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

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ClinicalTrials.gov Identifier: NCT03645044
Recruitment Status : Recruiting
First Posted : August 24, 2018
Last Update Posted : September 26, 2019
Sponsor:
Collaborators:
National Health and Medical Research Council, Australia
The University of Western Australia
University of Adelaide
The HIV Netherlands Australia Thailand Research Collaboration
University of Malaya
YR Gaitonde Centre for AIDS Research and Education
Melbourne Health
Information provided by (Responsible Party):
Joe Sasadeusz, University of Melbourne

Study Description
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Brief 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

Condition or disease
Hiv HBV Coinfection

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 Design
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Study Type : Observational
Estimated Enrollment : 150 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Towards a Functional Cure for HBV: Exploiting Lessons From HIV-HBV Co-infection: The COMMIT Cohort Study
Actual Study Start Date : May 24, 2018
Estimated Primary Completion Date : June 2021
Estimated Study Completion Date : December 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS

Groups and Cohorts
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Outcome Measures
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Primary Outcome Measures :
  1. HBsAg loss/seroconversion on ART [ Time Frame: 24 months ]
    Frequency of HBsAg loss/seroconversion in early (first 12 months) compared to later stage


Secondary Outcome Measures :
  1. HBeAg loss/seroconversion on ART [ Time Frame: 24 months ]
    Frequency of HBeAg loss/seroconversion in early (first 12 months) compared to later stage

  2. 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

  3. 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

  4. 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

  5. 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

  6. B cell subtypes [ Time Frame: 24 months ]
    Percentage of B cell subtypes at study entry and after 2 years of antiviral therapy


Biospecimen Retention:   Samples With DNA
peripheral blood mononuclear cells (PBMCs) and plasma

Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
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
Criteria

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.
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03645044


Contacts
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Contact: Jennifer Audsley, PhD +61383443266 jennifer.audsley@unimelb.edu.au

Locations
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India
YRGCare Not yet recruiting
Chennai, India
Contact: Nagalingeswaran Kumarasamy, MD    +91 44 71026610    info@yrgcare.org   
Malaysia
Clinical Investigation Centre (CIC), University of Malaya, Infectious Diseases Directorate Not yet recruiting
Kuala Lumpur, Malaysia
Contact: Iskandar Azwa, MD    +603-7949-3641    iskandar.azwa@gmail.com   
Thailand
HIV-NAT/Thai Red Cross AIDS Research Centre Recruiting
Bangkok, Thailand
Contact: Anchalee Avihingsanon, MD, PhD    +66 (0) 2652 3040    anchalee.a@hivnat.org)   
Sponsors and Collaborators
University of Melbourne
National Health and Medical Research Council, Australia
The University of Western Australia
University of Adelaide
The HIV Netherlands Australia Thailand Research Collaboration
University of Malaya
YR Gaitonde Centre for AIDS Research and Education
Melbourne Health
Investigators
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Principal Investigator: Joe Sasadeusz, MBBS, PhD University of Melbourne
More Information
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Responsible Party: Joe Sasadeusz, Infectious Diseases physician, University of Melbourne
ClinicalTrials.gov Identifier: NCT03645044    
Other Study ID Numbers: COMMIT study (NMHRC 1123988)
First Posted: August 24, 2018    Key Record Dates
Last Update Posted: September 26, 2019
Last Verified: September 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Joe Sasadeusz, University of Melbourne:
HBV sAg loss/seroconversion
HBV "e" antigen (eAg) loss/seroconversion
antiretroviral therapy
Additional relevant MeSH terms:
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Coinfection
Infection
Virus Diseases
Parasitic Diseases