Bictegravir + Lenacapavir for HIV
Recruiting in Palo Alto (17 mi)
+19 other locations
Age: < 18
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 2 & 3
Recruiting
Sponsor: Gilead Sciences
Must be taking:Complex ARV regimen
Disqualifiers: Low CD4 count, Hepatitis B, others
No Placebo Group
Prior Safety Data
Breakthrough Therapy
Approved in 4 jurisdictions
Trial Summary
What is the purpose of this trial?The goal of this clinical study is to learn about the safety and tolerability of bictegravir/lenacapavir (BIC/LEN) and to learn how the study drug interacts with the body in virologically suppressed (VS) children and adolescents with human immunodeficiency virus type 1 (HIV-1) on a stable and complex antiretroviral (ARV) regimen. The study will also assess the safe loading dose of LEN and pharmacokinetics (PK) of BIC/LEN.
The primary objectives of this study are:
* To evaluate the steady-state PK of BIC and LEN and confirm the dose of the LEN loading dose and BIC/LEN FDC in VS children and adolescents with HIV-1.
* To evaluate the safety and tolerability of BIC/LEN through Week 24 in VS children and adolescents with HIV-1.
Will I have to stop taking my current medications?
The trial does not specify if you need to stop your current medications, but it mentions that participants must be on a complex antiretroviral regimen. This suggests you may need to continue your current HIV treatment.
What data supports the effectiveness of the drug Bictegravir/Lenacapavir for HIV?
Bictegravir, a component of Biktarvy, has been shown to be effective in treating HIV-1 infection, both in patients new to treatment and those switching therapies, with studies indicating it is as effective as other similar drug combinations. It is recommended as a preferred treatment option in HIV guidelines due to its high barrier to resistance and limited drug interactions.
12345Is Bictegravir + Lenacapavir safe for 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 for treating HIV. There is no specific safety data available for the combination of Bictegravir and Lenacapavir.
12567What makes the drug Bictegravir/Lenacapavir unique for treating HIV?
Bictegravir/Lenacapavir is unique because it combines two potent components: bictegravir, a novel integrase strand transfer inhibitor (INSTI) with high resistance to mutations, and lenacapavir, which is being explored for its potential long-acting effects. This combination aims to provide a more resilient and possibly longer-lasting treatment option for HIV compared to existing therapies.
13568Eligibility Criteria
This trial is for children and adolescents with HIV-1 who are virologically suppressed on a complex ARV regimen. It includes three age-based cohorts: 12-18 years weighing ≥35kg, 6-12 years weighing ≥25 to <35kg, and 2-6 years weighing ≥10 to <25kg. Participants must have no resistance to certain HIV medications and meet specific health criteria like adequate neutrophil count and hemoglobin levels.Inclusion Criteria
Age and body weight at screening: Cohort 1: ≥ 12 years to < 18 years weighing ≥ 35 kg, Cohort 2: ≥ 6 years to < 12 years weighing ≥ 25 kg to < 35 kg, Cohort 3: ≥ 2 years to < 6 years weighing ≥ 10 kg to < 25 kg
My HIV-1 RNA levels have been undetectable or very low in the last 6 months.
My HIV does not have resistance to certain HIV medications.
I take more than one pill a day for HIV treatment.
Exclusion Criteria
I have hepatitis C with detectable virus levels.
I do not have severe liver problems or current issues with alcohol or substance use.
Participant Groups
The study tests the safety, tolerability, and body interaction of a combined drug bictegravir/lenacapavir (BIC/LEN) in children and adolescents with stable but complex anti-HIV treatment regimens. The trial aims to confirm appropriate dosing of LEN as well as understand how BIC/LEN works over time within the body.
3Treatment groups
Experimental Treatment
Group I: Cohort 3: Participants Aged ≥ 2 to < 6 years with Weight ≥ 10 kg to < 25 kgExperimental Treatment2 Interventions
All participants will receive a 2-day oral loading dose of LEN, and daily oral BIC and LEN dose starting on Day 1 through Week 48. Dose in cohort 3 to be defined.
Following Week 48, participants will have an option to continue BIC/LEN in the extension period.
Group II: Cohort 2: Participants Aged ≥ 6 to < 12 years with Weight ≥ 25 kg to < 35 kgExperimental Treatment2 Interventions
All participants will receive a 2-day oral loading dose of LEN, and daily oral BIC and LEN dose starting on Day 1 through Week 48. Dose in cohort 2 to be defined.
Following Week 48, participants will have an option to continue BIC/LEN in the extension period.
Group III: Cohort 1: Participants Aged ≥ 12 to < 18 years with Weight ≥ 35 kg: BIC/LEN 75/50 mg FDCExperimental Treatment2 Interventions
Participants will receive a 2-day oral loading dose of LEN (600 mg) on Days 1 and 2 and daily oral BIC/LEN 75/50 mg starting on Day 1 through Week 48.
Following Week 48, participants will have an option to continue BIC/LEN in the extension period.
Bictegravir/Lenacapavir is already approved in United States, European Union, United States, European Union for the following indications:
🇺🇸 Approved in United States as Biktarvy (bictegravir component) for:
- HIV-1 infection treatment in adults
🇪🇺 Approved in European Union as Biktarvy (bictegravir component) for:
- HIV-1 infection treatment in adults
🇺🇸 Approved in United States as Sunlenca (lenacapavir component) for:
- HIV-1 infection treatment for heavily treatment-experienced adults with multidrug-resistant HIV-1 infection
🇪🇺 Approved in European Union as Sunlenca (lenacapavir component) for:
- HIV-1 infection treatment for heavily treatment-experienced adults with multidrug-resistant HIV-1 infection
Find A Clinic Near You
Research locations nearbySelect from list below to view details:
University of South FloridaTampa, FL
Ann and Robert H. Lurie Children's Hospital of ChicagoChicago, IL
Children's National HospitalWashington, United States
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Who is running the clinical trial?
Gilead SciencesLead Sponsor
References
Bictegravir: First Global Approval. [2022]Gilead Sciences has developed a single tablet anti-HIV-1 medication (Biktarvy®) combining the novel integrase strand transfer inhibitor (INSTI) bictegravir with the nucleos(t)ide reverse transcriptase inhibitors (NRTIs) emtricitabine and tenofovir alafenamide. This fixed dose combination has demonstrated efficacy as treatment for both anti-retroviral naïve and virologically suppressed HIV-1 infection in patients switching therapy, and was recently approved in the USA. This article summarizes the milestones in the development of bictegravir leading to this first approval of bictegravir/emtricitabine/tenofovir alafenamide as treatment for HIV-1 infection.
Efficacy, safety and tolerability of Biktarvy in HIV-1 infection: A scoping review. [2023]Background: Biktarvy is approved for use in HIV-1 infection in both treatment-naïve and treatment-experienced individuals, after a series of successful phase III trials. However, studies on real-world evidence on its efficacy, safety and tolerability are limited. Purpose: The study aims to collate real-world evidence on the use of Biktarvy in clinical practice to identify gaps in knowledge. Research Design: Scoping review was undertaken using PRISMA guidelines and a systematic search strategy. The final search strategy used was (Bictegravir* OR biktarvy) AND (efficac* OR safe* OR effect* OR tolerab* OR 'side effect*' OR 'adverse effect*'). The last search was performed on the 12th of August 2021. Study Sample: Studies were eligible if they reported on the efficacy, effectiveness, safety or tolerability of bictegravir-based ART. Data Collection and/or Analysis: Data were collected from 17 studies that met the inclusion and exclusion criteria and summarised using a narrative synthesis. Results: The efficacy of Biktarvy in clinical practice is comparable to phase III trials. However, adverse effects and discontinuation rates were found to be higher in real-world studies. Conclusions: The cohorts in the included real-world studies showed more demographic diversity when compared to the drug approval trials, further prospective studies are required on under-represented groups such as women, pregnant people, ethnic minorities and older adults.
Bictegravir combined with emtricitabine and tenofovir alafenamide versus dolutegravir, abacavir, and lamivudine for initial treatment of HIV-1 infection: week 96 results from a randomised, double-blind, multicentre, phase 3, non-inferiority trial. [2022]Bictegravir co-formulated with emtricitabine and tenofovir alafenamide as a fixed-dose combination is recommended for treatment of HIV-1-infection and might be better tolerated than other integrase inhibitor-based single-tablet regimens, but long-term outcomes data are not available. We assessed the efficacy, safety and tolerability of bictegravir, emtricitabine, and tenofovir alafenamide compared with co-formulated dolutegravir, abacavir, and lamivudine at week 96.
Fixed-dose combination bictegravir, emtricitabine, and tenofovir alafenamide in adolescents and children with HIV: week 48 results of a single-arm, open-label, multicentre, phase 2/3 trial. [2021]Bictegravir is a potent integrase strand-transfer inhibitor (INSTI) with a high genetic barrier to resistance. Bictegravir, coformulated with emtricitabine and tenofovir alafenamide, is recommended by key European and US HIV treatment guidelines as the preferred single-tablet regimen for adults and adolescents. The aim of this study was to assess the pharmacokinetics, safety, and efficacy of switching to this regimen in virologically suppressed children and adolescents with HIV.
Biktarvy for the treatment of HIV infection: Progress and prospects. [2023]Bictegravir (BIC), a second-generation integrase strand-transfer inhibitor (INSTI) with high resilience to INSTI-resistance mutations, is integrated as a key component of Biktarvy® - a fixed-dose once-daily triple-drug regimen of bictegravir (BIC), emtricitabine (FTC) plus tenofovir alafenamide (TAF). Based on the accumulated evidence from HIV clinical trials and real-world studies, the clinical effectiveness of BIC + FTC + TAF has been proven non-inferior to other fixed-dose once-daily combinations such as dolutegravir + FTC + TAF and dolutegravir + abacavir + lamivudine. Biktarvy also shows limited drug-drug interactions and a high barrier to drug resistance. According to recent HIV guidelines, BIC + FTC + TAF is recommended as initial and long-term therapy for the treatment of HIV infection. For the pre-exposure prophylaxis, tenofovir disoproxil fumarate (TDF) or tenofovir alafenamide (TAF) remains advisable, but BIC may be possibly added to TDF or TAF. In the development of a long-acting once-monthly regimen, the novel nano-formulation of BIC + FTC + TAF could be possibly developed in the future.
Human and nonclinical disposition of [14C]bictegravir, a potent integrase strand-transfer inhibitor for the treatment of HIV-1 infection. [2023]Bictegravir (BIC) is a potent small-molecule integrase strand-transfer inhibitor (INSTI) and a component of Biktarvy®, a single-tablet combination regimen that is currently approved for the treatment of human immunodeficiency virus type 1 (HIV-1) infection. The absorption, metabolism, distribution, and elimination (ADME) characteristics of BIC were determined through in vivo nonclinical and clinical studies (IND 121318).[14C]BIC was rapidly absorbed orally in mice, rats, monkeys and human. The cumulative dose recovery was high in nonclinical species (>80%) and humans (95.3%), with most of the excreted dose recovered in faeces. Quantifiable radioactivity with declining concentration was observed in rat tissues suggesting reversible binding. Unchanged BIC was the most abundant circulating component in all species along with two notable metabolites M20 (a sulphate conjugate of hydroxylated BIC) and M15 (a glucuronide conjugate of BIC). BIC was primarily eliminated by hepatic metabolism followed by excretion of the biotransformed products into faeces. In vitro drug-drug interaction (DDI) studies with M15 and M20 demonstrated that no clinically relevant interactions were expected.Overall, BIC is a novel and potent INSTI with a favourable resistance, PK, and ADME profile that provides important improvements over other currently available INSTIs for the treatment of HIV-1.
Bictegravir, a novel integrase inhibitor for the treatment of HIV infection. [2021]Bictegravir (BIC), a second-generation integrase strand transfer inhibitor (INSTI) approved for HIV treatment in fixed-dose combination with emtricitabine and tenofovir alafenamide, has potent antiviral activity in vitro to wild-type virus and strains with resistance to first-generation INSTIs. As part of combination therapy, BIC's virologic suppression rates in clinical trials are comparable to those of first-line combination antiretroviral drug regimens. BIC has demonstrated a high genetic barrier to resistance development in vitro, can be administered with or without food, and has a bioavailability of > 70%. A median plasma half-life of 18 hours allows once-daily dosing. Clearance is primarily hepatic through cytochrome P450 3A4 (CYP3A4) oxidation and UDP-glucuronosyltransferase 1A1 (UGT1A1) glucuronidation. Thus, potent inducers of UGT1A1 and CYP3A4 (e.g., rifamycins/anticonvulsants) should be avoided due to significantly decreased BIC serum exposure. Chelation with polyvalent cations can decrease absorption; otherwise, drug-drug interactions are few. BIC is well tolerated; diarrhea, nausea and headache are the main adverse effects associated with its use.
[Effectiveness, safety, and economic impact of the bictegravir/emtricitabine/tenofovir alafenamide regimen in real clinical practice cohort of HIV-1 infected adult patients]. [2021]Among the new antiretroviral treatment (ART) regimens, bictegravir (BIC) stands out, a recently incorporated integrase inhibitor. BIC conjugated with emtricitabine (FTC) and tenofovir alafenamide (TAF) has been shown to be non-inferior in efficacy as initiation therapy in a single daily dose regimen compared to other initiation ART. The objective of our study is to evaluate the impact of the inclusion of this new ART scheme in real clinical practice.