Study of Lenacapavir and Emtricitabine/Tenofovir Disoprox... | NCT06101342

Status Module

Name	Class
HIV Prevention Trials Network	NETWORK
National Institute on Drug Abuse (NIDA)	NIH
National Institute of Allergy and Infectious Diseases (NIAID)	NIH

Description Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Randomized Phase: Lenacapavir (LEN) Group	Experimental	Participants will receive subcutaneous (SC) LEN 927 mg on Day 1 and Week 26 and oral LEN 600 mg on Days 1 and 2.	Drug: Lenacapavir Injection Drug: Lenacapavir Tablet
Randomized Phase: Emtricitabine/ Tenofovir Disoproxil Fumarate (F/TDF) Group	Experimental	Participants will receive daily F/TDF (200/300 mg) fixed dose combination (FDC) tablets for up to 52 weeks.	Drug: Emtricitabine/tenofovir disoproxil fumarate (F/TDF)
Open-label Extension Phase: LEN	Experimental	Participants 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.	Drug: Lenacapavir Injection Drug: Lenacapavir Tablet
Pharmacokinetic (PK) Tail Phase: F/TDF	Experimental	Participants eligible for the PK Tail Phase will receive open-label oral F/TDF once daily for up to 78 weeks and complete study visits every 13 weeks (± 7 days). PK Tail Day 1 visit will occur 26 weeks (± 7 days) after the last SC LEN injection.

Name	Type	Description	Arm Group Labels	Other Names
Lenacapavir Injection	Drug	Administered subcutaneously	Open-label Extension Phase: LEN Randomized Phase: Lenacapavir (LEN) Group

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
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 78
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 78

Secondary Outcomes

Measure	Description	Time Frame
General Acceptability of LEN and F/TDF as PrEP as Assessed by Percentage of Participants with Acceptability Questionnaire Responses	To assess the acceptability of the study drug, the participants will complete 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.

Eligibility Module

Eligibility Criteria

Key Inclusion Criteria:

Urine drug screen positive for any drug of misuse including, but not limited to, opioids (eg, fentanyl, heroin), stimulants (eg, cocaine, amphetamines), psychoactive drugs (eg, benzodiazepines), or a combination of these drugs.
Evidence of recent injection (eg, track marks).
Self-report of injection paraphernalia sharing in the prior 30 days.
Hepatitis B virus (HBV) surface antigen (HBsAg) negative.
Negative local rapid HIV-1/2 antibody (Ab)/antigen (Ag) test, central HIV-1/2 Ab/Ag, and HIV-1 RNA quantitative nucleic acid amplification testing (NAAT).
Estimated glomerular filtration rate (GFR) at least 60 mL/min at screening according to the Cockcroft-Gault formula for creatinine clearance (CLcr).

Key Exclusion Criteria:

Self-reported history of previous positive results on an HIV test.
Any reactive or positive HIV test result at screening or enrollment, even if HIV infection is not confirmed.
Coenrollment in any other interventional research study or other concurrent studies that may interfere with this study (as provided by self-report or other available documentation) without prior approval from the Medical Monitor/Joint Clinical Management Committee while participating in this study.
Past or current participation in HIV vaccine or HIV broadly neutralizing antibody study unless individual provides documentation of receipt of placebo (ie, not active product).
Prior use of long-acting systemic pre-exposure prophylaxis (PrEP) (including cabotegravir (CAB) or islatravir studies).
Acute viral hepatitis A or acute or chronic hepatitis B or C infection.
Have a suspected or known active, serious infection(s) (eg, active tuberculosis, etc).
Evidence of moderate or severe liver fibrosis or a history of or current clinical decompensated liver cirrhosis (eg, ascites, encephalopathy, variceal bleeding). In individuals with active hepatitis C, Fibrosis-4 (FIB-4) score > 3.25 (formula provided below).

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Name	Affiliation	Role
Gilead Study Director	Gilead Sciences	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
UCLA Vine Street Clinic		Los Angeles	California	90038	United States
UCSD AntiViral Research Center (AVRC)

PubMed Identifier	Type	Citation	Retractions
41498432	Derived	Martinez S, Garcia-Romeu A, Wisdom J, Jones J. Methamphetamine use and HIV prevention: a qualitative study on challenges and opportunities for PrEP utilization. AIDS Care. 2026 Apr;38(4):856-869. doi: 10.1080/09540121.2025.2611079. Epub 2026 Jan 7.

Label	URL
Gilead Clinical Trials Website	View source

ID	Term
C000730993	lenacapavir
D000068679	Emtricitabine
D000068698	Tenofovir
D000069480	Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination

Ancestor Terms

ID	Term
D003841	Deoxycytidine
D003562	Cytidine
D011741	Pyrimidine Nucleosides
D011743	Pyrimidines
D006573	Heterocyclic Compounds, 1-Ring
D006571	Heterocyclic Compounds
D003853	Deoxyribonucleosides
D009705	Nucleosides
D009706	Nucleic Acids, Nucleotides, and Nucleosides
D063065	Organophosphonates
D009943	Organophosphorus Compounds
D009930	Organic Chemicals
D000225	Adenine
D011687	Purines
D006574	Heterocyclic Compounds, 2-Ring
D000072471	Heterocyclic Compounds, Fused-Ring
D004338	Drug Combinations
D004364	Pharmaceutical Preparations