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

HIV Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02071082
• Other study ID #: GS-US-292-1249
• Status: Completed
• Phase: Phase 3
• Start date: February 25, 2014
• Est. completion date: October 26, 2016

Study information

• Verified date: October 2017
• Source: Gilead Sciences
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 79
• Est. completion date: October 26, 2016
• Est. primary completion date: January 23, 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• HBV
• Hepatitis B
• HIV

Intervention

Drug:
• E/C/F/TAF
E/C/F/TAF (150/150/200/10 mg) FDC tablet administered orally once daily with food

Locations

Country	Name	City	State
Canada	Maple Leaf Research/Maple Leaf Medical Clinic	Toronto	Ontario
Canada	University Health Network/Toronto General Hospital	Toronto	Ontario
Japan	Center Hospital of the National Center for Global Health and Medicine	Shinjuku-ku	Tokyo
United States	Central Texas Clinical Research	Austin	Texas
United States	St. Hope Foundation	Bellaire	Texas
United States	Be Well Medical Center PC	Berkley	Michigan
United States	AHF Research Center	Beverly Hills	California
United States	Barry M. Rodwick MD	Clearwater	Florida
United States	North Texas Infectious Diseases Consultants	Dallas	Texas
United States	Gary J Richmond M.D.,P.A.	Fort Lauderdale	Florida
United States	Midway Immunology and Research Center	Fort Pierce	Florida
United States	Gordon E. Crofoot MD PA	Houston	Texas
United States	Therapeutic Concepts	Houston	Texas
United States	KC Care Clinic	Kansas City	Missouri
United States	Anthony Mills MD, Inc	Los Angeles	California
United States	Peter J. Ruane MD, Inc.	Los Angeles	California
United States	AIDS Health Foundation/WPA	Miami Beach	Florida
United States	Spectrum Medical Group	Phoenix	Arizona
United States	Southampton Healthcare, Inc.	Saint Louis	Missouri
United States	Southwest CARE Center	Santa Fe	New Mexico
United States	Peter Shalit MD	Seattle	Washington
United States	AIDS Research and Treatment Center of the Treasure Coast	Vero Beach	Florida
United States	Whitman Walker Health	Washington	District of Columbia
United States	Triple O Research Institute PA	West Palm Beach	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Gilead Sciences

Countries where clinical trial is conducted

United States,  Canada,  Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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