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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

Primary Purpose

HIV-1 Infection

Status

Completed

Phase

Phase 3

Locations

International

Study Type

Interventional

Intervention

E/C/F/TAF

B/F/TAF

About this trial

This is an interventional treatment trial for HIV-1 Infection focused on measuring End stage renal disease, Hemodialysis, Open-label, HIV-1 Infection

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

Peter J Ruane MD Inc
University of California Davis
Midway Immunology & Research Center, LLC
Infectious Disease Consultants, M.D., P.A. d/b/a Orlando Immunology Center
Triple O Research Institute PA
Medical College of Georgia
Infectious Disease Specialists of Atlanta
Mercer University School of Medicine
The Research Institute
Henry Ford Health System
Prime Health Care Services - St Michael's LLC d/b/a Saint Michael's Medical Center
University of North Carolina at Chapel Hill / UNC School of Medicine
Duke University
Wake Forest University Baptist Medical Center
University of Cincinnati Med Center
MetroHealth Medical Center IRB
North Texas Infectious Diseases Consultants
Trinity Health and Wellness Center
Gordon E. Crofoot MD PA
Otto Wagner Spital
Hopital Henri Mondor
CHU de Nice-l Archet
Hopital Saint Louis
Hopital Bichat-Claude Bernard
Centre Hospitalier de Tourcoing
Klinikum rechts der Isar, TUM

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

E/C/F/TAF

Open-Label Rollover Extension B/F/TAF

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

GEN Phase: Percentage of Participants Experiencing Treatment-Emergent Grade 3 or Higher Adverse Events 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

GEN Phase: Percentage of Participants Experiencing Treatment-Emergent Grade 3 or Higher Adverse Events 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

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

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

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)

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

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

Cmax is defined as the maximum concentration of drug.

PK Parameter: Ctau of EVG, COBI, FTC, and TFV

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

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

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

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

BVY OL Extension Phase: Change From Baseline in CD4+ Cell Count at Week 48

GEN Phase: Change From Baseline in CD4 Percentage at Week 96

BVY OL Extension Phase: Change From Baseline in CD4 Percentage at Week 48

Full Information

NCT ID

NCT02600819

First Posted

November 6, 2015

Last Updated

October 13, 2020

Sponsor

Gilead Sciences

1. Study Identification

Unique Protocol Identification Number

NCT02600819

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

Study Type

Interventional

2. Study Status

Record Verification Date

October 2020

Overall Recruitment Status

Completed

Study Start Date

December 14, 2015 (Actual)

Primary Completion Date

September 29, 2017 (Actual)

Study Completion Date

October 15, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Gilead Sciences

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

HIV-1 Infection

Keywords

End stage renal disease, Hemodialysis, Open-label, HIV-1 Infection

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

55 (Actual)

8. Arms, Groups, and Interventions

Arm Title

E/C/F/TAF

Arm Type

Experimental

Arm Description

Arm Title

Open-Label Rollover Extension B/F/TAF

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

E/C/F/TAF

Other Intervention Name(s)

Genvoya®

Intervention Description

150/150/200/10 mg FDC tablets administered orally once daily

Intervention Type

Drug

Intervention Name(s)

B/F/TAF

Other Intervention Name(s)

Biktarvy®

Intervention Description

50/200/25 mg FDC tablets administered orally once daily

Primary Outcome Measure Information:

Title

GEN Phase: Percentage of Participants Experiencing Treatment-Emergent Grade 3 or Higher Adverse Events Up to Week 48

Description

Time Frame

First Dose Date Up to Week 48

Secondary Outcome Measure Information:

Title

GEN Phase: Percentage of Participants Experiencing Treatment-Emergent Grade 3 or Higher Adverse Events Up to Week 96

Description

Time Frame

First Dose Date Up to Week 96

Title

GEN Phase: Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 24 as Defined by the FDA Snapshot Algorithm

Description

Time Frame

Week 24

Title

GEN Phase: Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48 as Defined by the FDA Snapshot Algorithm

Description

Time Frame

Week 48

Title

GEN Phase: Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 96 as Defined by the FDA Snapshot Algorithm

Description

Time Frame

Week 96

Title

Pharmacokinetic (PK) Parameter: AUCtau of Elvitegravir (EVG), Cobicistat (COBI), Emtricitabine (FTC), and Tenofovir (TFV)

Description

AUCtau is defined as area under the concentration versus time curve over the dosing interval (i.e., concentration of drug over time).

Time Frame

0.5, 1, 2, 3, 4, 6, 8, and 24 hours postdose at or between Week 2 or Week 4

Title

PK Parameter: AUClast of EVG, COBI, FTC, Tenofovir Alafenamide (TAF), and TFV

Description

AUClast is defined as the area under the concentration versus time curve from time zero to the last observable concentration.

Time Frame

0.5, 1, 2, 3, 4, 6, 8, and 24 hours postdose at or between Week 2 or Week 4

Title

PK Parameter: Cmax of EVG, COBI, FTC, TAF, and TFV

Description

Cmax is defined as the maximum concentration of drug.

Time Frame

0.5, 1, 2, 3, 4, 6, 8, and 24 hours postdose at or between Week 2 or Week 4

Title

PK Parameter: Ctau of EVG, COBI, FTC, and TFV

Description

Time Frame

0.5, 1, 2, 3, 4, 6, 8, and 24 hours postdose at or between Week 2 or Week 4

Title

GEN Phase: Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 96 Using the Missing = Failure (M = F) Approach

Description

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.

Time Frame

Week 96

Title

GEN Phase: Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 96 Using the Missing = Excluded (M = E) Approach

Description

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.

Time Frame

Week 96

Title

BVY OL Extension Phase: Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48 Using the M = E Approach

Description

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.

Time Frame

Week 48 of the BVY OL Extension Phase

Title

GEN Phase: Change From Baseline in Cluster Determinant 4+ (CD4+) Cell Count at Week 96

Time Frame

Baseline; Week 96

Title

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

Title

GEN Phase: Change From Baseline in CD4 Percentage at Week 96

Time Frame

Baseline; Week 96

Title

BVY OL Extension Phase: Change From Baseline in CD4 Percentage at Week 48

Time Frame

Baseline; Week 48 of the BVY OL Extension Phase

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Gilead Study Director

Organizational Affiliation

Gilead Sciences

Official's Role

Study Director

Facility Information:

Facility Name

Peter J Ruane MD Inc

City

Los Angeles

State/Province

California

Country

United States

Facility Name

University of California Davis

City

Sacramento

State/Province

California

Country

United States

Facility Name

Midway Immunology & Research Center, LLC

City

Fort Pierce

State/Province

Florida

Country

United States

Facility Name

Infectious Disease Consultants, M.D., P.A. d/b/a Orlando Immunology Center

City

Orlando

State/Province

Florida

Country

United States

Facility Name

Triple O Research Institute PA

City

West Palm Beach

State/Province

Florida

Country

United States

Facility Name

Medical College of Georgia

City

Augusta

State/Province

Georgia

Country

United States

Facility Name

Infectious Disease Specialists of Atlanta

City

Decatur

State/Province

Georgia

Country

United States

Facility Name

Mercer University School of Medicine

City

Macon

State/Province

Georgia

Country

United States

Facility Name

The Research Institute

City

Springfield

State/Province

Massachusetts

Country

United States

Facility Name

Henry Ford Health System

City

Detroit

State/Province

Michigan

Country

United States

Facility Name

Prime Health Care Services - St Michael's LLC d/b/a Saint Michael's Medical Center

City

Newark

State/Province

New Jersey

Country

United States

Facility Name

University of North Carolina at Chapel Hill / UNC School of Medicine

City

Chapel Hill

State/Province

North Carolina

Country

United States

Facility Name

Duke University

City

Durham

State/Province

North Carolina

Country

United States

Facility Name

Wake Forest University Baptist Medical Center

City

Winston-Salem

State/Province

North Carolina

Country

United States

Facility Name

University of Cincinnati Med Center

City

Cincinnati

State/Province

Ohio

Country

United States

Facility Name

MetroHealth Medical Center IRB

City

Cleveland

State/Province

Ohio

Country

United States

Facility Name

North Texas Infectious Diseases Consultants

City

Dallas

State/Province

Texas

Country

United States

Facility Name

Trinity Health and Wellness Center

City

Fort Worth

State/Province

Texas

Country

United States

Facility Name

Gordon E. Crofoot MD PA

City

Houston

State/Province

Texas

Country

United States

Facility Name

Otto Wagner Spital

City

Wien

Country

Austria

Facility Name

Hopital Henri Mondor

City

Creteil

Country

France

Facility Name

CHU de Nice-l Archet

City

NICE Cedex 03

Country

France

Facility Name

Hopital Saint Louis

City

Paris Cedex 10

Country

France

Facility Name

Hopital Bichat-Claude Bernard

City

Paris

Country

France

Facility Name

Centre Hospitalier de Tourcoing

City

Tourcoing Cedex

Country

France

Facility Name

Klinikum rechts der Isar, TUM

City

Munchen

Country

Germany

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing 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.

IPD Sharing Time Frame

18 months after study completion

IPD Sharing Access Criteria

A secured external environment with username, password, and RSA code.

IPD Sharing URL

https://www.gilead.com/science-and-medicine/research/clinical-trials-transparency-and-data-sharing-policy

Citations:

PubMed Identifier

30555051

Citation

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:S2352-3018(18)30296-0. doi: 10.1016/S2352-3018(18)30296-0. Online ahead of print.

Results Reference

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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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