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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

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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:
Information provided by (Responsible Party):
Gilead Sciences

Tracking Information
First Submitted Date  ICMJE November 6, 2015
First Posted Date  ICMJE November 9, 2015
Results First Submitted Date  ICMJE September 21, 2018
Results First Posted Date  ICMJE October 16, 2018
Last Update Posted Date November 5, 2020
Actual Study Start Date  ICMJE December 14, 2015
Actual Primary Completion Date September 29, 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (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  ICMJE
 (submitted: November 6, 2015)
Incidence of treatment-emergent grade 3 or higher adverse events [ Time Frame: Week 48 ]
Change History
Current Secondary Outcome Measures  ICMJE
 (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  ICMJE
 (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  ICMJE 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  ICMJE 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  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE HIV-1 Infection
Intervention  ICMJE
  • 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  ICMJE
  • 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]

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: January 3, 2017)
55
Original Estimated Enrollment  ICMJE
 (submitted: November 6, 2015)
50
Actual Study Completion Date  ICMJE October 15, 2019
Actual Primary Completion Date September 29, 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Austria,   France,   Germany,   United States
Removed Location Countries United Kingdom
 
Administrative Information
NCT Number  ICMJE NCT02600819
Other Study ID Numbers  ICMJE 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  ICMJE
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  ICMJE Gilead Sciences
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Gilead Study Director Gilead Sciences
PRS Account Gilead Sciences
Verification Date October 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP