Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of E/C/F/TAF Fixed Dose Combination (FDC) in HIV-1 Infected Adults on Chronic Hemodialysis

• ClinicalTrials.gov Identifier: NCT02600819
• Recruitment Status: Completed
• First Posted: November 9, 2015
• Results First Posted: October 16, 2018
• Last Update Posted: November 5, 2020
• Sponsor: Gilead Sciences
• Information provided by (Responsible Party): Gilead Sciences

Tracking Information

• First Submitted Date: November 6, 2015
• First Posted Date: November 9, 2015
• Results First Submitted Date: September 21, 2018
• Results First Posted Date: October 16, 2018
• Last Update Posted Date: November 5, 2020
• Actual Study Start Date: December 14, 2015
• Actual Primary Completion Date: September 29, 2017 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 13, 2020)

GEN Phase: Percentage of Participants Experiencing Treatment-Emergent Grade 3 or Higher Adverse Events Up to Week 48 [ Time Frame: First Dose Date Up to Week 48 ]

Treatment-emergent Adverse Events (TEAE) were defined as AEs with onset dates on or after the study drug start date and no later than 30 days after the permanent discontinuation of the E/C/F/TAF (GEN Phase) study drug or all AEs for participants still on E/C/F/TAF. It also includes the AEs that led to premature discontinuation of E/C/F/TAF study drug. Clinical events and clinically significant laboratory abnormalities were graded according to the GSI Grading Scale for Severity of Adverse Events and Laboratory Abnormalities. Adverse events were graded as Grade 1 (mild), Grade 2 (moderate), Grade 3 (severe), or Grade 4 (life threatening).

• Original Primary Outcome Measures (submitted: November 6, 2015): Incidence of treatment-emergent grade 3 or higher adverse events [ Time Frame: Week 48 ]

Current Secondary Outcome Measures (submitted: October 13, 2020)

• GEN Phase: Percentage of Participants Experiencing Treatment-Emergent Grade 3 or Higher Adverse Events Up to Week 96 [ Time Frame: First Dose Date Up to Week 96 ]
  Treatment-emergent Adverse Events (TEAE) were defined as events that met 1 or both of the following criteria as any AEs with onset dates on or after the study drug start date and no later than 30 days after the permanent discontinuation of the E/C/F/TAF (GEN Phase) study drug for participants who did not participate in the BVY OL extension phase or the day prior to the date of the first B/F/TAF study drug dose for participants who participated in the BVY OL extension phase. It also includes the AEs that led to premature discontinuation of E/C/F/TAF study drug. Clinical events and clinically significant laboratory abnormalities were graded according to the GSI Grading Scale for Severity of Adverse Events and Laboratory Abnormalities. Adverse events were graded as Grade 1 (mild), Grade 2 (moderate), Grade 3 (severe), or Grade 4 (life threatening).
• GEN Phase: Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 24 as Defined by the FDA Snapshot Algorithm [ Time Frame: Week 24 ]
  The percentage of participants with HIV-1 RNA < 50 copies/mL at Week 24 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.
• GEN Phase: Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48 as Defined by the FDA Snapshot Algorithm [ Time Frame: Week 48 ]
  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.
• GEN Phase: Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 96 as Defined by the FDA Snapshot Algorithm [ Time Frame: Week 96 ]
  The percentage of participants with HIV-1 RNA < 50 copies/mL at Week 96 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.
• Pharmacokinetic (PK) Parameter: AUCtau of Elvitegravir (EVG), Cobicistat (COBI), Emtricitabine (FTC), and Tenofovir (TFV) [ Time Frame: 0.5, 1, 2, 3, 4, 6, 8, and 24 hours postdose at or between Week 2 or Week 4 ]
  AUCtau is defined as area under the concentration versus time curve over the dosing interval (i.e., concentration of drug over time).
• PK Parameter: AUClast of EVG, COBI, FTC, Tenofovir Alafenamide (TAF), and TFV [ Time Frame: 0.5, 1, 2, 3, 4, 6, 8, and 24 hours postdose at or between Week 2 or Week 4 ]
  AUClast is defined as the area under the concentration versus time curve from time zero to the last observable concentration.
• PK Parameter: Cmax of EVG, COBI, FTC, TAF, and TFV [ Time Frame: 0.5, 1, 2, 3, 4, 6, 8, and 24 hours postdose at or between Week 2 or Week 4 ]
  Cmax is defined as the maximum concentration of drug.
• PK Parameter: Ctau of EVG, COBI, FTC, and TFV [ Time Frame: 0.5, 1, 2, 3, 4, 6, 8, and 24 hours postdose at or between Week 2 or Week 4 ]
  Ctau is defined as the observed drug concentration at the end of the dosing interval. Ctau has been presented in lieu of Cmin (specified in the protocol) to align with other Gilead studies. This change has no impact on the PK analysis as Ctau and Cmin are equivalent for all analytes.
• GEN Phase: Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 96 Using the Missing = Failure (M = F) Approach [ Time Frame: Week 96 ]
  The percentage of participants with HIV-1 RNA < 50 copies/mL at Week 96 were analyzed using the M = F approach. In this approach, all missing data was treated as HIV-1 RNA ≥ 50 copies/mL.
• GEN Phase: Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 96 Using the Missing = Excluded (M = E) Approach [ Time Frame: Week 96 ]
  The percentage of participants with HIV-1 RNA < 50 copies/mL at Week 96 were analyzed using the M = E approach. In this approach, all missing data was excluded in the computation of the proportions.
• BVY OL Extension Phase: Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48 Using the M = E Approach [ Time Frame: Week 48 of the BVY OL Extension Phase ]
  The percentage of participants with HIV-1 RNA < 50 copies/mL at Week 48 were analyzed using the M = E approach. In this approach, all missing data was excluded in the computation of the proportions.
• GEN Phase: Change From Baseline in Cluster Determinant 4+ (CD4+) Cell Count at Week 96 [ Time Frame: Baseline; Week 96 ]
• BVY OL Extension Phase: Change From Baseline in CD4+ Cell Count at Week 48 [ Time Frame: Baseline; Week 48 of the BVY OL Extension Phase ]
• GEN Phase: Change From Baseline in CD4 Percentage at Week 96 [ Time Frame: Baseline; Week 96 ]
• BVY OL Extension Phase: Change From Baseline in CD4 Percentage at Week 48 [ Time Frame: Baseline; Week 48 of the BVY OL Extension Phase ]

Original Secondary Outcome Measures (submitted: November 6, 2015)

• Proportion of participants with HIV-1 RNA < 50 copies/mL as defined by the FDA snapshot algorithm [ Time Frame: Weeks 24 and 48 ]
• Pharmacokinetic (PK) Parameter: AUCtau of elvitegravir (EVG), cobicistat (COBI), emtricitabine (FTC), tenofovir alafenamide (TAF), and tenofovir (TFV) [ Time Frame: 0.5, 1, 2, 3, 4, 6, 8, and 24 hours postdose ]
  AUCtau is defined as concentration of drug over time.
• PK Parameter: AUClast of EVG, COBI, FTC, TAF, and TFV [ Time Frame: 0.5, 1, 2, 3, 4, 6, 8, and 24 hours postdose ]
  AUClast is defined as the concentration of drug from time zero to the last observable concentration.
• PK Parameter: Cmax of EVG, COBI, FTC, TAF, and TFV [ Time Frame: 0.5, 1, 2, 3, 4, 6, 8, and 24 hours postdose ]
  Cmax is defined as the maximum concentration of drug.
• PK Parameter: Cmin of EVG, COBI, FTC, TAF, and TFV [ Time Frame: 0.5, 1, 2, 3, 4, 6, 8, and 24 hours postdose ]
  Cmin is defined as the minimum observed concentration of drug.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of E/C/F/TAF Fixed Dose Combination (FDC) in HIV-1 Infected Adults on Chronic Hemodialysis
• Official Title: A Phase 3b Open-Label Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Efficacy of E/C/F/TAF Fixed Dose Combination (FDC) in HIV-1 Infected Subjects on Chronic Hemodialysis
• Brief Summary: The primary objective of this study is to evaluate the safety and tolerability of elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) fixed-dose combination (FDC) in human immunodeficiency virus (HIV-1) infected adults with end-stage renal disease (ESRD) on chronic hemodialysis (HD).
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Non-Randomized; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: HIV-1 Infection

Intervention

• Drug: E/C/F/TAF
  150/150/200/10 mg FDC tablets administered orally once daily
  Other Name: Genvoya®
• Drug: B/F/TAF
  50/200/25 mg FDC tablets administered orally once daily
  Other Name: Biktarvy®

Study Arms

• Experimental: E/C/F/TAF
  Participants will switch their current antiretroviral regimen to E/C/F/TAF and receive treatment for 96 weeks. After Week 96, participants in the United States (US) who wish to participate in the open-label (OL) rollover extension will continue to take E/C/F/TAF FDC until the End of E/C/F/TAF Visit.
  Intervention: Drug: E/C/F/TAF
• Experimental: Open-Label Rollover Extension B/F/TAF
  At Week 96 or the End of E/C/F/TAF Visit (whichever occurs last), participants will be given the option to receive open-label bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) for at least 48 weeks.
  Intervention: Drug: B/F/TAF

• Publications *: Eron JJ Jr, Lelievre JD, Kalayjian R, Slim J, Wurapa AK, Stephens JL, McDonald C, Cua E, Wilkin A, Schmied B, McKellar M, Cox S, Majeed SR, Jiang S, Cheng A, Das M, SenGupta D. Safety of elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide in HIV-1-infected adults with end-stage renal disease on chronic haemodialysis: an open-label, single-arm, multicentre, phase 3b trial. Lancet HIV. 2018 Dec 13. pii: S2352-3018(18)30296-0. doi: 10.1016/S2352-3018(18)30296-0. [Epub ahead of print]

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: January 3, 2017): 55
• Original Estimated Enrollment (submitted: November 6, 2015): 50
• Actual Study Completion Date: October 15, 2019
• Actual Primary Completion Date: September 29, 2017 (Final data collection date for primary outcome measure)

Eligibility Criteria

Key Inclusion Criteria:

• Currently on a stable antiretroviral regimen for ≥ 6 consecutive months
• Plasma HIV-1 ribonucleic acid (RNA) concentrations < 50 copies/mL for ≥ 6 months preceding the screening visit and have HIV-1 RNA < 50 copies/mL at screening
• No documented history of HIV-1 resistance to elvitegravir (EVG), emtricitabine (FTC), lamivudine (3TC) or tenofovir (TFV) and no history of switching off EVG, FTC, 3TC or TFV due to concern for resistance
• Cluster determinant 4 (CD4+) T cell count ≥ 200 cells/μL
• ESRD with estimated glomerular filtration rate (eGFR) < 15 mL/min by Cockcroft-Gault formula for creatinine clearance
• On chronic HD for ≥ 6 months prior to screening
• Adequate hematologic function (absolute neutrophil count ≥ 1,000/mm^3; platelets ≥ 50,000/mm^3; hemoglobin ≥ 8.5 g/dL)

Key Exclusion Criteria:

• Hepatitis B co-infection
• Any clinical history, condition, or test result that, in the opinion of the Investigator, would make the individual unsuitable for the study or unable to comply with dosing requirements
• Administration of other investigational agents (unless approved by Gilead Sciences). Participation in any other clinical trial, including observational trials, without prior approval from the sponsor is prohibited while participating in this trial.
• History or presence of allergy or intolerance to the study drugs or their components
• A new acquired immunodeficiency syndrome (AIDS)-defining condition (excluding CD4+ T cell count and percentage criteria) diagnosed within the 30 days prior to screening, with the exception of oropharyngeal candidiasis
• Received solid organ or bone marrow transplant

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Austria, France, Germany, United States
• Removed Location Countries: United Kingdom

Administrative Information

• NCT Number: NCT02600819
• Other Study ID Numbers: GS-US-292-1825; 2015-002713-30 ( EudraCT Number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: Qualified external researchers may request IPD for this study after study completion. For more information, please visit our website at https://www.gilead.com/science-and-medicine/research/clinical-trials-transparency-and-data-sharing-policy.
• Supporting Materials: Study Protocol
• Supporting Materials: Statistical Analysis Plan (SAP)
• Time Frame: 18 months after study completion
• Access Criteria: A secured external environment with username, password, and RSA code.
• URL: https://www.gilead.com/science-and-medicine/research/clinical-trials-transparency-and-data-sharing-policy

• Responsible Party: Gilead Sciences
• Study Sponsor: Gilead Sciences
• Collaborators: Not Provided

Investigators

• Study Director: Gilead Study Director; Gilead Sciences

• PRS Account: Gilead Sciences
• Verification Date: October 2020