Brief Summary
The primary objective of this study is to evaluate the efficacy of switching to a fixed-dose combination (FDC) of bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) versus continuing on a regimen consisting of boosted atazanavir (ATV) or darunavir (DRV) plus either emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) or abacavir/lamivudine (ABC/3TC) in HIV-1 infected adults who are virologically suppressed.
Brief Title
Study to Evaluate the Safety and Efficacy of Switching From Regimens Consisting of Boosted Atazanavir or Darunavir Plus Either Emtricitabine/Tenofovir or Abacavir/Lamivudine to Bictegravir/Emtricitabine/Tenofovir Alafenamide in Virologically Suppressed HIV-1 Infected Adults
Completion Date
Completion Date Type
Actual
Conditions
HIV-1 Infection
Eligibility Criteria
Key Inclusion Criteria:
* Currently receiving a once daily antiretroviral regimen consisting of ritonavir or cobicistat boosted ATV or DRV plus either FTC/TDF or ABC/3TC for ≥ 6 months preceding the screening visit
* Adequate renal function:
* Estimated glomerular filtration rate ≥ 50 mL/min (≥ 0.83 mL/sec) according to the Cockcroft-Gault formula
* Life expectancy ≥ 1 year
* Currently on a stable regimen for ≥ 6 months preceding the screening visit with documented plasma HIV-1 RNA \< 50 copies/mL for ≥ 6 months preceding the screening visit (or undetectable HIV-1 RNA level according to the local assay being used if the limit of detection is ≥ 50 copies/mL). Prior changes in antiretroviral regimen are only allowed due to tolerability issues or for regimen simplification. Unconfirmed virologic elevations of ≥ 50 copies/mL (transient detectable viremia, or "blip") prior to screening are acceptable. (If the lower limit of detection of the local HIV-1 RNA assay is \< 50 copies/mL \[e.g., \< 20 copies/mL\], the plasma HIV-1 RNA level cannot exceed 50 copies/mL on two consecutive HIV-1 RNA tests)
* Have no documented or suspected resistance to FTC, tenofovir, ABC or 3TC, including but not limited to the reverse transcriptase resistance mutations K65R and M184V/I
* No previous use of any approved or experimental integrase strand transfer inhibitor (INSTI)
Key Exclusion Criteria:
* An opportunistic illness indicative of stage 3 HIV diagnosed within the 30 days prior to screening
* Individuals experiencing decompensated cirrhosis (eg, ascites, encephalopathy, or variceal bleeding)
* Have been treated with immunosuppressant therapies or chemotherapeutic agents within 3 months of study screening, or expected to receive these agents or systemic steroids during the study (eg, corticosteroids, immunoglobulins, and other immune- or cytokine based therapies)
* Current alcohol or substance use judged by the Investigator to potentially interfere with subject study compliance
* A history of or ongoing malignancy (including untreated carcinoma in-situ) other than cutaneous Kaposi's sarcoma (KS), basal cell carcinoma, or resected, non-invasive cutaneous squamous carcinoma. Individuals with biopsy-confirmed cutaneous KS are eligible, but must not have received any systemic therapy for KS within 30 days of Day 1 and are not anticipated to require systemic therapy during the study
* Active, serious infections (other than HIV 1 infection) requiring parenteral antibiotic or antifungal therapy within 30 days prior to Day 1
* Participation in any other clinical trial, including observational studies, without prior approval from the sponsor is prohibited while participating in this trial
* Any other clinical condition or prior therapy that, in the opinion of the Investigator, would make the individual unsuitable for the study or unable to comply with the dosing requirements
* Any known allergies to the excipients of B/F/TAF FDC or ATV, RTV, DRV, COBI, FTC/TDF or ABC/3TC
* Females who are pregnant (as confirmed by positive serum pregnancy test)
* Females who are breastfeeding
* Acute hepatitis in the 30 days prior to study entry
* Chronic hepatitis B infection in individuals not on a TDF containing regimen, as determined by either:
* Positive hepatitis B virus (HBV) surface antigen and negative HBV surface antibody, regardless of HBV core antibody status, at the screening visit
* Positive HBV core antibody and negative HBV surface antibody, regardless of HBV surface antigen status, at the screening visit
* Active tuberculosis infection
Note: Other protocol defined Inclusion/Exclusion criteria may apply.
* Currently receiving a once daily antiretroviral regimen consisting of ritonavir or cobicistat boosted ATV or DRV plus either FTC/TDF or ABC/3TC for ≥ 6 months preceding the screening visit
* Adequate renal function:
* Estimated glomerular filtration rate ≥ 50 mL/min (≥ 0.83 mL/sec) according to the Cockcroft-Gault formula
* Life expectancy ≥ 1 year
* Currently on a stable regimen for ≥ 6 months preceding the screening visit with documented plasma HIV-1 RNA \< 50 copies/mL for ≥ 6 months preceding the screening visit (or undetectable HIV-1 RNA level according to the local assay being used if the limit of detection is ≥ 50 copies/mL). Prior changes in antiretroviral regimen are only allowed due to tolerability issues or for regimen simplification. Unconfirmed virologic elevations of ≥ 50 copies/mL (transient detectable viremia, or "blip") prior to screening are acceptable. (If the lower limit of detection of the local HIV-1 RNA assay is \< 50 copies/mL \[e.g., \< 20 copies/mL\], the plasma HIV-1 RNA level cannot exceed 50 copies/mL on two consecutive HIV-1 RNA tests)
* Have no documented or suspected resistance to FTC, tenofovir, ABC or 3TC, including but not limited to the reverse transcriptase resistance mutations K65R and M184V/I
* No previous use of any approved or experimental integrase strand transfer inhibitor (INSTI)
Key Exclusion Criteria:
* An opportunistic illness indicative of stage 3 HIV diagnosed within the 30 days prior to screening
* Individuals experiencing decompensated cirrhosis (eg, ascites, encephalopathy, or variceal bleeding)
* Have been treated with immunosuppressant therapies or chemotherapeutic agents within 3 months of study screening, or expected to receive these agents or systemic steroids during the study (eg, corticosteroids, immunoglobulins, and other immune- or cytokine based therapies)
* Current alcohol or substance use judged by the Investigator to potentially interfere with subject study compliance
* A history of or ongoing malignancy (including untreated carcinoma in-situ) other than cutaneous Kaposi's sarcoma (KS), basal cell carcinoma, or resected, non-invasive cutaneous squamous carcinoma. Individuals with biopsy-confirmed cutaneous KS are eligible, but must not have received any systemic therapy for KS within 30 days of Day 1 and are not anticipated to require systemic therapy during the study
* Active, serious infections (other than HIV 1 infection) requiring parenteral antibiotic or antifungal therapy within 30 days prior to Day 1
* Participation in any other clinical trial, including observational studies, without prior approval from the sponsor is prohibited while participating in this trial
* Any other clinical condition or prior therapy that, in the opinion of the Investigator, would make the individual unsuitable for the study or unable to comply with the dosing requirements
* Any known allergies to the excipients of B/F/TAF FDC or ATV, RTV, DRV, COBI, FTC/TDF or ABC/3TC
* Females who are pregnant (as confirmed by positive serum pregnancy test)
* Females who are breastfeeding
* Acute hepatitis in the 30 days prior to study entry
* Chronic hepatitis B infection in individuals not on a TDF containing regimen, as determined by either:
* Positive hepatitis B virus (HBV) surface antigen and negative HBV surface antibody, regardless of HBV core antibody status, at the screening visit
* Positive HBV core antibody and negative HBV surface antibody, regardless of HBV surface antigen status, at the screening visit
* Active tuberculosis infection
Note: Other protocol defined Inclusion/Exclusion criteria may apply.
Inclusion Criteria
Inclusion Criteria:
* Currently receiving a once daily antiretroviral regimen consisting of ritonavir or cobicistat boosted ATV or DRV plus either FTC/TDF or ABC/3TC for ≥ 6 months preceding the screening visit
* Adequate renal function:
* Estimated glomerular filtration rate ≥ 50 mL/min (≥ 0.83 mL/sec) according to the Cockcroft-Gault formula
* Life expectancy ≥ 1 year
* Currently on a stable regimen for ≥ 6 months preceding the screening visit with documented plasma HIV-1 RNA \< 50 copies/mL for ≥ 6 months preceding the screening visit (or undetectable HIV-1 RNA level according to the local assay being used if the limit of detection is ≥ 50 copies/mL). Prior changes in antiretroviral regimen are only allowed due to tolerability issues or for regimen simplification. Unconfirmed virologic elevations of ≥ 50 copies/mL (transient detectable viremia, or "blip") prior to screening are acceptable. (If the lower limit of detection of the local HIV-1 RNA assay is \< 50 copies/mL \[e.g., \< 20 copies/mL\], the plasma HIV-1 RNA level cannot exceed 50 copies/mL on two consecutive HIV-1 RNA tests)
* Have no documented or suspected resistance to FTC, tenofovir, ABC or 3TC, including but not limited to the reverse transcriptase resistance mutations K65R and M184V/I
* No previous use of any approved or experimental integrase strand transfer inhibitor (INSTI)
Inclusion/
* Currently receiving a once daily antiretroviral regimen consisting of ritonavir or cobicistat boosted ATV or DRV plus either FTC/TDF or ABC/3TC for ≥ 6 months preceding the screening visit
* Adequate renal function:
* Estimated glomerular filtration rate ≥ 50 mL/min (≥ 0.83 mL/sec) according to the Cockcroft-Gault formula
* Life expectancy ≥ 1 year
* Currently on a stable regimen for ≥ 6 months preceding the screening visit with documented plasma HIV-1 RNA \< 50 copies/mL for ≥ 6 months preceding the screening visit (or undetectable HIV-1 RNA level according to the local assay being used if the limit of detection is ≥ 50 copies/mL). Prior changes in antiretroviral regimen are only allowed due to tolerability issues or for regimen simplification. Unconfirmed virologic elevations of ≥ 50 copies/mL (transient detectable viremia, or "blip") prior to screening are acceptable. (If the lower limit of detection of the local HIV-1 RNA assay is \< 50 copies/mL \[e.g., \< 20 copies/mL\], the plasma HIV-1 RNA level cannot exceed 50 copies/mL on two consecutive HIV-1 RNA tests)
* Have no documented or suspected resistance to FTC, tenofovir, ABC or 3TC, including but not limited to the reverse transcriptase resistance mutations K65R and M184V/I
* No previous use of any approved or experimental integrase strand transfer inhibitor (INSTI)
Inclusion/
Gender
All
Gender Based
false
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT02603107
Org Class
Industry
Org Full Name
Gilead Sciences
Org Study Id
GS-US-380-1878
Overall Status
Completed
Phases
Phase 3
Primary Completion Date
Primary Completion Date Type
Actual
Official Title
A Phase 3, Randomized, Open-Label Study to Evaluate the Safety and Efficacy of Switching From Regimens Consisting of Boosted Atazanavir or Darunavir Plus Either Emtricitabine/Tenofovir or Abacavir/Lamivudine to GS-9883/Emtricitabine/Tenofovir Alafenamide in Virologically Suppressed HIV-1 Infected Adults
Primary Outcomes
Outcome Description
The percentage of participants with HIV-1 RNA ≥ 50 copies/mL at Week 48 was analyzed using the snapshot algorithm, which defines a participant'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.
Outcome Measure
Percentage of Participants With HIV-1 RNA ≥ 50 Copies/mL at Week 48 as Determined by the FDA-Defined Snapshot Algorithm
Outcome Time Frame
Week 48
Secondary Ids
Secondary Id
2015-004011-20
Secondary Outcomes
Outcome Description
The percentage of participants with HIV-1 RNA \< 50 copies/mL at Week 48 was analyzed using the snapshot algorithm, which defines a participant'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.
Outcome Time Frame
Week 48
Outcome Measure
Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48 as Determined by the FDA-Defined Snapshot Algorithm
Outcome Time Frame
Baseline to Week 48
Outcome Measure
Change From Baseline in CD4 Cell Count at Week 48
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Estimated
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Robert Grossberg
Investigator Email
rgrossbe@montefiore.org
Investigator Phone
718-920-5276
MeSH Terms
COBICISTAT
COBICISTAT MIXTURE WITH DARUNAVIR
EMTRICITABINE, TENOFOVIR DISOPROXIL FUMARATE DRUG COMBINATION
BICTEGRAVIR, EMTRICITABINE, TENOFOVIR ALAFENAMIDE, DRUG COMBINATION
CARBAMATES
ACIDS, ACYCLIC
CARBOXYLIC ACIDS
ORGANIC CHEMICALS
THIAZOLES
SULFUR COMPOUNDS
AZOLES
HETEROCYCLIC COMPOUNDS, 1-RING
HETEROCYCLIC COMPOUNDS
TENOFOVIR
ORGANOPHOSPHONATES
ORGANOPHOSPHORUS COMPOUNDS
EMTRICITABINE
DEOXYCYTIDINE
CYTIDINE
PYRIMIDINE NUCLEOSIDES
PYRIMIDINES
ADENINE
PURINES
HETEROCYCLIC COMPOUNDS, 2-RING
HETEROCYCLIC COMPOUNDS, FUSED-RING
DEOXYRIBONUCLEOSIDES
NUCLEOSIDES
NUCLEIC ACIDS, NUCLEOTIDES, AND NUCLEOSIDES
DRUG COMBINATIONS
PHARMACEUTICAL PREPARATIONS