Lenacapavir + F/TDF for HIV Prevention

(PURPOSE 4 Trial)

Recruiting at7 trial locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Gilead Sciences

Disqualifiers: HIV positive, Hepatitis, Liver fibrosis, others

No Placebo Group

Prior Safety Data

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the study team or your doctor.

What data supports the effectiveness of the drug Lenacapavir + F/TDF for HIV prevention?

Research shows that the combination of tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC) is effective in reducing the risk of HIV infection by 74 to 92% when used as pre-exposure prophylaxis (PrEP). ^{1 2 3 4 5}

What makes the drug Lenacapavir + F/TDF unique for HIV prevention?

Lenacapavir + F/TDF is unique for HIV prevention because it combines Lenacapavir, a long-acting injectable drug, with F/TDF, a daily oral pill, offering a novel approach that may improve adherence and convenience compared to daily oral regimens alone. ^{6 7 8 9 10}

Research Team

Gilead Study Director

Principal Investigator

Gilead Sciences

Eligibility Criteria

This trial is for people in the US who inject drugs and have shared needles within the last month. They must not have HIV or hepatitis B, should have a kidney function with GFR of at least 60 mL/min, and show recent signs of injection use. A positive drug screen for substances like opioids or stimulants is also required.

Inclusion Criteria

There is indication of recent intramuscular injection, such as needle marks.

My kidney function, measured by GFR, is 60 mL/min or higher.

You have tested positive for illicit drugs such as opioids, stimulants, psychoactive substances or any combination thereof.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Randomized Phase

Participants receive either subcutaneous LEN or daily F/TDF for up to 52 weeks

52 weeks

Visits at Day 1, Week 26, and every 13 weeks

Open-label Extension Phase

Participants may opt into continuation of treatment with SC LEN every 26 weeks

Long-term

Visits every 13 weeks

Pharmacokinetic (PK) Tail Phase

Participants receive open-label oral F/TDF once daily for up to 78 weeks

78 weeks

Visits every 13 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

1 visit (in-person)

Treatment Details

Interventions

• Emtricitabine/Tenofovir Disoproxil Fumarate (F/TDF) (Antiretroviral)
• Lenacapavir (Antiretroviral)

Trial Overview The study tests how lenacapavir (LEN), given as tablets and injections, moves through the body and its safety when combined with Truvada® (F/TDF) as a preventive treatment against HIV in those who inject drugs.

Participant Groups

Group I: Randomized Phase: Lenacapavir (LEN) Group Experimental Treatment 2 Interventions

Participants will receive subcutaneous (SC) LEN 927 mg on Day 1 and Week 26 and oral LEN 600 mg on Days 1 and 2.

Group II: Randomized Phase: Emtricitabine/ Tenofovir Disoproxil Fumarate (F/TDF) Group Experimental Treatment 1 Intervention

Participants will receive daily F/TDF (200/300 mg) fixed dose combination (FDC) tablets for up to 52 weeks.

Group III: Pharmacokinetic (PK) Tail Phase: F/TDF Experimental Treatment 1 Intervention

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.

Group IV: Open-label Extension Phase: LEN Experimental Treatment 2 Interventions

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.

Emtricitabine/Tenofovir Disoproxil Fumarate (F/TDF) is already approved in Canada for the following indications:

Approved in Canada as Truvada for:

• Pre-exposure prophylaxis (PrEP) for HIV-1 infection

Who Is Running the Clinical Trial?

Gilead Sciences

Lead Sponsor

Trials

1,150

Recruited

878,000+

Daniel O'Day

Gilead Sciences

Chief Executive Officer since 2019

MBA from Columbia University

Dietmar Berger

Gilead Sciences

Chief Medical Officer

MD and PhD from Albert-Ludwigs University School of Medicine

National Institute on Drug Abuse (NIDA)

Collaborator

Trials

2,658

Recruited

3,409,000+

Dr. Nora Volkow

National Institute on Drug Abuse (NIDA)

Chief Executive Officer since 2003

MD from National Autonomous University of Mexico

Dr. Nora Volkow

National Institute on Drug Abuse (NIDA)

Chief Medical Officer since 2003

MD from National Autonomous University of Mexico

HIV Prevention Trials Network

Collaborator

Trials

31

Recruited

569,000+

National Institute of Allergy and Infectious Diseases (NIAID)

Collaborator

Trials

3,361

Recruited

5,516,000+

Dr. Jeanne Marrazzo

National Institute of Allergy and Infectious Diseases (NIAID)

Chief Executive Officer since 2023

MD, MPH

Dr. H. Clifford Lane

National Institute of Allergy and Infectious Diseases (NIAID)

Chief Medical Officer

MD

Findings from Research

The combination of tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC) demonstrated additive to synergistic anti-HIV activity in vitro, particularly effective against both wild-type and mutant strains of the virus, based on studies in human T leukaemic cells and peripheral blood mononuclear cells (PBMCs).

Both drugs were efficiently converted to their active metabolites in the tested cells, with significant increases in the levels of these metabolites when used together, suggesting that their combined use enhances their effectiveness as a dual NRTI backbone in HIV-1 treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In vitro evaluation of the anti-HIV activity and metabolic interactions of tenofovir and emtricitabine. Borroto-Esoda, K., Vela, JE., Myrick, F., et al.[2015]

Tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC) are effective in reducing the risk of HIV infection by 74 to 92% when taken as pre-exposure prophylaxis (PrEP) with detectable drug levels.

While TDF-FTC can cause side effects like nausea and decreased bone mineral density, these risks can be managed through regular monitoring by healthcare providers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Drug safety evaluation of oral tenofovir disoproxil fumarate-emtricitabine for pre-exposure prophylaxis for human immunodeficiency virus infection. Trang, TP., Dong, BJ., Kojima, N., et al.[2017]

The study found that the combination of emtricitabine and tenofovir alafenamide (F/TAF) was safe and well-tolerated among HIV-uninfected women, with significantly lower gastrointestinal side effects compared to the older F/TDF combination.

F/TAF demonstrated higher concentrations of the active form of tenofovir (TFV-DP) in peripheral blood mononuclear cells and vaginal tissues compared to F/TDF, suggesting it may be a more effective option for HIV pre-exposure prophylaxis in women.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Pharmacokinetics of a Tenofovir Alafenamide Fumarate-Emtricitabine based Oral Antiretroviral Regimen for Prevention of HIV Acquisition in Women: A Randomized Controlled Trial. Thurman, AR., Schwartz, JL., Cottrell, ML., et al.[2022]

In a phase 3 trial with 663 HIV-infected adults, switching from tenofovir disoproxil fumarate (TDF) to tenofovir alafenamide (TAF) showed similar effectiveness in maintaining viral suppression, with 88.6% of TAF users and 89.1% of TDF users achieving HIV-1 RNA levels below 50 copies per milliliter after 96 weeks.

Patients switching to TAF experienced improvements in kidney function and bone mineral density compared to those remaining on TDF, indicating that TAF may offer a safer profile with better long-term health outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brief Report: Long-Term (96-Week) Efficacy and Safety After Switching From Tenofovir Disoproxil Fumarate to Tenofovir Alafenamide in HIV-Infected, Virologically Suppressed Adults. Raffi, F., Orkin, C., Clarke, A., et al.[2022]

The investigational coformulation of efavirenz (EFV), emtricitabine (FTC), and tenofovir disoproxil fumarate (TDF) is bioequivalent to the individual components, indicating it can be used interchangeably without loss of efficacy.

The study involved 48 healthy subjects, and all treatments were well tolerated, suggesting that the coformulation is safe for use in the target population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bioequivalence of efavirenz/emtricitabine/tenofovir disoproxil fumarate single-tablet regimen. Mathias, AA., Hinkle, J., Menning, M., et al.[2020]

Mometasone furoate and formoterol fumarate (MF/F) is an effective fixed-dose combination therapy for asthma in patients aged 12 and older, showing improvements in lung function and quality of life while reducing asthma exacerbations.

Clinical safety studies of MF/F, lasting up to one year, indicate a low incidence of both local and systemic side effects, suggesting it is a safe option for long-term asthma management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mometasone furoate/formoterol in the treatment of persistent asthma. Berger, WE.[2015]

In a clinical trial involving 1055 participants with moderate to very severe COPD, the combination of mometasone furoate/formoterol fumarate (MF/F) significantly improved lung function (FEV1) compared to individual components, showing effectiveness as a treatment.

Both doses of MF/F (400/10 μg and 200/10 μg) were well tolerated, with low rates of pneumonia (≤1.0%) and no significant differences in adverse events across treatment groups, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of a fixed-dose combination of mometasone furoate and formoterol fumarate in subjects with moderate to very severe COPD: results from a 52-week Phase III trial. Tashkin, DP., Doherty, DE., Kerwin, E., et al.[2021]

In a study involving 2251 patients with moderate to very severe COPD, the fixed-dose combination of mometasone furoate/formoterol fumarate (MF/F) significantly improved lung function, with greater increases in forced expiratory volume (FEV1) compared to placebo and individual components, particularly at the higher dose of MF/F 400/10 μg.

The treatment also led to better health status as measured by the St George's Respiratory Questionnaire and reduced exacerbation rates, with a similar safety profile to placebo, indicating that MF/F is both effective and safe for COPD management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety characteristics of mometasone furoate/formoterol fumarate fixed-dose combination in subjects with moderate to very severe COPD: findings from pooled analysis of two randomized, 52-week placebo-controlled trials. Tashkin, DP., Doherty, DE., Kerwin, E., et al.[2022]

In a 4-month study involving 2179 adult asthma patients, the extrafine formulation of beclomethasone/formoterol (BDP/F pMDI HFA) significantly improved asthma control, as shown by a decrease in the Asthma Control Questionnaire score from 1.62 to 0.94 (p < 0.001).

Patients reported better compliance with their medication, with those forgetting to take their medication dropping from 49.7% to 27.1% (p < 0.001), and most patients expressed satisfaction with the inhaler device, preferring it over dry powder inhalers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Improvement of asthma control in adult patients using extrafine inhaled beclomethasone/formoterol fixed combination as maintenance therapy as well as maintenance and reliever therapy - CONTROL study. Dębowski, T., Marko, M., Rogala, B., et al.[2023]

The fixed-dose combination (FDC) inhaler containing mometasone furoate and formoterol fumarate showed comparable pharmacokinetics to individual inhalers, indicating that the combination does not alter the absorption of either drug when used together.

In a study involving healthy subjects, the systemic exposure levels of mometasone furoate and formoterol were similar whether administered as a combination or as separate inhalers, suggesting that the FDC is safe and effective for asthma and potentially for COPD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of potential for pharmacokinetic interaction between mometasone furoate and formoterol fumarate after oral inhalation from a fixed-dose combination metered-dose inhaler device. Kosoglou, T., Hubbell, J., Johnson-Levonas, AO., et al.[2018]

References

1. England pubmed.ncbi.nlm.nih.gov

In vitro evaluation of the anti-HIV activity and metabolic interactions of tenofovir and emtricitabine. [2015]

2. England pubmed.ncbi.nlm.nih.gov

Drug safety evaluation of oral tenofovir disoproxil fumarate-emtricitabine for pre-exposure prophylaxis for human immunodeficiency virus infection. [2017]

3. England pubmed.ncbi.nlm.nih.gov

Safety and Pharmacokinetics of a Tenofovir Alafenamide Fumarate-Emtricitabine based Oral Antiretroviral Regimen for Prevention of HIV Acquisition in Women: A Randomized Controlled Trial. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Brief Report: Long-Term (96-Week) Efficacy and Safety After Switching From Tenofovir Disoproxil Fumarate to Tenofovir Alafenamide in HIV-Infected, Virologically Suppressed Adults. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Bioequivalence of efavirenz/emtricitabine/tenofovir disoproxil fumarate single-tablet regimen. [2020]

6. England pubmed.ncbi.nlm.nih.gov

Mometasone furoate/formoterol in the treatment of persistent asthma. [2015]

7. New Zealand pubmed.ncbi.nlm.nih.gov

Efficacy and safety of a fixed-dose combination of mometasone furoate and formoterol fumarate in subjects with moderate to very severe COPD: results from a 52-week Phase III trial. [2021]

8. New Zealand pubmed.ncbi.nlm.nih.gov

Efficacy and safety characteristics of mometasone furoate/formoterol fumarate fixed-dose combination in subjects with moderate to very severe COPD: findings from pooled analysis of two randomized, 52-week placebo-controlled trials. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Improvement of asthma control in adult patients using extrafine inhaled beclomethasone/formoterol fixed combination as maintenance therapy as well as maintenance and reliever therapy - CONTROL study. [2023]

10. United States pubmed.ncbi.nlm.nih.gov

Evaluation of potential for pharmacokinetic interaction between mometasone furoate and formoterol fumarate after oral inhalation from a fixed-dose combination metered-dose inhaler device. [2018]