GILEAD Study

GILEAD Study: A Phase 2/3, Open-Label Study of the Pharmacokinetics, Safety, and Antiviral Activity of the GS-9883/Emtricitabine/Tenofovir Alafenamide (GS-9883/F/TAF) Fixed Dose Combination (FDC) in HIV-1 Infected Adolescents and Children.

Study Rationale

The advent of Highly Active Antiretroviral Therapy (HAART) and the benefits of maximally suppressed viremia have transformed HIV treatment, shifting focus towards agents that optimize long-term safety and tolerability. While there are over 20 different ARV agents available for adults, adolescents and children with HIV infection face limited treatment options. Given that these young patients often require lifelong therapy, it is critical to develop effective, well-tolerated, and easily administered antiretroviral (ARV) regimens.

This study investigates the GS-9883/F/TAF fixed-dose combination (FDC) for adolescents and children, addressing the need for simplified regimens that combine efficacy, tolerability, and a favorable safety profile. The GS-9883/F/TAF FDC regimen, leveraging the unique metabolism of TAF, offers a promising solution with potentially lower toxicity compared to tenofovir disoproxil fumarate (TDF), which is associated with nephrotoxicity and decreased bone mineral density (BMD).

The study aims to evaluate the pharmacokinetics (PK), safety, tolerability, and antiviral activity of the GS-9883/F/TAF FDC in pediatric populations, addressing the unmet need for ARV regimens with validated pediatric dosing and simplified, once-daily formulations to improve adherence and clinical outcomes.

Primary Objectives

1. Cohorts 1 and 2:
   • Evaluate the steady-state PK of BIC and confirm the dose of the B/F/TAF 50/200/25 mg FDC in HIV-1 infected adolescents (12 to <18 years) and children (6 to <12 years).
   • Assess the safety and tolerability of the adult-strength B/F/TAF FDC through Week 24 in virologically suppressed adolescents and children.
2. Cohort 3:
   • Evaluate the steady-state PK of BIC and confirm the dose of B/F/TAF 30/120/15 mg FDC in HIV-1 infected children ≥2 years of age, weighing ≥14 to <25 kg.
   • Assess the safety and tolerability of the low-dose B/F/TAF FDC tablet through Week 24 in these children.
3. Cohort 4 (Group 1):
   • Assess the safety and tolerability of B/F/TAF 30/120/15 mg FDC in children ≥2 years of age, weighing ≥14 to <25 kg, unable to swallow tablets, through Week 24.
4. Cohort 4 (Group 2):
   • Evaluate the steady-state PK of BIC and TAF and confirm the dose of B/F/TAF 7.5/30/3.75 mg in HIV-1 infected children ≥1 month, weighing ≥10 to <14 kg.

Secondary Objectives

• Evaluate the safety, tolerability, and antiviral activity of B/F/TAF FDC through Weeks 24 and 48 for all cohorts, with a focus on minimizing virologic failure, improving long-term adherence, and optimizing treatment safety for children and adolescents.

Investigators

• Dr Muneerah Khan, Principal-Investigator
• Prof Lee Fairlie, Sub- Investigator
• Dr Faeezah Patel, Sub-Investigator
• Dr Elizea Horne, Sub-Investigator
• Dr Mrinmayee Dhar, Sub-Investigator
• Tiffany Seef, Clinical Associate
• Othusitse Segalo, Clinical Associate

Study Sites

The study will be conducted at multiple sites globally, with Wits RHI collaborating with various centers specializing in HIV treatment and pediatric care. The study will involve renowned experts in pediatric HIV treatment and pharmacokinetics, ensuring robust data collection and analysis.

Latest Update

March 2024

For more details about Gilead Study please email rhicomms@wrhi.ac.za