Trial Outcomes & Findings for Study to Evaluate the Safety and Efficacy of Lenacapavir (GS-6207) in Combination With an Optimized Background Regimen (OBR) in Heavily Treatment Experienced Participants Living With HIV-1 Infection With Multidrug Resistance (NCT NCT04150068)

NCT ID: NCT04150068

Last Updated: 2025-09-26

Results Overview

Recruitment status

ACTIVE_NOT_RECRUITING

Study phase

PHASE2/PHASE3

Target enrollment

72 participants

Primary outcome timeframe

Baseline up to Day 1 SC Visit (14 days after the first dose of oral lencapavir) or Day 15

Results posted on

2025-09-26

Participant Flow

Participants were enrolled at study sites in the United States, Thailand, Italy, Dominican Republic, Spain, France, Canada, Taiwan, South Africa, Japan, and Germany. The first participant was screened on 21 November 2019. Data submitted represent interim analysis performed on data collected by the Primary Completion Date 05 October 2020, and additional data collected after all participants in Cohort 1 completed Week 26 visit.

144 participants were screened.

Participant milestones

Participant milestones
Measure	Cohort 1A: Lenacapavir Participants with human-immunodeficiency virus-1 ribonucleic acid (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 anti-retroviral \[ARV\] regimen of any approved and unapproved agents) in blinded Functional Monotherapy Period (Baseline to Day 14); followed by unblinded Maintenance Period where participants received subcutaneous (SC) lenacapavir 927 mg and initiated an optimized background regimen (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.	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.	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.
Functional Mono/Oral Lead-in (14 Days) STARTED	24	12	36
Functional Mono/Oral Lead-in (14 Days) COMPLETED	24	12	36
Functional Mono/Oral Lead-in (14 Days) NOT COMPLETED	0	0	0
Maintenance Period (Week 26 Analysis) STARTED	24	12	36
Maintenance Period (Week 26 Analysis) COMPLETED	0	0	0
Maintenance Period (Week 26 Analysis) NOT COMPLETED	24	12	36

Reasons for withdrawal

Reasons for withdrawal
Measure	Cohort 1A: Lenacapavir Participants with human-immunodeficiency virus-1 ribonucleic acid (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 anti-retroviral \[ARV\] regimen of any approved and unapproved agents) in blinded Functional Monotherapy Period (Baseline to Day 14); followed by unblinded Maintenance Period where participants received subcutaneous (SC) lenacapavir 927 mg and initiated an optimized background regimen (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.	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.	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.
Maintenance Period (Week 26 Analysis) Still on study	24	12	35
Maintenance Period (Week 26 Analysis) Death	0	0	1

Baseline Characteristics

Study to Evaluate the Safety and Efficacy of Lenacapavir (GS-6207) in Combination With an Optimized Background Regimen (OBR) in Heavily Treatment Experienced Participants Living With HIV-1 Infection With Multidrug Resistance

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Cohort 1A: Lenacapavir n=24 Participants 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.	Cohort 1B: Placebo to Lenacapavir n=12 Participants 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.	Cohort 2: Lenacapavir n=36 Participants 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.	Total n=72 Participants Total of all reporting groups
Age, Continuous	54 years STANDARD_DEVIATION 11.3 • n=5 Participants	49 years STANDARD_DEVIATION 10.9 • n=7 Participants	48 years STANDARD_DEVIATION 13.7 • n=5 Participants	50 years STANDARD_DEVIATION 12.6 • n=4 Participants
Sex: Female, Male Female	7 Participants n=5 Participants	3 Participants n=7 Participants	8 Participants n=5 Participants	18 Participants n=4 Participants
Sex: Female, Male Male	17 Participants n=5 Participants	9 Participants n=7 Participants	28 Participants n=5 Participants	54 Participants n=4 Participants
Race/Ethnicity, Customized Race · Asian	2 Participants n=5 Participants	1 Participants n=7 Participants	12 Participants n=5 Participants	15 Participants n=4 Participants
Race/Ethnicity, Customized Race · Black	10 Participants n=5 Participants	6 Participants n=7 Participants	11 Participants n=5 Participants	27 Participants n=4 Participants
Race/Ethnicity, Customized Race · White	12 Participants n=5 Participants	4 Participants n=7 Participants	13 Participants n=5 Participants	29 Participants n=4 Participants
Race/Ethnicity, Customized Race · Not Permitted	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Race/Ethnicity, Customized Ethnicity · Hispanic or Latino	6 Participants n=5 Participants	4 Participants n=7 Participants	5 Participants n=5 Participants	15 Participants n=4 Participants
Race/Ethnicity, Customized Ethnicity · Not Hispanic or Latino	18 Participants n=5 Participants	7 Participants n=7 Participants	31 Participants n=5 Participants	56 Participants n=4 Participants
Race/Ethnicity, Customized Ethnicity · Not Permitted	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Region of Enrollment Canada	0 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants	2 Participants n=4 Participants
Region of Enrollment Dominican Republic	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Region of Enrollment France	0 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants	3 Participants n=4 Participants
Region of Enrollment Italy	1 Participants n=5 Participants	0 Participants n=7 Participants	6 Participants n=5 Participants	7 Participants n=4 Participants
Region of Enrollment South Africa	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants
Region of Enrollment Spain	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Region of Enrollment Taiwan	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants
Region of Enrollment Thailand	2 Participants n=5 Participants	1 Participants n=7 Participants	8 Participants n=5 Participants	11 Participants n=4 Participants
Region of Enrollment United States	20 Participants n=5 Participants	9 Participants n=7 Participants	13 Participants n=5 Participants	42 Participants n=4 Participants
Region of Enrollment Japan	0 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants	2 Participants n=4 Participants
Region of Enrollment Germany	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants
HIV-1 RNA (log10 copies/mL)	3.97 log10 copies/mL STANDARD_DEVIATION 0.922 • n=5 Participants	4.87 log10 copies/mL STANDARD_DEVIATION 0.393 • n=7 Participants	4.06 log10 copies/mL STANDARD_DEVIATION 1.164 • n=5 Participants	4.17 log10 copies/mL STANDARD_DEVIATION 1.034 • n=4 Participants
HIV-1 RNA Categories ≤ 100000 copies/mL	23 Participants n=5 Participants	6 Participants n=7 Participants	29 Participants n=5 Participants	58 Participants n=4 Participants
HIV-1 RNA Categories > 100000 copies/mL	1 Participants n=5 Participants	6 Participants n=7 Participants	7 Participants n=5 Participants	14 Participants n=4 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Cohort 1A: Lenacapavir n=24 Participants 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.	Cohort 1B: Placebo to Lenacapavir n=12 Participants 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.
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	16.7 percentage of participants

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Cohort 1A: Lenacapavir n=24 Participants 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.	Cohort 1B: Placebo to Lenacapavir n=12 Participants 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.
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 Interval 67.6 to 97.3	66.7 percentage of participants Interval 34.9 to 90.1

SECONDARY outcome

Timeframe: Week 26 (26 weeks after first dose of subcutaneous lenacapavir)

Population: Participants in the Full Analysis set for the All Lenacapavir Analysis were analyzed.

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.

Outcome measures

Outcome measures
Measure	Cohort 1A: Lenacapavir n=24 Participants 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.	Cohort 1B: Placebo to Lenacapavir n=12 Participants 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.
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 Interval 78.9 to 99.9	75.0 percentage of participants Interval 42.8 to 94.5

SECONDARY outcome

Timeframe: Week 52

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Week 52

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Week 104

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Week 104

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Week 156

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Week 156

Outcome measures

Outcome data not reported

Adverse Events

Cohort 1A: Lenacapavir

Serious events: 1 serious events

Other events: 20 other events

Deaths: 0 deaths

Cohort 1B: Placebo to Lenacapavir

Serious events: 1 serious events

Other events: 11 other events

Deaths: 0 deaths

Cohort 2: Lenacapavir

Serious events: 2 serious events

Other events: 30 other events

Deaths: 1 deaths

Serious adverse events

Serious adverse events
Measure	Cohort 1A: Lenacapavir n=24 participants at risk 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.	Cohort 1B: Placebo to Lenacapavir n=12 participants at risk 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.	Cohort 2: Lenacapavir n=36 participants at risk 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.
Gastrointestinal disorders Abdominal pain	0.00% 0/24 • All-Cause Mortality: Enrollment up to Week 26 (26 weeks after first dose of subcutaneous lenacapavir); Adverse Events: First dose date up to Week 26 (26 weeks after first dose of subcutaneous lenacapavir) All-Cause Mortality: All Enrolled Analysis Set included participants who were randomized into Cohort 1 or enrolled into Cohort 2. Adverse events: Safety Analysis Set included participants who were enrolled and received at least 1 dose of study drug.	8.3% 1/12 • All-Cause Mortality: Enrollment up to Week 26 (26 weeks after first dose of subcutaneous lenacapavir); Adverse Events: First dose date up to Week 26 (26 weeks after first dose of subcutaneous lenacapavir) All-Cause Mortality: All Enrolled Analysis Set included participants who were randomized into Cohort 1 or enrolled into Cohort 2. Adverse events: Safety Analysis Set included participants who were enrolled and received at least 1 dose of study drug.	0.00% 0/36 • All-Cause Mortality: Enrollment up to Week 26 (26 weeks after first dose of subcutaneous lenacapavir); Adverse Events: First dose date up to Week 26 (26 weeks after first dose of subcutaneous lenacapavir) All-Cause Mortality: All Enrolled Analysis Set included participants who were randomized into Cohort 1 or enrolled into Cohort 2. Adverse events: Safety Analysis Set included participants who were enrolled and received at least 1 dose of study drug.
Gastrointestinal disorders Pancreatic mass	0.00% 0/24 • All-Cause Mortality: Enrollment up to Week 26 (26 weeks after first dose of subcutaneous lenacapavir); Adverse Events: First dose date up to Week 26 (26 weeks after first dose of subcutaneous lenacapavir) All-Cause Mortality: All Enrolled Analysis Set included participants who were randomized into Cohort 1 or enrolled into Cohort 2. Adverse events: Safety Analysis Set included participants who were enrolled and received at least 1 dose of study drug.	8.3% 1/12 • All-Cause Mortality: Enrollment up to Week 26 (26 weeks after first dose of subcutaneous lenacapavir); Adverse Events: First dose date up to Week 26 (26 weeks after first dose of subcutaneous lenacapavir) All-Cause Mortality: All Enrolled Analysis Set included participants who were randomized into Cohort 1 or enrolled into Cohort 2. Adverse events: Safety Analysis Set included participants who were enrolled and received at least 1 dose of study drug.	0.00% 0/36 • All-Cause Mortality: Enrollment up to Week 26 (26 weeks after first dose of subcutaneous lenacapavir); Adverse Events: First dose date up to Week 26 (26 weeks after first dose of subcutaneous lenacapavir) All-Cause Mortality: All Enrolled Analysis Set included participants who were randomized into Cohort 1 or enrolled into Cohort 2. Adverse events: Safety Analysis Set included participants who were enrolled and received at least 1 dose of study drug.
Gastrointestinal disorders Proctalgia	4.2% 1/24 • All-Cause Mortality: Enrollment up to Week 26 (26 weeks after first dose of subcutaneous lenacapavir); Adverse Events: First dose date up to Week 26 (26 weeks after first dose of subcutaneous lenacapavir) All-Cause Mortality: All Enrolled Analysis Set included participants who were randomized into Cohort 1 or enrolled into Cohort 2. Adverse events: Safety Analysis Set included participants who were enrolled and received at least 1 dose of study drug.	0.00% 0/12 • All-Cause Mortality: Enrollment up to Week 26 (26 weeks after first dose of subcutaneous lenacapavir); Adverse Events: First dose date up to Week 26 (26 weeks after first dose of subcutaneous lenacapavir) All-Cause Mortality: All Enrolled Analysis Set included participants who were randomized into Cohort 1 or enrolled into Cohort 2. Adverse events: Safety Analysis Set included participants who were enrolled and received at least 1 dose of study drug.	0.00% 0/36 • All-Cause Mortality: Enrollment up to Week 26 (26 weeks after first dose of subcutaneous lenacapavir); Adverse Events: First dose date up to Week 26 (26 weeks after first dose of subcutaneous lenacapavir) All-Cause Mortality: All Enrolled Analysis Set included participants who were randomized into Cohort 1 or enrolled into Cohort 2. Adverse events: Safety Analysis Set included participants who were enrolled and received at least 1 dose of study drug.
Infections and infestations Clostridium difficile infection	0.00% 0/24 • All-Cause Mortality: Enrollment up to Week 26 (26 weeks after first dose of subcutaneous lenacapavir); Adverse Events: First dose date up to Week 26 (26 weeks after first dose of subcutaneous lenacapavir) All-Cause Mortality: All Enrolled Analysis Set included participants who were randomized into Cohort 1 or enrolled into Cohort 2. Adverse events: Safety Analysis Set included participants who were enrolled and received at least 1 dose of study drug.	8.3% 1/12 • All-Cause Mortality: Enrollment up to Week 26 (26 weeks after first dose of subcutaneous lenacapavir); Adverse Events: First dose date up to Week 26 (26 weeks after first dose of subcutaneous lenacapavir) All-Cause Mortality: All Enrolled Analysis Set included participants who were randomized into Cohort 1 or enrolled into Cohort 2. Adverse events: Safety Analysis Set included participants who were enrolled and received at least 1 dose of study drug.	0.00% 0/36 • All-Cause Mortality: Enrollment up to Week 26 (26 weeks after first dose of subcutaneous lenacapavir); Adverse Events: First dose date up to Week 26 (26 weeks after first dose of subcutaneous lenacapavir) All-Cause Mortality: All Enrolled Analysis Set included participants who were randomized into Cohort 1 or enrolled into Cohort 2. Adverse events: Safety Analysis Set included participants who were enrolled and received at least 1 dose of study drug.
Injury, poisoning and procedural complications Femoral neck fracture	0.00% 0/24 • All-Cause Mortality: Enrollment up to Week 26 (26 weeks after first dose of subcutaneous lenacapavir); Adverse Events: First dose date up to Week 26 (26 weeks after first dose of subcutaneous lenacapavir) All-Cause Mortality: All Enrolled Analysis Set included participants who were randomized into Cohort 1 or enrolled into Cohort 2. Adverse events: Safety Analysis Set included participants who were enrolled and received at least 1 dose of study drug.	0.00% 0/12 • All-Cause Mortality: Enrollment up to Week 26 (26 weeks after first dose of subcutaneous lenacapavir); Adverse Events: First dose date up to Week 26 (26 weeks after first dose of subcutaneous lenacapavir) All-Cause Mortality: All Enrolled Analysis Set included participants who were randomized into Cohort 1 or enrolled into Cohort 2. Adverse events: Safety Analysis Set included participants who were enrolled and received at least 1 dose of study drug.	2.8% 1/36 • All-Cause Mortality: Enrollment up to Week 26 (26 weeks after first dose of subcutaneous lenacapavir); Adverse Events: First dose date up to Week 26 (26 weeks after first dose of subcutaneous lenacapavir) All-Cause Mortality: All Enrolled Analysis Set included participants who were randomized into Cohort 1 or enrolled into Cohort 2. Adverse events: Safety Analysis Set included participants who were enrolled and received at least 1 dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasm malignant	0.00% 0/24 • All-Cause Mortality: Enrollment up to Week 26 (26 weeks after first dose of subcutaneous lenacapavir); Adverse Events: First dose date up to Week 26 (26 weeks after first dose of subcutaneous lenacapavir) All-Cause Mortality: All Enrolled Analysis Set included participants who were randomized into Cohort 1 or enrolled into Cohort 2. Adverse events: Safety Analysis Set included participants who were enrolled and received at least 1 dose of study drug.	0.00% 0/12 • All-Cause Mortality: Enrollment up to Week 26 (26 weeks after first dose of subcutaneous lenacapavir); Adverse Events: First dose date up to Week 26 (26 weeks after first dose of subcutaneous lenacapavir) All-Cause Mortality: All Enrolled Analysis Set included participants who were randomized into Cohort 1 or enrolled into Cohort 2. Adverse events: Safety Analysis Set included participants who were enrolled and received at least 1 dose of study drug.	2.8% 1/36 • All-Cause Mortality: Enrollment up to Week 26 (26 weeks after first dose of subcutaneous lenacapavir); Adverse Events: First dose date up to Week 26 (26 weeks after first dose of subcutaneous lenacapavir) All-Cause Mortality: All Enrolled Analysis Set included participants who were randomized into Cohort 1 or enrolled into Cohort 2. Adverse events: Safety Analysis Set included participants who were enrolled and received at least 1 dose of study drug.
Nervous system disorders Dizziness	0.00% 0/24 • All-Cause Mortality: Enrollment up to Week 26 (26 weeks after first dose of subcutaneous lenacapavir); Adverse Events: First dose date up to Week 26 (26 weeks after first dose of subcutaneous lenacapavir) All-Cause Mortality: All Enrolled Analysis Set included participants who were randomized into Cohort 1 or enrolled into Cohort 2. Adverse events: Safety Analysis Set included participants who were enrolled and received at least 1 dose of study drug.	0.00% 0/12 • All-Cause Mortality: Enrollment up to Week 26 (26 weeks after first dose of subcutaneous lenacapavir); Adverse Events: First dose date up to Week 26 (26 weeks after first dose of subcutaneous lenacapavir) All-Cause Mortality: All Enrolled Analysis Set included participants who were randomized into Cohort 1 or enrolled into Cohort 2. Adverse events: Safety Analysis Set included participants who were enrolled and received at least 1 dose of study drug.	2.8% 1/36 • All-Cause Mortality: Enrollment up to Week 26 (26 weeks after first dose of subcutaneous lenacapavir); Adverse Events: First dose date up to Week 26 (26 weeks after first dose of subcutaneous lenacapavir) All-Cause Mortality: All Enrolled Analysis Set included participants who were randomized into Cohort 1 or enrolled into Cohort 2. Adverse events: Safety Analysis Set included participants who were enrolled and received at least 1 dose of study drug.

Other adverse events

Additional Information

Gilead Clinical Study Information Center

Gilead Sciences

Phone: 1-833-445-3230 (GILEAD-0)

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee After conclusion of the study and without prior written approval from Gilead, investigators in this study may communicate, orally present, or publish in scientific journals or other media only after the following conditions have been met: * The results of the study in their entirety have been publicly disclosed by or with the consent of Gilead in an abstract, manuscript, or presentation form; or * The study has been completed at all study sites for at least 2 years
Publication restrictions are in place

Restriction type: OTHER