Towards a Functional Cure for HBV - The COMMIT Cohort Study (COMMIT)

December 19, 2023 updated by: Joe Sasadeusz, University of Melbourne

Towards a Functional Cure for HBV: Exploiting Lessons From HIV-HBV Co-infection: The COMMIT Cohort Study

Hepatitis B virus (HBV) infection can be treated, but therapy is usually lifelong and has side effects, so a cure for HBV is a critical endpoint. This study examines the key steps to HBV cure in the setting of HIV-HBV co-infection, where rates of development of antibodies against HBV after starting HBV treatment are higher than in people with HBV alone starting treatment. In Asia both HBV and HIV are common so this provides a unique opportunity to study HBV. We will investigate how an effective immune response against the two main HBV proteins is developed. If we can understand how the immune response works against HBV, this could be used to develop new therapies towards a cure for HBV

Study Overview

Status

Active, not recruiting

Conditions

Detailed Description

A) Aims and Objectives. Effective antiviral treatments of HBV are available, but treatment is lifelong in most so comes at considerable cost and with some toxicity. An effective therapeutic strategy to achieve a cure for HBV remains an unmet need. This project examines the key steps to HBV cure in the setting of HIV-HBV co-infection. Seroconversion is key to the cure. Seroconversion is the process where detectable antibody (specific protective protein produced by the immune system) against virus proteins (antigens) are developed in the blood. This proposed Asian HIV-HBV co-infection cohort (where treatment initiation is later and hence at lower cluster of differentiation 4 (CD4) counts) will provide a unique opportunity to test our hypothesis that following initiation of antiviral therapy, HB surface and "e" antigen loss is more frequent (i) early in treatment and (ii) with lower CD4 cell counts, and that predictors of losing HB surface and 'e" antigen (Ag) and gaining antibody (Ab) against them are directly associated with B-cell functions.

B) Key Questions. Primary objective: to determine the rates & clinical determinants of HBsAg and HBeAg loss and seroconversion in HIV-HBV co-infected patients commencing HBV-active antiretroviral (ART). We will test the hypotheses that: (i) seroconversion occurs predominantly in the early phase of treatment (≤12 months) with HBV active ART and (ii) seroconversion is more frequent in HIV-HBV co-infected individuals commencing treatment with lower CD4+ T cell counts (≤100 cells/mm3) compared to those with higher counts (>100 cells/mm3).

Secondary objectives: (i) identify predictive biomarkers of HBsAg loss/seroconversion and (ii) examine predictors of HBeAg loss/seroconversion in this setting

C) Research Design. This is a large prospective, observational cohort study of treatment-naïve HIV-HBV co-infected patients (n=150). Clinical sites are - (1) HIV-Netherland-Australia-Thailand (HIV-NAT)/Thai Red Cross AIDS Research Centre, Bangkok, Thailand; (2) Y.R. Gaitonde Centre for AIDS Research and Education (YRG CARE), Chennai, India; and (3) Clinical Investigation Centre (CIC), University of Malaya, Infectious Diseases Directorate, Kuala Lumpur, Malaysia. Participants will be followed for 2 years, with study visits at baseline (study entry/initiation of treatment), months 3, 6, 12, 18, and 24 of follow-up. Clinical and laboratory information/data and blood samples will be collected at study visits.

Study Type

Observational

Enrollment (Actual)

102

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

      • Chennai, India
        • YRGCare
      • Kuala Lumpur, Malaysia
        • Clinical Investigation Centre (CIC), University of Malaya, Infectious Diseases Directorate
      • Bangkok, Thailand
        • HIV-NAT/Thai Red Cross AIDS Research Centre

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

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

Anti-retroviral treatment (ART) naïve (or within 7-10 days of ART start where immediate ART start (test and treat) is practice) HIV-HBV co-infected individuals about to commence ART, aged 18 years and older

Description

Inclusion Criteria:

  • Male or female, aged 18 years and older
  • HIV antibody positive
  • Chronically-infected with HBV, as defined by:

    i. Positive Hepatitis B surface antigen HBsAg) or HBV DNA result with a subsequent positive HBsAg or HBV DNA result at least 6 months after first positive result (the 2nd HBsAg test may be taken at the baseline visit) ii. HBsAg positive with the absence of immunoglobulin M antibodies to HBV core at screening

  • Current or ever hepatitis C virus (HCV) antibody negative
  • Hepatitis D virus (HDV) negative
  • ART naïve or within 7-10 days of ART start at sites where immediate ART start (test and treat) is practice
  • Provide signed and dated informed consent form.
  • Willing to comply with all study procedures and be available for the duration of the study.

Exclusion Criteria:

  • Hepatitis C virus (HCV) antibody positive
  • Hepatitis delta antibody positive
  • Anything that would place the individual at increased risk or preclude the individual's full compliance with or completion of the study.

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

  • Observational Models: Cohort
  • Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
HBsAg loss/seroconversion on ART
Time Frame: 24 months
Frequency of HBsAg loss/seroconversion in early (first 12 months) compared to later stage
24 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
HBeAg loss/seroconversion on ART
Time Frame: 24 months
Frequency of HBeAg loss/seroconversion in early (first 12 months) compared to later stage
24 months
HBsAg epitope profiles
Time Frame: 24 months
HBsAg epitope profiles at study entry and after 2 years of antiviral therapy in HBsAg responders and non-responders
24 months
Differential B cell gene expression
Time Frame: 24 months
Differential B cell gene expression (genetic testing) in HBsAg responders and non-responders after 2 years of antiviral therapy
24 months
B-cell activating factor (BAFF) levels
Time Frame: 24 months
Levels of BAFF in plasma at study entry and after 2 years of antiviral therapy in HBsAg responders and non-responders
24 months
HBeAg and HBsAg specific memory B cells
Time Frame: 24 months
Proportion of HBeAg and HBsAg specific memory B cells at study entry and after 2 years of antiviral therapy
24 months
B cell subtypes
Time Frame: 24 months
Percentage of B cell subtypes at study entry and after 2 years of antiviral therapy
24 months

Collaborators and Investigators

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

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)

May 24, 2018

Primary Completion (Actual)

April 29, 2022

Study Completion (Estimated)

December 1, 2024

Study Registration Dates

First Submitted

August 22, 2018

First Submitted That Met QC Criteria

August 22, 2018

First Posted (Actual)

August 24, 2018

Study Record Updates

Last Update Posted (Actual)

December 21, 2023

Last Update Submitted That Met QC Criteria

December 19, 2023

Last Verified

December 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • COMMIT study (NMHRC 1123988)

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

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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