Efficacy and Safety of E/C/F/TAF (Genvoya®) in HIV-1/Hepatitis B Co-infected Adults

Study Overview
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Brief Summary
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This study will assess the efficacy, safety, and tolerability of elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) fixed-dose combination (FDC) in human immunodeficiency virus (HIV)/hepatitis B virus (HBV) coinfected adults. Participants will be enrolled into two cohorts: Cohort 1: HIV/HBV coinfected adults who are HIV treatment-naive and HBV treatment-naive Cohort 2: HIV/HBV coinfected adults who are HIV-suppressed

Official Title
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A Phase 3b Open-label Study of the Efficacy and Safety of Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide Single-Tablet Regimen in HIV-1/Hepatitis B Co-infected Adults

Conditions
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HIV, HBV

Intervention / Treatment
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* Drug: E/C/F/TAF


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Both Cohorts 1 and 2: The ability to understand and sign a written informed consent form, which must be obtained prior to initiation of study procedures HIV/HBV co-infected adult males and non-pregnant and non-lactating females No evidence of hepatocellular carcinoma (HCC) or clinical or imaging evidence of cirrhosis (ascites, variceal bleeding, encephalopathy). --- Subjects should have documentation of an abdominal ultrasound in the 12 months prior to screening, or an abdominal ultrasound at screening, demonstrating the absence of cirrhosis and HCC. Acute Hepatitis A virus (HAV) immunoglobulin M (IgM) negative Hepatitis C virus (HCV) Ab negative, or HCV Ab positive with negative HCV RNA Hepatitis D virus (HDV) Ab negative, or HDV Ab positive with negative HDV RNA Estimated glomerular filtration rate (eGFR) ≥ 50 mL/min according to the Cockcroft-Gault formula CD4+ count of > 200 cells/μL Chronic HBV infection as defined by HBsAg positive for ≥ 6 months Or HBsAg positive at screening and either hepatitis B e antigen (HBeAg) or HBV DNA positive ≥ 6 months Or At screening: positive total hepatitis B core antibody (HBcAb) and negative immunoglobulin M antibody to hepatitis B core antigen (HBcIgM) antibody, and HBsAg positive, or HBeAg positive, or HBV DNA positive Cohort 1 (HIV and HBV treatment naive) only: No current or prior anti-HIV treatment, including antiretroviral medications received for prevention (PrEP), or post exposure prophylaxis (PEP) No current or prior anti-HBV treatment Plasma HIV-1 RNA level ≥ 500 copies/mL at screening Screening HBV DNA ≥ 3 log10 IU/mL and < 9 log10 IU/mL Cohort 2 (HIV suppressed) only: Receiving current antiretroviral regimen for at least 4 consecutive months No current or prior regimen containing 3 active anti-HBV agents (i.e. cannot be on tenofovir alafenamide (TDF)/emtricitabine (FTC)/Entecavir or TDF/lamivudine(3TC)/Entecavir) Maintained plasma HIV-1 RNA < 50 copies/mL for 6 consecutive months prior to and at the time of the screening visit. Unconfirmed virologic evaluation of ≥ 50 copies/mL after previously reaching viral suppression (transient detectable viremia, or blip) and prior to screening is acceptable Documented positive HIV antibody test Screening HBV DNA < 9 log10 IU/mL Key Exclusion Criteria: Females who are breastfeeding Positive serum pregnancy test (female of childbearing potential) Have an implanted defibrillator or pacemaker Current alcohol or substance use A history of malignancy within the past 5 years (prior to screening) or ongoing malignancy other than cutaneous Kaposi's sarcoma (KS), basal cell carcinoma, or resected, non-invasive carcinoma. Received solid organ or bone marrow transplant Any history of, or current evidence of, clinical hepatic decompensation (e.g., ascites, encephalopathy or variceal hemorrhage). Significant bone disease (e.g., osteomalacia, chronic osteomyelitis, osteogenesis imperfecta, osteochondroses), or multiple bone fractures Active, serious infections (other than HIV-1 infection) requiring parenteral antibiotic or antifungal therapy within 30 days prior to Day 1 Subjects on hemodialysis, other forms of renal replacement therapy, or on treatment for underlying kidney diseases (including prednisolone, and dexamethasone) Any other clinical condition or prior therapy that, in the opinion of the Investigator, would make the subject unsuitable for the study or unable to comply with the dosing requirements Investigational agents (unless approved by Gilead Sciences). Participation in any other clinical trial without prior approval from the sponsor is prohibited while participating in this trial Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: HIV treatment-naive and HBV treatment-naive<br>HIV/HBV coinfected participants who are HIV treatment-naive and HBV treatment-naive will receive E/C/F/TAF for 48 weeks. | Drug: E/C/F/TAF<br>* E/C/F/TAF (150/150/200/10 mg) FDC tablet administered orally once daily with food<br>* Other names: Genvoya®;|
| Experimental: HIV-suppressed<br>HIV/HBV coinfected participants who are HIV-suppressed will receive E/C/F/TAF for 48 weeks. | Drug: E/C/F/TAF<br>* E/C/F/TAF (150/150/200/10 mg) FDC tablet administered orally once daily with food<br>* Other names: Genvoya®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Plasma HIV-1 RNA Level < 50 Copies/mL | The percentage of participants achieving HIV-1 RNA < 50 copies/mL at Week 24 was analyzed using the snapshot algorithm, which defines a patient's virologic response status using only the viral load at the predefined time point within an allowed window of time, along with study drug discontinuation status. | Week 24 | 
| Percentage of Participants With Plasma HBV DNA Levels < 29 IU/mL | The percentage of participants with HBV DNA < 29 IU/mL at Week 24 was calculated using the missing = failure method. | Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Plasma HIV-1 RNA Level < 50 Copies/mL | The percentage of participants achieving HIV-1 RNA < 50 copies/mL at Week 48 was analyzed using the snapshot algorithm, which defines a patient's virologic response status using only the viral load at the predefined time point within an allowed window of time, along with study drug discontinuation status. | Week 48 | 
| Percentage of Participants With Plasma HBV DNA Levels < 29 IU/mL | The percentage of participants with HBV DNA < 29 IU/mL at Week 48 was calculated using the missing = failure method. | Week 48 | 
| Percentage of Participants With Normalized Alanine Aminotransferase (ALT) at Week 24 | ALT normalization was defined as an ALT value that changed from above the normal range at baseline to within the normal range at the given postbaseline visit. | Baseline; Week 24 | 
| Percentage of Participants With Normalized ALT at Week 48 | ALT normalization was defined as an ALT value that changed from above the normal range at baseline to within the normal range at the given postbaseline visit. | Baseline; Week 48 | 
| Percentage of Participants With Seroconversion to Hepatitis B Surface Antibody (Anti-HBs) at Week 24 | Seroconversion to antibody is defined as (1) antigen loss and (2) positive postbaseline antibody value. Missing = excluded method. | Baseline; Week 24 | 
| Percentage of Participants With Seroconversion to Anti-HBs at Week 48 | Seroconversion to antibody is defined as (1) antigen loss and (2) positive postbaseline antibody value. Missing = excluded method. | Baseline; Week 48 | 
| Percentage of Participants With Seroconversion to Hepatitis B e Antibody (Anti-HBe) at Week 24 | Seroconversion to antibody is defined as (1) antigen loss and (2) positive postbaseline antibody value. Missing = excluded method. | Baseline; Week 24 | 
| Percentage of Participants With Seroconversion to Anti-HBe at Week 48 | Seroconversion to antibody is defined as (1) antigen loss and (2) positive postbaseline antibody value. Missing = excluded method. | Baseline; Week 48 | 
| Change From Baseline in FibroTest® Score at Week 24 | The FibroTest® score is used to assess liver fibrosis. Scores range from 0.00 to 1.00, with higher scores indicating a greater degree of fibrosis. | Baseline; Week 24 | 
| Change From Baseline in FibroTest® Score at Week 48 | The FibroTest® score is used to assess liver fibrosis. Scores range from 0.00 to 1.00, with higher scores indicating a greater degree of fibrosis. | Baseline; Week 48 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HIV, HBV, Coinfection