Bictegravir + Lenacapavir for HIV

(ARTISTRY-2 Trial)

Recruiting at 105 trial locations

Overseen By Gilead Clinical Study Information Center

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Gilead Sciences

Must be taking: B/F/TAF

Must not be taking: LEN

Disqualifiers: Pregnancy, Breastfeeding, Active infections, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: Unknown

577 Participants Needed

Trial Summary

What is the purpose of this trial?

The goal of this clinical study is to learn more about the effects of switching to the study drugs, bictegravir (BIC)/lenacapavir (LEN), fixed-dose combination (FDC) versus current therapy bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) FDC in people living with HIV-1 (PWH). The primary objective of this study is to learn how effective it is to switch to BIC/LEN FDC tablets versus continuing on B/F/TAF FDC tablets in virologically suppressed PWH.

Do I have to stop taking my current medications for this trial?

The trial requires participants to switch from their current B/F/TAF medication to the study drugs BIC/LEN. If you are on B/F/TAF, you will need to stop taking it to participate in the trial.

Will I have to stop taking my current medications?

The trial requires participants to switch from their current B/F/TAF medication to the study drugs BIC/LEN. If you are taking other medications, the protocol does not specify if you need to stop them, but you should discuss this with the study team.

What data supports the idea that Bictegravir + Lenacapavir for HIV is an effective drug?

The available research does not provide any data on Bictegravir + Lenacapavir for HIV. Instead, it focuses on treatments for advanced biliary tract cancer, so there is no information here to support the effectiveness of Bictegravir + Lenacapavir for HIV. ^{1 2 3 4 5}

What safety data exists for Bictegravir and Lenacapavir in HIV treatment?

Bictegravir (BIC), a component of Biktarvy, has been shown to be well-tolerated with main adverse effects including diarrhea, nausea, and headache. Real-world studies indicate higher adverse effects and discontinuation rates compared to clinical trials. BIC has a high genetic barrier to resistance and limited drug-drug interactions. Lenacapavir, marketed as Sunlenca, is not specifically mentioned in the provided research, so its safety data is not covered here. ^{6 7 8 9 10}

What safety data exists for Bictegravir and Lenacapavir in humans?

Bictegravir, a component of Biktarvy, is generally well tolerated in humans, with common side effects including diarrhea, nausea, and headache. Real-world studies have shown higher rates of adverse effects and discontinuation compared to clinical trials, but it is considered safe with limited drug interactions. There is no specific safety data for Lenacapavir in the provided research articles. ^{6 7 8 9 10}

Is the drug Bictegravir, Lenacapavir a promising treatment for HIV?

Yes, Bictegravir, Lenacapavir is a promising drug for HIV because it is part of a single-tablet regimen that is safe, effective, and easy to take. It helps improve the lives of people with HIV by addressing other health issues they might face, like heart disease or bone problems, and has a strong ability to fight the virus without developing resistance. ^{1 3 11 12 13}

What makes the drug Bictegravir + Lenacapavir unique for treating HIV?

Bictegravir + Lenacapavir is unique because it combines a novel integrase strand transfer inhibitor (Bictegravir) with a long-acting formulation (Lenacapavir), potentially allowing for less frequent dosing compared to standard daily regimens. This combination aims to improve adherence and reduce the risk of drug resistance, offering a new approach to HIV treatment. ^{6 7 8 9 14}

Research Team

Gilead Study Director

Principal Investigator

Gilead Sciences

Eligibility Criteria

This trial is for people with HIV-1 who have been successfully treated with Biktarvy (B/F/TAF) for at least 6 months, have undetectable viral loads (<50 copies/mL), and adequate kidney function. They must not have resistance to the drugs Bictegravir or Tenofovir Alafenamide.

Inclusion Criteria

Plasma HIV-1 RNA levels < 50 copies/mL at screening

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

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

Exclusion Criteria

Positive serum pregnancy test or pregnant at screening or a positive pregnancy test prior to Day 1 randomization

Participation or planned participation in any other clinical study without prior approval from the sponsor

Abnormal laboratory values at screening

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Blinded Treatment

Participants switch to BIC/LEN FDC tablets or continue B/F/TAF FDC tablets with placebo-to-match for the other treatment

Until end of blinded treatment visit

Open-label Phase

Participants receive BIC/LEN FDC tablets through Week 48, with an option to continue until the conclusion of the OL Phase

48 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Bictegravir
• Lenacapavir

Trial Overview The study compares a new combination of HIV medications, Bictegravir/Lenacapavir (BIC/LEN), against the current therapy of Biktarvy (B/F/TAF). It aims to see if switching treatments maintains virus suppression in people with HIV.

Participant Groups

Group I: Treatment Group 2: B/F/TAF (50/200/25 mg) + PTM BIC/LEN Experimental Treatment 4 Interventions

Blinded Phase: Participants will continue with their B/F/TAF (50/200/25 mg) FDC tablets and start PTM BIC/LEN tablets on Day 1. Participants will receive PTM LEN tablets for 2 days (2 PTM LEN tablets on Day 1 and on Day 2. The blinded phase will continue until the EBT visit. Open Label Phase: Participants in Treatment Group 2 who complete the EBT visit will be given the option to enter the OL phase to receive BIC/LEN FDC tablets until the conclusion of the OL Phase.

Group II: Treatment Group 1: Bictegravir (BIC)/ Lenacapavir (LEN) (75/50 mg) + PTM B/F/TAF Experimental Treatment 3 Interventions

Blinded Phase: Participants will switch from bictegravir/emtricitabine/tenofovir (B/F/TAF) FDC tablets to BIC/LEN (75/50 mg) FDC tablets and placebo-to-match (PTM) B/F/TAF. Participants will receive a 2-day oral loading dose of LEN 600 mg on Day 1 and on Day 2, in addition to the daily doses of BIC/LEN FDC tablet starting on Day 1 up to end of blinded treatment (EBT) visit. Open-label (OL) Phase: Following treatment in the Blinded Phase, participants from Treatment Group 1 will receive BIC/LEN FDC tablets through Week 48 in the Open-label Phase. At the OL Week 48 visit, participants from Treatment Group 1 will be given the option to continue to receive BIC/LEN FDC tablets until the conclusion of the OL Phase.

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

Findings from Research

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]

In a study of 33 patients with relapse and unresectable biliary tract cancer treated with S-1 after failing gemcitabine, the neutrophil-lymphocyte ratio (NLR) and prognostic nutritional index (PNI) were identified as significant poor prognostic factors for overall survival.

Changes in the PNI from the start of S-1 treatment to the end were significantly associated with therapeutic efficacy, suggesting that monitoring PNI could help predict treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Evaluation of Prognostic Factors in Patients with Relapse and Unresectable Biliary Tract Cancer, Treated with S-1 after Failure of Gemcitabine]. Nakai, M., Kikkawa, A., Funahara, H., et al.[2022]

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]

In a phase I study involving 19 patients with advanced solid tumors, the combination of vinorelbine and gemcitabine was found to be feasible and well-tolerated, with a recommended dose of vinorelbine 30 mg/m² and gemcitabine 2500 mg/m² administered biweekly.

The treatment showed promising clinical activity, with an overall response rate of 31%, including one complete response and four partial responses among the 16 evaluable patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biweekly vinorelbine and gemcitabine: a phase I dose-finding study in patients with advanced solid tumors. Castellano, D., Hitt, R., Ciruelos, E., et al.[2022]

A modified biweekly regimen of cisplatin and gemcitabine in 107 patients with advanced biliary tract cancer showed a median overall survival of 10.32 months and a median progression-free survival of 8.34 months, indicating maintained efficacy.

This biweekly treatment resulted in a more favorable toxicity profile, with the most common severe side effects being neutropenia (11%) and fatigue (10%), suggesting that it may allow for prolonged treatment with fewer adverse effects compared to traditional weekly regimens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biweekly cisplatin and gemcitabine in patients with advanced biliary tract cancer. Ahn, DH., Reardon, J., Ahn, CW., et al.[2022]

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]

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]

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]

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]

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]

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]

Biktarvy®, a single tablet combining bictegravir, emtricitabine, and tenofovir alafenamide, has shown efficacy in treating both treatment-naïve and virologically suppressed HIV-1 patients, leading to its recent approval in the USA.

The development of bictegravir as an integrase strand transfer inhibitor (INSTI) represents a significant advancement in HIV treatment, providing a convenient fixed-dose option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bictegravir: First Global Approval. Markham, A.[2022]

References

1. China (Republic : 1949- ) 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. [2023]

2. Japan pubmed.ncbi.nlm.nih.gov

[Evaluation of Prognostic Factors in Patients with Relapse and Unresectable Biliary Tract Cancer, Treated with S-1 after Failure of Gemcitabine]. [2022]

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

A phase II trial of tegafur-uracil plus leucovorin (LV) in the treatment of advanced biliary tract carcinomas. [2019]

4. England pubmed.ncbi.nlm.nih.gov

Biweekly vinorelbine and gemcitabine: a phase I dose-finding study in patients with advanced solid tumors. [2022]

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

Biweekly cisplatin and gemcitabine in patients with advanced biliary tract cancer. [2022]

6. England 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. [2023]

7. England pubmed.ncbi.nlm.nih.gov

Biktarvy for the treatment of HIV infection: Progress and prospects. [2023]

8. England 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. [2023]

9. Spain pubmed.ncbi.nlm.nih.gov

Bictegravir, a novel integrase inhibitor for the treatment of HIV infection. [2021]

10. England pubmed.ncbi.nlm.nih.gov

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

11. England 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. [2021]

12. England pubmed.ncbi.nlm.nih.gov

NUC-1031/cisplatin versus gemcitabine/cisplatin in untreated locally advanced/metastatic biliary tract cancer (NuTide:121). [2022]

13. England pubmed.ncbi.nlm.nih.gov

Phase II activity of belinostat (PXD-101), carboplatin, and paclitaxel in women with previously treated ovarian cancer. [2018]

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

Bictegravir: First Global Approval. [2022]