Safety and Efficacy of Bictegravir + Emtricitabine/Tenofovir Alafenamide Versus Dolutegravir + Emtricitabine/Tenofovir Alafenamide in HIV-1 Infected, Antiretroviral Treatment-Naive Adults

HIV-1 Infection Clinical Trial

Official title:

A Phase 2, Randomized, Double-Blinded Study of the Safety and Efficacy of GS-9883 + Emtricitabine/Tenofovir Alafenamide Versus Dolutegravir + Emtricitabine/Tenofovir Alafenamide in HIV-1 Infected, Antiretroviral Treatment-Naive Adults

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02397694
• Other study ID #: GS-US-141-1475
• Status: Completed
• Phase: Phase 2
• Start date: March 23, 2015
• Est. completion date: February 27, 2019

Study information

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

Clinical Trial Summary

This study will evaluate the efficacy, safety and tolerability of bictegravir (BIC) + emtricitabine/tenofovir alafenamide (F/TAF) fixed dose combination (FDC) versus dolutegravir (DTG) + F/TAF in HIV-1 Infected, antiretroviral treatment-naive adults. This study will also evaluate the pharmacokinetic (PK) profile of BIC, emtricitabine and TAF.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 98
• Est. completion date: February 27, 2019
• Est. primary completion date: November 30, 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Key Inclusion Criteria:

• Antiretroviral naive (= 10 days of prior therapy with any antiretroviral agent)

• Plasma HIV-1 RNA levels = 1,000 copies/mL at screening

• Screening genotype report provided by Gilead Sciences must show sensitivity to tenofovir (TFV) and emtricitabine (FTC)

• Adequate renal function as measured by estimated glomerular filtration rate = 70 mL/min according to the Cockcroft-Gault formula

• CD4+ cell count = 200 cells/µL at screening

Key Exclusion Criteria:

• A new AIDS-defining condition diagnosed within the 30 days prior to screening as defined in the study protocol

• Prior use of antiretrovirals in the setting of pre-exposure prophylaxis (PrEP) or post exposure prophylaxis (PEP)

• Chronic hepatitis B virus (HBV) infection

• Hepatitis C infection (Individuals who are hepatitis C virus (HCV) Ab positive, but have a documented negative HCV RNA, are eligible)

• Active, serious infections (other than HIV-1 infection) requiring parenteral antibiotic or antifungal therapy within 30 days prior to baseline

• Participation in any other clinical trial without prior approval from the sponsor is prohibited while participating in this trial

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

Related Conditions & MeSH terms

• HIV-1 Infection

Intervention

Drug:
• BIC
75 mg tablet administered orally once daily
• F/TAF
200/25 mg FDC tablet administered orally once daily
• DTG
50 mg tablet administered orally once daily
• BIC Placebo
Tablet administered orally once daily
• DTG Placebo
Tablet administered orally once daily
• B/F/TAF
50/200/25 mg FDC tablet administered orally once daily

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Gilead Sciences

Country where clinical trial is conducted

United States, 

References & Publications (2)

Sax PE, DeJesus E, Crofoot G, Ward D, Benson P, Dretler R, Mills A, Brinson C, Peloquin J, Wei X, White K, Cheng A, Martin H, Quirk E. Bictegravir versus dolutegravir, each with emtricitabine and tenofovir alafenamide, for initial treatment of HIV-1 infec — View Citation

Sax PE, DeJesus E, Crofoot G, Ward D, Benson P, Dretler R, Mills A, Brinson C, Wei X, Collins SE, Cheng A. Coformulated bictegravir, emtricitabine, tenofovir alafenamide after initial treatment with bictegravir or dolutegravir and emtricitabine/tenofovir — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants With HIV-1 RNA < 50 Copies/mL as Determined by the FDA-defined Snapshot Algorithm.	The percentage of participants achieving 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	Percentage of Participants With HIV-1 RNA < 50 Copies/mL as Determined by the FDA-defined Snapshot Algorithm at Week 12	The percentage of participants achieving HIV-1 RNA < 50 copies/mL at Week 12 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 12
Secondary	Percentage of Participants With HIV-1 RNA < 50 Copies/mL as Determined by the FDA-defined Snapshot Algorithm at Week 48	The percentage of participants achieving 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	The Change From Baseline in log10 HIV-1 RNA at Week 12		Baseline; Week 12
Secondary	The Change From Baseline in log10 HIV-1 RNA at Week 24		Baseline; Week 24
Secondary	The Change From Baseline in log10 HIV-1 RNA at Week 48		Baseline; Week 48
Secondary	The Change From Baseline in Cluster of Differentiation 4 Positive (CD4+) Cell Count at Week 12		Baseline; Week 12
Secondary	The Change From Baseline in CD4+ Cell Count at Week 24		Baseline; Week 24
Secondary	The Change From Baseline in CD4+ Cell Count at Week 48		Baseline; Week 48
Secondary	Percentage of Participants With Treatment Emergent Adverse Events (TEAEs) During Double-Blinded Randomized Phase		First dose date up to last dose (maximum duration: 58 Weeks) plus 30 days (During Double-Blinded Randomized Phase)
Secondary	Percentage of Participants With Treatment Emergent Laboratory Abnormalities During Double-Blind Randomized Phase		First dose date up to last dose (maximum duration: 58 Weeks) plus 30 days (During Double-Blinded Randomized Phase)
Secondary	PK Parameter: Cmax for Bictegravir (BIC), Emtricitabine (FTC), Tenofovir Alafenamide (TAF) and Tenofavir (TFV) at Steady-State	Cmax is the maximum observed plasma concentration of the drug.	0.5, 1, 1.5, 2, 3, 4, 6, 8, and 24 hours postdose at Week 4 or 8
Secondary	PK Parameter: Tmax for BIC, FTC, TAF, and TFV at Steady-State	Tmax was defined as the time to Cmax.	0.5, 1, 1.5, 2, 3, 4, 6, 8, and 24 hours postdose at Week 4 or 8
Secondary	PK Parameter:Ctau for BIC, FTC and TFV	Ctau was defined as the observed drug concentration at the end of the dosing interval.	0.5, 1, 1.5, 2, 3, 4, 6, 8, and 24 hours postdose at Week 4 or 8
Secondary	PK Parameter: AUCtau for BIC, FTC, TAF, and TFV	AUCtau is defined as the area under the concentration-time curve of the drug over time.	0.5, 1, 1.5, 2, 3, 4, 6, 8, and 24 hours postdose at Week 4 or 8
Secondary	PK Parameter: t1/2 of BIC, FTC, TAF, and TFV	t1/2 was defined as the terminal elimination half-life of the drug	0.5, 1, 1.5, 2, 3, 4, 6, 8, and 24 hours postdose at Week 4 or 8