Study to Evaluate Safety, Pharmacokinetics, and Antiviral Activity of Bictegravir (GS-9883) in Human Immunodeficiency Virus (HIV)-1 Infected Participants

Study Overview
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Brief Summary
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The primary objective of the study is to investigate the short-term antiviral potency of bictegravir at multiple doses in antiretroviral (ART) treatment-naive adult participants and participants who are ART-experienced but integrase strand transfer inhibitor (INSTI) naive.

Official Title
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A Phase 1b Randomized, Double-Blinded, Sequential Cohort Placebo-Controlled Study of the Safety, Pharmacokinetics, and Antiviral Activity of GS-9883 in HIV-1 Infected Subjects

Conditions
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HIV-1 Infection

Intervention / Treatment
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* Drug: Bictegravir
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: No current or prior anti-HIV treatment, including ART medications received for prevention (preexposure prophylaxis [PrEP]), or postexposure prophylaxis (PEP) within 12 weeks of screening Plasma HIV-1 ribonucleic acid (RNA) ≥ 10,000 copies/mL but ≤ 400,000 copies/mL at screening Cluster of differentiation 4+ (CD4+) cell count > 200 cells/mm^3 Key Exclusion Criteria: Anticipated to start HIV-1 therapy during the study period Active participation in another study of investigational or approved ART agents A new acquired immunodeficiency syndrome (AIDS)-defining condition diagnosed within the 30 days prior to screening Participants with positive hepatitis C antibody at screening Chronic hepatitis B virus (HBV) infection Active, serious infections (other than HIV-1 infection) requiring parenteral antibiotic or antifungal therapy within 42 days prior to Day 1 (baseline) Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Bictegravir 5 mg<br>Bictegravir 5 mg (1 × 5 mg tablet) for 10 days | Drug: Bictegravir<br>* Bictegravir tablet(s) administered orally once daily<br>|
| Experimental: Bictegravir 25 mg<br>Bictegravir 25 mg (1 × 25 mg tablet) for 10 days | Drug: Bictegravir<br>* Bictegravir tablet(s) administered orally once daily<br>|
| Experimental: Bictegravir 50 mg<br>Bictegravir 50 mg (2 × 25 mg tablets) for 10 days | Drug: Bictegravir<br>* Bictegravir tablet(s) administered orally once daily<br>|
| Experimental: Bictegravir 100 mg<br>Bictegravir 100 mg (1 × 100 mg tablet) for 10 days | Drug: Bictegravir<br>* Bictegravir tablet(s) administered orally once daily<br>|
| Placebo Comparator: Placebo<br>Placebo matched to bictegravir tablet for 10 days | Drug: Placebo<br>* Placebo to match bictegravir administered orally once daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time-Weighted Average Change From Baseline up to Day 11 (DAVG11) in Plasma HIV-1 RNA | DAVG11 was defined as the time-weighted average between the first postbaseline value through the last available on-treatment (ie, the last dose date + 1) value up to Day 11 minus the baseline value in plasma HIV-1 RNA (log10 copies/mL). All HIV-1 RNA data up to Day 11 were used for this analysis. DAVG11 was calculated using the trapezoidal rule and the area-under-the-curve concept. | Baseline up to Day 11 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Who Experienced Treatment-Emergent Adverse Events (AEs) |  | First dose date up to last dose date plus 30 days (Maximum: 40 days) | 
| Percentage of Participants Who Experienced Graded Laboratory Abnormalities | A treatment-emergent graded laboratory abnormality was defined as an increase of at least 1 toxicity grade from predose assessment and occurring after the predose visit and on or before the date of the last dose of study drug plus 30 days. If the predose assessment was missing, then any abnormality of at least Grade 1 associated with the study drug was considered a treatment-emergent graded laboratory abnormality. The most severe graded abnormality from all tests was counted for each participant. | First dose date up to last dose date plus 30 days (Maximum: 40 days) | 
| Maximum Reduction From Baseline Through Day 17 in Plasma HIV-1 RNA | Maximum reduction from baseline was defined as the minimum of change from baseline in plasma HIV-1 RNA (i.e. smallest change in HIV-RNA from baseline). | Baseline to Day 17 | 
| Viral Decay Slope in Plasma HIV-1 RNA | Viral Decay Slope = (log10 [HIV-1 RNA on Day x] - log10 [HIV-1 RNA on Day 1]) / (x-1), where x is the collection day of the last available on treatment HIV-1 RNA collected up to Day 7. | Baseline up to Day 11 | 
| Percentage of Participants With HIV-1 RNA < 50 Copies/mL |  | Day 17 | 
| Pharmacokinetic (PK) Parameter: Cmax of Bictegravir Following Single-Dose and Multiple-Dose Administration | Cmax is defined as the maximum concentration of drug. | 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 24 hours postdose at Day 1 for single dose and Day 10 for multiple dose | 
| PK Parameter: Tmax of Bictegravir Following Single-Dose and Multiple-Dose Administration | Tmax is defined as the time (observed time point) of Cmax. | 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 24 hours postdose at Day 1 for single dose and Day 10 for multiple dose | 
| PK Parameter: AUC0-24 of Bictegravir Following Single-Dose Administration | AUC0-24 is defined as the concentration of drug over time from time zero to time 24 hours. | 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 24 hours postdose at Day 1 | 
| PK Parameter: AUClast of Bictegravir Following Single-Dose Administration | AUClast is defined as the concentration of drug from time zero to the last observable concentration. | 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 24 hours postdose at Day 1 | 
| PK Parameter: AUCtau of Bictegravir Following Multiple-Dose Administration | AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval). | 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 24 hours postdose at Day 10 | 
| PK Parameter: t1/2 of Bictegravir Following Multiple-Dose Administration | t1/2 is defined as the estimate of the terminal elimination half-life of the drug. | 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 24 hours postdose at Day 10 | 
| PK Parameter: Ctau of Bictegravir Following Multiple-Dose Administration | Ctau is defined as the observed drug concentration at the end of the dosing interval. | 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 24 hours postdose at Day 10 | 
| PK Parameter: CLss/F of Bictegravir Following Multiple-Dose Administration | CLss/F is defined as the apparent oral clearance following multiple-dose administration of the drug. | 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 24 hours postdose at Day 10 | 
| PK Parameter: AR_AUC of Bictegravir Following Multiple-Dose Administration | Accumulation ratio of AUC (AR_AUC) = AUCtau on Day 10 / AUC0-24 on Day 1. Percentage of accumulation ratio has been reported. | 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 24 hours postdose at Day 1 and 10 | 
| PK Parameter: AR_Cmax of Bictegravir Following Multiple-Dose Administration | Accumulation ratio of Cmax (AR_Cmax) = Cmax on Day 10 / Cmax on Day 1. Percentage of accumulation ratio has been reported. | 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 24 hours postdose at Day 1 and 10 | 
| PK/Pharmacodynamic (PD) Analysis: Pearson Correlation Between AUCtau of Bictegravir and DAVG11 in Plasma HIV-1 RNA | AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval). DAVG11 was defined as the time-weighted average between the first postbaseline value through the last available on-treatment (ie, the last dose date + 1) value up to Day 11 minus the baseline value in plasma HIV-1 RNA (log10 copies/mL). | 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 24 hours postdose at Day 10 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HIV-1 Infected, Adults, Treatment Naive