Bictegravir + Lenacapavir for HIV

(ARTISTRY-1 Trial)

Not currently recruiting at 111 trial locations

Overseen By Gilead Clinical Study Information Center

Age: 18+

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: Gilead Sciences

Must be taking: Antiretrovirals

Disqualifiers: Tuberculosis, Hepatitis B, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests two HIV medications, bictegravir and lenacapavir, to compare them with current HIV treatments. The study aims to determine if switching to these new drugs can be more effective for people living with HIV. Participants will either switch to one of the new drug combinations or continue with their current treatment for comparison. The trial seeks individuals who have been on a complex HIV treatment plan for at least six months and have consistently low viral levels. It is not suitable for those who have used lenacapavir before, have active tuberculosis, or chronic hepatitis B. As a Phase 2 trial, this research measures how well the treatment works in an initial, smaller group of people, offering participants a chance to contribute to important advancements in HIV care.

Will I have to stop taking my current medications?

The trial involves switching to the study drugs, so you may need to stop your current HIV medications. The protocol does not specify a washout period, but it seems likely that you will transition from your current regimen to the study drugs.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that the combination of bictegravir and lenacapavir is generally well-tolerated by people living with HIV. Bictegravir, part of the medication Biktarvy, is usually easy for patients to handle, with common side effects such as diarrhea, nausea, and headache. Lenacapavir is approved for certain uses and has undergone safety studies in people with HIV-1.

Early trials found that using these two drugs together was safe and effective, with manageable side effects. Since bictegravir is already part of an approved drug (Biktarvy), it indicates a good safety record for treating HIV. However, the combination of bictegravir and lenacapavir remains under study, and their safety and effectiveness together are not yet fully confirmed. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Bictegravir and Lenacapavir for HIV because they represent a novel combination approach to treatment. Unlike current standard treatments, which often involve multiple pills and complex regimens, this combination offers a fixed-dose option that simplifies the daily routine for patients. Lenacapavir has a unique mechanism as a capsid inhibitor, potentially offering a new way to suppress the virus. Additionally, the loading dose regimen is designed to rapidly establish effective drug levels, potentially improving treatment outcomes. This streamlined and innovative approach could make managing HIV more manageable for patients.

What evidence suggests that this trial's treatments could be effective for HIV?

Research has shown that the combination of bictegravir and lenacapavir is effective for people with HIV who have the virus under control (meaning the virus is at very low levels in their body). In this trial, participants will join different treatment arms to evaluate the effectiveness of various dosages of bictegravir and lenacapavir combinations. Studies have found that switching to these combinations maintains viral control for at least 24 weeks. This is crucial because keeping the virus under control is the main goal of HIV treatment. Additionally, these combinations have been found safe, with no serious side effects reported in these studies. These positive results suggest that bictegravir and lenacapavir could be a strong option for managing HIV. ^{1 5 6 7 8}

Who Is on the Research Team?

Gilead Study Director

Principal Investigator

Gilead Sciences

Are You a Good Fit for This Trial?

This trial is for people with HIV-1 who have been successfully treated but are on complex regimens, including multiple pills or injections plus oral meds. They should have no resistance to bictegravir, stable kidney function (not on dialysis), and undetectable HIV levels for at least 6 months. It's not for those with active tuberculosis, prior lenacapavir use, or chronic hepatitis B.

Inclusion Criteria

At least one documented plasma HIV-1 RNA level measured between 6 and 12 months (± 2 months) prior to screening must be < 50 copies/mL

My kidneys work well enough, and I don't need dialysis.

Plasma HIV-1 RNA measurements in the 6 months prior to screening must be < 50 copies/mL

Exclusion Criteria

I have chronic hepatitis B.

I do not have an active tuberculosis infection.

I have previously used or been exposed to lenacapavir.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Phase 2

Participants switch from their stable baseline regimen to a regimen of BIC 75 mg + LEN 25 mg or BIC 75 mg + LEN 50 mg, with a 2-day loading dose regimen of LEN 600 mg, treated for at least 24 weeks

24 weeks

Treatment Phase 3

Participants switch to BIC/LEN 75 mg/50 mg fixed-dose combination, treated for at least 48 weeks

48 weeks

Extension Period

Participants have the option to continue receiving BIC/LEN 75 mg/50 mg FDC

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Bictegravir
• Lenacapavir

Trial Overview The study compares the effects of switching to a new regimen of bictegravir plus lenacapavir versus continuing current therapy in Phase 2. In Phase 3, it looks at a fixed-dose combination of these drugs against current treatments in people living with HIV.

How Is the Trial Designed?

Group I: Phase 3: BIC/LEN 75 mg/50 mg Fixed-dose Combination (FDC) Experimental Treatment 1 Intervention

Participants will switch from their SBR to a regimen of BIC/LEN 75 mg/50 mg FDC. Participants will receive a 2-day loading dose regimen of LEN 600 mg, in addition to the daily doses of BIC/LEN 75 mg/50 mg FDC starting on Day 1 up to the ERT visit, participants will be treated for at least 48 weeks during the Randomized Period. Following Randomized Period, the participants will have an option to participate in an Extension Period to receive BIC/LEN 75 mg/50 mg FDC.

Group II: Phase 2: Bictegravir (BIC) 75 mg + Lenacapavir (LEN) 25 mg Experimental Treatment 2 Interventions

Participants will switch from their stable baseline regimen (SBR) to a regimen of BIC 75 mg + LEN 25 mg. Participants will receive a 2-day loading dose regimen of LEN 600 mg, in addition to the daily doses of BIC 75 mg + LEN 25 mg starting on Day 1 up to the end of randomized treatment (ERT) visit, participants will be treated for at least 24 weeks during the Randomized Period. Following Randomized Period, the participants will have an option to participate in an Extension Period to receive BIC/LEN 75 mg/50 mg fixed dose combination (FDC).

Group III: Phase 2: BIC 75 mg + LEN 50 mg Experimental Treatment 2 Interventions

Participants will switch from their SBR to a regimen of BIC 75 mg + LEN 50 mg. Participants will receive a 2-day loading dose regimen of LEN 600 mg, in addition to the daily doses of BIC 75 mg + LEN 50 mg starting on Day 1 up to the ERT visit, participants will be treated for at least 24 weeks during the Randomized Period. Following Randomized Period, the participants will have an option to participate in an Extension Period to receive BIC/LEN 75 mg/50 mg FDC.

Group IV: Phase 2: Stable Baseline Regimen (SBR) Active Control 1 Intervention

Participants will continue with their SBR per prescription for up to the ERT visit, participants will be treated for at least 24 weeks during the Randomized Period. Following Randomized Period, the participants will have an option to participate in an Extension Period to receive BIC/LEN 75 mg/50 mg FDC.

Group V: Phase 3: Stable Baseline Regimen Active Control 1 Intervention

Participants will continue with their SBR per prescription for up to the ERT visit, participants will be treated for at least 48 weeks during the Randomized Period. Following Randomized Period, the participants will have an option to participate in an Extension Period to receive BIC/LEN 75 mg/50 mg FDC.

Bictegravir is already approved in European Union, United States, Canada for the following indications:

Approved in European Union as Bictegravir for:

• HIV-1 infection

Approved in United States as Bictegravir for:

• HIV-1 infection

Approved in Canada as Bictegravir 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

Published Research Related to This Trial

In a study of 16 patients with advanced biliary tract carcinoma, oral tegafur-uracil combined with leucovorin was found to be well tolerated, with only two patients experiencing significant toxicities (grade III/IV).

Despite its safety profile, the treatment showed no objective responses, with the majority of patients experiencing disease progression, indicating that it is ineffective for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II trial of tegafur-uracil plus leucovorin (LV) in the treatment of advanced biliary tract carcinomas. Chen, JS., Yang, TS., Lin, YC., et al.[2019]

Bictegravir (BIC) is a highly effective integrase strand-transfer inhibitor for treating HIV-1, showing rapid absorption and high cumulative dose recovery in both humans (95.3%) and nonclinical species (>80%).

BIC has a favorable pharmacokinetic and metabolic profile, with minimal clinically relevant drug-drug interactions, making it a promising option compared to other integrase inhibitors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Human and nonclinical disposition of [14C]bictegravir, a potent integrase strand-transfer inhibitor for the treatment of HIV-1 infection. Subramanian, R., Ling, J., Wang, J., et al.[2023]

The single-tablet regimen (STR) of bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) has shown non-inferior virological efficacy compared to traditional dolutegravir-based regimens in treating HIV, based on large clinical trials over 96 weeks.

BIC/FTC/TAF is designed to be highly tolerable and has a high barrier against drug resistance, making it a promising option for managing HIV while also addressing associated comorbidities like cardiovascular disease and renal impairment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The potential role of bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) single-tablet regimen in the expanding spectrum of fixed-dose combination therapy for HIV. Stellbrink, HJ., Lazzarin, A., Woolley, I., et al.[2021]

Bictegravir (BIC) combined with emtricitabine (FTC) and tenofovir alafenamide (TAF) in the fixed-dose regimen Biktarvy® has been shown to be as effective as other leading HIV treatments, making it a strong option for initial and long-term therapy.

Biktarvy® has a high barrier to drug resistance and limited drug-drug interactions, which enhances its safety profile and makes it a recommended choice in recent HIV treatment guidelines.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biktarvy for the treatment of HIV infection: Progress and prospects. De Clercq, E., Zhang, Z., Huang, J., et al.[2023]

Bictegravir (BIC) is an effective integrase strand-transfer inhibitor used in the treatment of HIV-1, showing low potential for drug-drug interactions due to its metabolism primarily through CYP3A and UDP-glucuronosyltransferase 1A1 enzymes.

Phase 1 studies in healthy subjects confirmed the predicted pharmacokinetics of BIC, indicating that the methods used for predicting its behavior in humans could be beneficial for other drugs with similar challenges.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Human pharmacokinetics prediction with an in&#160;vitro-in&#160;vivo correction factor approach and in&#160;vitro drug-drug interaction profile of bictegravir, a potent integrase-strand transfer inhibitor component in approved biktarvy&#174; for the treatment of HIV-1 infection. Subramanian, R., Wang, J., Murray, B., et al.[2023]

The Phase Ib ABC-08 study indicated that the combination of NUC-1031 and cisplatin may be more effective than the standard gemcitabine/cisplatin treatment for advanced biliary tract cancer, prompting further investigation in the larger NuTide:121 study.

The upcoming NuTide:121 study will involve 828 patients with untreated advanced biliary tract cancer, comparing the efficacy and safety of NUC-1031/cisplatin against the standard treatment, with primary goals of overall survival and response rates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

NUC-1031/cisplatin versus gemcitabine/cisplatin in untreated locally advanced/metastatic biliary tract cancer (NuTide:121). McNamara, MG., Goyal, L., Doherty, M., et al.[2022]

Bictegravir (BIC) is a highly effective second-generation HIV treatment that shows strong antiviral activity against both wild-type and resistant strains, with virologic suppression rates comparable to first-line therapies in clinical trials.

BIC has a high genetic barrier to resistance, can be taken once daily due to its long half-life of 18 hours, and is generally well tolerated, with only mild side effects like diarrhea, nausea, and headache.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bictegravir, a novel integrase inhibitor for the treatment of HIV infection. Zeuli, J., Rizza, S., Bhatia, R., et al.[2021]

Biktarvy has shown efficacy in real-world clinical practice that is comparable to results from phase III trials, indicating it is effective for treating HIV-1 infection.

However, real-world studies reported higher rates of adverse effects and discontinuation compared to clinical trials, highlighting the need for further research on diverse populations, including women and ethnic minorities.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy, safety and tolerability of Biktarvy in HIV-1 infection: A scoping review. Peters, E., Iwuji, AC.[2023]

In a phase 2 study involving 35 women with recurrent epithelial ovarian cancer, the combination of belinostat, carboplatin, and paclitaxel showed a promising overall response rate of 43%, indicating potential efficacy in heavily-pretreated patients.

The treatment was generally well tolerated, with common side effects including nausea (83%) and fatigue (74%), and a 6-month progression-free survival rate of 48%, suggesting that this combination therapy could be a viable option for patients with challenging cases of ovarian cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II activity of belinostat (PXD-101), carboplatin, and paclitaxel in women with previously treated ovarian cancer. Dizon, DS., Damstrup, L., Finkler, NJ., et al.[2018]

The combination of nab-paclitaxel and S-1 demonstrated a 27.5% objective response rate in patients with advanced biliary tract carcinoma, indicating significant antitumor activity, especially in gallbladder carcinoma (53.8% response).

The treatment showed a favorable safety profile, with the most common severe side effects being neutropenia and stomatitis, and median progression-free survival and overall survival were 6.0 months and 13.2 months, respectively.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nab-paclitaxel plus tegafur gimeracil oteracil potassium capsule (S-1) as first-line treatment for advanced biliary tract adenocarcinoma: a phase 2 clinical trial. Zhang, W., Sun, Y., Jiang, Z., et al.[2023]

Citations

1. gilead.com gilead.com/news/news-details/2024/gilead-presents-research-data-across-its-broad-and-innovative-hiv-treatment-portfolio-and-pipeline

Gilead Presents Research Data Across Its Broad and ... The 24-week primary efficacy and safety outcomes for bictegravir + lenacapavir in people with HIV who are virologically suppressed on a ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39589133/

Efficacy and Safety of Switching to Daily Bictegravir Plus ... Efficacy and safety outcomes were evaluated after a switch to bictegravir (BIC) (75-mg) + lenacapavir (LEN) (25- or 50-mg) regimens ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05502341

NCT05502341 | Study to Compare Bictegravir/Lenacapavir ... The goal of this clinical study is to learn more about the effects of switching to the study drugs, bictegravir (BIC) plus lenacapavir (LEN), versus current ...

4. pharmacytimes.com pharmacytimes.com/view/new-data-on-hiv-1-treatments-including-biktarvy-and-novel-lenacapavir-combination-regimen-presented-at-croi-2025

New Data on HIV-1 Treatments, Including Biktarvy and ... Lenacapavir with bNAbs showed promising results in a phase 2 trial, achieving effective virologic suppression with no serious adverse events, ...

5. idse.net idse.net/HIV-AIDS/Article/02-25/Promising-Results-HIV-Care-Lenacapavir-and-Bictegravir/76279

Promising Results HIV Care Lenacapavir and Bictegravir Late-breaking clinical data from a pair of studies funded by Gilead Sciences show promising results for products aimed at addressing unmet needs in HIV care.

6. askgileadmedical.com askgileadmedical.com/docs/sunlenca/sunlenca-safety-overview

For HCP's | Sunlenca® (lenacapavir) Safety Overview This document is in response to your request for information regarding the safety of Sunlenca® (lenacapavir [LEN]) in people with HIV-1 (PWH).

7. withpower.com withpower.com/trial/phase-3-human-immunodeficiency-virus-type-1-hiv-1-infection-2-2024-9a0d5

Bictegravir + Lenacapavir for HIV (ARTISTRY-2 Trial) Bictegravir (BIC), a component of Biktarvy, has been shown to be well-tolerated with main adverse effects including diarrhea, nausea, and headache. Real-world ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10786069/

lenacapavir + bictegravir as a potential treatment for HIV In early clinical trials, the therapeutic combination of BIC/LEN, an INSTI and a HIV-1 capsid inhibitor, is well-tolerated and has been shown to be an effective ...