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

Recruiting at 15 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

129 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests a single pill combining four HIV medications in adolescents and children. It aims to find the right dose and ensure safety for those new to treatment and those already on it. The pill works by stopping the virus from growing and spreading.

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.

What data supports the effectiveness of the drug Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide (E/C/F/TAF) for HIV-1 infection?

Research shows that E/C/F/TAF is effective in treating HIV-1, with studies demonstrating high rates of treatment success and better safety outcomes for bones and kidneys compared to older regimens. It has been shown to maintain viral suppression in both treatment-naïve and experienced patients, including those with renal impairment. ^{1 2 3 4 5}

Is E/C/F/TAF safe for humans?

E/C/F/TAF is generally considered safe for humans, with studies showing improved kidney and bone safety compared to older treatments. However, there may be interactions with calcium-containing products, so it's important to discuss all medications and supplements with a healthcare provider. ^{1 3 4 6 7}

How is the drug E/C/F/TAF unique for treating HIV-1 infection?

E/C/F/TAF is unique because it includes tenofovir alafenamide (TAF), which is safer for the kidneys and bones compared to the older version, tenofovir disoproxil fumarate (TDF). This drug is a once-daily single tablet regimen, making it convenient for patients, and it has shown superior efficacy and safety in long-term studies. ^{1 2 4 5 7}

Research Team

Gilead Study Director

Principal Investigator

Gilead Sciences

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Efficacy and safety of co-formulated elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide in HIV-positive patients: real-world data. [2021]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Rare emergence of drug resistance in HIV-1 treatment-naïve patients receiving elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide for 144 weeks. [2019]

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

Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide: A Review in HIV-1 Infection. [2021]

4. United States 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. [2021]

5. England pubmed.ncbi.nlm.nih.gov

Elvitegravir, cobicistat, emtricitabine and tenofovir alafenamide for the treatment of HIV in adults. [2021]

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

Brief Report: Efficacy and Safety of Switching to a Single-Tablet Regimen of Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide in HIV-1/Hepatitis B-Coinfected Adults. [2022]

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

HIV Viral Rebound Due to a Possible Drug-Drug Interaction between Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide and Calcium-Containing Products: Report of 2 Cases. [2021]