HIV-1-infection
Conditions
Brief summary
The primary objective of this study is to evaluate the antiviral activity of lenacapavir (formerly GS-6207) administered as an add-on to a failing regimen for 14 days (functional monotherapy) in people with human immunodeficiency virus type 1 (HIV-1) (PWH) with multi-drug resistance (MDR).
Interventions
DRUGOral Lenacapavir
Tablets administered without regard to food
DRUGOral Lenacapavir Placebo
Tablets administered without regard to food
Administered in the abdomen via subcutaneous injections
DRUGFailing ARV Regimen
Failing antiretroviral (ARV) regimen defined by the lack of efficacy. Any combination of approved and unapproved agents that could potentially be part of the failing regimen.
Optimized background regimen as prescribed by the Investigator
Sponsors
Gilead Sciences
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
12 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Adult aged ≥ 18 years (at all sites) or adolescent aged ≥ 12 and weighing ≥ 35 kg (at sites in North America and Dominican Republic) * Currently receiving a stable failing ARV regimen for \> 8 weeks * Have HIV-1 RNA ≥ 400 copies/mL at screening * Have multidrug resistance (resistance to ≥2 agents from ≥3 of the 4 main classes of ARV) * Have no more than 2 fully active ARV remaining from the 4 main classes that can be effectively combined to form a viable regimen * Able and willing to receive an OBR together with lenacapavir * No Hepatitis C virus (HCV) ongoing infection Note: Other protocol defined Inclusion/
Exclusion criteria
may apply.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Percentage of Participants in Cohort 1 Achieving a Reduction of ≥ 0.5 log10 Copies/mL in Human Immunodeficiency Virus-1 Ribonucleic Acid (HIV-1 RNA) From Baseline to the End of Functional Monotherapy Period | Baseline up to Day 1 SC Visit (14 days after the first dose of oral lencapavir) or Day 15 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants in Cohort 1 With Plasma HIV-1 RNA < 50 Copies/mL at Week 26 Based on the US FDA-defined Snapshot Algorithm | Week 26 (26 weeks after first dose of subcutaneous lenacapavir) | The percentage of participants in cohort 1 with plasma HIV-1 RNA \< 50 copies/mL at Week 26 was analyzed using the United States Food and Drug Administration (US FDA)-defined 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. |
| Percentage of Participants in Cohort 1 With Plasma HIV-1 RNA < 200 Copies/mL at Week 26 Based on the US FDA-defined Snapshot Algorithm | Week 26 (26 weeks after first dose of subcutaneous lenacapavir) | The percentage of participants in cohort 1 with plasma HIV-1 RNA \< 200 copies/mL at Week 26 was analyzed using the US FDA-defined 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. |
| Percentage of Participants in Cohort 1 With Plasma HIV-1 RNA < 50 Copies/mL at Week 52 Based on the US FDA-defined Snapshot Algorithm | Week 52 (52 weeks after first dose of subcutaneous lenacapavir) | The percentage of participants in cohort 1 with plasma HIV-1 RNA \< 50 copies/mL at Week 52 was analyzed using the US FDA-defined 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. Percentages were rounded off. |
| Percentage of Participants in Cohort 1 With Plasma HIV-1 RNA < 200 Copies/mL at Week 52 Based on the US FDA-defined Snapshot Algorithm | Week 52 (52 weeks after first dose of subcutaneous lenacapavir) | The percentage of participants in cohort 1 with plasma HIV-1 RNA \< 200 copies/mL at Week 52 was analyzed using the US FDA-defined 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. Percentages were rounded off. |
| Percentage of Participants in Combined Cohorts 1 and 2 With Plasma HIV-1 RNA < 50 Copies/mL at Week 104 Based on the US FDA-defined Snapshot Algorithm | Week 104 (104 weeks after first dose of subcutaneous lenacapavir) | The percentage of participants in combined cohorts 1 and 2 with plasma HIV-1 RNA \< 50 copies/mL at Week 104 was analyzed using the US FDA-defined 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. Percentages were rounded off. |
| Percentage of Participants in Combined Cohorts 1 and 2 With Plasma HIV-1 RNA < 200 Copies/mL at Week 104 Based on the US FDA-defined Snapshot Algorithm | Week 104 (104 weeks after first dose of subcutaneous lenacapavir) | The percentage of participants in combined cohorts 1 and 2 with plasma HIV-1 RNA \< 200 copies/mL at Week 104 was analyzed using the US FDA-defined 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. Percentages were rounded off. |
| Percentage of Participants in Combined Cohorts 1 and 2 With Plasma HIV-1 RNA < 50 Copies/mL at Week 156 Based on the US FDA-defined Snapshot Algorithm | Week 156 (156 weeks after first dose of subcutaneous lenacapavir) | The percentage of participants in combined cohorts 1 and 2 with plasma HIV-1 RNA \< 50 copies/mL at Week 156 was analyzed using the US FDA-defined 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. Percentages were rounded off. |
| Percentage of Participants in Combined Cohorts 1 and 2 With Plasma HIV-1 RNA < 200 Copies/mL at Week 156 Based on the US FDA-defined Snapshot Algorithm | Week 156 (156 weeks after first dose of subcutaneous lenacapavir) | The percentage of participants in combined cohorts 1 and 2 with plasma HIV-1 RNA \< 200 copies/mL at Week 156 was analyzed using the US FDA-defined 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. Percentages were rounded off. |
Countries
Canada, Dominican Republic, France, Germany, Italy, Japan, South Africa, Spain, Taiwan, Thailand, United States
Contacts
STUDY_DIRECTORGilead Study Director
Gilead Sciences
Participant flow
Recruitment details
Participants were enrolled at study sites in the United States, Thailand, Italy, Dominican Republic, Spain, France, Canada, Taiwan, South Africa, Japan, and Germany.
Pre-assignment details
144 participants were screened. Data submitted represent primary analysis performed on data collected by the Primary Completion Date and additional data collected up to Week 156 (29 January 2024). Complete data will be submitted within 1 year of the study completion date.
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1A: Lenacapavir Participants with HIV-1 RNA ≥ 400 copies/mL and with a \<0.5 log10 HIV-1 RNA decline at the Cohort Selection visit compared with screening visit received oral lenacapavir 600 mg tablet on Days 1 and 2 and 300 mg tablet on Day 8, while continuing their failing regimen (previous ARV regimen of any approved and unapproved agents) in blinded Functional Monotherapy Period (Baseline to Day 14); followed by unblinded Maintenance Period where participants received SC lenacapavir 927 mg and initiated an OBR (as prescribed by the Investigator) at Day 1 SC Visit (14 days after the first dose of oral lenacapavir). Participants received their subsequent SC lenacapavir injection at the Week 26 Visit (relative to Day 1 SC).
At Week 52 (relative to Day 1 SC), participants will be given an option to receive SC lenacapavir injections every 6 months (26 weeks), while continuing their OBR, until the product became accessible to participants through an access program or until Gilead elected to discontinue the study in the country. | 24 |
| Cohort 1B: Placebo to Lenacapavir Participants with HIV-1 RNA ≥ 400 copies/mL and with a \<0.5 log10 HIV-1 RNA decline at the Cohort Selection visit compared with screening visit received oral lenacapavir placebo on Days 1, 2, and 8 while continuing their failing regimen (previous ARV regimen of any approved and unapproved agents) in blinded Functional Monotherapy Period (Baseline to Day 14); followed by unblinded Maintenance Period where participants received oral lenacapavir 600 mg tablet on Days 15 and 16 and 300 mg on Day 22, and initiated an OBR (as prescribed by the Investigator) on Day 15. At Day 1 SC (14 days after the first dose of oral lenacapavir), participants received SC lenacapavir 927 mg while continuing their OBR. Participants received their subsequent SC lenacapavir injection at the Week 26 Visit (relative to Day 1 SC).
At Week 52 (relative to Day 1 SC), participants will be given an option to receive SC lenacapavir injections every 6 months (26 weeks), while continuing their OBR, until the product became accessible to participants through an access program or until Gilead elected to discontinue the study in the country. | 12 |
| Cohort 2: Lenacapavir Participants were enrolled in Cohort 2 if Cohort 1 was fully enrolled or if they did not meet the criteria for randomization in Cohort 1 (ie, they had ≥ 0.5 log10 HIV-1 RNA decline compared to the Screening visit and/or HIV-1 RNA \< 400 copies/mL at the Cohort Selection visit). Participants received oral lenacapavir 600 mg tablet on Days 1 and 2 and 300 mg tablet on Day 8, and will initiate an OBR on Day 1 in Oral Lead-in Period (Baseline to Day 14); followed by Maintenance Period where participants received SC lenacapavir 927 mg at Day 1 SC Visit (14 days after the first dose of oral lenacapavir) while continuing their OBR. Participants received their subsequent SC lenacapavir injection at the Week 26 Visit (relative to Day 1 SC).
At Week 52 (relative to Day 1 SC), participants will be given the option to receive SC lenacapavir injections every 6 months (26 weeks), while continuing their OBR, until the product became accessible to participants through an access program or until Gilead elected to discontinue the study in the country. | 36 |
| Total | 72 |
Baseline characteristics
| Characteristic | Total | Cohort 1A: Lenacapavir | Cohort 1B: Placebo to Lenacapavir | Cohort 2: Lenacapavir |
|---|---|---|---|---|
| Age, Continuous | 50 years STANDARD_DEVIATION 12.6 | 54 years STANDARD_DEVIATION 11.3 | 49 years STANDARD_DEVIATION 10.9 | 48 years STANDARD_DEVIATION 13.7 |
| HIV-1 RNA Categories ≤ 100000 copies/mL | 58 Participants | 23 Participants | 6 Participants | 29 Participants |
| HIV-1 RNA Categories > 100000 copies/mL | 14 Participants | 1 Participants | 6 Participants | 7 Participants |
| HIV-1 RNA (log10 copies/mL) | 4.17 log10 copies/mL STANDARD_DEVIATION 1.034 | 3.97 log10 copies/mL STANDARD_DEVIATION 0.922 | 4.87 log10 copies/mL STANDARD_DEVIATION 0.393 | 4.06 log10 copies/mL STANDARD_DEVIATION 1.164 |
| Race/Ethnicity, Customized Ethnicity Hispanic or Latino | 15 Participants | 6 Participants | 4 Participants | 5 Participants |
| Race/Ethnicity, Customized Ethnicity Not Hispanic or Latino | 56 Participants | 18 Participants | 7 Participants | 31 Participants |
| Race/Ethnicity, Customized Ethnicity Not Permitted | 1 Participants | 0 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized Race Asian | 15 Participants | 2 Participants | 1 Participants | 12 Participants |
| Race/Ethnicity, Customized Race Black | 27 Participants | 10 Participants | 6 Participants | 11 Participants |
| Race/Ethnicity, Customized Race Not Permitted | 1 Participants | 0 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized Race White | 29 Participants | 12 Participants | 4 Participants | 13 Participants |
| Region of Enrollment Canada | 2 Participants | 0 Participants | 0 Participants | 2 Participants |
| Region of Enrollment Dominican Republic | 1 Participants | 0 Participants | 1 Participants | 0 Participants |
| Region of Enrollment France | 3 Participants | 0 Participants | 1 Participants | 2 Participants |
| Region of Enrollment Germany | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Region of Enrollment Italy | 7 Participants | 1 Participants | 0 Participants | 6 Participants |
| Region of Enrollment Japan | 2 Participants | 0 Participants | 0 Participants | 2 Participants |
| Region of Enrollment South Africa | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Region of Enrollment Spain | 1 Participants | 1 Participants | 0 Participants | 0 Participants |
| Region of Enrollment Taiwan | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Region of Enrollment Thailand | 11 Participants | 2 Participants | 1 Participants | 8 Participants |
| Region of Enrollment United States | 42 Participants | 20 Participants | 9 Participants | 13 Participants |
| Sex: Female, Male Female | 18 Participants | 7 Participants | 3 Participants | 8 Participants |
| Sex: Female, Male Male | 54 Participants | 17 Participants | 9 Participants | 28 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 24 | 0 / 12 | 3 / 36 |
| other Total, other adverse events | 23 / 24 | 12 / 12 | 35 / 36 |
| serious Total, serious adverse events | 7 / 24 | 4 / 12 | 11 / 36 |
Outcome results
Primary
Percentage of Participants in Cohort 1 Achieving a Reduction of ≥ 0.5 log10 Copies/mL in Human Immunodeficiency Virus-1 Ribonucleic Acid (HIV-1 RNA) From Baseline to the End of Functional Monotherapy Period
Time frame: Baseline up to Day 1 SC Visit (14 days after the first dose of oral lencapavir) or Day 15
Population: Full Analysis Set for the Functional Monotherapy Period analysis included participants who were randomized in the Functional Monotherapy Period and received at least 1 dose of blinded study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1A: Lenacapavir | Percentage of Participants in Cohort 1 Achieving a Reduction of ≥ 0.5 log10 Copies/mL in Human Immunodeficiency Virus-1 Ribonucleic Acid (HIV-1 RNA) From Baseline to the End of Functional Monotherapy Period | 87.5 percentage of participants |
| Cohort 1B: Placebo to Lenacapavir | Percentage of Participants in Cohort 1 Achieving a Reduction of ≥ 0.5 log10 Copies/mL in Human Immunodeficiency Virus-1 Ribonucleic Acid (HIV-1 RNA) From Baseline to the End of Functional Monotherapy Period | 16.7 percentage of participants |
p-value: <0.000195% CI: [34.9, 90]Chan & Zhang method
Secondary
Percentage of Participants in Cohort 1 With Plasma HIV-1 RNA < 200 Copies/mL at Week 26 Based on the US FDA-defined Snapshot Algorithm
The percentage of participants in cohort 1 with plasma HIV-1 RNA \< 200 copies/mL at Week 26 was analyzed using the US FDA-defined 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.
Time frame: Week 26 (26 weeks after first dose of subcutaneous lenacapavir)
Population: Participants in the Full Analysis set for the All Lenacapavir Analysis were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1A: Lenacapavir | Percentage of Participants in Cohort 1 With Plasma HIV-1 RNA < 200 Copies/mL at Week 26 Based on the US FDA-defined Snapshot Algorithm | 95.8 percentage of participants |
| Cohort 1B: Placebo to Lenacapavir | Percentage of Participants in Cohort 1 With Plasma HIV-1 RNA < 200 Copies/mL at Week 26 Based on the US FDA-defined Snapshot Algorithm | 75.0 percentage of participants |
Secondary
Percentage of Participants in Cohort 1 With Plasma HIV-1 RNA < 200 Copies/mL at Week 52 Based on the US FDA-defined Snapshot Algorithm
Time frame: Week 52
Secondary
Percentage of Participants in Cohort 1 With Plasma HIV-1 RNA < 50 Copies/mL at Week 26 Based on the US FDA-defined Snapshot Algorithm
The percentage of participants in cohort 1 with plasma HIV-1 RNA \< 50 copies/mL at Week 26 was analyzed using the United States Food and Drug Administration (US FDA)-defined 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.
Time frame: Week 26 (26 weeks after first dose of subcutaneous lenacapavir)
Population: Full Analysis Set for the All Lenacapavir Analysis included participants who were enrolled into the study and received at least 1 dose of SC lenacapavir.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1A: Lenacapavir | Percentage of Participants in Cohort 1 With Plasma HIV-1 RNA < 50 Copies/mL at Week 26 Based on the US FDA-defined Snapshot Algorithm | 87.5 percentage of participants |
| Cohort 1B: Placebo to Lenacapavir | Percentage of Participants in Cohort 1 With Plasma HIV-1 RNA < 50 Copies/mL at Week 26 Based on the US FDA-defined Snapshot Algorithm | 66.7 percentage of participants |
Secondary
Percentage of Participants in Cohort 1 With Plasma HIV-1 RNA < 50 Copies/mL at Week 52 Based on the US FDA-defined Snapshot Algorithm
Time frame: Week 52
Secondary
Percentage of Participants in Combined Cohorts 1 and 2 With Plasma HIV-1 RNA < 200 Copies/mL From the First SC Dose of Lenacapavir Based on the US FDA-defined Snapshot Algorithm
Time frame: Week 156
Secondary
Percentage of Participants in Combined Cohorts 1 and 2 With Plasma HIV-1 RNA < 200 Copies/mL From the First SC Dose of Lenacapavir Based on the US FDA-defined Snapshot Algorithm
Time frame: Week 104
Secondary
Percentage of Participants in Combined Cohorts 1 and 2 With Plasma HIV-1 RNA < 50 Copies/mL From the First SC Dose of Lenacapavir Based on the US FDA-defined Snapshot Algorithm
Time frame: Week 156
Secondary
Percentage of Participants in Combined Cohorts 1 and 2 With Plasma HIV-1 RNA < 50 Copies/mL From the First Subcutaneous (SC) Dose of Lenacapavir Based on the US FDA-defined Snapshot Algorithm
Time frame: Week 104