline HBV-DNA level. Baseline HBV-DNA was the HBV-DNA level within 2 weeks prior to initial ICI therapy. For patients who had prior experience with antiviral therapy, the antiviral therapy would be continued. For patients who did not have prior experience with antiviral therapy, antiviral therapy would be administered after patients was confirmed with positive HBsAg or positive HBV-DNA level. Prior use of antiviral therapy was defined that patients have taken antiviral therapy for a period of time before they received ICI therapy. Antiviral prophylaxis was defined as anti-HBV treatment administered before and during ICI therapy. Antiviral treatment was continued even though ICI therapy was terminated.

Description

Inclusion Criteria:

  • The diagnosis of HCC was based on the diagnostic criteria for HCC used by the European Association for the Study of the Liver (EASL)
  • Seropositive for hepatitis B surface antigen (HBsAg)
  • Received concurrent antiviral prophylaxis and at least one cycle of ICI treatment. Prior use of antiviral therapy was allowed
  • Adherence to antiviral therapy
  • A life expectancy of 3 months or more
  • An Eastern Cooperative Oncology Group performance status (ECOG PS) of 0-2

Exclusion Criteria:

  • other positive viral markers, including IgM antibodies to hepatitis A virus, the hepatitis C virus viral load, IgG antibodies to hepatitis D virus, IgM antibodies to hepatitis E virus
  • Antibodies to human immunodeficiency virus,
  • A lack of HBV DNA and liver function testing before the first immunotherapy and during the follow-up period.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort

Group / Cohort

A group or subgroup of participants in an observational study that is assessed for biomedical or health outcomes.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
high HBV-DNA group
patients with HBV-DNA >500 IU/ml
Drug: ICI
Patients received ICI, including PD-1 inhibitor (pembrolizumab, toripalimab, nivolumab, sintilimab, camrelizumab) or PD-L1 inhibitor (atezolizumab)
Drug: Antiviral Prophylaxis
Patient received concurrent antiviral prophylaxis, such as tenofovir, entecavir
low HBV-DNA group
patients with HBV-DNA≤500 IU/ml
Drug: ICI
Patients received ICI, including PD-1 inhibitor (pembrolizumab, toripalimab, nivolumab, sintilimab, camrelizumab) or PD-L1 inhibitor (atezolizumab)
Drug: Antiviral Prophylaxis
Patient received concurrent antiviral prophylaxis, such as tenofovir, entecavir

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
HBV Reactivation rate
Time Frame: 2 months
HBV Reactivation rate was defined as one of the following according to the American Association for the Study of Liver Diseases (AASLD) 2018 hepatitis B guidelines: (i) a ≥2 log (100-fold) increase in HBV DNA compared to the baseline level, (ii) HBV DNA ≥3 log (1,000) IU/mL in a patient with previously undetectable level (since HBV DNA levels fluctuate)
2 months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
overall survival
Time Frame: 12 months
12 months
HBV-associated hepatitis
Time Frame: 2 months
HBV-associated hepatitis was defined as HBV Reactivation plus an ALT increase to ≥3 times the baseline level and >100 U/L according to the AASLD 2018 Hepatitis B Guidance
2 months
PD-1 inhibitor disruption due to hepatitis
Time Frame: 2 months
PD-1 inhibitor disruption due to hepatitis was defined as either premature termination or a delay of at least 7 days between PD-1 inhibitor cycles because of hepatitis.
2 months
adverse event
Time Frame: 30 Days after ICI
30 Days after ICI

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Sun Yat-sen University

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Guangzhou No.12 People's Hospital
Kaiping Central Hospital
ZhongShan People 's Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
December 25, 2020

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 31, 2023

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 31, 2023

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
December 17, 2020

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 22, 2020

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
December 23, 2020

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
August 2, 2023

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 1, 2023

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
August 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • SH003

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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