Brief Summary
The primary objective of this study is to evaluate the non-inferiority of switching to emtricitabine/rilpivirine/tenofovir alafenamide (FTC/RPV/TAF) fixed dose combination (FDC) as compared to continuing the non-nucleoside reverse transcriptase inhibitor (NNRTI) regimen of efavirenz /FTC/tenofovir disoproxil fumarate (EFV/FTC/TDF) FDC in virologically-suppressed HIV-1 infected participants.
Brief Title
Study to Evaluate Switching From a Regimen Consisting of Efavirenz/Emtricitabine/Tenofovir Disoproxil Fumarate (EFV/FTC/TDF) Fixed Dose Combination (FDC) to Emtricitabine/Rilpivirine/Tenofovir Alafenamide (FTC/RPV/TAF) FDC in Virologically-Suppressed, HIV-1 Infected Adults
Completion Date
Completion Date Type
Actual
Conditions
HIV-1 Infection
Eligibility Criteria
Key Inclusion Criteria:
* The ability to understand and sign a written informed consent form, which must be obtained prior to initiation of study procedures
* Currently receiving EFV/FTC/TDF FDC for ≥ 6 consecutive months preceding the screening visit
* Documented plasma HIV-1 RNA levels \< 50 copies/mL (or undetectable HIV-1 RNA level according to the local assay being used if the limit of detection is \> 50 copies/mL) for ≥ 6 months preceding the screening visit. Unconfirmed virologic elevation of ≥ 50 copies/mL after previously reaching viral suppression (transient detectable viremia, or "blip") and prior to screening is acceptable
* Have no documented resistance to any of the study agents at any time in the past
* HIV-1 RNA \< 50 copies/mL at the screening visit
* Hepatic transaminases (AST and ALT) ≤ 5 × upper limit of normal (ULN)
* Total bilirubin ≤ 1.5 mg/dL, or normal direct bilirubin
* Adequate hematologic function (absolute neutrophil count ≥ 1,000/mm\^3; platelets ≥ 50,000/mm\^3; hemoglobin ≥ 8.5 g/dL)
* Serum amylase ≤ 5 × ULN (individuals with serum amylase \> 5 × ULN will remain eligible if serum lipase is ≤ 5 × ULN)
* Normal ECG (or if abnormal, determined by the Investigator to be not clinically significant)
* Adequate renal function: Estimated glomerular filtration rate ≥ 50 mL/min according to the Cockcroft-Gault formula
Key Exclusion Criteria:
* Hepatitis B surface antigen (HBsAg) positive
* Hepatitis C antibody positive with detectable hepatitis C virus (HCV) RNA (individuals who have HCV antibody but no detectable HCV RNA are eligible to enroll)
* Individuals experiencing or with a medical history of decompensated cirrhosis (e.g., ascites, encephalopathy, etc.)
* Females who are breastfeeding
* Positive serum pregnancy test
* Current alcohol or substance use judged by the Investigator to potentially interfere with the individual's study compliance
* 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 cutaneous squamous carcinoma. Individuals with cutaneous KS are eligible, but must not have received any systemic therapy for KS within 30 days of Baseline/Day 1 and must not be 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 Baseline/Day 1
* 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 dosing requirements
* Participation in any other clinical trial (including observational trials) without prior approval from the sponsor is prohibited while participating in this trial
* Individuals receiving ongoing therapy with any of the disallowed medications listed in the protocol, including drugs not to be used with FTC, RPV and/or TAF; or individuals with any known allergies to the excipients of FTC/RPV/TAF
Note: Other protocol defined inclusion/exclusion criteria may apply.
* The ability to understand and sign a written informed consent form, which must be obtained prior to initiation of study procedures
* Currently receiving EFV/FTC/TDF FDC for ≥ 6 consecutive months preceding the screening visit
* Documented plasma HIV-1 RNA levels \< 50 copies/mL (or undetectable HIV-1 RNA level according to the local assay being used if the limit of detection is \> 50 copies/mL) for ≥ 6 months preceding the screening visit. Unconfirmed virologic elevation of ≥ 50 copies/mL after previously reaching viral suppression (transient detectable viremia, or "blip") and prior to screening is acceptable
* Have no documented resistance to any of the study agents at any time in the past
* HIV-1 RNA \< 50 copies/mL at the screening visit
* Hepatic transaminases (AST and ALT) ≤ 5 × upper limit of normal (ULN)
* Total bilirubin ≤ 1.5 mg/dL, or normal direct bilirubin
* Adequate hematologic function (absolute neutrophil count ≥ 1,000/mm\^3; platelets ≥ 50,000/mm\^3; hemoglobin ≥ 8.5 g/dL)
* Serum amylase ≤ 5 × ULN (individuals with serum amylase \> 5 × ULN will remain eligible if serum lipase is ≤ 5 × ULN)
* Normal ECG (or if abnormal, determined by the Investigator to be not clinically significant)
* Adequate renal function: Estimated glomerular filtration rate ≥ 50 mL/min according to the Cockcroft-Gault formula
Key Exclusion Criteria:
* Hepatitis B surface antigen (HBsAg) positive
* Hepatitis C antibody positive with detectable hepatitis C virus (HCV) RNA (individuals who have HCV antibody but no detectable HCV RNA are eligible to enroll)
* Individuals experiencing or with a medical history of decompensated cirrhosis (e.g., ascites, encephalopathy, etc.)
* Females who are breastfeeding
* Positive serum pregnancy test
* Current alcohol or substance use judged by the Investigator to potentially interfere with the individual's study compliance
* 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 cutaneous squamous carcinoma. Individuals with cutaneous KS are eligible, but must not have received any systemic therapy for KS within 30 days of Baseline/Day 1 and must not be 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 Baseline/Day 1
* 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 dosing requirements
* Participation in any other clinical trial (including observational trials) without prior approval from the sponsor is prohibited while participating in this trial
* Individuals receiving ongoing therapy with any of the disallowed medications listed in the protocol, including drugs not to be used with FTC, RPV and/or TAF; or individuals with any known allergies to the excipients of FTC/RPV/TAF
Note: Other protocol defined inclusion/exclusion criteria may apply.
Inclusion Criteria
Inclusion Criteria:
* The ability to understand and sign a written informed consent form, which must be obtained prior to initiation of study procedures
* Currently receiving EFV/FTC/TDF FDC for ≥ 6 consecutive months preceding the screening visit
* Documented plasma HIV-1 RNA levels \< 50 copies/mL (or undetectable HIV-1 RNA level according to the local assay being used if the limit of detection is \> 50 copies/mL) for ≥ 6 months preceding the screening visit. Unconfirmed virologic elevation of ≥ 50 copies/mL after previously reaching viral suppression (transient detectable viremia, or "blip") and prior to screening is acceptable
* Have no documented resistance to any of the study agents at any time in the past
* HIV-1 RNA \< 50 copies/mL at the screening visit
* Hepatic transaminases (AST and ALT) ≤ 5 × upper limit of normal (ULN)
* Total bilirubin ≤ 1.5 mg/dL, or normal direct bilirubin
* Adequate hematologic function (absolute neutrophil count ≥ 1,000/mm\^3; platelets ≥ 50,000/mm\^3; hemoglobin ≥ 8.5 g/dL)
* Serum amylase ≤ 5 × ULN (individuals with serum amylase \> 5 × ULN will remain eligible if serum lipase is ≤ 5 × ULN)
* Normal ECG (or if abnormal, determined by the Investigator to be not clinically significant)
* Adequate renal function: Estimated glomerular filtration rate ≥ 50 mL/min according to the Cockcroft-Gault formula
inclusion/
* The ability to understand and sign a written informed consent form, which must be obtained prior to initiation of study procedures
* Currently receiving EFV/FTC/TDF FDC for ≥ 6 consecutive months preceding the screening visit
* Documented plasma HIV-1 RNA levels \< 50 copies/mL (or undetectable HIV-1 RNA level according to the local assay being used if the limit of detection is \> 50 copies/mL) for ≥ 6 months preceding the screening visit. Unconfirmed virologic elevation of ≥ 50 copies/mL after previously reaching viral suppression (transient detectable viremia, or "blip") and prior to screening is acceptable
* Have no documented resistance to any of the study agents at any time in the past
* HIV-1 RNA \< 50 copies/mL at the screening visit
* Hepatic transaminases (AST and ALT) ≤ 5 × upper limit of normal (ULN)
* Total bilirubin ≤ 1.5 mg/dL, or normal direct bilirubin
* Adequate hematologic function (absolute neutrophil count ≥ 1,000/mm\^3; platelets ≥ 50,000/mm\^3; hemoglobin ≥ 8.5 g/dL)
* Serum amylase ≤ 5 × ULN (individuals with serum amylase \> 5 × ULN will remain eligible if serum lipase is ≤ 5 × ULN)
* Normal ECG (or if abnormal, determined by the Investigator to be not clinically significant)
* Adequate renal function: Estimated glomerular filtration rate ≥ 50 mL/min according to the Cockcroft-Gault formula
inclusion/
Gender
All
Gender Based
false
Keywords
HIV
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT02345226
Org Class
Industry
Org Full Name
Gilead Sciences
Org Study Id
GS-US-366-1160
Overall Status
Completed
Phases
Phase 3
Primary Completion Date
Primary Completion Date Type
Actual
Official Title
A Phase 3b, Randomized, Double-Blind Study to Evaluate Switching From a Regimen Consisting of Efavirenz/Emtricitabine/Tenofovir Disoproxil Fumarate (EFV/FTC/TDF) Fixed Dose Combination (FDC) to Emtricitabine/Rilpivirine/ Tenofovir Alafenamide (FTC/RPV/TAF) FDC in Virologically-Suppressed, HIV-1 Infected Subjects
Primary Outcomes
Outcome Description
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.
Outcome Measure
Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48 as Defined by the US FDA-defined Snapshot Algorithm
Outcome Time Frame
Week 48
Secondary Ids
Secondary Id
2014-004779-21
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 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.
Outcome Time Frame
Week 48
Outcome Measure
Percentage of Participants With HIV-1 RNA ≥ 50 Copies/mL at Week 48 as Defined by the US FDA-defined Snapshot Algorithm
Outcome Description
The percentage of participants with HIV-1 RNA ≥ 50 copies/mL at Week 96 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.
Outcome Time Frame
Week 96
Outcome Measure
Percentage of Participants With HIV-1 RNA ≥ 50 Copies/mL at Week 96 as Defined by the US FDA-defined Snapshot Algorithm
Outcome Description
The percentage of participants with HIV-1 RNA \< 50 copies/mL at Week 96 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.
Outcome Time Frame
Week 96
Outcome Measure
Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 96 as Defined by the US FDA-defined Snapshot
Outcome Time Frame
Baseline; Week 48
Outcome Measure
Change From Baseline in CD4+ Cell Count at Week 48
Outcome Time Frame
Baseline; Week 96
Outcome Measure
Change From Baseline in CD4+ Cell Count at Week 96
Outcome Description
Hip BMD was assessed by dual energy x-ray absorptiometry (DXA) scan.
Outcome Time Frame
Baseline; Week 48
Outcome Measure
Percent Change From Baseline in Hip Bone Mineral Density (BMD) at Week 48
Outcome Description
Hip BMD was assessed by DXA scan.
Outcome Time Frame
Baseline; Week 96
Outcome Measure
Percent Change From Baseline in Hip BMD at Week 96
Outcome Description
Spine BMD was assessed by DXA scan.
Outcome Time Frame
Baseline; Week 48
Outcome Measure
Percent Change From Baseline in Spine BMD at Week 48
Outcome Description
Spine BMD was assessed by DXA scan.
Outcome Time Frame
Baseline; Week 96
Outcome Measure
Percent Change From Baseline in Spine BMD at Week 96
Outcome Description
The HIV Symptoms Index was a 20-item, self-reported measure that addressed presence and perceived distress linked to symptoms commonly associated with HIV or its treatment. Twenty HIV symptoms including Fatigue, Fever, Dizziness, Hand/Foot Pain, Memory Loss, Nausea, Diarrhea, Sadness, Nervous/anxious, Sleep Trouble, Skin Problems, Cough, Headache, Appetite Loss, Stomach Pain, Muscle/Joint Pain, Sex Problems, Change in Fat Deposits, Weight Loss, and Hair Loss were assessed. There were 5 possible responses (0 = I don't have this symptom; 1 = It doesn't bother me; 2 = It bothers me a little; 3 = It bothers me; and 4 = It bothers me a lot) for each HIV symptom. Total HIV Symptoms Index Score was derived from all 20 HIV symptoms by counting the number of bothersome symptoms. Total score would be missing if any of the individual items were missing.
Outcome Time Frame
Baseline; Week 48
Outcome Measure
Change From Baseline in HIV Symptoms Index Score (HIVSI) at Week 48
Outcome Description
The HIV Symptoms Index was a 20-item, self-reported measure that addressed presence and perceived distress linked to symptoms commonly associated with HIV or its treatment. Twenty HIV symptoms including Fatigue, Fever, Dizziness, Hand/Foot Pain, Memory Loss, Nausea, Diarrhea, Sadness, Nervous/anxious, Sleep Trouble, Skin Problems, Cough, Headache, Appetite Loss, Stomach Pain, Muscle/Joint Pain, Sex Problems, Change in Fat Deposits, Weight Loss, and Hair Loss were assessed. There were 5 possible responses (0 = I don't have this symptom; 1 = It doesn't bother me; 2 = It bothers me a little; 3 = It bothers me; and 4 = It bothers me a lot) for each HIV symptom. Total HIV Symptoms Index Score was derived from all 20 HIV symptoms by counting the number of bothersome symptoms. Total score would be missing if any of the individual items were missing.
Outcome Time Frame
Baseline; Week 96
Outcome Measure
Change From Baseline in HIVSI Score at Week 96
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
EFAVIRENZ, EMTRICITABINE, TENOFOVIR DISOPROXIL FUMARATE DRUG COMBINATION
TENOFOVIR
ORGANOPHOSPHONATES
ORGANOPHOSPHORUS COMPOUNDS
ORGANIC CHEMICALS
OXAZINES
HETEROCYCLIC COMPOUNDS, 1-RING
HETEROCYCLIC COMPOUNDS
EMTRICITABINE
DEOXYCYTIDINE
CYTIDINE
PYRIMIDINE NUCLEOSIDES
PYRIMIDINES
ADENINE
PURINES
HETEROCYCLIC COMPOUNDS, 2-RING
HETEROCYCLIC COMPOUNDS, FUSED-RING
DRUG COMBINATIONS
PHARMACEUTICAL PREPARATIONS