Towards a Functional Cure for HBV - The COMMIT Cohort Study

Hiv Clinical Trial

— COMMIT  

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03645044
• Other study ID #: COMMIT study (NMHRC 1123988)
• Status: Active, not recruiting
• Start date: May 24, 2018
• Est. completion date: December 2024

Study information

• Verified date: December 2023
• Source: University of Melbourne
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 102
• Est. completion date: December 2024
• Est. primary completion date: April 29, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Coinfection
• HBV Coinfection
• Hiv

Locations

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

Sponsors (8)

Lead Sponsor	Collaborator
University of Melbourne	Melbourne Health, National Health and Medical Research Council, Australia, The HIV Netherlands Australia Thailand Research Collaboration, The University of Western Australia, University of Adelaide, University of Malaya, YR Gaitonde Centre for AIDS Research and Education

Countries where clinical trial is conducted

India,  Malaysia,  Thailand, 

Outcome

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