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

HIV-1 Infection Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02600819
• Other study ID #: GS-US-292-1825
• Secondary ID: 2015-002713-30
• Status: Completed
• Phase: Phase 3
• Start date: December 14, 2015
• Est. completion date: October 15, 2019

Study information

• Verified date: October 2020
• Source: Gilead Sciences
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 55
• Est. completion date: October 15, 2019
• Est. primary completion date: September 29, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• HIV-1 Infection
• Infection

Intervention

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

Locations

Country	Name	City	State
Austria	Otto Wagner Spital	Wien
France	Hopital Henri Mondor	Creteil
France	CHU de Nice-l Archet	NICE Cedex 03
France	Hopital Bichat-Claude Bernard	Paris
France	Hopital Saint Louis	Paris Cedex 10
France	Centre Hospitalier de Tourcoing	Tourcoing Cedex
Germany	Klinikum rechts der Isar, TUM	Munchen
United States	Medical College of Georgia	Augusta	Georgia
United States	University of North Carolina at Chapel Hill / UNC School of Medicine	Chapel Hill	North Carolina
United States	University of Cincinnati Med Center	Cincinnati	Ohio
United States	MetroHealth Medical Center IRB	Cleveland	Ohio
United States	North Texas Infectious Diseases Consultants	Dallas	Texas
United States	Infectious Disease Specialists of Atlanta	Decatur	Georgia
United States	Henry Ford Health System	Detroit	Michigan
United States	Duke University	Durham	North Carolina
United States	Midway Immunology & Research Center, LLC	Fort Pierce	Florida
United States	Trinity Health and Wellness Center	Fort Worth	Texas
United States	Gordon E. Crofoot MD PA	Houston	Texas
United States	Peter J Ruane MD Inc	Los Angeles	California
United States	Mercer University School of Medicine	Macon	Georgia
United States	Prime Health Care Services - St Michael's LLC d/b/a Saint Michael's Medical Center	Newark	New Jersey
United States	Infectious Disease Consultants, M.D., P.A. d/b/a Orlando Immunology Center	Orlando	Florida
United States	University of California Davis	Sacramento	California
United States	The Research Institute	Springfield	Massachusetts
United States	Triple O Research Institute PA	West Palm Beach	Florida
United States	Wake Forest University Baptist Medical Center	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Gilead Sciences

Countries where clinical trial is conducted

United States,  Austria,  France,  Germany, 

References & Publications (1)

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] — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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).	First Dose Date Up to Week 48
Secondary	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).	First Dose Date Up to Week 96
Secondary	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.	Week 24
Secondary	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.	Week 48
Secondary	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.	Week 96
Secondary	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).	0.5, 1, 2, 3, 4, 6, 8, and 24 hours postdose at or between Week 2 or Week 4
Secondary	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.	0.5, 1, 2, 3, 4, 6, 8, and 24 hours postdose at or between Week 2 or Week 4
Secondary	PK Parameter: Cmax of EVG, COBI, FTC, TAF, and TFV	Cmax is defined as the maximum concentration of drug.	0.5, 1, 2, 3, 4, 6, 8, and 24 hours postdose at or between Week 2 or Week 4
Secondary	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.	0.5, 1, 2, 3, 4, 6, 8, and 24 hours postdose at or between Week 2 or Week 4
Secondary	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.	Week 96
Secondary	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.	Week 96
Secondary	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.	Week 48 of the BVY OL Extension Phase
Secondary	GEN Phase: Change From Baseline in Cluster Determinant 4+ (CD4+) Cell Count at Week 96		Baseline; Week 96
Secondary	BVY OL Extension Phase: Change From Baseline in CD4+ Cell Count at Week 48		Baseline; Week 48 of the BVY OL Extension Phase
Secondary	GEN Phase: Change From Baseline in CD4 Percentage at Week 96		Baseline; Week 96
Secondary	BVY OL Extension Phase: Change From Baseline in CD4 Percentage at Week 48		Baseline; Week 48 of the BVY OL Extension Phase