HIV-1-infection
Conditions
Brief summary
The primary objective of this study is to evaluate the efficacy of lenacapavir (formerly GS-6207) containing regimens in people living with human immunodeficiency virus (HIV) (PLWH).
Interventions
DRUGOral Lenacapavir
Tablets administered without regard to food
DRUGF/TAF
Tablets administered without regard to food
Administered in the abdomen via subcutaneous injections
DRUGTAF
Tablets administered without regard to food
DRUGBIC
Tablets administered without regard to food
DRUGB/F/TAF
Tablets administered without regard to food
Sponsors
Gilead Sciences
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Antiretroviral (ARV) naive with no use of any ARV within one month of screening. Use of pre-exposure prophylaxis (PrEP) (any duration), post-exposure prophylaxis (PEP) (any duration), or HIV-1 treatment (\< 10 days therapy total) \> 1 month prior to screening is permitted * HIV-1 ribonucleic acid (RNA) ≥ 200 copies/mL at screening * Cluster Determinant 4+ (CD4+) cell count ≥ 200 cells/microliter at screening Key
Exclusion criteria
* Current Hepatitis B Virus (HBV) or Hepatitis C virus (HCV) infection Note: Other protocol defined Inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Human Immunodeficiency Virus-1 Ribonucleic Acid (HIV-1 RNA) < 50 Copies/mL at Week 54 as Determined by the United States Food and Drug Administration (US FDA)-Defined Snapshot Algorithm | Week 54 | The percentage of participants with HIV-1 RNA \< 50 copies/mL at Week 54 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 54 window was between Day 323 and 413 (inclusive). Percentages were rounded off. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 38 as Determined by the US FDA-defined Snapshot Algorithm | Week 38 | The percentage of participants with HIV-1 RNA \< 50 copies/mL at Week 38 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 38 window was between Days 232 and 322 (inclusive). Percentages were rounded off. |
| Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 80 as Determined by the US FDA-defined Snapshot Algorithm | Week 80 | The percentage of participants with HIV-1 RNA \< 50 copies/mL at Week 80 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. The Week 80 window was between Days 505 and 595 (inclusive). Percentages were rounded off. |
| Change From Baseline in Log10 HIV-1 RNA at Week 28 | Baseline, Week 28 | — |
| Change From Baseline in Log10 HIV-1 RNA at Week 38 | Baseline, Week 38 | — |
| Change From Baseline in Log10 HIV-1 RNA at Week 54 | Baseline, Week 54 | — |
| Change From Baseline in Log10 HIV-1 RNA at Week 80 | Baseline, Week 80 | — |
| Change From Baseline in Clusters of Differentiation 4+ (CD4+) Cell Count at Week 28 | Baseline, Week 28 | — |
| Change From Baseline in CD4+ Cell Count at Week 38 | Baseline, Week 38 | — |
| Change From Baseline in CD4+ Cell Count at Week 54 | Baseline, Week 54 | — |
| Change From Baseline in CD4+ Cell Count at Week 80 | Baseline, Week 80 | — |
| Percentage of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs) | Up to 174.9 weeks | TEAEs were defined as 1 or both of any AEs leading to premature discontinuation of study drug, or any AEs with an onset date on or after the study drug start date and no later than the last exposure date after permanent discontinuation of the study drug. Percentages were rounded off. |
| Percentage of Participants Who Experienced Maximum Postbaseline Laboratory Abnormalities | Up to 174.9 weeks | Treatment-emergent laboratory abnormalities were defined as values that increase at least 1 toxicity grade from baseline at any postbaseline visit, up to last exposure date for participants who permanently discontinued study drug. Grade 1: mild; Grade 2: moderate; Grade 3: severe; Grade 4: life-threatening. Percentages were rounded off. |
| Pharmacokinetics (PK) of LEN: Plasma LEN Pre-dose Concentrations for SC LEN | Day 2, 8, Day 1 SC (Day 15), Week 28 and Week 54 | — |
| PK of LEN : Plasma LEN Single Anytime Concentrations for the Oral LEN + DVY | Day 2, 8, 15 , Week 28 and Week 54 | — |
| PK of TAF (Tenofovir Alafenamide) and TFV (Tenofovir): Area Under the Concentration Versus Time Curve (AUClast) on Day 1 | 0 hours (Predose) and at 0.5, 1, 2, 3, 4, 5, 6, and 8 hours postdose on Day 1 | AUClast is defined as area under the concentration versus time curve from time zero to the last quantifiable concentration. A PK substudy was conducted in at least 10 participants in each of the treatment groups receiving SC LEN (Treatment Groups 1 and 2) and at least 15 participants in the treatment group receiving oral LEN (Treatment Group 3). Key PK parameters of TAF and TFV were summarized for participants in the PK Sub study Analysis Set by treatment group, analyte and visit. PK substudy analysis was conducted for Group 1 and 2 on Day 1. |
| PK of TAF and TFV (Tenofovir): Maximum Observed Concentration of Drug (Cmax) on Day 1 | 0 hours (Predose) and at 0.5, 1, 2, 3, 4, 5, 6, and 8 hours postdose on Day 1 | Cmax is defined as the maximum observed concentration of drug. A PK substudy was conducted in at least 10 participants in each of the treatment groups receiving SC LEN (Treatment Groups 1 and 2). Key PK parameters of TAF and TFV were summarized for participants in the PK Sub study Analysis Set by treatment group, analyte and visit. PK substudy analysis was conducted for Group 1 and 2 on Day 1. |
| Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 28 as Determined by the US FDA-defined Snapshot Algorithm | Week 28 | The percentage of participants with HIV-1 RNA \< 50 copies/mL at Week 28 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 28 window was between Days 176 and 231 (inclusive). Percentages were rounded off. |
| PK of TFV: Last Observed Quantifiable Concentration of the Drug (Clast) on Day 1 | 0 hours (Predose) and at 0.5, 1, 2, 3, 4, 5, 6, and 8 hours postdose on Day 1 | Clast is defined as the last observable concentration of drug. A PK substudy was conducted in at least 10 participants in each of the treatment groups receiving SC LEN (Treatment Groups 1 and 2). Key PK parameters of TFV were summarized for participants in the PK Sub study Analysis Set by treatment group, analyte and visit. PK sub study analysis was conducted for Group 1 and 2 on Day 1. |
| PK of TAF and TFV: AUClast at Weeks 16, 22, or 28 | 0 hours (Predose) and at 0.5, 1, 2, 3, 4, 5, 6, and 8 hours postdose | AUClast is defined as area under the concentration versus time curve from time zero to the last quantifiable concentration. A PK substudy was conducted in at least 15 participants in the treatment group receiving oral LEN (Treatment Group 3). Key PK parameters of TAF and TFV were summarized for participants in the PK Sub study Analysis Set by treatment group, analyte and visit. For each participant, PK samples were taken at only one of the three possible visits: Weeks 16, 22, or 28. The PK results were combined and summarized without regard to specific study visit within the range of prespecified study visits. |
| PK of TAF and TFV: Cmax at Weeks 16, 22, or 28 | 0 hours (Predose) and at 0.5, 1, 2, 3, 4, 5, 6, and 8 hours postdose | Cmax is defined as the maximum observed concentration of drug. A PK substudy was conducted in at least 15 participants in the treatment group receiving oral LEN (Treatment Group 3). Key PK parameters of TAF and TFV were summarized for participants in the PK Sub study Analysis Set by treatment group, analyte and visit. For each participant, PK samples were taken at only one of the three possible visits: Weeks 16, 22, or 28. The PK results were combined and summarized without regard to specific study visit within the range of prespecified study visits. |
| PK of TAF and TFV: Tmax at Weeks 16, 22, or 28 | 0 hours (Predose) and at 0.5, 1, 2, 3, 4, 5, 6, and 8 hours postdose | Tmax is defined as the time (observed time point) of Cmax. A PK substudy was conducted in at least 15 participants in the treatment group receiving oral LEN (Treatment Group 3). Key PK parameters of TAF and TFV were summarized for participants in the PK Sub study Analysis Set by treatment group, analyte and visit. For each participant, PK samples were taken at only one of the three possible visits: Weeks 16, 22, or 28. The PK results were combined and summarized without regard to specific study visit within the range of prespecified study visits. |
| PK of TFV: Clast at Weeks 16, 22, or 28 | 0 hours (Predose) and at 0.5, 1, 2, 3, 4, 5, 6, and 8 hours postdose | Clast is defined as the last observable concentration of drug. A PK substudy was conducted in at least 15 participants in the treatment group receiving oral LEN (Treatment Group 3). Key PK parameters of TFV was summarized for participants in the PK Sub study Analysis Set by treatment group, analyte and visit. For each participant, PK samples were taken at only one of the three possible visits: Weeks 16, 22, or 28. The PK results were combined and summarized without regard to specific study visit within the range of prespecified study visits. |
| PK of TAF: AUClast at Week 38 | 0 hours (Predose) and at 0.5, 1, 2, 3, 4, 5, 6, and 8 hours postdose | AUClast is defined as area under the concentration versus time curve from time zero to the last quantifiable concentration. A PK substudy was conducted in at least 10 participants in each of the treatment groups receiving SC LEN (Treatment Groups 1 and 2). Key PK parameters of TAF was summarized for participants in the PK Sub study Analysis Set by treatment group, analyte and visit. PK substudy analysis was conducted for Group 1 at Week 38. |
| PK of TAF: Cmax at Week 38 | 0 hours (Predose) and at 0.5, 1, 2, 3, 4, 5, 6, and 8 hours postdose | Cmax is defined as the maximum observed concentration of drug. A PK substudy was conducted in at least 10 participants in each of the treatment groups receiving SC LEN (Treatment Groups 1 and 2). Key PK parameters of TAF was summarized for participants in the PK Sub study Analysis Set by treatment group, analyte and visit. PK substudy analysis was conducted for Group 1 at Week 38. |
| PK of TAF: Tmax at Week 38 | 0 hours (Predose) and at 0.5, 1, 2, 3, 4, 5, 6, and 8 hours postdose | Tmax is defined as the time (observed time point) of Cmax. A PK substudy was conducted in at least 10 participants in each of the treatment groups receiving SC LEN (Treatment Groups 1 and 2). Key PK parameters of TAF was summarized for participants in the PK Sub study Analysis Set by treatment group, analyte and visit. PK substudy analysis was conducted for Group 1 at Week 38. |
| PK of Tenofovir Diphosphate (TFV-DP): AUClast at Weeks 4, 10, 16, or 22 | 0 hours (Predose) and at 1, 2, and 6 hours postdose | AUClast is defined as area under the concentration versus time curve from time zero to the last quantifiable concentration. A peripheral blood mononuclear cell (PBMC) substudy was conducted in a total of approximately 15 participants in Treatment Groups 1 and 2. For each participant, PK samples were taken at only one of the four possible visits: Weeks 4, 10, 16, or 22. A 12-hour postdose sample was collected, if possible. The PK results were combined and summarized without regard to specific study visit within the range of prespecified study visits. |
| PK of TFV-DP: Cmax at Weeks 4, 10, 16, or 22 | 0 hours (Predose) and at 1, 2, and 6 hours postdose | Cmax is defined as the maximum observed concentration of drug. A PBMC substudy was conducted in a total of approximately 15 participants in Treatment Groups 1 and 2. For each participant, PK samples were taken at only one of the four possible visits: Weeks 4, 10, 16, or 22. A 12-hour postdose sample was collected, if possible. The PK results were combined and summarized without regard to specific study visit within the range of prespecified study visits. |
| PK of TFV-DP: Tmax at Weeks 4, 10, 16, or 22 | 0 hours (Predose) and at 1, 2, and 6 hours postdose | Tmax is defined as the time (observed time point) of Cmax. A PBMC substudy was conducted in a total of approximately 15 participants in Treatment Groups 1 and 2. For each participant, PK samples were taken at only one of the four possible visits: Weeks 4, 10, 16, or 22. A 12-hour postdose sample was collected, if possible. The PK results were combined and summarized without regard to specific study visit within the range of prespecified study visits. |
| PK of Bictegravir (BIC): AUClast at Week 38 | 0 hours (Predose) and at 0.5, 1, 2, 3, 4, 5, 6, and 8 hours postdose | AUClast is defined as area under the concentration versus time curve from time zero to the last quantifiable concentration. A PK substudy was conducted in at least 10 participants in each of the treatment groups receiving SC LEN (Treatment Groups 1 and 2). At Week 38, samples were analyzed for BIC only in Treatment Group 2. |
| PK of BIC: Cmax at Week 38 | 0 hours (Predose) and at 0.5, 1, 2, 3, 4, 5, 6, and 8 hours postdose | Cmax is defined as the maximum observed concentration of drug. A PK substudy was conducted in at least 10 participants in each of the treatment groups receiving SC LEN (Treatment Groups 1 and 2). At Week 38, samples were analyzed for BIC only in Treatment Group 2. |
| PK of BIC: Tmax at Week 38 | 0 hours (Predose) and at 0.5, 1, 2, 3, 4, 5, 6, and 8 hours postdose | Tmax is defined as the time (observed time point) of Cmax. A PK substudy was conducted in at least 10 participants in each of the treatment groups receiving SC LEN (Treatment Groups 1 and 2). At Week 38, samples were analyzed for BIC only in Treatment Group 2. |
| PK of BIC: Clast at Week 38 | 0 hours (Predose) and at 0.5, 1, 2, 3, 4, 5, 6, and 8 hours postdose | Clast is defined as the last observable concentration of drug. A PK substudy was conducted in at least 10 participants in each of the treatment groups receiving SC LEN (Treatment Groups 1 and 2). At Week 38, samples were analyzed for BIC only in Treatment Group 2. |
| PK of TAF and TFV: Time (Observed Time Point) of Cmax (Tmax) on Day 1 | 0 hours (Predose) and at 0.5, 1, 2, 3, 4, 5, 6, and 8 hours postdose on Day 1 | Tmax is defined as the time (observed time point) of Cmax. A PK substudy was conducted in at least 10 participants in each of the treatment groups receiving SC LEN (Treatment Groups 1 and 2). Key PK parameters of TAF and TFV were summarized for participants in the PK Sub study Analysis Set by treatment group, analyte and visit. PK substudy analysis was conducted for Group 1 and 2 on Day 1. |
Countries
Dominican Republic, Puerto Rico, United States
Participant flow
Recruitment details
Participants were enrolled at study sites in Dominican Republic, Puerto Rico, and the United States.
Pre-assignment details
249 participants were screened.
Participants by arm
| Arm | Count |
|---|---|
| Group 1: SC LEN+(F/TAF→ TAF) Induction phase: Participants received lenacapavir (LEN) 600 mg (2 X 300 mg, tablet) orally on Days 1 and 2, followed by LEN 300 mg tablet orally on Day 8 plus emtricitabine/ tenofovir alafenamide (F/TAF) (200/25 mg) fixed-dose combination (FDC) tablets once daily orally from Day 1 to Week 28 plus LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via subcutaneous (SC) injection on Day 15.
Maintenance phase: Participants received LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via SC injection on Week 28 and every 6 months (26 weeks) thereafter plus TAF 25 mg tablets once daily orally at Week 28 and continued up to Week 80.
Participants willing to continue the study beyond Week 80 continued to receive SC LEN 927 mg injection every 6 months (26 weeks) and oral daily TAF 25 mg tablets from Week 80 onwards. | 52 |
| Group 2: SC LEN + (F/TAF → BIC) Induction phase: Participants received LEN 600 mg (2 X 300 mg, tablet) orally on Days 1 and 2, followed by LEN 300 mg tablet orally on Day 8 plus F/TAF (200/25 mg) FDC tablets once daily orally from Day 1 to Week 28 plus LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via SC injection on Day 15.
Maintenance phase: Participants received LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via SC injection on Week 28 and every 6 months (26 weeks) thereafter plus bictegravir (BIC) 75 mg tablets once daily orally at Week 28 and continued up to Week 80.
Participants willing to continue the study beyond Week 80 continued to receive SC LEN 927 mg injection every 6 months (26 weeks) and oral daily BIC 75 mg tablets from Week 80 onwards. | 53 |
| Group 3: Oral LEN + F/TAF Participants received LEN 600 mg (2 X 300 mg, tablet) orally on Days 1 and 2, followed by LEN 50 mg tablets once daily orally from Day 3 and continued up to Week 80. Participants received F/TAF (200/25 mg) FDC tablets once daily orally from Day 1 and continued up to Week 80.
Participants willing to continue the study beyond Week 80 continued to receive oral daily LEN 50 mg tablets and oral daily F/TAF 200/25 mg FDC tablets from Week 80 onwards. | 52 |
| Group 4: B/F/TAF Participants received bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) (50/200/25 mg) FDC tablets once daily orally from Day 1 and throughout their participation in the study up to Week 80. | 25 |
| Total | 182 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 | 0 | 0 |
| Overall Study | Death | 1 | 0 | 1 | 0 |
| Overall Study | Investigator's discretion | 2 | 2 | 0 | 0 |
| Overall Study | Lack of Efficacy | 1 | 1 | 0 | 0 |
| Overall Study | Lost to Follow-up | 3 | 5 | 11 | 0 |
| Overall Study | Pregnancy | 0 | 0 | 1 | 0 |
| Overall Study | Randomized but never treated | 0 | 0 | 0 | 1 |
| Overall Study | Withdrew consent | 3 | 10 | 3 | 1 |
Baseline characteristics
| Characteristic | Group 1: SC LEN+(F/TAF→ TAF) | Group 2: SC LEN + (F/TAF → BIC) | Group 3: Oral LEN + F/TAF | Group 4: B/F/TAF | Total |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Age, Categorical Between 18 and 65 years | 52 Participants | 53 Participants | 51 Participants | 25 Participants | 181 Participants |
| Age, Continuous | 33 years STANDARD_DEVIATION 9.5 | 30 years STANDARD_DEVIATION 8.8 | 32 years STANDARD_DEVIATION 12.3 | 33 years STANDARD_DEVIATION 11.1 | 32 years STANDARD_DEVIATION 10.4 |
| CD4 Cell Count Categories >= 200 to < 350 cells/μL | 17 Participants | 15 Participants | 16 Participants | 4 Participants | 52 Participants |
| CD4 Cell Count Categories >= 350 to < 500 cells/μL | 17 Participants | 15 Participants | 15 Participants | 11 Participants | 58 Participants |
| CD4 Cell Count Categories >= 500 cells/μL | 18 Participants | 22 Participants | 18 Participants | 10 Participants | 68 Participants |
| CD4 Cell Count Categories < 50 cells/μL | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| CD4 Cell Count Categories >= 50 to < 200 cells/μL | 0 Participants | 1 Participants | 3 Participants | 0 Participants | 4 Participants |
| CD4 Percentage (%) | 24.2 percentage of CD4 cells STANDARD_DEVIATION 9.92 | 24.1 percentage of CD4 cells STANDARD_DEVIATION 8.04 | 22.7 percentage of CD4 cells STANDARD_DEVIATION 8.28 | 26.2 percentage of CD4 cells STANDARD_DEVIATION 8.18 | 24.0 percentage of CD4 cells STANDARD_DEVIATION 8.7 |
| Clusters of Differentiation 4+ (CD4) Cell Count | 506 cells/μL STANDARD_DEVIATION 297 | 490 cells/μL STANDARD_DEVIATION 209.9 | 470 cells/μL STANDARD_DEVIATION 221.7 | 534 cells/μL STANDARD_DEVIATION 260 | 495 cells/μL STANDARD_DEVIATION 246.5 |
| HIV-1 RNA Categories <= 100,000 copies/mL | 47 Participants | 44 Participants | 43 Participants | 21 Participants | 155 Participants |
| HIV-1 RNA Categories > 100,000 copies/mL | 5 Participants | 9 Participants | 9 Participants | 4 Participants | 27 Participants |
| Human Immunodeficiency Virus-1 Ribonucleic Acid (HIV-1 RNA) | 4.18 log10 copies/mL STANDARD_DEVIATION 0.672 | 4.35 log10 copies/mL STANDARD_DEVIATION 0.67 | 4.33 log10 copies/mL STANDARD_DEVIATION 0.722 | 4.35 log10 copies/mL STANDARD_DEVIATION 0.78 | 4.30 log10 copies/mL STANDARD_DEVIATION 0.7 |
| Race/Ethnicity, Customized Ethnicity Hispanic or Latino | 25 Participants | 21 Participants | 24 Participants | 12 Participants | 82 Participants |
| Race/Ethnicity, Customized Ethnicity Not Hispanic or Latino | 27 Participants | 32 Participants | 28 Participants | 13 Participants | 100 Participants |
| Race/Ethnicity, Customized Race American Indian or Alaska Native | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Race Asian | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized Race Black | 24 Participants | 24 Participants | 31 Participants | 16 Participants | 95 Participants |
| Race/Ethnicity, Customized Race Native Hawaiian or Pacific Islander | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized Race Other | 2 Participants | 0 Participants | 1 Participants | 1 Participants | 4 Participants |
| Race/Ethnicity, Customized Race White | 23 Participants | 28 Participants | 19 Participants | 8 Participants | 78 Participants |
| Region of Enrollment Dominican Republic | 14 Participants | 10 Participants | 10 Participants | 3 Participants | 37 Participants |
| Region of Enrollment Puerto Rico | 1 Participants | 1 Participants | 5 Participants | 1 Participants | 8 Participants |
| Region of Enrollment United States | 37 Participants | 42 Participants | 37 Participants | 21 Participants | 137 Participants |
| Sex: Female, Male Female | 5 Participants | 1 Participants | 6 Participants | 0 Participants | 12 Participants |
| Sex: Female, Male Male | 47 Participants | 52 Participants | 46 Participants | 25 Participants | 170 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 52 | 0 / 53 | 1 / 52 | 0 / 26 |
| other Total, other adverse events | 47 / 52 | 46 / 53 | 42 / 52 | 19 / 25 |
| serious Total, serious adverse events | 4 / 52 | 4 / 53 | 7 / 52 | 0 / 25 |
Outcome results
Primary
Percentage of Participants With Human Immunodeficiency Virus-1 Ribonucleic Acid (HIV-1 RNA) < 50 Copies/mL at Week 54 as Determined by the United States Food and Drug Administration (US FDA)-Defined Snapshot Algorithm
The percentage of participants with HIV-1 RNA \< 50 copies/mL at Week 54 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 54 window was between Day 323 and 413 (inclusive). Percentages were rounded off.
Time frame: Week 54
Population: Full Analysis Set included all randomized participants who were randomized and received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Group 1: SC LEN+(F/TAF→ TAF) | Percentage of Participants With Human Immunodeficiency Virus-1 Ribonucleic Acid (HIV-1 RNA) < 50 Copies/mL at Week 54 as Determined by the United States Food and Drug Administration (US FDA)-Defined Snapshot Algorithm | 90.4 percentage of participants |
| Group 2: SC LEN + (F/TAF → BIC) | Percentage of Participants With Human Immunodeficiency Virus-1 Ribonucleic Acid (HIV-1 RNA) < 50 Copies/mL at Week 54 as Determined by the United States Food and Drug Administration (US FDA)-Defined Snapshot Algorithm | 84.9 percentage of participants |
| Group 3: Oral LEN + F/TAF | Percentage of Participants With Human Immunodeficiency Virus-1 Ribonucleic Acid (HIV-1 RNA) < 50 Copies/mL at Week 54 as Determined by the United States Food and Drug Administration (US FDA)-Defined Snapshot Algorithm | 84.6 percentage of participants |
| Group 4: B/F/TAF | Percentage of Participants With Human Immunodeficiency Virus-1 Ribonucleic Acid (HIV-1 RNA) < 50 Copies/mL at Week 54 as Determined by the United States Food and Drug Administration (US FDA)-Defined Snapshot Algorithm | 92.0 percentage of participants |
p-value: 0.717895% CI: [-18.4, 13.2]Cochran-Mantel-Haenszel
p-value: 0.3995% CI: [-23.4, 9.3]Cochran-Mantel-Haenszel
p-value: 0.379795% CI: [-23.5, 9.1]Cochran-Mantel-Haenszel
Secondary
Change From Baseline in CD4+ Cell Count at Week 38
Time frame: Baseline, Week 38
Population: Participants in the Full Analysis Set with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Group 1: SC LEN+(F/TAF→ TAF) | Change From Baseline in CD4+ Cell Count at Week 38 | 195 cells/µL | Standard Deviation 164.6 |
| Group 2: SC LEN + (F/TAF → BIC) | Change From Baseline in CD4+ Cell Count at Week 38 | 220 cells/µL | Standard Deviation 187.5 |
| Group 3: Oral LEN + F/TAF | Change From Baseline in CD4+ Cell Count at Week 38 | 211 cells/µL | Standard Deviation 166.2 |
| Group 4: B/F/TAF | Change From Baseline in CD4+ Cell Count at Week 38 | 232 cells/µL | Standard Deviation 209.3 |
p-value: 0.482795% CI: [-119, 57]ANOVA
p-value: 0.796395% CI: [-106, 81]ANOVA
p-value: 0.616995% CI: [-111, 67]ANOVA
Secondary
Change From Baseline in CD4+ Cell Count at Week 54
Time frame: Baseline, Week 54
Population: Participants in the Full Analysis Set with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Group 1: SC LEN+(F/TAF→ TAF) | Change From Baseline in CD4+ Cell Count at Week 54 | 204 cells/µL | Standard Deviation 189.1 |
| Group 2: SC LEN + (F/TAF → BIC) | Change From Baseline in CD4+ Cell Count at Week 54 | 213 cells/µL | Standard Deviation 187.2 |
| Group 3: Oral LEN + F/TAF | Change From Baseline in CD4+ Cell Count at Week 54 | 220 cells/µL | Standard Deviation 175.5 |
| Group 4: B/F/TAF | Change From Baseline in CD4+ Cell Count at Week 54 | 193 cells/µL | Standard Deviation 191.1 |
p-value: 0.661495% CI: [-73, 115]ANOVA
p-value: 0.679195% CI: [-75, 115]ANOVA
p-value: 0.556395% CI: [-65, 120]ANOVA
Secondary
Change From Baseline in CD4+ Cell Count at Week 80
Time frame: Baseline, Week 80
Population: Participants in the Full Analysis Set with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Group 1: SC LEN+(F/TAF→ TAF) | Change From Baseline in CD4+ Cell Count at Week 80 | 275 cells/μL | Standard Deviation 211.8 |
| Group 2: SC LEN + (F/TAF → BIC) | Change From Baseline in CD4+ Cell Count at Week 80 | 262 cells/μL | Standard Deviation 184.4 |
| Group 3: Oral LEN + F/TAF | Change From Baseline in CD4+ Cell Count at Week 80 | 245 cells/μL | Standard Deviation 237.4 |
| Group 4: B/F/TAF | Change From Baseline in CD4+ Cell Count at Week 80 | 248 cells/μL | Standard Deviation 218.7 |
p-value: 0.549295% CI: [-75, 140]ANOVA
p-value: 0.72295% CI: [-80, 115]Difference in LSM
p-value: 0.948695% CI: [-118, 110]ANOVA
Secondary
Change From Baseline in Clusters of Differentiation 4+ (CD4+) Cell Count at Week 28
Time frame: Baseline, Week 28
Population: Participants in the Full Analysis Set with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Group 1: SC LEN+(F/TAF→ TAF) | Change From Baseline in Clusters of Differentiation 4+ (CD4+) Cell Count at Week 28 | 172 cells/µL | Standard Deviation 178.2 |
| Group 2: SC LEN + (F/TAF → BIC) | Change From Baseline in Clusters of Differentiation 4+ (CD4+) Cell Count at Week 28 | 158 cells/µL | Standard Deviation 164.1 |
| Group 3: Oral LEN + F/TAF | Change From Baseline in Clusters of Differentiation 4+ (CD4+) Cell Count at Week 28 | 206 cells/µL | Standard Deviation 154.6 |
| Group 4: B/F/TAF | Change From Baseline in Clusters of Differentiation 4+ (CD4+) Cell Count at Week 28 | 163 cells/µL | Standard Deviation 157.7 |
p-value: 0.775195% CI: [-73, 97]ANOVA
p-value: 0.954995% CI: [-79, 75]ANOVA
p-value: 0.260395% CI: [-33, 120]ANOVA
Secondary
Change From Baseline in Log10 HIV-1 RNA at Week 28
Time frame: Baseline, Week 28
Population: Participants in the Full Analysis Set with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Group 1: SC LEN+(F/TAF→ TAF) | Change From Baseline in Log10 HIV-1 RNA at Week 28 | -2.92 log10 copies/mL | Standard Deviation 0.649 |
| Group 2: SC LEN + (F/TAF → BIC) | Change From Baseline in Log10 HIV-1 RNA at Week 28 | -3.04 log10 copies/mL | Standard Deviation 0.638 |
| Group 3: Oral LEN + F/TAF | Change From Baseline in Log10 HIV-1 RNA at Week 28 | -3.01 log10 copies/mL | Standard Deviation 0.716 |
| Group 4: B/F/TAF | Change From Baseline in Log10 HIV-1 RNA at Week 28 | -3.07 log10 copies/mL | Standard Deviation 0.774 |
p-value: 0.575595% CI: [-0.2, 0.37]ANOVA
p-value: 0.869795% CI: [-0.25, 0.29]ANOVA
p-value: 0.705295% CI: [-0.23, 0.35]ANOVA
Secondary
Change From Baseline in Log10 HIV-1 RNA at Week 38
Time frame: Baseline, Week 38
Population: Participants in the Full Analysis Set with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Group 1: SC LEN+(F/TAF→ TAF) | Change From Baseline in Log10 HIV-1 RNA at Week 38 | -2.96 log10 copies/mL | Standard Deviation 0.639 |
| Group 2: SC LEN + (F/TAF → BIC) | Change From Baseline in Log10 HIV-1 RNA at Week 38 | -3.06 log10 copies/mL | Standard Deviation 0.641 |
| Group 3: Oral LEN + F/TAF | Change From Baseline in Log10 HIV-1 RNA at Week 38 | -3.02 log10 copies/mL | Standard Deviation 0.771 |
| Group 4: B/F/TAF | Change From Baseline in Log10 HIV-1 RNA at Week 38 | -3.04 log10 copies/mL | Standard Deviation 0.76 |
p-value: 0.905895% CI: [-0.28, 0.25]ANOVA
p-value: 0.812995% CI: [-0.27, 0.35]ANOVA
p-value: 0.894295% CI: [-0.26, 0.3]ANOVA
Secondary
Change From Baseline in Log10 HIV-1 RNA at Week 54
Time frame: Baseline, Week 54
Population: Participants in the Full Analysis Set with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Group 1: SC LEN+(F/TAF→ TAF) | Change From Baseline in Log10 HIV-1 RNA at Week 54 | -2.95 log10 copies/mL | Standard Deviation 0.636 |
| Group 2: SC LEN + (F/TAF → BIC) | Change From Baseline in Log10 HIV-1 RNA at Week 54 | -3.12 log10 copies/mL | Standard Deviation 0.589 |
| Group 3: Oral LEN + F/TAF | Change From Baseline in Log10 HIV-1 RNA at Week 54 | -2.85 log10 copies/mL | Standard Deviation 0.84 |
| Group 4: B/F/TAF | Change From Baseline in Log10 HIV-1 RNA at Week 54 | -3.08 log10 copies/mL | Standard Deviation 0.787 |
p-value: 0.701395% CI: [-0.31, 0.21]ANOVA
p-value: 0.275395% CI: [-0.18, 0.62]ANOVA
p-value: 0.786495% CI: [-0.25, 0.33]ANOVA
Secondary
Change From Baseline in Log10 HIV-1 RNA at Week 80
Time frame: Baseline, Week 80
Population: Participants in the Full Analysis Set with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Group 1: SC LEN+(F/TAF→ TAF) | Change From Baseline in Log10 HIV-1 RNA at Week 80 | -2.96 log10 Copies/mL | Standard Deviation 0.539 |
| Group 2: SC LEN + (F/TAF → BIC) | Change From Baseline in Log10 HIV-1 RNA at Week 80 | -3.08 log10 Copies/mL | Standard Deviation 0.592 |
| Group 3: Oral LEN + F/TAF | Change From Baseline in Log10 HIV-1 RNA at Week 80 | -2.96 log10 Copies/mL | Standard Deviation 0.747 |
| Group 4: B/F/TAF | Change From Baseline in Log10 HIV-1 RNA at Week 80 | -3.09 log10 Copies/mL | Standard Deviation 0.755 |
p-value: 0.56495% CI: [-0.19, 0.34]ANOVA
p-value: 0.955595% CI: [-0.28, 0.26]ANOVA
p-value: 0.402595% CI: [-0.19, 0.46]ANOVA
Secondary
Percentage of Participants Who Experienced Maximum Postbaseline Laboratory Abnormalities
Treatment-emergent laboratory abnormalities were defined as values that increase at least 1 toxicity grade from baseline at any postbaseline visit, up to last exposure date for participants who permanently discontinued study drug. Grade 1: mild; Grade 2: moderate; Grade 3: severe; Grade 4: life-threatening. Percentages were rounded off.
Time frame: Up to 174.9 weeks
Population: Participants in the Safety Analysis Set were analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Group 1: SC LEN+(F/TAF→ TAF) | Percentage of Participants Who Experienced Maximum Postbaseline Laboratory Abnormalities | Grade 1 | 9.6 percentage of participants |
| Group 1: SC LEN+(F/TAF→ TAF) | Percentage of Participants Who Experienced Maximum Postbaseline Laboratory Abnormalities | Grade 2 | 55.8 percentage of participants |
| Group 1: SC LEN+(F/TAF→ TAF) | Percentage of Participants Who Experienced Maximum Postbaseline Laboratory Abnormalities | Grade 3 | 17.3 percentage of participants |
| Group 1: SC LEN+(F/TAF→ TAF) | Percentage of Participants Who Experienced Maximum Postbaseline Laboratory Abnormalities | Grade 4 | 13.5 percentage of participants |
| Group 2: SC LEN + (F/TAF → BIC) | Percentage of Participants Who Experienced Maximum Postbaseline Laboratory Abnormalities | Grade 2 | 56.6 percentage of participants |
| Group 2: SC LEN + (F/TAF → BIC) | Percentage of Participants Who Experienced Maximum Postbaseline Laboratory Abnormalities | Grade 3 | 28.3 percentage of participants |
| Group 2: SC LEN + (F/TAF → BIC) | Percentage of Participants Who Experienced Maximum Postbaseline Laboratory Abnormalities | Grade 4 | 9.4 percentage of participants |
| Group 2: SC LEN + (F/TAF → BIC) | Percentage of Participants Who Experienced Maximum Postbaseline Laboratory Abnormalities | Grade 1 | 3.8 percentage of participants |
| Group 3: Oral LEN + F/TAF | Percentage of Participants Who Experienced Maximum Postbaseline Laboratory Abnormalities | Grade 3 | 30.8 percentage of participants |
| Group 3: Oral LEN + F/TAF | Percentage of Participants Who Experienced Maximum Postbaseline Laboratory Abnormalities | Grade 2 | 42.3 percentage of participants |
| Group 3: Oral LEN + F/TAF | Percentage of Participants Who Experienced Maximum Postbaseline Laboratory Abnormalities | Grade 4 | 13.5 percentage of participants |
| Group 3: Oral LEN + F/TAF | Percentage of Participants Who Experienced Maximum Postbaseline Laboratory Abnormalities | Grade 1 | 9.6 percentage of participants |
| Group 4: B/F/TAF | Percentage of Participants Who Experienced Maximum Postbaseline Laboratory Abnormalities | Grade 4 | 0 percentage of participants |
| Group 4: B/F/TAF | Percentage of Participants Who Experienced Maximum Postbaseline Laboratory Abnormalities | Grade 2 | 76.0 percentage of participants |
| Group 4: B/F/TAF | Percentage of Participants Who Experienced Maximum Postbaseline Laboratory Abnormalities | Grade 1 | 0 percentage of participants |
| Group 4: B/F/TAF | Percentage of Participants Who Experienced Maximum Postbaseline Laboratory Abnormalities | Grade 3 | 24.0 percentage of participants |
Secondary
Percentage of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs)
TEAEs were defined as 1 or both of any AEs leading to premature discontinuation of study drug, or any AEs with an onset date on or after the study drug start date and no later than the last exposure date after permanent discontinuation of the study drug. Percentages were rounded off.
Time frame: Up to 174.9 weeks
Population: Safety Analysis Set included all participants who were randomized and received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Group 1: SC LEN+(F/TAF→ TAF) | Percentage of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs) | 98.1 percentage of participants |
| Group 2: SC LEN + (F/TAF → BIC) | Percentage of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs) | 88.7 percentage of participants |
| Group 3: Oral LEN + F/TAF | Percentage of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs) | 90.4 percentage of participants |
| Group 4: B/F/TAF | Percentage of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs) | 84.0 percentage of participants |
Secondary
Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 28 as Determined by the US FDA-defined Snapshot Algorithm
The percentage of participants with HIV-1 RNA \< 50 copies/mL at Week 28 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 28 window was between Days 176 and 231 (inclusive). Percentages were rounded off.
Time frame: Week 28
Population: Participants in the Full Analysis Set were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Group 1: SC LEN+(F/TAF→ TAF) | Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 28 as Determined by the US FDA-defined Snapshot Algorithm | 94.2 percentage of participants |
| Group 2: SC LEN + (F/TAF → BIC) | Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 28 as Determined by the US FDA-defined Snapshot Algorithm | 92.5 percentage of participants |
| Group 3: Oral LEN + F/TAF | Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 28 as Determined by the US FDA-defined Snapshot Algorithm | 94.2 percentage of participants |
| Group 4: B/F/TAF | Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 28 as Determined by the US FDA-defined Snapshot Algorithm | 100.0 percentage of participants |
p-value: 0.239895% CI: [-15.9, 4.8]Cochran-Mantel-Haenszel
p-value: 0.163995% CI: [-18.3, 3.4]Cochran-Mantel-Haenszel
p-value: 0.230795% CI: [-16.3, 4.9]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 38 as Determined by the US FDA-defined Snapshot Algorithm
The percentage of participants with HIV-1 RNA \< 50 copies/mL at Week 38 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 38 window was between Days 232 and 322 (inclusive). Percentages were rounded off.
Time frame: Week 38
Population: Participants in the Full Analysis Set were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Group 1: SC LEN+(F/TAF→ TAF) | Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 38 as Determined by the US FDA-defined Snapshot Algorithm | 90.4 percentage of participants |
| Group 2: SC LEN + (F/TAF → BIC) | Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 38 as Determined by the US FDA-defined Snapshot Algorithm | 88.7 percentage of participants |
| Group 3: Oral LEN + F/TAF | Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 38 as Determined by the US FDA-defined Snapshot Algorithm | 88.5 percentage of participants |
| Group 4: B/F/TAF | Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 38 as Determined by the US FDA-defined Snapshot Algorithm | 96.0 percentage of participants |
p-value: 0.314295% CI: [-20.7, 7.3]Cochran-Mantel-Haenszel
p-value: 0.300995% CI: [-21.3, 6.8]Cochran-Mantel-Haenszel
p-value: 0.285995% CI: [-21.8, 6.7]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 80 as Determined by the US FDA-defined Snapshot Algorithm
The percentage of participants with HIV-1 RNA \< 50 copies/mL at Week 80 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. The Week 80 window was between Days 505 and 595 (inclusive). Percentages were rounded off.
Time frame: Week 80
Population: Participants in the Full Analysis Set were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Group 1: SC LEN+(F/TAF→ TAF) | Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 80 as Determined by the US FDA-defined Snapshot Algorithm | 86.5 percentage of participants |
| Group 2: SC LEN + (F/TAF → BIC) | Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 80 as Determined by the US FDA-defined Snapshot Algorithm | 75.5 percentage of participants |
| Group 3: Oral LEN + F/TAF | Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 80 as Determined by the US FDA-defined Snapshot Algorithm | 86.5 percentage of participants |
| Group 4: B/F/TAF | Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 80 as Determined by the US FDA-defined Snapshot Algorithm | 92 percentage of participants |
p-value: 0.368695% CI: [-23.2, 9]Cochran-Mantel-Haenszel
p-value: 0.088795% CI: [-34, 1]Cochran-Mantel-Haenszel
p-value: 0.494995% CI: [-21.5, 10.7]Cochran-Mantel-Haenszel
Secondary
Pharmacokinetics (PK) of LEN: Plasma LEN Pre-dose Concentrations for SC LEN
Time frame: Day 2, 8, Day 1 SC (Day 15), Week 28 and Week 54
Population: Participants in the PK Substudy Analysis Set with available data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group 1: SC LEN+(F/TAF→ TAF) | Pharmacokinetics (PK) of LEN: Plasma LEN Pre-dose Concentrations for SC LEN | Day 8 | 34.5 ng/mL | Standard Deviation 20.96 |
| Group 1: SC LEN+(F/TAF→ TAF) | Pharmacokinetics (PK) of LEN: Plasma LEN Pre-dose Concentrations for SC LEN | Week 28 | 22.0 ng/mL | Standard Deviation 11.7 |
| Group 1: SC LEN+(F/TAF→ TAF) | Pharmacokinetics (PK) of LEN: Plasma LEN Pre-dose Concentrations for SC LEN | Day 1 SC (Day 15) | 30.9 ng/mL | Standard Deviation 16.76 |
| Group 1: SC LEN+(F/TAF→ TAF) | Pharmacokinetics (PK) of LEN: Plasma LEN Pre-dose Concentrations for SC LEN | Week 54 | 26.9 ng/mL | Standard Deviation 14.19 |
| Group 1: SC LEN+(F/TAF→ TAF) | Pharmacokinetics (PK) of LEN: Plasma LEN Pre-dose Concentrations for SC LEN | Day 2 | 28.3 ng/mL | Standard Deviation 27.15 |
| Group 2: SC LEN + (F/TAF → BIC) | Pharmacokinetics (PK) of LEN: Plasma LEN Pre-dose Concentrations for SC LEN | Week 54 | 26.4 ng/mL | Standard Deviation 12.1 |
| Group 2: SC LEN + (F/TAF → BIC) | Pharmacokinetics (PK) of LEN: Plasma LEN Pre-dose Concentrations for SC LEN | Day 2 | 26.1 ng/mL | Standard Deviation 20.46 |
| Group 2: SC LEN + (F/TAF → BIC) | Pharmacokinetics (PK) of LEN: Plasma LEN Pre-dose Concentrations for SC LEN | Day 8 | 32.1 ng/mL | Standard Deviation 14.71 |
| Group 2: SC LEN + (F/TAF → BIC) | Pharmacokinetics (PK) of LEN: Plasma LEN Pre-dose Concentrations for SC LEN | Day 1 SC (Day 15) | 31.2 ng/mL | Standard Deviation 14.66 |
| Group 2: SC LEN + (F/TAF → BIC) | Pharmacokinetics (PK) of LEN: Plasma LEN Pre-dose Concentrations for SC LEN | Week 28 | 23.0 ng/mL | Standard Deviation 14.81 |
Secondary
PK of BIC: Clast at Week 38
Clast is defined as the last observable concentration of drug. A PK substudy was conducted in at least 10 participants in each of the treatment groups receiving SC LEN (Treatment Groups 1 and 2). At Week 38, samples were analyzed for BIC only in Treatment Group 2.
Time frame: 0 hours (Predose) and at 0.5, 1, 2, 3, 4, 5, 6, and 8 hours postdose
Population: Participants in the PK Substudy Analysis Set with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Group 1: SC LEN+(F/TAF→ TAF) | PK of BIC: Clast at Week 38 | 8474.5 ng/mL | Standard Deviation 33.3 |
Secondary
PK of BIC: Cmax at Week 38
Cmax is defined as the maximum observed concentration of drug. A PK substudy was conducted in at least 10 participants in each of the treatment groups receiving SC LEN (Treatment Groups 1 and 2). At Week 38, samples were analyzed for BIC only in Treatment Group 2.
Time frame: 0 hours (Predose) and at 0.5, 1, 2, 3, 4, 5, 6, and 8 hours postdose
Population: Participants in the PK Substudy Analysis Set with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Group 1: SC LEN+(F/TAF→ TAF) | PK of BIC: Cmax at Week 38 | 10180.0 ng/mL | Standard Deviation 42.8 |
Secondary
PK of Bictegravir (BIC): AUClast at Week 38
AUClast is defined as area under the concentration versus time curve from time zero to the last quantifiable concentration. A PK substudy was conducted in at least 10 participants in each of the treatment groups receiving SC LEN (Treatment Groups 1 and 2). At Week 38, samples were analyzed for BIC only in Treatment Group 2.
Time frame: 0 hours (Predose) and at 0.5, 1, 2, 3, 4, 5, 6, and 8 hours postdose
Population: Participants in the PK Substudy Analysis Set with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Group 1: SC LEN+(F/TAF→ TAF) | PK of Bictegravir (BIC): AUClast at Week 38 | 72865.9 h*ng/mL | Standard Deviation 31 |
Secondary
PK of BIC: Tmax at Week 38
Tmax is defined as the time (observed time point) of Cmax. A PK substudy was conducted in at least 10 participants in each of the treatment groups receiving SC LEN (Treatment Groups 1 and 2). At Week 38, samples were analyzed for BIC only in Treatment Group 2.
Time frame: 0 hours (Predose) and at 0.5, 1, 2, 3, 4, 5, 6, and 8 hours postdose
Population: Participants in the PK Substudy Analysis Set with available data were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Group 1: SC LEN+(F/TAF→ TAF) | PK of BIC: Tmax at Week 38 | 2.00 hours |
Secondary
PK of LEN : Plasma LEN Single Anytime Concentrations for the Oral LEN + DVY
Time frame: Day 2, 8, 15 , Week 28 and Week 54
Population: Participants in the PK Substudy Analysis Set with available data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group 1: SC LEN+(F/TAF→ TAF) | PK of LEN : Plasma LEN Single Anytime Concentrations for the Oral LEN + DVY | Day 2 | 29.8 ng/mL | Standard Deviation 42.7 |
| Group 1: SC LEN+(F/TAF→ TAF) | PK of LEN : Plasma LEN Single Anytime Concentrations for the Oral LEN + DVY | Day 8 | 78.7 ng/mL | Standard Deviation 55.9 |
| Group 1: SC LEN+(F/TAF→ TAF) | PK of LEN : Plasma LEN Single Anytime Concentrations for the Oral LEN + DVY | Day 15 | 97.2 ng/mL | Standard Deviation 67.25 |
| Group 1: SC LEN+(F/TAF→ TAF) | PK of LEN : Plasma LEN Single Anytime Concentrations for the Oral LEN + DVY | Week 28 | 96.6 ng/mL | Standard Deviation 76.4 |
| Group 1: SC LEN+(F/TAF→ TAF) | PK of LEN : Plasma LEN Single Anytime Concentrations for the Oral LEN + DVY | Week 54 | 98.4 ng/mL | Standard Deviation 85.25 |
Secondary
PK of TAF and TFV: AUClast at Weeks 16, 22, or 28
AUClast is defined as area under the concentration versus time curve from time zero to the last quantifiable concentration. A PK substudy was conducted in at least 15 participants in the treatment group receiving oral LEN (Treatment Group 3). Key PK parameters of TAF and TFV were summarized for participants in the PK Sub study Analysis Set by treatment group, analyte and visit. For each participant, PK samples were taken at only one of the three possible visits: Weeks 16, 22, or 28. The PK results were combined and summarized without regard to specific study visit within the range of prespecified study visits.
Time frame: 0 hours (Predose) and at 0.5, 1, 2, 3, 4, 5, 6, and 8 hours postdose
Population: Participants in the PK Substudy Analysis Set with available data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group 1: SC LEN+(F/TAF→ TAF) | PK of TAF and TFV: AUClast at Weeks 16, 22, or 28 | TAF | 231.2 h*ng/mL | Standard Deviation 60 |
| Group 1: SC LEN+(F/TAF→ TAF) | PK of TAF and TFV: AUClast at Weeks 16, 22, or 28 | TFV | 173.1 h*ng/mL | Standard Deviation 52.5 |
Secondary
PK of TAF and TFV: Cmax at Weeks 16, 22, or 28
Cmax is defined as the maximum observed concentration of drug. A PK substudy was conducted in at least 15 participants in the treatment group receiving oral LEN (Treatment Group 3). Key PK parameters of TAF and TFV were summarized for participants in the PK Sub study Analysis Set by treatment group, analyte and visit. For each participant, PK samples were taken at only one of the three possible visits: Weeks 16, 22, or 28. The PK results were combined and summarized without regard to specific study visit within the range of prespecified study visits.
Time frame: 0 hours (Predose) and at 0.5, 1, 2, 3, 4, 5, 6, and 8 hours postdose
Population: Participants in the PK Substudy Analysis Set with available data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group 1: SC LEN+(F/TAF→ TAF) | PK of TAF and TFV: Cmax at Weeks 16, 22, or 28 | TAF | 308.7 ng/mL | Standard Deviation 74.7 |
| Group 1: SC LEN+(F/TAF→ TAF) | PK of TAF and TFV: Cmax at Weeks 16, 22, or 28 | TFV | 31.2 ng/mL | Standard Deviation 51.7 |
Secondary
PK of TAF and TFV (Tenofovir): Maximum Observed Concentration of Drug (Cmax) on Day 1
Cmax is defined as the maximum observed concentration of drug. A PK substudy was conducted in at least 10 participants in each of the treatment groups receiving SC LEN (Treatment Groups 1 and 2). Key PK parameters of TAF and TFV were summarized for participants in the PK Sub study Analysis Set by treatment group, analyte and visit. PK substudy analysis was conducted for Group 1 and 2 on Day 1.
Time frame: 0 hours (Predose) and at 0.5, 1, 2, 3, 4, 5, 6, and 8 hours postdose on Day 1
Population: Participants in the PK Substudy Analysis Set with available data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group 1: SC LEN+(F/TAF→ TAF) | PK of TAF and TFV (Tenofovir): Maximum Observed Concentration of Drug (Cmax) on Day 1 | TAF | 278.8 ng/mL | Standard Deviation 87.7 |
| Group 1: SC LEN+(F/TAF→ TAF) | PK of TAF and TFV (Tenofovir): Maximum Observed Concentration of Drug (Cmax) on Day 1 | TFV | 5.4 ng/mL | Standard Deviation 26.5 |
| Group 2: SC LEN + (F/TAF → BIC) | PK of TAF and TFV (Tenofovir): Maximum Observed Concentration of Drug (Cmax) on Day 1 | TAF | 318.4 ng/mL | Standard Deviation 57.7 |
| Group 2: SC LEN + (F/TAF → BIC) | PK of TAF and TFV (Tenofovir): Maximum Observed Concentration of Drug (Cmax) on Day 1 | TFV | 13.8 ng/mL | Standard Deviation 160.2 |
Secondary
PK of TAF and TFV: Time (Observed Time Point) of Cmax (Tmax) on Day 1
Tmax is defined as the time (observed time point) of Cmax. A PK substudy was conducted in at least 10 participants in each of the treatment groups receiving SC LEN (Treatment Groups 1 and 2). Key PK parameters of TAF and TFV were summarized for participants in the PK Sub study Analysis Set by treatment group, analyte and visit. PK substudy analysis was conducted for Group 1 and 2 on Day 1.
Time frame: 0 hours (Predose) and at 0.5, 1, 2, 3, 4, 5, 6, and 8 hours postdose on Day 1
Population: Participants in the PK Substudy Analysis Set with available data were analyzed.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Group 1: SC LEN+(F/TAF→ TAF) | PK of TAF and TFV: Time (Observed Time Point) of Cmax (Tmax) on Day 1 | TAF | 0.50 hours |
| Group 1: SC LEN+(F/TAF→ TAF) | PK of TAF and TFV: Time (Observed Time Point) of Cmax (Tmax) on Day 1 | TFV | 1.50 hours |
| Group 2: SC LEN + (F/TAF → BIC) | PK of TAF and TFV: Time (Observed Time Point) of Cmax (Tmax) on Day 1 | TAF | 0.50 hours |
| Group 2: SC LEN + (F/TAF → BIC) | PK of TAF and TFV: Time (Observed Time Point) of Cmax (Tmax) on Day 1 | TFV | 1.00 hours |
Secondary
PK of TAF and TFV: Tmax at Weeks 16, 22, or 28
Tmax is defined as the time (observed time point) of Cmax. A PK substudy was conducted in at least 15 participants in the treatment group receiving oral LEN (Treatment Group 3). Key PK parameters of TAF and TFV were summarized for participants in the PK Sub study Analysis Set by treatment group, analyte and visit. For each participant, PK samples were taken at only one of the three possible visits: Weeks 16, 22, or 28. The PK results were combined and summarized without regard to specific study visit within the range of prespecified study visits.
Time frame: 0 hours (Predose) and at 0.5, 1, 2, 3, 4, 5, 6, and 8 hours postdose
Population: Participants in the PK Substudy Analysis Set with available data were analyzed.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Group 1: SC LEN+(F/TAF→ TAF) | PK of TAF and TFV: Tmax at Weeks 16, 22, or 28 | TAF | 0.53 hours |
| Group 1: SC LEN+(F/TAF→ TAF) | PK of TAF and TFV: Tmax at Weeks 16, 22, or 28 | TFV | 1.00 hours |
Secondary
PK of TAF: AUClast at Week 38
AUClast is defined as area under the concentration versus time curve from time zero to the last quantifiable concentration. A PK substudy was conducted in at least 10 participants in each of the treatment groups receiving SC LEN (Treatment Groups 1 and 2). Key PK parameters of TAF was summarized for participants in the PK Sub study Analysis Set by treatment group, analyte and visit. PK substudy analysis was conducted for Group 1 at Week 38.
Time frame: 0 hours (Predose) and at 0.5, 1, 2, 3, 4, 5, 6, and 8 hours postdose
Population: Participants in the PK Substudy Analysis Set with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Group 1: SC LEN+(F/TAF→ TAF) | PK of TAF: AUClast at Week 38 | 211.5 h*ng/mL | Standard Deviation 74.1 |
Secondary
PK of TAF: Cmax at Week 38
Cmax is defined as the maximum observed concentration of drug. A PK substudy was conducted in at least 10 participants in each of the treatment groups receiving SC LEN (Treatment Groups 1 and 2). Key PK parameters of TAF was summarized for participants in the PK Sub study Analysis Set by treatment group, analyte and visit. PK substudy analysis was conducted for Group 1 at Week 38.
Time frame: 0 hours (Predose) and at 0.5, 1, 2, 3, 4, 5, 6, and 8 hours postdose
Population: Participants in the PK Substudy Analysis Set with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Group 1: SC LEN+(F/TAF→ TAF) | PK of TAF: Cmax at Week 38 | 279.0 ng/mL | Standard Deviation 67.8 |
Secondary
PK of TAF (Tenofovir Alafenamide) and TFV (Tenofovir): Area Under the Concentration Versus Time Curve (AUClast) on Day 1
AUClast is defined as area under the concentration versus time curve from time zero to the last quantifiable concentration. A PK substudy was conducted in at least 10 participants in each of the treatment groups receiving SC LEN (Treatment Groups 1 and 2) and at least 15 participants in the treatment group receiving oral LEN (Treatment Group 3). Key PK parameters of TAF and TFV were summarized for participants in the PK Sub study Analysis Set by treatment group, analyte and visit. PK substudy analysis was conducted for Group 1 and 2 on Day 1.
Time frame: 0 hours (Predose) and at 0.5, 1, 2, 3, 4, 5, 6, and 8 hours postdose on Day 1
Population: PK Substudy Analysis Set included participants who were randomized into the study, were enrolled into the PK Substudy, had received at least 1 dose of active study drug, and had at least 1 nonmissing intensive PK substudy concentration value for any analyte of interest reported by the PK lab.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group 1: SC LEN+(F/TAF→ TAF) | PK of TAF (Tenofovir Alafenamide) and TFV (Tenofovir): Area Under the Concentration Versus Time Curve (AUClast) on Day 1 | TAF | 298.0 hours*nanogram/mL (h*ng/mL) | Standard Deviation 88 |
| Group 1: SC LEN+(F/TAF→ TAF) | PK of TAF (Tenofovir Alafenamide) and TFV (Tenofovir): Area Under the Concentration Versus Time Curve (AUClast) on Day 1 | TFV | 27.1 hours*nanogram/mL (h*ng/mL) | Standard Deviation 27.9 |
| Group 2: SC LEN + (F/TAF → BIC) | PK of TAF (Tenofovir Alafenamide) and TFV (Tenofovir): Area Under the Concentration Versus Time Curve (AUClast) on Day 1 | TAF | 260.0 hours*nanogram/mL (h*ng/mL) | Standard Deviation 63.5 |
| Group 2: SC LEN + (F/TAF → BIC) | PK of TAF (Tenofovir Alafenamide) and TFV (Tenofovir): Area Under the Concentration Versus Time Curve (AUClast) on Day 1 | TFV | 40.5 hours*nanogram/mL (h*ng/mL) | Standard Deviation 59.7 |
Secondary
PK of TAF: Tmax at Week 38
Tmax is defined as the time (observed time point) of Cmax. A PK substudy was conducted in at least 10 participants in each of the treatment groups receiving SC LEN (Treatment Groups 1 and 2). Key PK parameters of TAF was summarized for participants in the PK Sub study Analysis Set by treatment group, analyte and visit. PK substudy analysis was conducted for Group 1 at Week 38.
Time frame: 0 hours (Predose) and at 0.5, 1, 2, 3, 4, 5, 6, and 8 hours postdose
Population: Participants in the PK Substudy Analysis Set with available data were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Group 1: SC LEN+(F/TAF→ TAF) | PK of TAF: Tmax at Week 38 | 0.50 hours |
Secondary
PK of Tenofovir Diphosphate (TFV-DP): AUClast at Weeks 4, 10, 16, or 22
AUClast is defined as area under the concentration versus time curve from time zero to the last quantifiable concentration. A peripheral blood mononuclear cell (PBMC) substudy was conducted in a total of approximately 15 participants in Treatment Groups 1 and 2. For each participant, PK samples were taken at only one of the four possible visits: Weeks 4, 10, 16, or 22. A 12-hour postdose sample was collected, if possible. The PK results were combined and summarized without regard to specific study visit within the range of prespecified study visits.
Time frame: 0 hours (Predose) and at 1, 2, and 6 hours postdose
Population: The PBMC PK Substudy Analysis Set included all randomized participants who took at least 1 dose of study drug, participated in the PBMC substudy, and have at least 1 nonmissing postdose concentration value for tenofovir diphosphate (TFV-DP). The PBMC PK Substudy Analysis Set was used for PK analyses of TFV-DP.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Group 1: SC LEN+(F/TAF→ TAF) | PK of Tenofovir Diphosphate (TFV-DP): AUClast at Weeks 4, 10, 16, or 22 | 16.2 h*μM | Standard Deviation 68.3 |
| Group 2: SC LEN + (F/TAF → BIC) | PK of Tenofovir Diphosphate (TFV-DP): AUClast at Weeks 4, 10, 16, or 22 | 21.6 h*μM | Standard Deviation 71.9 |
Secondary
PK of TFV: Clast at Weeks 16, 22, or 28
Clast is defined as the last observable concentration of drug. A PK substudy was conducted in at least 15 participants in the treatment group receiving oral LEN (Treatment Group 3). Key PK parameters of TFV was summarized for participants in the PK Sub study Analysis Set by treatment group, analyte and visit. For each participant, PK samples were taken at only one of the three possible visits: Weeks 16, 22, or 28. The PK results were combined and summarized without regard to specific study visit within the range of prespecified study visits.
Time frame: 0 hours (Predose) and at 0.5, 1, 2, 3, 4, 5, 6, and 8 hours postdose
Population: Participants in the PK Substudy Analysis Set with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Group 1: SC LEN+(F/TAF→ TAF) | PK of TFV: Clast at Weeks 16, 22, or 28 | 22.2 ng/mL | Standard Deviation 62.6 |
Secondary
PK of TFV-DP: Cmax at Weeks 4, 10, 16, or 22
Cmax is defined as the maximum observed concentration of drug. A PBMC substudy was conducted in a total of approximately 15 participants in Treatment Groups 1 and 2. For each participant, PK samples were taken at only one of the four possible visits: Weeks 4, 10, 16, or 22. A 12-hour postdose sample was collected, if possible. The PK results were combined and summarized without regard to specific study visit within the range of prespecified study visits.
Time frame: 0 hours (Predose) and at 1, 2, and 6 hours postdose
Population: Participants in the PBMC PK Substudy Analysis Set with the available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Group 1: SC LEN+(F/TAF→ TAF) | PK of TFV-DP: Cmax at Weeks 4, 10, 16, or 22 | 3.3 micrometer (μM) | Standard Deviation 37.5 |
| Group 2: SC LEN + (F/TAF → BIC) | PK of TFV-DP: Cmax at Weeks 4, 10, 16, or 22 | 4.3 micrometer (μM) | Standard Deviation 71.8 |
Secondary
PK of TFV-DP: Tmax at Weeks 4, 10, 16, or 22
Tmax is defined as the time (observed time point) of Cmax. A PBMC substudy was conducted in a total of approximately 15 participants in Treatment Groups 1 and 2. For each participant, PK samples were taken at only one of the four possible visits: Weeks 4, 10, 16, or 22. A 12-hour postdose sample was collected, if possible. The PK results were combined and summarized without regard to specific study visit within the range of prespecified study visits.
Time frame: 0 hours (Predose) and at 1, 2, and 6 hours postdose
Population: Participants in the PBMC PK Substudy Analysis Set with the available data were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Group 1: SC LEN+(F/TAF→ TAF) | PK of TFV-DP: Tmax at Weeks 4, 10, 16, or 22 | 2.00 hours |
| Group 2: SC LEN + (F/TAF → BIC) | PK of TFV-DP: Tmax at Weeks 4, 10, 16, or 22 | 6.00 hours |
Secondary
PK of TFV: Last Observed Quantifiable Concentration of the Drug (Clast) on Day 1
Clast is defined as the last observable concentration of drug. A PK substudy was conducted in at least 10 participants in each of the treatment groups receiving SC LEN (Treatment Groups 1 and 2). Key PK parameters of TFV were summarized for participants in the PK Sub study Analysis Set by treatment group, analyte and visit. PK sub study analysis was conducted for Group 1 and 2 on Day 1.
Time frame: 0 hours (Predose) and at 0.5, 1, 2, 3, 4, 5, 6, and 8 hours postdose on Day 1
Population: Participants in the PK Substudy Analysis Set with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Group 1: SC LEN+(F/TAF→ TAF) | PK of TFV: Last Observed Quantifiable Concentration of the Drug (Clast) on Day 1 | 2.7 ng/mL | Standard Deviation 23.1 |
| Group 2: SC LEN + (F/TAF → BIC) | PK of TFV: Last Observed Quantifiable Concentration of the Drug (Clast) on Day 1 | 3.9 ng/mL | Standard Deviation 38 |