HIV-1 Infection
Conditions
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.
Interventions
DRUGLenacapavir
Administered subcutaneously in the abdomen
DRUGPlacebo
Administered subcutaneously in the abdomen
DRUGB/F/TAF
50/200/25 mg tablets administered orally once daily
DRUGTAF
Tablets administered orally
Sponsors
Gilead Sciences
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
Key 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 Key
Exclusion criteria
* Pregnant or lactating females Note: Other protocol defined Inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 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 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 | — |
| Part B: Number of Participants Experiencing Any Emergence of TAF Resistance | Day 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 | AUClast is defined as area under the concentration versus time curve from time zero to the last quantifiable concentration. |
Countries
United States
Participant flow
Recruitment details
Participants were enrolled at study sites in the United States. The first participant was screened on 26 November 2018. The last study visit occurred on 15 June 2020.
Pre-assignment details
89 participants were screened.
Participants by arm
| Arm | Count |
|---|---|
| Part A: Lenacapavir 20 mg Participants received a single dose of lenacapavir 20 mg subcutaneously in the abdomen on Day 1 followed by B/F/TAF as per standard-care therapy started on Day 10 through Day 225. | 6 |
| Part A: Lenacapavir 50 mg Participants received a single dose of lenacapavir 50 mg subcutaneously in the abdomen on Day 1 followed by B/F/TAF as per standard-care therapy started on Day 10 through Day 225. | 6 |
| Part A: Lenacapavir 150 mg Participants received a single dose of lenacapavir 150 mg subcutaneously in the abdomen on Day 1 followed by B/F/TAF as per standard-care therapy started on Day 10 through Day 225. | 6 |
| Part A: Lenacapavir 450 mg Participants received a single dose of lenacapavir 450 mg subcutaneously in the abdomen on Day 1 followed by B/F/TAF as per standard-care therapy started on Day 10 through Day 225. | 6 |
| Part A: Lenacapavir 750 mg Participants received a single dose of lenacapavir 750 mg subcutaneously in the abdomen on Day 1 followed by B/F/TAF as per standard-care therapy started on Day 10 through Day 225. | 5 |
| Part A: Placebo Participants received a single dose of placebo matched to lenacapavir subcutaneously in the abdomen on Day 1 followed by B/F/TAF as per standard-care therapy started on Day 10 through Day 225. | 10 |
| Part B: TAF 200 mg Participants received a single oral dose of TAF 200 mg on Day 1 followed by B/F/TAF as per standard-care therapy started on Day 10 through Day 225. | 7 |
| Part B: TAF 600 mg Participants received a single oral dose of TAF 600 mg on Day 1 followed by B/F/TAF as per standard-care therapy on started on Day 10 through Day 225. | 5 |
| Total | 51 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 |
|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Enrolled but not treated | 0 | 0 | 1 | 0 | 1 | 0 | 0 | 0 |
| Overall Study | Lost to Follow-up | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Part A: Lenacapavir 50 mg | Part A: Lenacapavir 20 mg | Total | Part B: TAF 600 mg | Part B: TAF 200 mg | Part A: Placebo | Part A: Lenacapavir 750 mg | Part A: Lenacapavir 450 mg | Part A: Lenacapavir 150 mg |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 36 years STANDARD_DEVIATION 14.4 | 33 years STANDARD_DEVIATION 4.4 | 34 years STANDARD_DEVIATION 11.5 | 40 years STANDARD_DEVIATION 8.7 | 29 years STANDARD_DEVIATION 8.7 | 29 years STANDARD_DEVIATION 9.3 | 37 years STANDARD_DEVIATION 17.7 | 36 years STANDARD_DEVIATION 15.5 | 39 years STANDARD_DEVIATION 11.5 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 1 Participants | 13 Participants | 2 Participants | 5 Participants | 1 Participants | 3 Participants | 1 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 6 Participants | 5 Participants | 38 Participants | 3 Participants | 2 Participants | 9 Participants | 2 Participants | 5 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| HIV-1 RNA | 4.44 log10 copies/mL STANDARD_DEVIATION 0.328 | 4.46 log10 copies/mL STANDARD_DEVIATION 0.428 | 4.50 log10 copies/mL STANDARD_DEVIATION 0.403 | 4.97 log10 copies/mL STANDARD_DEVIATION 0.439 | 4.23 log10 copies/mL STANDARD_DEVIATION 0.621 | 4.50 log10 copies/mL STANDARD_DEVIATION 0.371 | 4.56 log10 copies/mL STANDARD_DEVIATION 0.305 | 4.52 log10 copies/mL STANDARD_DEVIATION 0.19 | 4.48 log10 copies/mL STANDARD_DEVIATION 0.161 |
| Race/Ethnicity, Customized Race Asian | 1 Participants | 1 Participants | 3 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Race Black | 2 Participants | 0 Participants | 13 Participants | 0 Participants | 1 Participants | 4 Participants | 1 Participants | 2 Participants | 3 Participants |
| Race/Ethnicity, Customized Race Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Race Other | 0 Participants | 1 Participants | 3 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Race White | 3 Participants | 4 Participants | 31 Participants | 5 Participants | 5 Participants | 5 Participants | 3 Participants | 4 Participants | 2 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 4 Participants | 0 Participants | 0 Participants | 1 Participants | 2 Participants | 0 Participants | 1 Participants |
| Sex: Female, Male Male | 6 Participants | 6 Participants | 47 Participants | 5 Participants | 7 Participants | 9 Participants | 3 Participants | 6 Participants | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk |
|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 5 | 0 / 10 | 0 / 7 | 0 / 5 |
| other Total, other adverse events | 5 / 6 | 6 / 6 | 5 / 6 | 6 / 6 | 4 / 5 | 7 / 10 | 6 / 7 | 5 / 5 |
| serious Total, serious adverse events | 0 / 6 | 0 / 6 | 0 / 6 | 1 / 6 | 0 / 5 | 1 / 10 | 0 / 7 | 0 / 5 |
Outcome results
Primary
Part A and Part B: Maximum Reduction From Day 1 (Baseline) Through Day 10 in Plasma HIV-1 RNA
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).
Time frame: Day 1 through Day 10
Population: The Full Analysis Set (FAS) included all participants who were randomized/enrolled and received at least 1 full dose of study drug.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A: Lenacapavir 20 mg | Part A and Part B: Maximum Reduction From Day 1 (Baseline) Through Day 10 in Plasma HIV-1 RNA | -1.35 log10 copies/mL | Standard Deviation 0.318 |
| Part A: Lenacapavir 50 mg | Part A and Part B: Maximum Reduction From Day 1 (Baseline) Through Day 10 in Plasma HIV-1 RNA | -1.79 log10 copies/mL | Standard Deviation 0.476 |
| Part A: Lenacapavir 150 mg | Part A and Part B: Maximum Reduction From Day 1 (Baseline) Through Day 10 in Plasma HIV-1 RNA | -1.76 log10 copies/mL | Standard Deviation 0.203 |
| Part A: Lenacapavir 450 mg | Part A and Part B: Maximum Reduction From Day 1 (Baseline) Through Day 10 in Plasma HIV-1 RNA | -2.20 log10 copies/mL | Standard Deviation 0.468 |
| Part A: Lenacapavir 750 mg | Part A and Part B: Maximum Reduction From Day 1 (Baseline) Through Day 10 in Plasma HIV-1 RNA | -2.26 log10 copies/mL | Standard Deviation 0.662 |
| Part A: Placebo | Part A and Part B: Maximum Reduction From Day 1 (Baseline) Through Day 10 in Plasma HIV-1 RNA | -0.17 log10 copies/mL | Standard Deviation 0.128 |
| Part B: TAF 200 mg | Part A and Part B: Maximum Reduction From Day 1 (Baseline) Through Day 10 in Plasma HIV-1 RNA | -0.75 log10 copies/mL | Standard Deviation 0.27 |
| Part B: TAF 600 mg | Part A and Part B: Maximum Reduction From Day 1 (Baseline) Through Day 10 in Plasma HIV-1 RNA | -0.91 log10 copies/mL | Standard Deviation 0.294 |
p-value: <0.0001t-test, 2 sided
p-value: <0.0001t-test, 2 sided
p-value: <0.0001t-test, 2 sided
p-value: <0.0001t-test, 2 sided
p-value: <0.0001t-test, 2 sided
Secondary
Part A and Part B: Percentage of Participants Experiencing Treatment Emergent Adverse Events (TEAEs)
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.
Time frame: Day 1 through 225 days
Population: The Safety Analysis Set included all participants who were randomized/enrolled and received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A: Lenacapavir 20 mg | Part A and Part B: Percentage of Participants Experiencing Treatment Emergent Adverse Events (TEAEs) | 83.3 percentage of participants |
| Part A: Lenacapavir 50 mg | Part A and Part B: Percentage of Participants Experiencing Treatment Emergent Adverse Events (TEAEs) | 100 percentage of participants |
| Part A: Lenacapavir 150 mg | Part A and Part B: Percentage of Participants Experiencing Treatment Emergent Adverse Events (TEAEs) | 83.3 percentage of participants |
| Part A: Lenacapavir 450 mg | Part A and Part B: Percentage of Participants Experiencing Treatment Emergent Adverse Events (TEAEs) | 100 percentage of participants |
| Part A: Lenacapavir 750 mg | Part A and Part B: Percentage of Participants Experiencing Treatment Emergent Adverse Events (TEAEs) | 80 percentage of participants |
| Part A: Placebo | Part A and Part B: Percentage of Participants Experiencing Treatment Emergent Adverse Events (TEAEs) | 70 percentage of participants |
| Part B: TAF 200 mg | Part A and Part B: Percentage of Participants Experiencing Treatment Emergent Adverse Events (TEAEs) | 85.7 percentage of participants |
| Part B: TAF 600 mg | Part A and Part B: Percentage of Participants Experiencing Treatment Emergent Adverse Events (TEAEs) | 100 percentage of participants |
Secondary
Part A and Part B: Percentage of Participants Experiencing Treatment Emergent Laboratory Abnormalities
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.
Time frame: Day 1 through 225 days
Population: Participants in the Safety Analysis Set were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A: Lenacapavir 20 mg | Part A and Part B: Percentage of Participants Experiencing Treatment Emergent Laboratory Abnormalities | 83.3 percentage of participants |
| Part A: Lenacapavir 50 mg | Part A and Part B: Percentage of Participants Experiencing Treatment Emergent Laboratory Abnormalities | 83.3 percentage of participants |
| Part A: Lenacapavir 150 mg | Part A and Part B: Percentage of Participants Experiencing Treatment Emergent Laboratory Abnormalities | 100.0 percentage of participants |
| Part A: Lenacapavir 450 mg | Part A and Part B: Percentage of Participants Experiencing Treatment Emergent Laboratory Abnormalities | 66.7 percentage of participants |
| Part A: Lenacapavir 750 mg | Part A and Part B: Percentage of Participants Experiencing Treatment Emergent Laboratory Abnormalities | 100.0 percentage of participants |
| Part A: Placebo | Part A and Part B: Percentage of Participants Experiencing Treatment Emergent Laboratory Abnormalities | 80.0 percentage of participants |
| Part B: TAF 200 mg | Part A and Part B: Percentage of Participants Experiencing Treatment Emergent Laboratory Abnormalities | 100.0 percentage of participants |
| Part B: TAF 600 mg | Part A and Part B: Percentage of Participants Experiencing Treatment Emergent Laboratory Abnormalities | 80.0 percentage of participants |
Secondary
Part A and Part B Pharmacokinetic (PK) Parameter: AUCinf of Lenacapavir, TAF and Its Metabolite TFV
AUCinf is defined as area under the concentration versus time curve from time zero to infinity.
Time frame: 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
Population: Participants in the PK Analysis Set were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Lenacapavir 20 mg | Part A and Part B Pharmacokinetic (PK) Parameter: AUCinf of Lenacapavir, TAF and Its Metabolite TFV | Part A: Lenacapavir | 6564.3 h*ng/mL | Standard Deviation 2562.02 |
| Part A: Lenacapavir 50 mg | Part A and Part B Pharmacokinetic (PK) Parameter: AUCinf of Lenacapavir, TAF and Its Metabolite TFV | Part A: Lenacapavir | 9124.1 h*ng/mL | Standard Deviation 4443.03 |
| Part A: Lenacapavir 150 mg | Part A and Part B Pharmacokinetic (PK) Parameter: AUCinf of Lenacapavir, TAF and Its Metabolite TFV | Part A: Lenacapavir | 31537.0 h*ng/mL | Standard Deviation 6811.74 |
| Part A: Lenacapavir 450 mg | Part A and Part B Pharmacokinetic (PK) Parameter: AUCinf of Lenacapavir, TAF and Its Metabolite TFV | Part A: Lenacapavir | 106041.1 h*ng/mL | Standard Deviation 19939.41 |
| Part A: Lenacapavir 750 mg | Part A and Part B Pharmacokinetic (PK) Parameter: AUCinf of Lenacapavir, TAF and Its Metabolite TFV | Part A: Lenacapavir | 181861.0 h*ng/mL | Standard Deviation 73100.91 |
| Part A: Placebo | Part A and Part B Pharmacokinetic (PK) Parameter: AUCinf of Lenacapavir, TAF and Its Metabolite TFV | Part B: TAF | 1270.3 h*ng/mL | Standard Deviation 346.47 |
| Part A: Placebo | Part A and Part B Pharmacokinetic (PK) Parameter: AUCinf of Lenacapavir, TAF and Its Metabolite TFV | Part B: TFV | 2807.9 h*ng/mL | Standard Deviation 904.23 |
| Part B: TAF 200 mg | Part A and Part B Pharmacokinetic (PK) Parameter: AUCinf of Lenacapavir, TAF and Its Metabolite TFV | Part B: TAF | 3556.1 h*ng/mL | Standard Deviation 1396.81 |
| Part B: TAF 200 mg | Part A and Part B Pharmacokinetic (PK) Parameter: AUCinf of Lenacapavir, TAF and Its Metabolite TFV | Part B: TFV | 13435.4 h*ng/mL | Standard Deviation 1748.6 |
Secondary
Part A and Part B PK Parameter: AUClast of Lenacapavir, TAF and Its Metabolite TFV
AUClast is defined as area under the concentration versus time curve from time zero to the last quantifiable concentration.
Time frame: 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
Population: Participants in the PK Analysis Set were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Lenacapavir 20 mg | Part A and Part B PK Parameter: AUClast of Lenacapavir, TAF and Its Metabolite TFV | Part A: Lenacapavir | 5084.3 h*ng/mL | Standard Error 2143.03 |
| Part A: Lenacapavir 50 mg | Part A and Part B PK Parameter: AUClast of Lenacapavir, TAF and Its Metabolite TFV | Part A: Lenacapavir | 7524.4 h*ng/mL | Standard Error 4140.4 |
| Part A: Lenacapavir 150 mg | Part A and Part B PK Parameter: AUClast of Lenacapavir, TAF and Its Metabolite TFV | Part A: Lenacapavir | 28866.4 h*ng/mL | Standard Error 8247.37 |
| Part A: Lenacapavir 450 mg | Part A and Part B PK Parameter: AUClast of Lenacapavir, TAF and Its Metabolite TFV | Part A: Lenacapavir | 102919.0 h*ng/mL | Standard Error 19984.5 |
| Part A: Lenacapavir 750 mg | Part A and Part B PK Parameter: AUClast of Lenacapavir, TAF and Its Metabolite TFV | Part A: Lenacapavir | 171173.9 h*ng/mL | Standard Error 80524.85 |
| Part A: Placebo | Part A and Part B PK Parameter: AUClast of Lenacapavir, TAF and Its Metabolite TFV | Part B: TAF | 1265.8 h*ng/mL | Standard Error 350.75 |
| Part A: Placebo | Part A and Part B PK Parameter: AUClast of Lenacapavir, TAF and Its Metabolite TFV | Part B: TFV | 2706.7 h*ng/mL | Standard Error 877.05 |
| Part B: TAF 200 mg | Part A and Part B PK Parameter: AUClast of Lenacapavir, TAF and Its Metabolite TFV | Part B: TAF | 3553.0 h*ng/mL | Standard Error 1396.14 |
| Part B: TAF 200 mg | Part A and Part B PK Parameter: AUClast of Lenacapavir, TAF and Its Metabolite TFV | Part B: TFV | 12682.5 h*ng/mL | Standard Error 1780.31 |
Secondary
Part A and Part B PK Parameter: Cmax of Lenacapavir, TAF and Its Metabolite TFV
Cmax is defined as the maximum observed concentration of drug.
Time frame: 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
Population: Participants in the PK Analysis Set were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Lenacapavir 20 mg | Part A and Part B PK Parameter: Cmax of Lenacapavir, TAF and Its Metabolite TFV | Part A: Lenacapavir | 3.0 ng/mL | Standard Deviation 1 |
| Part A: Lenacapavir 50 mg | Part A and Part B PK Parameter: Cmax of Lenacapavir, TAF and Its Metabolite TFV | Part A: Lenacapavir | 5.4 ng/mL | Standard Deviation 4 |
| Part A: Lenacapavir 150 mg | Part A and Part B PK Parameter: Cmax of Lenacapavir, TAF and Its Metabolite TFV | Part A: Lenacapavir | 17.1 ng/mL | Standard Deviation 7.33 |
| Part A: Lenacapavir 450 mg | Part A and Part B PK Parameter: Cmax of Lenacapavir, TAF and Its Metabolite TFV | Part A: Lenacapavir | 60.1 ng/mL | Standard Deviation 16.92 |
| Part A: Lenacapavir 750 mg | Part A and Part B PK Parameter: Cmax of Lenacapavir, TAF and Its Metabolite TFV | Part A: Lenacapavir | 116.6 ng/mL | Standard Deviation 40.38 |
| Part A: Placebo | Part A and Part B PK Parameter: Cmax of Lenacapavir, TAF and Its Metabolite TFV | Part B: TAF | 1919.0 ng/mL | Standard Deviation 822.57 |
| Part A: Placebo | Part A and Part B PK Parameter: Cmax of Lenacapavir, TAF and Its Metabolite TFV | Part B: TFV | 93.0 ng/mL | Standard Deviation 36.97 |
| Part B: TAF 200 mg | Part A and Part B PK Parameter: Cmax of Lenacapavir, TAF and Its Metabolite TFV | Part B: TAF | 3934.0 ng/mL | Standard Deviation 742.85 |
| Part B: TAF 200 mg | Part A and Part B PK Parameter: Cmax of Lenacapavir, TAF and Its Metabolite TFV | Part B: TFV | 371.0 ng/mL | Standard Deviation 72.76 |
Secondary
Part A: Number of Participants Experiencing Any Emergence of Capsid Inhibitor Resistance
Time frame: Day 10
Population: Participants in the End of Monotherapy Resistance Analysis Population who had received 1 dose of study drug or placebo, regardless of virologic status were analyzed. One participant in 'Part A: Lenacapavir 750 mg' group had assay failure and thus was not included in the analysis.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A: Lenacapavir 20 mg | Part A: Number of Participants Experiencing Any Emergence of Capsid Inhibitor Resistance | 1 Participants |
| Part A: Lenacapavir 50 mg | Part A: Number of Participants Experiencing Any Emergence of Capsid Inhibitor Resistance | 1 Participants |
| Part A: Lenacapavir 150 mg | Part A: Number of Participants Experiencing Any Emergence of Capsid Inhibitor Resistance | 0 Participants |
| Part A: Lenacapavir 450 mg | Part A: Number of Participants Experiencing Any Emergence of Capsid Inhibitor Resistance | 0 Participants |
| Part A: Lenacapavir 750 mg | Part A: Number of Participants Experiencing Any Emergence of Capsid Inhibitor Resistance | 0 Participants |
| Part A: Placebo | Part A: Number of Participants Experiencing Any Emergence of Capsid Inhibitor Resistance | 0 Participants |
Secondary
Part A: Number of Participants Experiencing Any Emergence of Capsid Inhibitor Resistance
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.
Time frame: Day 10 through Day 225
Population: Participants in the Post-Monotherapy Resistance Analysis Population were analyzed.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A: Lenacapavir 20 mg | Part A: Number of Participants Experiencing Any Emergence of Capsid Inhibitor Resistance | 0 Participants |
| Part A: Lenacapavir 50 mg | Part A: Number of Participants Experiencing Any Emergence of Capsid Inhibitor Resistance | 0 Participants |
| Part A: Lenacapavir 150 mg | Part A: Number of Participants Experiencing Any Emergence of Capsid Inhibitor Resistance | 0 Participants |
| Part A: Lenacapavir 450 mg | Part A: Number of Participants Experiencing Any Emergence of Capsid Inhibitor Resistance | 0 Participants |
| Part A: Lenacapavir 750 mg | Part A: Number of Participants Experiencing Any Emergence of Capsid Inhibitor Resistance | 0 Participants |
| Part A: Placebo | Part A: Number of Participants Experiencing Any Emergence of Capsid Inhibitor Resistance | 0 Participants |
Secondary
Part A: Percentage of Participants Ever Achieving HIV-1 RNA < 50 Copies/mL by Day 10
Time frame: Day 10
Population: Participants in the FAS Analysis Set were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A: Lenacapavir 20 mg | Part A: Percentage of Participants Ever Achieving HIV-1 RNA < 50 Copies/mL by Day 10 | 0 percentage of participants |
| Part A: Lenacapavir 50 mg | Part A: Percentage of Participants Ever Achieving HIV-1 RNA < 50 Copies/mL by Day 10 | 16.7 percentage of participants |
| Part A: Lenacapavir 150 mg | Part A: Percentage of Participants Ever Achieving HIV-1 RNA < 50 Copies/mL by Day 10 | 0 percentage of participants |
| Part A: Lenacapavir 450 mg | Part A: Percentage of Participants Ever Achieving HIV-1 RNA < 50 Copies/mL by Day 10 | 16.7 percentage of participants |
| Part A: Lenacapavir 750 mg | Part A: Percentage of Participants Ever Achieving HIV-1 RNA < 50 Copies/mL by Day 10 | 20.0 percentage of participants |
| Part A: Placebo | Part A: Percentage of Participants Ever Achieving HIV-1 RNA < 50 Copies/mL by Day 10 | 0 percentage of participants |
Secondary
Part B: Number of Participants Experiencing Any Emergence of TAF Resistance
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
Time frame: Day 10 through Day 225
Population: Data was not collected as no participants met the specified Post-Monotherapy Resistance Analysis Population criteria.
Secondary
Part B: Number of Participants Experiencing Any Emergence of TAF Resistance
Time frame: Day 10
Population: Participants in the Post-Monotherapy Resistance Analysis Population were analyzed. One participant in 'Part B: TAF 200 mg' group and one participant in 'Part B: TAF 600 mg' group had assay failure and thus were not included in the analysis.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A: Lenacapavir 20 mg | Part B: Number of Participants Experiencing Any Emergence of TAF Resistance | 0 Participants |
| Part A: Lenacapavir 50 mg | Part B: Number of Participants Experiencing Any Emergence of TAF Resistance | 0 Participants |
Secondary
Part B PK Parameter: AUCinf of TFV-DP Metabolite of TAF
AUCinf is defined as area under the concentration versus time curve from time zero to infinity.
Time frame: 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
Population: The peripheral blood mononuclear cell (PBMC) PK Analysis Set included all participants who are enrolled in Part B of the study, received at least 1 dose of study drug, and had at least 1 nonmissing TFV-DP concentration. Participants with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A: Lenacapavir 20 mg | Part B PK Parameter: AUCinf of TFV-DP Metabolite of TAF | 599.7 h*uM | Standard Deviation 299.36 |
| Part A: Lenacapavir 50 mg | Part B PK Parameter: AUCinf of TFV-DP Metabolite of TAF | 7981.4 h*uM | Standard Deviation 3852.75 |
Secondary
Part B PK Parameter: AUClast of TFV-DP Metabolite of TAF
AUClast is defined as area under the concentration versus time curve from time zero to the last quantifiable concentration.
Time frame: 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
Population: Participants in the PBMC PK Analysis Set with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A: Lenacapavir 20 mg | Part B PK Parameter: AUClast of TFV-DP Metabolite of TAF | 390.9 h*uM | Standard Deviation 372.31 |
| Part A: Lenacapavir 50 mg | Part B PK Parameter: AUClast of TFV-DP Metabolite of TAF | 7749.3 h*uM | Standard Deviation 3731.57 |
Secondary
Part B PK Parameter: Cmax of TFV-DP Metabolite of TAF
Cmax is defined as the maximum observed concentration of drug.
Time frame: 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
Population: Participants in the PBMC PK Analysis Set with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A: Lenacapavir 20 mg | Part B PK Parameter: Cmax of TFV-DP Metabolite of TAF | 8.5 uM | Standard Deviation 9.94 |
| Part A: Lenacapavir 50 mg | Part B PK Parameter: Cmax of TFV-DP Metabolite of TAF | 163.0 uM | Standard Deviation 118.75 |