Study to Evaluate Safety, Pharmacokinetics, and Antiviral Activity of Lenacapavir Administered Subcutaneously in Human Immunodeficiency Virus (HIV) -1 Infected Adults
- Conditions
- HIV-1 Infection
- Interventions
- Registration Number
- NCT03739866
- Lead Sponsor
- Gilead Sciences
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 53
- 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
Key
- Pregnant or lactating females
Note: Other protocol defined Inclusion/Exclusion criteria may apply.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Part A: Lenacapavir 50 mg Lenacapavir 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. Part A: Lenacapavir 150 mg Lenacapavir 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. Part A: Lenacapavir 450 mg Lenacapavir 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. Part A: Lenacapavir 750 mg Lenacapavir 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. Part B: TAF 600 mg TAF 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. Part B: TAF 200 mg TAF 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. Part A: Lenacapavir 750 mg B/F/TAF 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. Part A: Placebo B/F/TAF 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. Part A: Lenacapavir 20 mg B/F/TAF 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. Part A: Lenacapavir 50 mg B/F/TAF 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. Part A: Lenacapavir 150 mg B/F/TAF 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. Part B: TAF 200 mg B/F/TAF 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. Part A: Placebo 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. Part A: Lenacapavir 450 mg B/F/TAF 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. Part B: TAF 600 mg B/F/TAF 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. Part A: Lenacapavir 20 mg Lenacapavir 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.
- Primary Outcome Measures
Name Time Method Part A and Part B: Maximum Reduction From Day 1 (Baseline) Through Day 10 in Plasma HIV-1 RNA 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 Outcome Measures
Name Time Method Part A and Part B: Percentage of Participants Experiencing Treatment Emergent Adverse Events (TEAEs) Day 1 through 225 days An AE was any untoward medical occurrence in a clinical study participant administered a medicinal product, which does not necessarily have a causal relationship with the treatment. An AE could therefore be any unfavorable and/or unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. TEAEs were defined as any AE with an onset date on or after the study drug start date.
Part A and Part B: Percentage of Participants Experiencing Treatment Emergent Laboratory Abnormalities Day 1 through 225 days Treatment-emergent laboratory abnormalities were defined as values that increase at least one toxicity grade from baseline. The most severe graded abnormality from all tests was counted for each participant.
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 AUCinf is defined as area under the concentration versus time curve from time zero to infinity.
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 AUClast is defined as area under the concentration versus time curve from time zero to the last quantifiable concentration.
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 Cmax is defined as the maximum observed concentration of drug.
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 AUCinf is defined as area under the concentration versus time curve from time zero to infinity.
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 AUClast is defined as area under the concentration versus time curve from time zero to the last quantifiable concentration.
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 Cmax is defined as the maximum observed concentration of drug.
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 Post-Monotherapy Resistance Analysis Population analyzed for this outcome measure included any participant who received at least 1 dose of study drug/placebo, maintained their study drug regimen, \& met one of following virologic failure criteria:
* HIV-1 RNA ≥ 50 copies/mL \& \< 1 log10 HIV-1 RNA reduction from Day 10 at Day 57 visit, confirmed at a scheduled or unscheduled visit at least 2 weeks following Day 57
* At any visit following Day 10, after achieving HIV-1 RNA \< 50 copies/mL, a rebound in HIV-1 RNA to ≥ 50 copies/mL, which was subsequently confirmed at following scheduled or unscheduled visit; OR At any visit, a \> 1 log10 increase in HIV-1 RNA from nadir, which was subsequently confirmed at following scheduled or unscheduled visit;
* Any participant with HIV-1 RNA ≥ 50 copies/mL at study endpoint or study discontinuation who didn't meet any of criteria above also had protease (PR)/reverse transcriptase (RT), integrase (IN), \&capsid (CA) genotyping \& phenotyping performed.Part B: Number of Participants Experiencing Any Emergence of TAF Resistance Day 10 through Day 225 TAF Resistance testing was performed for any participant meeting Post-Monotherapy Resistance Analysis Population criteria - it included any participant who received at least 1 dose of study drug/placebo, maintained their study drug regimen, \& met one of the following virologic failure criteria:
* HIV-1 RNA ≥50 copies/mL \& \< 1 log10 HIV-1 RNA reduction from D10 at the D57 visit, confirmed at scheduled or unscheduled visit at least 2 weeks following D57
* At any visit following D10, after achieving HIV-1 RNA\< 50 copies/mL, a rebound in HIV-1 RNA to ≥50 copies/mL, which was subsequently confirmed at the following scheduled/unscheduled visit; OR At any visit, a \> 1 log10 increase in HIV-1 RNA from nadir, which was subsequently confirmed at the following scheduled or unscheduled visit;
* Any participant with HIV-1 RNA ≥50 copies/mL at study endpoint or study discontinuation who didn't meet any of the criteria above also had PR/RT, IN, and CA genotyping \& phenotyping performed.
D = Day
Trial Locations
- Locations (12)
Orlando Immunology Center PA
🇺🇸Orlando, Florida, United States
Mills Clinical Research
🇺🇸Los Angeles, California, United States
The Lundquist Institute for BioMedical Innovation at Harbor-UCLA Medical Center
🇺🇸Torrance, California, United States
Triple O Research Institute, P.A.
🇺🇸West Palm Beach, Florida, United States
Be Well Medical Center
🇺🇸Berkley, Michigan, United States
North Texas Infectious Diseases Consultants, P.A.
🇺🇸Dallas, Texas, United States
Ruane Clinical Research Group, Inc.
🇺🇸Los Angeles, California, United States
One Community
🇺🇸Sacramento, California, United States
Midway Immunology and Research Center
🇺🇸Fort Pierce, Florida, United States
AIDS Arms, Inc., DBA Prism Health North Texas
🇺🇸Dallas, Texas, United States
Tarrant County Infectious Disease Associates
🇺🇸Fort Worth, Texas, United States
The Crofoot Research Center, INC (dba Gordon E. Crofoot MD PA)
🇺🇸Houston, Texas, United States