Bictegravir + Lenacapavir for HIV

(ARTISTRY-1 Trial)

Recruiting at 98 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

689 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing two HIV medications, bictegravir and lenacapavir, either separately or combined into one pill. It aims to see if these new treatments work better than current therapies for people living with HIV. These drugs help control HIV by stopping the virus from making more copies of itself. Bictegravir is a newly approved medication combined with other drugs, while lenacapavir is a long-acting medication recently approved in the EU.

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 Bictegravir (BIC) safe for humans?

Bictegravir (BIC), 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 still considered safe for treating HIV. ^{1 2 3 4 5}

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

Bictegravir + Lenacapavir is unique because it combines two potent antiretroviral drugs, offering a high barrier to resistance and potentially simplifying treatment with fewer pills, which can improve adherence and outcomes for people living with HIV. ^{6 7 8 9 10}

Research Team

Gilead Study Director

Principal Investigator

Gilead Sciences

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

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]

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]

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]

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]

References

1. Spain pubmed.ncbi.nlm.nih.gov

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

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

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

3. 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]

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

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

5. 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]

6. 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]

7. 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]

8. England pubmed.ncbi.nlm.nih.gov

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

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

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

10. 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]