A Phase 3 Open-label Safety Study of Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide Single-Tablet Regimen in HIV-1 Positive Patients With Mild to Moderate Renal Impairment

Gilead Sciences70 sites in 1 country252 target enrollmentMarch 27, 2013

ConditionsHIV HIV Infections

InterventionsE/C/F/TAF

DrugsE/C/F/TAF

Overview

Phase: Phase 3
Intervention: E/C/F/TAF
Conditions: HIV
Sponsor: Gilead Sciences
Enrollment: 252
Locations: 70
Primary Endpoint: Change From Baseline in the Estimated Glomerular Filtration Rate Calculated by the Cockcroft-Gault Formula (eGFR_CG) at Week 24
Status: Completed
Last Updated: 6 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

The primary objective of this study is to evaluate the effect of elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) fixed-dose combination (FDC) tablet on renal parameters at Week 24 in treatment-naive and treatment-experienced HIV-positive, adults with mild to moderate renal impairment.

Registry

clinicaltrials.gov

Start Date

March 27, 2013

End Date

July 18, 2018

Last Updated

6 years ago

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

Gilead Sciences

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Cohort 1 (treatment-experienced switch)
•Must not have a history of known resistance to elvitegravir (EVG), tenofovir disoproxil fumarate (TDF), or emtricitabine (FTC)
•Plasma HIV-1 RNA concentrations (at least two measurements) at undetectable levels (according to the local assay being used) in the 6 months preceding the screening visit and have HIV-1 RNA \< 50 copies/mL at screening
•Estimated glomerular filtration rate (GFR) 30-69 mL/min according to the Cockcroft-Gault formula for creatinine clearance, using actual weight
•May be currently enrolled in Gilead studies GS-US-236-0102, GS-US-236-0103, and GS-US-216-0114, but will be eligible to enroll only after the Week 144 visit for that study is complete; or currently receiving Stribild® (STB) or atazanavir (ATV)/cobicistat (COBI) + Truvada (TVD) in Gilead studies GS-US-236-0104 or GS-US-216-0105, but will be eligible to enroll only after the Week 48 visit for that study is complete.
•Cohort 2 (treatment-naive)
•Plasma HIV-1 RNA levels ≥ 1,000 copies/mL at screening
•Screening genotype report provided by Gilead Sciences must show sensitivity to EVG, FTC, and TDF
•No prior use of any approved or investigational antiretroviral drug for any length of time, except the use for pre-exposure prophylaxis (PrEP), or post-exposure prophylaxis (PEP), up to 6 months prior to screening
•Estimated GFR 30-69 mL/min according to the Cockcroft Gault formula for creatinine clearance, using actual weight

Exclusion Criteria

•A new AIDS-defining condition (excluding CD4 cell count and percentage criteria) diagnosed within the 30 days prior to screening,with the exception of the first two bullet points
•Hepatitis C virus (HCV) antibody positive. Individuals who are HCV positive, but have a documented negative HCV RNA, are eligible
•Hepatitis B surface antigen (HBVsAg) positive
•Individuals receiving drug treatment for Hepatitis C, or individuals who are anticipated to receive treatment for Hepatitis C during the course of the study
•Individuals experiencing decompensated cirrhosis (eg, ascites, encephalopathy, etc.)
•Females who are breastfeeding
•Positive serum pregnancy test
•Have an implanted defibrillator or pacemaker
•Current alcohol or substance use judged by the Investigator to potentially interfere with study compliance
•A history of malignancy within the past 5 years or ongoing malignancy other than cutaneous Kaposi's sarcoma, basal cell carcinoma, or resected, non-invasive cutaneous squamous carcinoma

Arms & Interventions

E/C/F/TAF

Participants will receive E/C/F/TAF for 144 weeks. Following Week 144, in countries where E/C/F/TAF is not available (except for the United Kingdom), participants will be given the option to continue in the study and receive E/C/F/TAF for another 48 weeks, or until the product becomes available through an access program, or until Gilead Sciences elects to discontinue the study in that country, whichever comes first.

Intervention: E/C/F/TAF

Outcomes

Primary Outcomes

Change From Baseline in the Estimated Glomerular Filtration Rate Calculated by the Cockcroft-Gault Formula (eGFR_CG) at Week 24

Time Frame: Baseline; Week 24

eGFR is a measurement of the kidney's ability to filter blood.

Change From Baseline in eGFR Calculated by the Chronic Kidney Disease Epidemiology Collaboration Method Based on Cystatin C (eGFR_CKD-EPI,cysC) at Week 24

Time Frame: Baseline; Week 24

eGFR is a measurement of the kidney's ability to filter blood. The eGFR_CKD-EPI,cysC method is adjusted for age and sex.

Change From Baseline in eGFR Calculated by the CKD-EPI Method Based on Serum Creatinine (eGFR_CKD-EPI,Creatinine) at Week 24

Time Frame: Baseline; Week 24

eGFR is a measurement of the kidney's ability to filter blood. The eGFR_CKD-EPI,creatinine method is adjusted for age, race, and sex.

Secondary Outcomes

Change From Baseline in Actual GFR (aGFR) of E/C/F/TAF for Participants Enrolled in the PK/PD Substudy(Baseline; Week 2, 4, or 8; Week 24)
Percentage of Participants Experiencing Adverse Events or Graded Laboratory Abnormalities(Baseline up to Week 240 plus 30 days)
PK Parameter: Clast of TAF(Predose, and 5 minutes, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 8, and 24 hours postdose)
PK Parameter: Tlast of TAF(Predose, and 5 minutes, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 8, and 24 hours postdose)
Percentage of Participants Achieving HIV-1 RNA < 50 Copies/mL at Weeks 24, 48, 96, and 144(Weeks 24, 48, 96, and 144)
Percent Change From Baseline in C-type Collagen Sequence (CTX) at Weeks 24 and 48(Baseline; Weeks 24 and 48)
Percent Change From Baseline in Procollagen Type 1 N-terminal Propeptide (P1NP) at Weeks 24 and 48(Baseline; Weeks 24 and 48)
Percent Change From Baseline in Retinol Binding Protein (RBP) to Creatinine Ratio (μg/g) at Weeks 24, 48, 96, and 144(Baseline; Weeks 24, 48, 96, and 144)
PK Parameter: AUCtau of Tenofovir Diphosphate (TFV-DP) in Peripheral Blood Mononuclear Cell (PBMC) for Participants Enrolled in PK/PD Sub-study(Predose, and 5 minutes, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 8, and 24 hours postdose)
Percent Change From Baseline in Urine Beta-2-microglobulin to Creatinine Ratio (μg/g) at Weeks 24, 48, 96, and 144(Baseline; Weeks 24, 48, 96, and 144)
Pharmacokinetic (PK) Parameter: Cmax of TAF(Predose, and 5 minutes, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 8, and 24 hours postdose)
PK Parameter: Tmax of TAF(Predose, and 5 minutes, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 8, and 24 hours postdose)
PK Parameter: t1/2 of TAF(Predose, and 5 minutes, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 8, and 24 hours postdose)
PK Parameter: λz of TAF(Predose, and 5 minutes, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 8, and 24 hours postdose)
PK Parameter: AUCtau of TAF(Predose, and 5 minutes, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 8, and 24 hours postdose)
Change From Baseline in eGFR_CKD-EPI,cysC at Weeks 48, 96, and 144(Baseline; Weeks 48, 96, and 144)
Change From Baseline in the eGFR_CG at Weeks 48, 96, and 144(Baseline; Weeks 48, 96, and 144)
Change From Baseline in eGFR_CKD-EPI,Creatinine at Weeks 48, 96, and 144(Baseline; Weeks 48, 96, and 144)