Gilead Sciences, a biopharmaceutical company based in Foster City, Calif., has initiated the first of two phase III clinical trials (Study 104) evaluating a single tablet regimen containing tenofovir alafenamide (TAF) for the treatment of HIV-1 infection in treatment-naïve adults.
TAF is a novel prodrug of tenofovir, the active agent in Viread (tenofovir disoproxil fumarate). The phase III studies will examine a once-daily single tablet regimen of TAF 10mg, elvitegravir 150mg, cobicistat 150mg, emtricitabine 200mg compared to Gilead's Stribild (elvitegravir 150mg, cobicistat 150mg, emtricitabine 200mg, tenofovir disoproxil fumarate 300mg) among patients new to HIV therapy. The second phase III study (Study 111) will be initiated later this quarter.
"We are pleased to move TAF into phase III clinical research," said Norbert Bischofberger, PhD, executive vice president of R&D and CSO of Gilead Sciences. "We believe that TAF's smaller milligram size has the potential to offer safety and tolerability advantages over existing therapies, and may enable the creation of new single tablet regimens for HIV."
Study 104 and Study 111 are randomized, double-blind, 96-week clinical trials among treatment-naïve HIV-1 infected adults with viral load greater than or equal to 1,000 copies/mL. In each study, a total of 840 patients will be randomized to receive a once-daily tablet containing TAF 10mg, elvitegravir 150mg, cobicistat 150mg, emtricitabine 200mg (n=420) or Stribild (n=420).
The primary endpoint of the studies will be the proportion of patients with viral load <50 copies/mL at 48 weeks of treatment as determined by the FDA-defined snapshot analysis. Secondary endpoints will include the proportion of patients with viral load <20 copies/mL and <200 copies/mL at 48 and 96 weeks of therapy as defined by the FDA snapshot analysis; the proportion of patients with viral load <50 copies/mL at week 48 as defined by the FDA Time to Loss of Virologic Response (TLOVR) analysis; the proportion of patients with viral load <50 copies/mL at week 96 as defined by the FDA snapshot and TLOVR analyses; and change from baseline in CD4+ cell count at weeks 48 and 96.
The studies will include patients with impaired renal function and who have an estimated glomerular filtration rate between 50mL/mn and 90mL/mn (according to the Cockcroft-Gault formula). Bone mineral density will be assessed for all patients by DEXA scans at baseline and every 24 weeks. After week 96, patients will continue to take their blinded study drug until treatment assignments have been unblinded, at which point all will be given the option to participate in an open-label rollover extension and receive the TAF-based single tablet regimen.