NCT06101342

Brief Summary

The goals of this clinical study are to look at how lenacapavir (LEN) passes through the body and to assess the safety of LEN and emtricitabine/tenofovir disoproxil fumarate (F/TDF) for pre-exposure prophylaxis (PrEP) in people who inject drugs (PWID) in the United States (US). The primary objectives of this study are to characterize the pharmacokinetics (PK) of LEN and to evaluate the safety of LEN and F/TDF for PrEP in US PWID.

Trial Health

75
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
181

participants targeted

Target at P75+ for phase_2

Timeline
20mo left

Started Dec 2023

Typical duration for phase_2

Geographic Reach
1 country

9 active sites

Status
active not recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress59%
Dec 2023Jan 2028

First Submitted

Initial submission to the registry

October 20, 2023

Completed
6 days until next milestone

First Posted

Study publicly available on registry

October 26, 2023

Completed
2 months until next milestone

Study Start

First participant enrolled

December 13, 2023

Completed
4.1 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 1, 2028

Expected
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

January 1, 2028

Last Updated

March 2, 2026

Status Verified

February 1, 2026

Enrollment Period

4.1 years

First QC Date

October 20, 2023

Last Update Submit

February 27, 2026

Conditions

Pre-Exposure Prophylaxis of HIV Infection

Outcome Measures

Primary Outcomes (4)

  • 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 (5)

  • General Acceptability of LEN and F/TDF as PrEP as Assessed by Percentage of Participants with Acceptability Questionnaire Responses

    Up to Week 52

  • Satisfaction With Use of LEN and F/TDF as PrEP as Assessed by Percentage of Participants with Satisfaction Questionnaire Responses

    Up to Week 52

  • 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

  • Number of Participants with Adherence to LEN, as Assessed by On-time LEN Injections Received

    Up to Week 26

  • Number of Participants with Adherence to F/TDF as Assessed by Adherence Levels Based on Intracellular Tenofovir-diphosphate (TFV-DP) Concentrations in Dried Blood Spot (DBS)

    Up to Week 78

Study Arms (4)

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 InjectionDrug: 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 InjectionDrug: 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.

Drug: Emtricitabine/tenofovir disoproxil fumarate (F/TDF)

Interventions

Lenacapavir InjectionDRUG

Administered subcutaneously

Also known as: GS-6207, Yeztugo®
Open-label Extension Phase: LENRandomized Phase: Lenacapavir (LEN) Group
Lenacapavir TabletDRUG

Administered orally

Also known as: GS-6207
Open-label Extension Phase: LENRandomized Phase: Lenacapavir (LEN) Group
Emtricitabine/tenofovir disoproxil fumarate (F/TDF)DRUG

Administered orally

Also known as: Truvada®
Pharmacokinetic (PK) Tail Phase: F/TDFRandomized Phase: Emtricitabine/ Tenofovir Disoproxil Fumarate (F/TDF) Group

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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).

You may not qualify if:

  • 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).

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (9)

UCLA Vine Street Clinic

Los Angeles, California, 90038, United States

Location

UCSD AntiViral Research Center (AVRC)

San Diego, California, 92103, United States

Location

University of Miami - Converge Miami Building

Miami, Florida, 33136, United States

Location

Johns Hopkins Medicine Institute for Clinical and Translational Research, Clinical Research

Baltimore, Maryland, 21287, United States

Location

Rutgers New Jersey Medical School, Department of Medicine

Newark, New Jersey, 07103, United States

Location

ICAP at Columbia University- Bronx Prevention Center

The Bronx, New York, 10451, United States

Location

University of Pennsylvania, Division of Infectious Diseases Penn Prevention Research Unit

Philadelphia, Pennsylvania, 19104, United States

Location

Houston AIDS Research Team CRS

Houston, Texas, 77030, United States

Location

West Virginia University

Morgantown, West Virginia, 26506, United States

Location

Related Publications (1)

  • 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 Jan 7:1-14. doi: 10.1080/09540121.2025.2611079. Online ahead of print.

    PMID: 41498432DERIVED

Related Links

MeSH Terms

Interventions

lenacapavirEmtricitabineTenofovirEmtricitabine, Tenofovir Disoproxil Fumarate Drug Combination

Intervention Hierarchy (Ancestors)

DeoxycytidineCytidinePyrimidine NucleosidesPyrimidinesHeterocyclic Compounds, 1-RingHeterocyclic CompoundsDeoxyribonucleosidesNucleosidesNucleic Acids, Nucleotides, and NucleosidesOrganophosphonatesOrganophosphorus CompoundsOrganic ChemicalsAdeninePurinesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingDrug CombinationsPharmaceutical Preparations

Study Officials

  • Gilead Study Director

    Gilead Sciences

    STUDY DIRECTOR

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
NONE
Purpose
PREVENTION
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

October 20, 2023

First Posted

October 26, 2023

Study Start

December 13, 2023

Primary Completion (Estimated)

January 1, 2028

Study Completion (Estimated)

January 1, 2028

Last Updated

March 2, 2026

Record last verified: 2026-02

Data Sharing

IPD Sharing
Will not share

Locations

US(9)