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Lenacapavir

Phase 3

HIV Infections | Small molecule | Infectious Disease |Gilead Sciences, Inc.|Last Updated: Aug 28, 2026

Target and mechanism

ModalitySmall molecule

Also known as Lenacapavir Injection, Lenacapavir Tablet, Oral Lenacapavir, Oral Lenacapavir (LEN)

Success Probability

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Market & Valuation

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Trial Design

RandomizedACTIVE_CONTROLLEDDMC
Total Trials1
Total Enrollment590

FDA Designations

No designations recorded

Clinical trial landscape

Lenacapavir · 14 trials · 5 indications

Phase 3 5Phase 2 7Phase 1 2
NCT07682961Study of Lenacapavir, Teropavimab, and Zinlirvimab Versus Cabotegravir and Rilpivirine in Virologically Suppressed Adults With HIV-1 on Oral Daily Antiretroviral TherapyHIV Infections
RECRUITING590 Analytics
NCT07683000Study of Lenacapavir, Teropavimab, and Zinlirvimab in Virologically Suppressed Adults With HIV-1 on Stable Oral Treatment RegimensHIV-1-infection
RECRUITING590 Analytics
NCT07047716Study of Lenacapavir as a Once-Yearly Injection for HIV Pre-exposure Prophylaxis (PrEP)HIV Pre-exposure Prophylaxis
ACTIVE NOT_RECRUITING339 Analytics
NCT04994509Pre-Exposure Prophylaxis Study of Lenacapavir and Emtricitabine/Tenofovir Alafenamide in Adolescent Girls and Young Women at Risk of HIV InfectionPre-Exposure Prophylaxis of HIV Infection
ACTIVE NOT_RECRUITING5,368 Analytics
NCT04925752Study of Lenacapavir for HIV Pre-Exposure Prophylaxis in People Who Are at Risk for HIV InfectionPre-Exposure Prophylaxis of HIV Infection
ACTIVE NOT_RECRUITING3,292 Analytics
PHASE3RECRUITING
Study of Lenacapavir, Teropavimab, and Zinlirvimab Versus Cabotegravir and Rilpivirine in Virologically Suppressed Adults With HIV-1 on Oral Daily Antiretroviral Therapy
HIV InfectionsUnlock trial analytics
PHASE3RECRUITING
Study of Lenacapavir, Teropavimab, and Zinlirvimab in Virologically Suppressed Adults With HIV-1 on Stable Oral Treatment Regimens
HIV-1-infectionUnlock trial analytics
PHASE3ACTIVE NOT_RECRUITING
Study of Lenacapavir as a Once-Yearly Injection for HIV Pre-exposure Prophylaxis (PrEP)
HIV Pre-exposure ProphylaxisUnlock trial analytics
PHASE3ACTIVE NOT_RECRUITING
Pre-Exposure Prophylaxis Study of Lenacapavir and Emtricitabine/Tenofovir Alafenamide in Adolescent Girls and Young Women at Risk of HIV Infection
Pre-Exposure Prophylaxis of HIV InfectionUnlock trial analytics
PHASE3ACTIVE NOT_RECRUITING
Study of Lenacapavir for HIV Pre-Exposure Prophylaxis in People Who Are at Risk for HIV Infection
Pre-Exposure Prophylaxis of HIV InfectionUnlock trial analytics

Study Endpoints

Primary Endpoints

Proportion of Participants With HIV-1 ribonucleic acid (RNA) ≥ 50 Copies/mL at Week 52 as Defined by the United States (US) Food and Drug Administration (FDA) Snapshot Algorithm.
Week 52
Proportion of Participants With HIV-1 RNA ≥ 50 Copies/mL at Week 52 as Defined by the United States (US) Food and Drug Administration (FDA) Snapshot Algorithm.
Week 52
Plasma LEN Ctrough at Week 52
Week 52

Ctrough is defined as the concentration at the end of the dosing interval.

Percentage of Participants Experiencing Treatment-emergent Adverse Event (TEAEs)
First dose up to 30 days post last dose (approximately 3 years)
Percentage of Participants Experiencing Treatment-emergent Clinical Laboratory Abnormalities
First dose up to 30 days post last dose (up approximately 3 years)
Percentage of Participants With Discontinuation due to Adverse Event
First dose up to 30 days post last dose (approximately 3 years)
Incidence Phase: Recent Infection Testing Algorithm (RITA) Estimate of the Background Human Immunodeficiency-1 Virus Infection Incidence Rate (bHIV) Per 100 Person Years (PY)
Incidence Phase Screening Visit (Day 1)

bHIV per 100 PY in the Incidence Phase was calculated using RITA. The RITA incorporated HIV-1 testing results and recency assay testing results to estimate the bHIV. Recency assay testing was performed for participants in the All Screened Set found to have HIV-1 infection at the Incidence Phase Screening Visit as defined below. Participants were considered to have recent HIV-1 infection if the normalized optical density (ODn) was below 1.5 threshold using the Sedia limiting antigen avidity enzyme immunoassay (LAg-EIA) and the HIV-1 RNA (viral load) was \> 75 copies/mL of blood. HIV-1 infection was defined as participants having at least one of the following central lab results at the Incidence Phase screening visit: * Positive HIV-1/2 differentiation Ab, OR * Positive HIV-1 ribonucleic acid (RNA) qualitative test, OR * HIV-1 RNA quantitative test ≥200 copies/mL.

Randomized Blinded Phase: HIV-1 Incidence Reported Per 100 PY for LEN and F/TAF Compared to Participants in All Screened Set
When at least 50% of the participants completed 52 weeks of follow-up after randomization or permanently discontinued from the study (maximum 143 weeks)

HIV-1 incidence per 100 PY for LEN and F/TAF was calculated as the number of participants who acquired HIV-1 divided by the total of a) for participants not diagnosed with HIV-1, sum of all duration of follow-up time in years, while at risk of HIV-1 infection (where a year is 365.25 days) and b) for participants diagnosed with HIV-1, sum of all duration of follow-up time up to confirmed HIV-1 diagnoses. HIV-1 diagnosis was determined by an HIV adjudication committee who reviewed potential HIV-1 infection events in the randomized participants. The committee, in a blinded, consistent, and unbiased manner, determined whether HIV test results confirmed HIV-1 infection and determined the date of diagnosis for each case, defined as the date of the earliest study visit with evidence of HIV infection considering both prospective HIV testing and back-testing of archived samples. bHIV incidence per 100 PY in All Screened Set was estimated as described in outcome measure#1.

Randomized Blinded Phase: HIV-1 Incidence Reported Per 100 PY for LEN Compared to Background HIV (bHIV, Participants in All Screened Set)
Up to 149 weeks

HIV-1 incidence per 100 PY for LEN was calculated as the number of participants who acquired HIV-1 divided by the total of a) for participants not diagnosed with HIV-1, sum of all duration of follow-up time in years, while at risk of HIV-1 infection (where a year is 365.25 days) and b) for participants diagnosed with HIV-1, sum of all duration of follow-up time up to confirmed HIV-1 diagnoses. HIV-1 diagnosis was determined by an HIV adjudication committee who reviewed potential HIV-1 infection events in the randomized participants. The committee, in a blinded, consistent, and unbiased manner, determined whether HIV test results confirmed HIV-1 infection and determined the date of diagnosis for each case, defined as the date of the earliest study visit with evidence of HIV infection considering both prospective HIV testing and back-testing of archived samples. bHIV incidence per 100 PY in All Screened Set was estimated as described in outcome measure#1.

Pharmacokinetic (PK) Parameter: Ctrough, W26 of Lenacapavir (LEN)
Week 26

Ctrough, W26 is defined as the plasma concentration at the end of the dosing interval at Week 26.

Percentage of Participants Experiencing Treatment-Emergent Adverse Events (AEs) Through Week 26
First dose date up to Week 26
Percentage of Participants Experiencing Treatment-Emergent Laboratory Abnormalities Through Week 26
First dose date up to Week 26
PK Parameter: Cmax of BIC and LEN at Steady State
Day 1 up to Week 24, as appropriate

Cmax is defined as the maximum observed concentration of drug at steady state.

PK Parameter: AUCtau of BIC and LEN at Steady State
Day 1 up to Week 24, as appropriate

AUCtau is defined as the area under the concentration versus time curve over the dosing interval at steady state.

PK Parameter: Ctrough of BIC and LEN at Steady State
Day 1 up to Week 24, as appropriate

Ctrough is defined as the observed drug concentration at the end of the dosing interval at steady state.

Percentage of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs) Through Week 24
First dose date up to Week 24
Percentage of Participants Experiencing Treatment-Emergent Laboratory Abnormalities Through Week 24
First dose date up to Week 24
Percentage of Participants with LEN and F/TDF Persistence through 52 Weeks
Up to Week 52

This outcome measure will compare LEN and F/TDF persistence through 52 weeks, where persistence is defined by On-time LEN Injection at Day 1/Baseline and Week 26 and On-time Follow-up Visit at Week 52 for LEN arm and by Adherence Levels Based on tenofovir diphosphate (TFV-DP) concentrations in red blood cells consistent with ≥ 4 doses/week (≥ 700 fmol/punch) in dried blood spot (DBS) at Weeks 13, 26, 39, and 52 for F/TDF arm.

Pharmacokinetic (PK) Parameter: Ctrough for Lenacapavir (LEN): LEN Plasma concentration at the End of the Dosing Interval (Week 26)
Week 26
PK Parameter: Ctrough for LEN: LEN Plasma concentration at the End of the Dosing Interval (Week 52)
Week 52
Percentage of Participants Experiencing Treatment-emergent Adverse Events (TEAEs)
First dose date up to 30 days post last dose at Week 52
Percentage of Participants Experiencing Treatment-emergent Clinical Laboratory Abnormalities with LEN and F/TDF
First dose date up to 30 days post last dose at Week 52
Pharmacokinetic (PK) Parameter: Ctrough for Lenacapavir (LEN) at the End of Week 26
Week 26

Ctrough is defined as the concentration at the end of the dosing interval.

PK Parameter: Ctrough for LEN at the End of Week 52
Week 52

Ctrough is defined as the concentration at the end of the dosing interval.

General Acceptability of LEN and F/TDF as PrEP as Assessed by Percentage of Participants with Acceptability Questionnaire Responses
Up to Week 52

To assess the acceptability of the study drug, participants will complete the questionnaire including a question on general acceptability of the assigned study drug on an ordinal 5-category scale with a response of: Completely unacceptable, Unacceptable, No opinion, Acceptable, or Completely acceptable.

Satisfaction With Use of LEN and F/TDF as PrEP as Assessed by Percentage of Participants with Satisfaction Questionnaire Responses
Up to Week 52

To assess the satisfaction with use of the study drug, participants will complete the questionnaire including a question on satisfaction with use of the assigned study drug on an ordinal 5-category scale with a response of: Very satisfied, Satisfied, Neutral, Dissatisfied, or Very dissatisfied.

Willingness to Use LEN and F/TDF as PrEP as Assessed by Percentage of Participants with Willingness to Use Questionnaire Responses
Up to Week 52

To assess the willingness to use the study drug, participants will complete the questionnaire including a question on willingness to use the assigned study drug on an ordinal 5-category scale with a response of: Definitely Yes, Probably yes, Not sure/undecided, Probably No, or Definitely No.

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.

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
Primary Cohort: Percentage of Participants Experiencing Treatment-Emergent Serious Adverse Events (SAEs)
Day 1 up to Week 26

A treatment emergent SAE was defined as an event that, at any dose, resulted in the following: death; life-threatening situation; in-patient hospitalization or prolongation of existing hospitalization; persistent or significant disability/incapacity; a congenital anomaly/birth defect; a medically important event or reaction: such events may not be immediately life-threatening or result in death or hospitalization but may jeopardize the subject or may require intervention to prevent one of the other outcomes constituting SAEs. These events had an onset date on or after the study drug start date and prior to the last exposure date of long-acting (LA) regimen period for the LA regimen period analysis. The long acting regimen period included participants who were randomized and received at least one dose of the complete LA study drug regimen (ie, SC LEN + Teropavimab + Zinlirvimab).

Part A and Part B: Maximum Reduction From Day 1 (Baseline) Through Day 10 in Plasma HIV-1 RNA
Day 1 through Day 10

Maximum reduction is defined as the minimum of change from baseline in plasma HIV-1 RNA (i.e. smallest change in HIV-RNA from baseline).

Secondary Endpoints

Proportion of Participants With HIV-1 RNA ≥ 50 Copies/mL at Week 92 as Defined by the US FDA Snapshot Algorithm.
Week 92
Proportion of Participants With HIV-1 RNA < 50 Copies/mL at Week 52 as Determined by the US FDA Snapshot Algorithm
Week 52
Proportion of Participants with HIV-1 RNA < 50 copies/mL at Week 92 as Determined by the US FDA Snapshot Algorithm.
Week 92
Unlock Study Endpoints

Study Design & Arms

AllocationRANDOMIZED
MaskingNONE
ModelPARALLEL
PurposeTREATMENT

Treatment Arms

ArmTypeDescription
Treatment Group 1: Lenacapavir(LEN)+ Teropavimab(TAB)+ Zinlirvimab (ZAB)EXPERIMENTALParticipants will receive oral LEN 600 mg, subcutaneous (SC) LEN 927 mg, and intravenously (IV) infusions of TAB and ZAB on Day 1. Participants will self-administer oral LEN 600 mg on Day 2. Every 26 weeks, participants will receive SC LEN and IV infusions of TAB and ZAB up to Week 92. After Week 92, eligible participants will have an option to continue LEN + TAB + ZAB in the extension phase, until completion of the extension phase, permanently discontinuing the extension phase or the extension is discontinued at the sponsor's sole discretion, whichever occurs first.
Treatment Group 2: Cabotegravir (CAB) + Rilpivirine (RPV)ACTIVE_COMPARATORParticipants will discontinue their baseline oral antiretroviral therapy (ART) and will receive intramuscular (IM) CAB 600 mg + RPV 900 mg on Day 1, Week 4 and then every 8 weeks for up to 92 weeks. After Week 92, eligible participants will have an option to continue LEN + TAB + ZAB in the extension phase, until completion of the extension phase, permanently discounting the extension phase or the extension is discontinued at the sponsor's sole discretion, whichever occurs first.
Treatment Group 2: Stable Baseline Regimen (SBR)EXPERIMENTALParticipants will continue their SBR through at least Week 92. Oral SBRs will be taken per local prescribing information. After Week 92, eligible participants will have an option to switch to LEN + TAB + ZAB in the study extension phase until completion of the extension phase, permanently discounting the extension phase or the extension is discontinued at the sponsor's sole discretion, whichever occurs first.
Lenacapavir (LEN)EXPERIMENTALParticipants with an indication for pre-exposure prophylaxis will receive for approximately 52 weeks: * LEN 3000 mg injection once on Day 1 * Oral LEN 600 mg on Day 1 and Day 2 during the Main Study Period Participant will receive additional oral LEN if IM injection are not available. If participants choose to not receive additional LEN injections, they will continue onto the pharmacokinetic (PK) Tail Phase for up to 52 weeks.
LEN Extension PhaseEXPERIMENTALParticipants with an indication for pre-exposure prophylaxis will receive LEN 3000 mg injection once on Day 1 (approximately one year after their initial dose) during the Extension Phase. Participants will receive oral LEN if IM injections are not available. If participants choose to not receive additional LEN injections, they will continue onto the PK Tail Phase for up to 52 weeks.
Randomized Blinded Phase: LenacapavirEXPERIMENTALParticipants will receive lenacapavir (LEN) 927 mg injection, every 26 weeks starting on Day 1 for up to approximately 52 weeks. Participants will also receive loading dose of LEN 600 mg, tablet, once daily on Day 1 and Day 2. Participants will receive placebo to match (PTM) emtricitabine/tenofovir disoproxil fumarate (F/TDF) or PTM emtricitabine/tenofovir alafenamide (F/TAF), once daily, up to approximately 52 weeks.
Randomized Blinded Phase: F/TAFEXPERIMENTALParticipants will receive F/TAF, once daily up to approximately 52 weeks. Participants will also receive PTM LEN injection, every 26 weeks, starting on Day 1 up to approximately 52 weeks. Participants will receive PTM LEN tablet, once daily on Day 1 and Day 2.
Randomized Blinded Phase: F/TDFEXPERIMENTALParticipants will receive F/TDF, once daily up to approximately 52 weeks. Participants will also receive PTM LEN injection, every 26 weeks starting on Day 1 up to approximately 52 weeks. Participants will receive PTM LEN tablet, once daily on Day 1 and Day 2.
LEN Open-Label Extension (OLE) PhaseEXPERIMENTALAfter completion of the Blinded phase, participants will be offered entry into the LEN OLE Phase. Participants randomized to LEN will continue to receive LEN 927 mg injection, every 26 weeks until LEN becomes available or the sponsor elects to discontinue the study, whichever occurs first. Participants randomized to F/TAF or F/TDF will receive LEN 927 mg injection on OLE Day 1, Week 26, and every 26 weeks thereafter. Participants will also receive LEN 600 mg tablet on OLE Days 1 and 2.
Pharmacokinetic (PK) Tail Coverage PhaseEXPERIMENTALParticipants who prematurely discontinue study drug in the randomized blinded phase will transition into the PK Tail Coverage phase. Participants will receive F/TDF, once daily, for 78 weeks beginning 26 weeks after the last LEN injection.
Randomized Blinded Phase: LEN + Placebo-to-match (PTM) F/TDFEXPERIMENTALParticipants will receive the following for up to approximately 52 weeks: * Subcutaneous (SC) lenacapavir (LEN) 927 mg every 26 weeks * Oral PTM Emtricitabine/Tenofovir Disoproxil Fumarate (F/TDF) once daily * Oral LEN 600 mg on Days 1 and 2 Participants will receive oral LEN if SC injections are not available.
Randomized Blinded Phase: Placebo LEN + F/TDFEXPERIMENTALParticipants will receive the following for up to approximately 52 weeks: * SC LEN placebo every 26 weeks * Oral F/TDF 200/300 mg once daily * PTM Oral LEN on Days 1 and 2 Participants will receive oral LEN placebo if SC injections are not available.
Pharmacokinetic (PK) Tail PhaseEXPERIMENTALParticipants who prematurely discontinue study drug during the Randomized Blinded Phase and participants that were randomized to LEN who choose not to continue in the LEN OLE Phase will transition to the PK Tail Phase. Participants will receive oral F/TDF (or Emtricitabine/Tenofovir Alafenamide (F/TAF) for US participants only) once daily for 78 weeks to cover the PK tail and complete visits every 13 weeks (+/- 7 days). Upon unblinding, participants who were randomized to F/TDF in the Randomized Blinded Phase who decline to participate in the LEN OLE Phase will complete the ESDD visit, transition to local HIV prevention services, and return for a 30-day follow-up visit.
LENEXPERIMENTALParticipants will receive oral LEN 600 mg on Days 1 and 2. Participants will also receive 2 doses of LEN 927 mg as subcutaneous (SC) injection on Day 1 and Week 26 along with their OBR per clinical practice. At the Week 52, participants will be given the option to receive SC LEN every 6 months while continuing their OBR for at least another 2 SC LEN doses in the extension phase.
Cohort 1: Participants Aged ≥ 12 to < 18 years with Weight ≥ 35 kg: BIC/LEN 75/50 mg FDCEXPERIMENTALParticipants will receive a 2-day oral loading dose of LEN (600 mg) on Days 1 and 2 and daily oral BIC/LEN 75/50 mg starting on Day 1 through Week 48. Following Week 48, participants will have an option to continue BIC/LEN in the extension period.
Cohort 2: Participants Aged ≥ 6 to < 12 years with Weight ≥ 25 kg to < 35 kgEXPERIMENTALAll participants will receive a 2-day oral loading dose of LEN, and daily oral BIC and LEN dose starting on Day 1 through Week 48. Dose in cohort 2 to be defined. Following Week 48, participants will have an option to continue BIC/LEN in the extension period.
Cohort 3: Participants Aged ≥ 2 to < 6 years with Weight ≥ 10 kg to < 25 kgEXPERIMENTALAll participants will receive a 2-day oral loading dose of LEN, and daily oral BIC and LEN dose starting on Day 1 through Week 48. Dose in cohort 3 to be defined. Following Week 48, participants will have an option to continue BIC/LEN in the extension period.
Randomized Phase: Lenacapavir (LEN) GroupEXPERIMENTALParticipants will receive subcutaneous (SC) LEN 927 mg on Day 1 and 26 weeks and oral LEN 600 mg on Day 1 and 2.
Randomized Phase: F/TDFACTIVE_COMPARATORParticipants will receive daily F/TDF (200/300 mg) fixed dose combination (FDC) tablets for up to 52 weeks.
LEN Open Label Extension (OLE) PhaseEXPERIMENTALParticipants in the F/TDF group will transition to get LEN and participants in the LEN group will continue to get LEN. All participants will get SC LEN on Day 1 and week 26 of the OLE phase.
Pharmacokinetic (PK) Tail Phase: F/TDFEXPERIMENTALAfter completion of the LEN OLE Phase or upon discontinuation from the Randomized Phase for those receiving LEN, participants will be transitioned to receive F/TDF in the PK Tail Phase. Participants will receive once daily F/TDF for 78 weeks, beginning 26 weeks after the last LEN injection
Randomized Phase: Emtricitabine/ Tenofovir Disoproxil Fumarate (F/TDF) GroupEXPERIMENTALParticipants will receive daily F/TDF (200/300 mg) fixed dose combination (FDC) tablets for up to 52 weeks.
Open-label Extension Phase: LENEXPERIMENTALParticipants randomized to LEN in the Randomized Phase who choose to participate in the LEN Open-Label Extension (OLE) Phase will receive SC LEN every 26 weeks (± 7 days) and have study visits every 13 weeks (± 7 days). Participants randomized to F/TDF in the Randomized Phase who choose to participate in LEN OLE Phase will switch to SC LEN and have study visits at LEN OLE Day 1, Week 4 (± 2 days), Week 13 (± 7 days), and every 13 weeks (± 7 days) thereafter. SC LEN will be administered at the LEN OLE Day 1 visit and every 26 weeks thereafter. These participants will also receive loading doses of oral LEN on OLE Days 1 and 2. Upon completion of the LEN OLE Phase, participants will transition to local HIV prevention services and return for a 30-day follow-up visit. At that time, participation in the study will end.
Randomized Phase: Emtricitabine/Tenofovir Disoproxil Fumarate (F/TDF) GroupEXPERIMENTALParticipants will receive oral F/TDF (200/300 mg) daily for 52 weeks.
PK Tail Phase: F/TDFEXPERIMENTALAfter the completion of the Randomized Phase, participants in LEN group will be transitioned to receive F/TDF and participants in F/TDF group will continue to receive F/TDF in the PK Tail Phase. All participants will receive F/TDF, once daily for 78 weeks beginning 26 weeks after the last LEN injection.
Lenacapavir, F/TAF, and TAFEXPERIMENTALInduction phase: Participants will receive 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 will receive 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 will continue up to Week 80. Participants willing to continue the study beyond Week 80 will continue to receive SC LEN 927 mg injection every 6 months (26 weeks) and oral daily TAF 25 mg tablets from Week 80 onwards.
Lenacapavir, F/TAF, and BICEXPERIMENTALInduction phase: Participants will receive 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 will receive 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 will continue up to Week 80. Participants willing to continue the study beyond Week 80 will continue to receive SC LEN 927 mg injection every 6 months (26 weeks) and oral daily BIC 75 mg tablets from Week 80 onwards.
Lenacapavir and F/TAFEXPERIMENTALInduction phase: Participants will receive 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 will receive 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 will continue up to Week 80. Participants willing to continue the study beyond Week 80 will continue to receive SC LEN 927 mg injection every 6 months (26 weeks) and oral daily BIC 75 mg tablets from Week 80 onwards.
B/F/TAFACTIVE_COMPARATORParticipants will receive 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
Cohort 1A: LenacapavirEXPERIMENTALParticipants with HIV-1 ribonucleic acid (RNA) ≥ 400 copies/mL and with a \<0.5 log10 HIV-1 RNA decline at Cohort Selection visit compared with screening visit will receive oral lenacapavir (LEN) 600 mg tablet on Days 1 and 2 and 300 mg tablet on Day 8, while continuing their failing regimen in the blinded Functional Monotherapy Period (Baseline to Day 14); followed by unblinded Maintenance Period where participants will receive subcutaneous (SC) LEN 927 mg and will initiate an optimized background regimen (OBR) at Day 1 SC Visit (14 days after the first dose of oral LEN). 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 becomes accessible to participants through an access program or until Gilead elects to discontinue the study in the country.
Cohort 1B: Placebo to LenacapavirPLACEBO_COMPARATORParticipants 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 will receive oral LEN placebo on Days 1, 2, and 8 while continuing their failing regimen in the blinded Functional Monotherapy Period (Baseline to Day 14); followed by unblinded Maintenance Period where participants will receive oral LEN 600 mg on Days 15 and 16 and 300 mg on Day 22, and will initiate an OBR on Day 15. At Day 1 SC (14 days after the first dose of oral LEN), participants will receive SC LEN 927 mg while continuing OBR. 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 becomes accessible to participants through an access program or until Gilead elects to discontinue the study in the country.
Cohort 2: LenacapavirEXPERIMENTALParticipants with a ≥ 0.5 log10 copies/mL HIV-1 RNA decline at the Cohort Selection Visit compared with the screening visit or with HIV-1 RNA \< 400 copies/mL or if Cohort 1 is fully enrolled will receive oral LEN 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 will receive SC LEN 927 mg at Day 1 SC Visit (14 days after the first dose of oral LEN) while continuing their OBR. 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 becomes accessible to participants through an access program or until Gilead elects to discontinue the study in the country.
Primary Cohort: Lenacapavir (LEN) + Teropavimab + Zinlirvimab 10 mg/kgEXPERIMENTALParticipants will receive a loading dose of 600 milligrams (mg) LEN orally on Day 1 and Day 2, along with 927 mg LEN as subcutaneous (SC) injection on Day 1. Thereafter, participants will receive 30 mg/kg teropavimab and then 10 mg/kg zinlirvimab as an intravenous (IV) infusion on Day 1.
Primary Cohort: LEN + Teropavimab + Zinlirvimab 30 mg/kgEXPERIMENTALParticipants will receive a loading dose of 600 mg LEN orally on Day 1 and Day 2, along with 927 mg LEN as SC injection on Day 1. Thereafter, participants will receive 30 mg/kg teropavimab and then 30 mg/kg zinlirvimab as an IV infusion on Day 1.
Pilot Cohort: LEN +Teropavimab +Zinlirvimab 10 mg/kgEXPERIMENTALParticipants will receive a loading dose of 600 mg LEN orally on Day 1 and Day 2, along with 927 mg LEN as SC injection on Day 1. Thereafter, participants will receive 30 mg/kg teropavimab and then 10 mg/kg zinlirvimab as an IV infusion on Day 1.
Pilot Cohort: LEN +Teropavimab +Zinlirvimab 30 mg/kgEXPERIMENTALParticipants will receive a loading dose of 600 mg LEN orally on Day 1 and Day 2, along with 927 mg LEN as SC injection on Day 1. Thereafter, participants will receive 30 mg/kg teropavimab and then 30 mg/kg zinlirvimab as an IV infusion on Day 1.
Part A: Lenacapavir 20 mgEXPERIMENTALParticipants will receive single dose of lenacapavir 20 mg on Day 1 followed by bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) as per standard-care therapy starting on Day 10 through Day 225.
Part A: Lenacapavir 50 mgEXPERIMENTALParticipants will receive single dose of lenacapavir 50 mg on Day 1 followed by B/F/TAF as per standard-care therapy starting on Day 10 through Day 225.
Part A: Lenacapavir 150 mgEXPERIMENTALParticipants will receive single dose of lenacapavir 150 mg on Day 1 followed by B/F/TAF as per standard-care therapy starting on Day 10 through Day 225.
Part A: Lenacapavir 450 mgEXPERIMENTALParticipants will receive single dose of lenacapavir 450 mg on Day 1 followed by B/F/TAF as per standard-care therapy starting on Day 10 through Day 225.
Part A: Lenacapavir 750 mgEXPERIMENTALParticipants will receive single dose of lenacapavir 750 mg on Day 1 followed by B/F/TAF as per standard-care therapy starting on Day 10 through Day 225.
Part A: PlaceboPLACEBO_COMPARATORParticipants will receive single dose of placebo matched to lenacapavir on Day 1 followed by B/F/TAF as per standard-care therapy starting on Day 10 through Day 225.
Part B: TAF 200 mgEXPERIMENTALParticipants will receive a single dose of TAF 200 mg on Day 1 followed by B/F/TAF as per standard-care therapy starting on Day 10 through Day 225.
Part B: TAF 600 mgEXPERIMENTALParticipants will receive a single dose of TAF 600 mg on Day 1 followed by B/F/TAF as per standard-care therapy starting on Day 10 through Day 225.

Interventions

NameTypeDescription
LenacapavirDRUGAdministered subcutaneously
Lenacapavir TabletDRUGAdministered orally
TeropavimabDRUGAdministered intravenously (IV)
ZinlirvimabDRUGAdministered IV
CabotegravirDRUGAdministered intramuscular (IM)
RilpivirineDRUGAdministered IM
SBRDRUGSBRs administered orally. SBRs include medicines like bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) or dolutegravir (DTG)+ tenofovir alafenamide (TAF)+ emtricitabine (FTC).
Lenacapavir InjectionDRUGAdministered intramuscularly
Oral Lenacapavir (LEN)DRUGTablets administered orally without regard to food
Subcutaneous (SC) Lenacapavir (LEN)DRUGAdministered via SC injections
F/TAFDRUGTablets administered orally
F/TDFDRUGTablets administered orally
Placebo SC LENDRUGAdministered via SC injections
PTM Oral LENDRUGTablets administered orally
PTM F/TAFDRUGTablets administered orally
PTM F/TDFDRUGTablets administered orally
Sub-cutaneous (SC) Lenacapavir (LEN)DRUGAdministered via SC injections
F/TAF (for US participants only)DRUGF/TAF tablets administered orally once daily
Oral LenacapavirDRUGTablets administered without regard to food
Subcutaneous LenacapavirDRUGAdministered via subcutaneous injections
Optimized Background Regimen (OBR)DRUGOptimized background regimen as prescribed by the Investigator
BIC/LEN FDCDRUGTablets administered orally without regard to food
Emtricitabine/tenofovir disoproxil fumarate (F/TDF)DRUGAdministered orally
TAFDRUGTablets administered without regard to food
BICDRUGTablets administered without regard to food
B/F/TAFDRUGTablets administered without regard to food
Oral Lenacapavir PlaceboDRUGTablets administered without regard to food
Failing ARV RegimenDRUGFailing 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.
PlaceboDRUGAdministered subcutaneously in the abdomen
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Eligibility Criteria

Age Range18 Years to N/A
SexALL
Healthy VolunteersNo
Study Sites19

Key Inclusion Criteria: * Human immunodeficiency virus type 1 (HIV-1) susceptibility results from screening meeting specific criteria: 1\) Proviral phenotypic susceptibility to both TAB and ZAB by the investigational protocol-defined assay at screening. * At least 1 documented HIV-1 RNA level me...

Countries:United StatesAustraliaJapanSouth AfricaUgandaArgentinaBrazilMexicoPeruPuerto RicoThailandItalySpainFranceUnited KingdomDominican RepublicCanadaGermanyTaiwan
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Recent Changes (Last 90 Days)

LOWAug 28, 2026NCT07047716lastUpdatePostDate: changed
LOWAug 28, 2026NCT07047716lastUpdatePostDate: changed
LOWAug 17, 2026NCT06101329primaryCompletionDate: changed
LOWAug 17, 2026NCT06101329primaryCompletionDate: changed
LOWAug 14, 2026NCT07682961lastUpdatePostDate: changed
LOWAug 14, 2026NCT06101342primaryCompletionDate: changed
LOWAug 14, 2026NCT07682961lastUpdatePostDate: changed
LOWAug 14, 2026NCT06101342primaryCompletionDate: changed
LOWAug 14, 2026NCT06101342primaryCompletionDate: changed
LOWAug 7, 2026NCT04994509lastUpdatePostDate: changed
LOWAug 7, 2026NCT04994509lastUpdatePostDate: changed
LOWJul 30, 2026NCT07683000Status: NOT_YET_RECRUITING → RECRUITING
LOWJul 30, 2026NCT07683000Status: NOT_YET_RECRUITING → RECRUITING
LOWJul 22, 2026NCT07682961Status: NOT_YET_RECRUITING → RECRUITING
LOWJul 22, 2026NCT07682961Status: NOT_YET_RECRUITING → RECRUITING
LOWJul 6, 2026NCT07683000NEW_TRIAL: changed
LOWJul 6, 2026NCT07682961NEW_TRIAL: changed
LOWJul 6, 2026NCT07683000NEW_TRIAL: changed
LOWJul 6, 2026NCT07682961NEW_TRIAL: changed
MEDIUMJun 22, 2026NCT07047716Status: RECRUITING → ACTIVE_NOT_RECRUITING

Frequently asked questions about Lenacapavir

What is Lenacapavir used for?

Lenacapavir is an investigational small molecule being developed for HIV-1 infection and for pre-exposure prophylaxis (PrEP) of HIV infection. It is being studied in Phase 3 clinical trials for these indications, including as a once-yearly injection for HIV PrEP.

How does Lenacapavir work?

Lenacapavir is a small molecule that targets HIV-1. It is being studied for its ability to treat and prevent HIV-1 infection. The specific molecular target is not disclosed in the available information.

Who makes Lenacapavir?

Lenacapavir is being developed by Gilead Sciences, Inc., a biopharmaceutical company traded on the NASDAQ under the ticker GILD. Gilead is conducting clinical trials to evaluate the drug for HIV treatment and prevention.

What phase is Lenacapavir in?

Lenacapavir is in Phase 3 clinical development. It is being studied in active Phase 3 trials for HIV pre-exposure prophylaxis and for HIV-1 infection treatment. It is not yet approved and remains an investigational drug.

What clinical trials is Lenacapavir in?

Lenacapavir is being studied in several clinical trials. NCT07047716 is a Phase 3 trial of lenacapavir as a once-yearly injection for HIV pre-exposure prophylaxis. NCT07682961 is a Phase 3 trial comparing lenacapavir with teropavimab and zinlirvimab to cabotegravir and rilpivirine in virologically suppressed adults with HIV-1.

Is Lenacapavir the same as oral lenacapavir?

Lenacapavir is available in multiple formulations, including as an injection and as an oral tablet. The oral form is referred to as oral lenacapavir or oral lenacapavir (LEN). These are all the same drug, lenacapavir, in different dosage forms.