A Phase 1b Randomized, Double-Blinded, Placebo Controlled, Multi-Cohort Study of the Safety, Pharmacokinetics, and Antiviral Activity of GS-6207 Administered Subcutaneously in HIV-1 Infected Subjects
Overview
- Phase
- Phase 1
- Intervention
- Lenacapavir
- Conditions
- HIV-1 Infection
- Sponsor
- Gilead Sciences
- Enrollment
- 53
- Locations
- 12
- Primary Endpoint
- Part A and Part B: Maximum Reduction From Day 1 (Baseline) Through Day 10 in Plasma HIV-1 RNA
- Status
- Completed
- Last Updated
- 5 years ago
Overview
Brief Summary
The primary objectives of this study are:
Part A: To evaluate the short-term antiviral activity of lenacapavir (formerly GS-6207) with respect to the maximum reduction of plasma HIV-1 RNA (log10 copies/mL) from Day 1 through Day 10 compared to placebo in HIV-1 infected adults who are antiretroviral treatment naive or are experienced but capsid inhibitor (CAI) naive.
Part B: To evaluate the short-term antiviral activity of tenofovir alafenamide (TAF) with respect to the maximum reduction of plasma HIV-1 RNA (log10 copies/mL) from Day 1 through Day 10 in HIV-1 infected adult subjects who are antiretroviral treatment naïve or are experienced but without resistance to TAF.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Plasma HIV-1 RNA ≥ 5,000 copies/mL but ≤ 400,000 copies/mL and CD4+ cell count \> 200 cells/mm\^3
- •Treatment naive or experienced but CAI (for Part A only) and integrase strand transfer inhibitor (INSTI) naïve, and have not received any antiretroviral therapy (ART) within 12 weeks of screening
- •Screening genotype report must show sensitivity to B/F/TAF to allow its initiation on Day 10
- •Screening genotype report must show sensitivity to at least one agent in either non-nucleoside reverse transcriptase inhibitor (NNRTI) or protease inhibitor (PI) class to allow its use as part of standard of care oral antiretroviral treatment in the future
- •Have adequate renal function (estimated glomerular filtration rate ≥ 70 mL/min)
- •No clinically significant abnormalities in electrocardiography (ECG) at Screening
- •Willing to initiate B/F/TAF on Day 10 after completion of all assessments
Exclusion Criteria
- •Pregnant or lactating females
- •Note: Other protocol defined Inclusion/Exclusion criteria may apply.
Arms & Interventions
Part A: Lenacapavir 20 mg
Participants will receive single dose of lenacapavir 20 mg on Day 1 followed by bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) as per standard-care therapy starting on Day 10 through Day 225.
Intervention: Lenacapavir
Part A: Lenacapavir 20 mg
Participants will receive single dose of lenacapavir 20 mg on Day 1 followed by bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) as per standard-care therapy starting on Day 10 through Day 225.
Intervention: B/F/TAF
Part A: Lenacapavir 50 mg
Participants will receive single dose of lenacapavir 50 mg on Day 1 followed by B/F/TAF as per standard-care therapy starting on Day 10 through Day 225.
Intervention: Lenacapavir
Part A: Lenacapavir 50 mg
Participants will receive single dose of lenacapavir 50 mg on Day 1 followed by B/F/TAF as per standard-care therapy starting on Day 10 through Day 225.
Intervention: B/F/TAF
Part A: Lenacapavir 150 mg
Participants will receive single dose of lenacapavir 150 mg on Day 1 followed by B/F/TAF as per standard-care therapy starting on Day 10 through Day 225.
Intervention: Lenacapavir
Part A: Lenacapavir 150 mg
Participants will receive single dose of lenacapavir 150 mg on Day 1 followed by B/F/TAF as per standard-care therapy starting on Day 10 through Day 225.
Intervention: B/F/TAF
Part A: Lenacapavir 450 mg
Participants will receive single dose of lenacapavir 450 mg on Day 1 followed by B/F/TAF as per standard-care therapy starting on Day 10 through Day 225.
Intervention: Lenacapavir
Part A: Lenacapavir 450 mg
Participants will receive single dose of lenacapavir 450 mg on Day 1 followed by B/F/TAF as per standard-care therapy starting on Day 10 through Day 225.
Intervention: B/F/TAF
Part A: Lenacapavir 750 mg
Participants will receive single dose of lenacapavir 750 mg on Day 1 followed by B/F/TAF as per standard-care therapy starting on Day 10 through Day 225.
Intervention: Lenacapavir
Part A: Lenacapavir 750 mg
Participants will receive single dose of lenacapavir 750 mg on Day 1 followed by B/F/TAF as per standard-care therapy starting on Day 10 through Day 225.
Intervention: B/F/TAF
Part A: Placebo
Participants will receive single dose of placebo matched to lenacapavir on Day 1 followed by B/F/TAF as per standard-care therapy starting on Day 10 through Day 225.
Intervention: Placebo
Part A: Placebo
Participants will receive single dose of placebo matched to lenacapavir on Day 1 followed by B/F/TAF as per standard-care therapy starting on Day 10 through Day 225.
Intervention: B/F/TAF
Part B: TAF 200 mg
Participants will receive a single dose of TAF 200 mg on Day 1 followed by B/F/TAF as per standard-care therapy starting on Day 10 through Day 225.
Intervention: B/F/TAF
Part B: TAF 200 mg
Participants will receive a single dose of TAF 200 mg on Day 1 followed by B/F/TAF as per standard-care therapy starting on Day 10 through Day 225.
Intervention: TAF
Part B: TAF 600 mg
Participants will receive a single dose of TAF 600 mg on Day 1 followed by B/F/TAF as per standard-care therapy starting on Day 10 through Day 225.
Intervention: B/F/TAF
Part B: TAF 600 mg
Participants will receive a single dose of TAF 600 mg on Day 1 followed by B/F/TAF as per standard-care therapy starting on Day 10 through Day 225.
Intervention: TAF
Outcomes
Primary Outcomes
Part A and Part B: Maximum Reduction From Day 1 (Baseline) Through Day 10 in Plasma HIV-1 RNA
Time Frame: Day 1 through Day 10
Maximum reduction is defined as the minimum of change from baseline in plasma HIV-1 RNA (i.e. smallest change in HIV-RNA from baseline).
Secondary Outcomes
- Part A and Part B: Percentage of Participants Experiencing Treatment Emergent Adverse Events (TEAEs)(Day 1 through 225 days)
- Part A and Part B: Percentage of Participants Experiencing Treatment Emergent Laboratory Abnormalities(Day 1 through 225 days)
- Part A and Part B Pharmacokinetic (PK) Parameter: AUCinf of Lenacapavir, TAF and Its Metabolite TFV(Part A: 0 (predose),1,2,4,8,12,24 h postdose on Day 1, anytime on Days 3,4,7,8,9,10,14,29,43,57,85,113,141,169,197,225; Part B: 0 (predose),0.5,1,2,3,4,6,8,10,12,24 and 48 h postdose on Day 1, approximately Day 1 predose time on Days 4,5,6,7,8,9,10)
- Part A and Part B PK Parameter: AUClast of Lenacapavir, TAF and Its Metabolite TFV(Part A: 0 (predose),1,2,4,8,12,24 h postdose on Day 1, anytime on Days 3,4,7,8,9,10,14,29,43,57,85,113,141,169,197,225; Part B: 0 (predose),0.5,1,2,3,4,6,8,10,12,24 and 48 h postdose on Day 1, approximately Day 1 predose time on Days 4,5,6,7,8,9,10)
- Part A and Part B PK Parameter: Cmax of Lenacapavir, TAF and Its Metabolite TFV(Part A: 0 (predose),1,2,4,8,12,24 h postdose on Day 1, anytime on Days 3,4,7,8,9,10,14,29,43,57,85,113,141,169,197,225; Part B: 0 (predose),0.5,1,2,3,4,6,8,10,12,24 and 48 h postdose on Day 1, approximately Day 1 predose time on Days 4,5,6,7,8,9,10)
- Part B PK Parameter: AUCinf of TFV-DP Metabolite of TAF(Part B: 0 (predose), 1, 2, 4, 6, 8, 12, 24 and 48 hours post dose on Day 1, approximately Day 1 predose time on Days 4, 5 (if possible), 6 (if possible), 7, 8, 9, 10)
- Part B PK Parameter: AUClast of TFV-DP Metabolite of TAF(Part B: 0 (predose), 1, 2, 4, 6, 8, 12, 24 and 48 hours post dose on Day 1, approximately Day 1 predose time on Days 4, 5 (if possible), 6 (if possible), 7, 8, 9, 10)
- Part B PK Parameter: Cmax of TFV-DP Metabolite of TAF(Part B: 0 (predose), 1, 2, 4, 6, 8, 12, 24 and 48 hours post dose on Day 1, approximately Day 1 predose time on Days 4, 5 (if possible), 6 (if possible), 7, 8, 9, 10)
- Part A: Percentage of Participants Ever Achieving HIV-1 RNA < 50 Copies/mL by Day 10(Day 10)
- Part A: Number of Participants Experiencing Any Emergence of Capsid Inhibitor Resistance(Day 10 through Day 225)
- Part B: Number of Participants Experiencing Any Emergence of TAF Resistance(Day 10 through Day 225)