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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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
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

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).

Condition or disease Intervention/treatment Phase
HIV-1 Infection Drug: E/C/F/TAF Drug: B/F/TAF Phase 3

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 55 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : December 14, 2015
Actual Primary Completion Date : September 29, 2017
Actual Study Completion Date : October 15, 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Dialysis HIV/AIDS

Arm Intervention/treatment
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.
Drug: E/C/F/TAF
150/150/200/10 mg FDC tablets administered orally once daily
Other Name: Genvoya®

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.
Drug: B/F/TAF
50/200/25 mg FDC tablets administered orally once daily
Other Name: Biktarvy®




Primary Outcome Measures :
  1. 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).


Secondary Outcome Measures :
  1. 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).

  2. 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.

  3. 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.

  4. 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.

  5. 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).

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. GEN Phase: Change From Baseline in Cluster Determinant 4+ (CD4+) Cell Count at Week 96 [ Time Frame: Baseline; Week 96 ]
  13. 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 ]
  14. GEN Phase: Change From Baseline in CD4 Percentage at Week 96 [ Time Frame: Baseline; Week 96 ]
  15. BVY OL Extension Phase: Change From Baseline in CD4 Percentage at Week 48 [ Time Frame: Baseline; Week 48 of the BVY OL Extension Phase ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02600819


Locations
Show Show 26 study locations
Sponsors and Collaborators
Gilead Sciences
Investigators
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Study Director: Gilead Study Director Gilead Sciences
  Study Documents (Full-Text)

Documents provided by Gilead Sciences:
Statistical Analysis Plan  [PDF] December 2, 2019
Study Protocol: Original  [PDF] July 8, 2015
Study Protocol: Amendment 1  [PDF] October 13, 2015
Study Protocol: Amendment 2  [PDF] November 28, 2016
Study Protocol: Amendment 2.1  [PDF] May 1, 2018

Publications:
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Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT02600819    
Other Study ID Numbers: GS-US-292-1825
2015-002713-30 ( EudraCT Number )
First Posted: November 9, 2015    Key Record Dates
Results First Posted: October 16, 2018
Last Update Posted: November 5, 2020
Last Verified: October 2020
Individual Participant Data (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
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

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Gilead Sciences:
End stage renal disease
Hemodialysis
Open-label
HIV-1 Infection
Additional relevant MeSH terms:
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Infection
Genvoya
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents