E/C/F/TAF for HIV-1 Infection

No longer recruiting at 16 trial locations

Age: < 18

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: Gilead Sciences

Must be taking: Antiretrovirals

Disqualifiers: Hepatitis B, Hepatitis C, Tuberculosis, 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

Duration: 48 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to evaluate the effectiveness and safety of a new HIV treatment for young people. The treatment combines four drugs: Elvitegravir, Cobicistat, Emtricitabine, and Tenofovir Alafenamide (E/C/F/TAF). It is being tested on three groups: adolescents who haven't received HIV treatment, children with controlled HIV, and younger children with controlled HIV. Adolescents who are HIV-positive but untreated, or children with stable HIV without drug resistance, may be suitable candidates. As a Phase 2/3 trial, this study assesses the treatment's effectiveness in a smaller group and represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking HIV treatment advancements.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop your current medications. However, for Cohorts 2 and 3, participants must have been on a stable antiretroviral regimen for at least 6 months before joining the trial.

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

Research shows that the combination treatment Genvoya, which includes elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide (E/C/F/TAF), is generally safe for both adults and children with HIV-1. Studies have tested this treatment in teenagers aged 12 to 18 years, and results indicate it is safe, with most side effects being mild to moderate, such as headaches and diarrhea.

For children aged 6 to 12 years, research also supports the safety of E/C/F/TAF. This age group has tolerated the treatment well, experiencing similar mild side effects.

Furthermore, a low-dose version of the treatment for children as young as 2 years old has shown promising safety results. In these studies, the treatment was generally well-received, with any side effects typically being mild.

Overall, evidence supports that both standard and low doses of E/C/F/TAF are safe for children and teenagers with HIV-1. Extensive research, including studies on patients new to treatment and those with controlled virus levels, backs this conclusion. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide (E/C/F/TAF) is unique because it combines four powerful antiretroviral drugs into a single, once-daily pill. Unlike older HIV treatments that often require multiple pills taken at different times, E/C/F/TAF simplifies the regimen, making it easier for patients to adhere to their treatment. Additionally, Tenofovir Alafenamide (TAF) is a newer form of Tenofovir that is effective at lower doses, which can reduce potential side effects on the kidneys and bones compared to earlier versions. Researchers are excited about E/C/F/TAF because it offers a more convenient and potentially safer option for managing HIV-1, especially in younger populations.

What evidence suggests that this trial's treatments could be effective for HIV-1 infection?

Research has shown that the combination treatment E/C/F/TAF effectively manages HIV-1 infection. In this trial, participants will receive different dosages based on age and weight. For instance, Cohort 3, which includes younger children, will receive a low dose of E/C/F/TAF (90/90/120/6 mg). Studies have found this dosage safe and effective for this age group. Meanwhile, Cohorts 1 and 2, which include older children and teenagers, will receive the regular dose, which has also effectively controlled the virus. Overall, E/C/F/TAF has demonstrated positive results in managing HIV-1 across various age groups in this trial. ^{3 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 HIV-1 infected adolescents who haven't had anti-HIV drugs (12-<18 years, over 35kg) and children both new to treatment (6-<12 years, over 25kg) and those already on a stable regimen without resistance to the study drug components. Excluded are those with hepatitis B/C, recent tuberculosis, or pregnant/lactating females.

Inclusion Criteria

I am 12-17 years old, weigh at least 35 kg, have HIV with specific criteria, and have never used HIV drugs.

I am 6-11 years old, weigh at least 55 lbs, have had undetectable HIV for 6 months, and no resistance to my current HIV treatment.

I am over 2 years old, weigh between 31 and 55 lbs, have had undetectable HIV levels for 6 months, and no resistance to my current HIV treatment.

Exclusion Criteria

My liver is severely damaged and not functioning properly.

Pregnant or lactating females

I have an infection with hepatitis B or C.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive E/C/F/TAF fixed-dose combination once daily

48 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Open-label extension (optional)

Participants may opt into continuation of treatment long-term until certain conditions are met

Long-term

What Are the Treatments Tested in This Trial?

Interventions

• Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide (E/C/F/TAF)
• Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide (E/C/F/TAF) (Low Dose)

Trial Overview The trial tests E/C/F/TAF single tablet regimens at standard and low doses in different age groups. It aims to understand how the body processes the medication (pharmacokinetics), confirm dosing for effectiveness, and assess safety over a period of up to 24 weeks.

How Is the Trial Designed?

Group I: Cohort 3: Age ≥2 Years and Weight ≥ 14 to <25 kg Experimental Treatment 2 Interventions

Virologically suppressed HIV-infected children (≥ 2 years of age weighing ≥ 14 to \< 25 kg) will receive E/C/F/TAF (90/90/120/6 mg) FDC once daily for 48 weeks. Participants who attain a weight of ≥ 25 kg during the course of the study will switch to adult E/C/F/TAF (150/150/200/10 mg) tablets. Participants who complete 48 weeks of study treatment will have the option to receive E/C/F/TAF in an extension phase of the study until: a) the participant turns 18 years old and E/C/F/TAF is commercially available for adults in the country in which the participant is enrolled; b) age-appropriate E/C/F/TAF became commercially available in the country in which the participant is enrolled; or c) Gilead elects to terminate development of E/C/F/TAF in that country.

Group II: Cohort 2: Age 6 to < 12 Years and Weight ≥ 25 kg Experimental Treatment 1 Intervention

Virologically suppressed HIV-infected children (6 to \< 12 years of age weighing ≥ 25 kg) will receive E/C/F/TAF (150/150/200/10 mg) FDC once daily for 48 weeks. Participants who complete 48 weeks of study treatment will have the option to receive E/C/F/TAF in an extension phase of the study until: a) the participant turns 18 years old and E/C/F/TAF is commercially available for adults in the country in which the participant is enrolled; b) age-appropriate E/C/F/TAF become commercially available in the country in which the participant is enrolled; or c) Gilead elects to terminate development of E/C/F/TAF in that country.

Group III: Cohort 1: Age 12 to < 18 Years and Weight ≥ 35 kg Experimental Treatment 1 Intervention

HIV-infected, ARV treatment-naive adolescents (12 to \< 18 years of age weighing ≥ 35 kg) will receive E/C/F/TAF (150/150/200/10 mg) fixed-dose combination (FDC) once daily for 48 weeks. Participants who complete 48 weeks of study treatment will have the option to receive E/C/F/TAF in an extension phase of the study until: a) the participant turns 18 years old and E/C/F/TAF is commercially available for adults in the country in which the participant is enrolled; b) age-appropriate E/C/F/TAF become commercially available in the country in which the participant is enrolled; or c) Gilead elects to terminate development of E/C/F/TAF in that country.

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 242 HIV-1-infected patients with mild to moderate renal impairment, switching to a once-daily regimen of elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) showed no significant change in kidney function after 48 weeks, indicating its safety for this population.

Patients experienced significant improvements in proteinuria and bone mineral density, with 92% maintaining viral suppression, demonstrating the efficacy of E/C/F/TAF without the need for dose adjustments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Switching to Tenofovir Alafenamide, Coformulated With Elvitegravir, Cobicistat, and Emtricitabine, in HIV-Infected Patients With Renal Impairment: 48-Week Results From a Single-Arm, Multicenter, Open-Label Phase 3 Study. Pozniak, A., Arribas, JR., Gathe, J., et al.[2021]

The single tablet regimen elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) is as effective as the traditional TDF-based regimen for treating HIV in naive patients and shows improved efficacy in those switching from TDF-based treatments.

E/C/F/TAF demonstrates significant safety benefits, including improved renal function and bone mineral density compared to TDF, making it a promising option for enhancing the tolerability of HIV treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Elvitegravir, cobicistat, emtricitabine and tenofovir alafenamide for the treatment of HIV in adults. Bonora, S., Calcagno, A., Trentalange, A., et al.[2021]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39476488/

Final 24-month results from the prospective German ... Real-world data confirmed a favorable safety profile and high virologic effectiveness with high treatment satisfaction on F/TAF-based ART.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT02276612?intr=elvitegravir%2Fcobicistat%2Femtricitabine%2Ftenofovir%20alafenamide%20&aggFilters=ages:child&rank=1

Efficacy and Safety of Elvitegravir/Cobicistat/Emtricitabine ... The primary objective of this study is to evaluate the safety and tolerability of elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) in HIV ...

3. tandfonline.com tandfonline.com/doi/full/10.1080/15284336.2019.1589232

Full article: Efficacy and safety of elvitegravir/cobicistat ... Efficacy and safety of elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide in Asian participants with human immunodeficiency virus 1 ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39888251/

Pharmacokinetics, safety and efficacy of elvitegravir ... Elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) was efficacious and well tolerated in children/adolescents with HIV (aged ≥6 years, ...

5. thelancet.com thelancet.com/journals/lancet/article/PIIS0140-6736(15)60616-X/abstract

Tenofovir alafenamide versus tenofovir disoproxil fumarate, ... Patients were randomly assigned (1:1) to receive once-daily oral tablets containing 150 mg elvitegravir, 150 mg cobicistat, 200 mg emtricitabine, and 10 mg ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/30555051/

Safety of elvitegravir, cobicistat, emtricitabine, and tenofovir ... Safety of elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide in HIV-1-infected adults with end-stage renal disease on ...

7. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2016/207561s002lbl.pdf

GENVOYA (elvitegravir, cobicistat, emtricitabine, and tenofovir ... The safety of GENVOYA in HIV-1 infected, treatment-naïve pediatric subjects aged 12 to less than 18 years and weighing at least 35 kg (77 lbs) was evaluated ...

8. ema.europa.eu ema.europa.eu/en/documents/product-information/genvoya-epar-product-information_en.pdf

Genvoya, INN-elvitegravir / cobicistat / emtricitabine / tenofovir ... Based on these limited data, the safety profile of Genvoya in patients with. HIV/HBV co-infection was similar to that in patients with HIV-1 monoinfection.