Efficacy and Safety of E/C/F/TAF (Genvoya®) in HIV-1/Hepatitis B Co-infected Adults
19. oktober 2018 opdateret af: Gilead Sciences
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
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
Studieoversigt
Undersøgelsestype
Interventionel
Tilmelding (Faktiske)
79
Fase
- Fase 3
Kontakter og lokationer
Dette afsnit indeholder kontaktoplysninger for dem, der udfører undersøgelsen, og oplysninger om, hvor denne undersøgelse udføres.
Studiesteder
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Ontario
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Toronto, Ontario, Canada, M5G 2N2
- University Health Network/Toronto General Hospital
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Toronto, Ontario, Canada, M5G1K2
- Maple Leaf Research/Maple Leaf Medical Clinic
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Arizona
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Phoenix, Arizona, Forenede Stater, 85012
- Spectrum Medical Group
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California
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Beverly Hills, California, Forenede Stater, 90211
- AHF Research Center
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Los Angeles, California, Forenede Stater, 90036
- Peter J. Ruane MD, Inc.
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Los Angeles, California, Forenede Stater, 90069
- Anthony Mills MD, Inc
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District of Columbia
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Washington, District of Columbia, Forenede Stater, 20009
- Whitman Walker Health
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Florida
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Clearwater, Florida, Forenede Stater, 33765
- Barry M. Rodwick MD
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Fort Lauderdale, Florida, Forenede Stater, 33316
- Gary J Richmond M.D.,P.A.
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Fort Pierce, Florida, Forenede Stater, 34982
- Midway Immunology and Research Center
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Miami Beach, Florida, Forenede Stater, 33139
- AIDS Health Foundation/WPA
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Vero Beach, Florida, Forenede Stater, 32960
- AIDS Research and Treatment Center of the Treasure Coast
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West Palm Beach, Florida, Forenede Stater, 33401
- Triple O Research Institute PA
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Michigan
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Berkley, Michigan, Forenede Stater, 48072
- Be Well Medical Center PC
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Missouri
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Kansas City, Missouri, Forenede Stater, 64111
- KC Care Clinic
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Saint Louis, Missouri, Forenede Stater, 63139
- Southampton Healthcare, Inc.
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New Mexico
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Santa Fe, New Mexico, Forenede Stater, 87505
- Southwest CARE Center
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Texas
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Austin, Texas, Forenede Stater, 78705
- Central Texas Clinical Research
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Bellaire, Texas, Forenede Stater
- St. Hope Foundation
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Dallas, Texas, Forenede Stater, 75246
- North Texas Infectious Diseases Consultants
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Houston, Texas, Forenede Stater, 77004
- Therapeutic Concepts
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Houston, Texas, Forenede Stater, 77098
- Gordon E. Crofoot MD PA
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Washington
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Seattle, Washington, Forenede Stater, 98104
- Peter Shalit MD
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Tokyo
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Shinjuku-ku, Tokyo, Japan, 1628655
- Center Hospital of the National Center for Global Health and Medicine
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Deltagelseskriterier
Forskere leder efter personer, der passer til en bestemt beskrivelse, kaldet berettigelseskriterier. Nogle eksempler på disse kriterier er en persons generelle helbredstilstand eller tidligere behandlinger.
Berettigelseskriterier
Aldre berettiget til at studere
18 år og ældre (Voksen, Ældre voksen)
Tager imod sunde frivillige
Ingen
Køn, der er berettiget til at studere
Alle
Beskrivelse
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.
Studieplan
Dette afsnit indeholder detaljer om studieplanen, herunder hvordan undersøgelsen er designet, og hvad undersøgelsen måler.
Hvordan er undersøgelsen tilrettelagt?
Design detaljer
- Primært formål: Behandling
- Tildeling: Ikke-randomiseret
- Interventionel model: Parallel tildeling
- Maskning: Ingen (Åben etiket)
Våben og indgreb
Deltagergruppe / Arm |
Intervention / Behandling |
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Eksperimentel: HIV treatment-naive and HBV treatment-naive
HIV/HBV coinfected participants who are HIV treatment-naive and HBV treatment-naive will receive E/C/F/TAF for 48 weeks.
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E/C/F/TAF (150/150/200/10 mg) FDC tablet administered orally once daily with food
Andre navne:
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Eksperimentel: HIV-suppressed
HIV/HBV coinfected participants who are HIV-suppressed will receive E/C/F/TAF for 48 weeks.
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E/C/F/TAF (150/150/200/10 mg) FDC tablet administered orally once daily with food
Andre navne:
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Hvad måler undersøgelsen?
Primære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
|---|---|---|
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Percentage of Participants With Plasma HIV-1 RNA Level < 50 Copies/mL
Tidsramme: Week 24
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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.
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Week 24
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Percentage of Participants With Plasma HBV DNA Levels < 29 IU/mL
Tidsramme: Week 24
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The percentage of participants with HBV DNA < 29 IU/mL at Week 24 was calculated using the missing = failure method.
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Week 24
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Sekundære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
|---|---|---|
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Percentage of Participants With Plasma HIV-1 RNA Level < 50 Copies/mL
Tidsramme: Week 48
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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.
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Week 48
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Percentage of Participants With Plasma HBV DNA Levels < 29 IU/mL
Tidsramme: Week 48
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The percentage of participants with HBV DNA < 29 IU/mL at Week 48 was calculated using the missing = failure method.
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Week 48
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Percentage of Participants With Normalized Alanine Aminotransferase (ALT) at Week 24
Tidsramme: Baseline; Week 24
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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.
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Baseline; Week 24
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Percentage of Participants With Normalized ALT at Week 48
Tidsramme: Baseline; Week 48
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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.
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Baseline; Week 48
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Percentage of Participants With Seroconversion to Hepatitis B Surface Antibody (Anti-HBs) at Week 24
Tidsramme: Baseline; Week 24
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Seroconversion to antibody is defined as (1) antigen loss and (2) positive postbaseline antibody value.
Missing = excluded method.
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Baseline; Week 24
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Percentage of Participants With Seroconversion to Anti-HBs at Week 48
Tidsramme: Baseline; Week 48
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Seroconversion to antibody is defined as (1) antigen loss and (2) positive postbaseline antibody value.
Missing = excluded method.
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Baseline; Week 48
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Percentage of Participants With Seroconversion to Hepatitis B e Antibody (Anti-HBe) at Week 24
Tidsramme: Baseline; Week 24
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Seroconversion to antibody is defined as (1) antigen loss and (2) positive postbaseline antibody value.
Missing = excluded method.
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Baseline; Week 24
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Percentage of Participants With Seroconversion to Anti-HBe at Week 48
Tidsramme: Baseline; Week 48
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Seroconversion to antibody is defined as (1) antigen loss and (2) positive postbaseline antibody value.
Missing = excluded method.
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Baseline; Week 48
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Change From Baseline in FibroTest® Score at Week 24
Tidsramme: Baseline; Week 24
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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.
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Baseline; Week 24
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Change From Baseline in FibroTest® Score at Week 48
Tidsramme: Baseline; Week 48
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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.
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Baseline; Week 48
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Samarbejdspartnere og efterforskere
Det er her, du vil finde personer og organisationer, der er involveret i denne undersøgelse.
Sponsor
Datoer for undersøgelser
Disse datoer sporer fremskridtene for indsendelser af undersøgelsesrekord og resumeresultater til ClinicalTrials.gov. Studieregistreringer og rapporterede resultater gennemgås af National Library of Medicine (NLM) for at sikre, at de opfylder specifikke kvalitetskontrolstandarder, før de offentliggøres på den offentlige hjemmeside.
Studer store datoer
Studiestart (Faktiske)
25. februar 2014
Primær færdiggørelse (Faktiske)
23. januar 2015
Studieafslutning (Faktiske)
26. oktober 2016
Datoer for studieregistrering
Først indsendt
21. februar 2014
Først indsendt, der opfyldte QC-kriterier
21. februar 2014
Først opslået (Skøn)
25. februar 2014
Opdateringer af undersøgelsesjournaler
Sidste opdatering sendt (Faktiske)
16. november 2018
Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier
19. oktober 2018
Sidst verificeret
1. oktober 2017
Mere information
Begreber relateret til denne undersøgelse
Nøgleord
Yderligere relevante MeSH-vilkår
- Sygdomme i fordøjelsessystemet
- Virussygdomme
- Infektioner
- Blodbårne infektioner
- Overførbare sygdomme
- Leversygdomme
- Hepatitis, viral, menneskelig
- Hepadnaviridae infektioner
- DNA-virusinfektioner
- Hepatitis
- Hepatitis B
- Anti-infektionsmidler
- Antivirale midler
- Anti-HIV-midler
- Anti-retrovirale midler
- Elvitegravir, Cobicistat, Emtricitabin, Tenofovir Disoproxil Fumarate Lægemiddelkombination
Andre undersøgelses-id-numre
- GS-US-292-1249
Plan for individuelle deltagerdata (IPD)
Planlægger du at dele individuelle deltagerdata (IPD)?
Ja
IPD-planbeskrivelse
Qualified external researchers may request IPD for this study after study completion.
For more information, please visit our website at http://www.gilead.com/research/disclosure-and-transparency.
IPD-delingstidsramme
18 months after study completion
IPD-delingsadgangskriterier
A secured external environment with username, password, and RSA code.
IPD-deling Understøttende informationstype
- Studieprotokol
- Statistisk analyseplan (SAP)
Disse oplysninger blev hentet direkte fra webstedet clinicaltrials.gov uden ændringer. Hvis du har nogen anmodninger om at ændre, fjerne eller opdatere dine undersøgelsesoplysninger, bedes du kontakte register@clinicaltrials.gov. Så snart en ændring er implementeret på clinicaltrials.gov, vil denne også blive opdateret automatisk på vores hjemmeside .