BACKGROUND: RNA interference (RNAi) provides an attractive tool to modulate biological systems, and ultimately, to treat human diseases. We describe early results from a Phase Ib, first-in-human safety and tolerability study of an RNAi-based therapy, NUC B1000, among patients with mild to moderate chronic HBV. METHODS: Three subjects received a single 5 mg DNA dose of NUC B1000 as part of a planned dose escalation study. RESULTS: All participants reported pharyngitis, chills, myalgia and fever approximately 4-7 h after dosing. All subjects were asymptomatic after a single antipyretic dose with no symptom recurrences. Measurements of interferon (IFN)-α and -γ, interleukin (IL)-10, 12 18, 8 and 6, and tumour necrosis factor-α performed before and after dosing revealed cytokine increases before study drug administration. After drug administration, IFN-γ and IL-10 increased in two patients; IL-8 increased in one. Most increases returned to pretreatment levels within 1 week. Two patients were subsequently successfully treated with entecavir indicating that NUC B1000 does not compromise subsequent antiviral therapy. CONCLUSIONS: Thus far, NUC B1000 appears safe and well-tolerated; safety and efficacy studies across a larger, more diverse patient spectrum using increasing doses are needed to determine its appropriate role in the antiviral armamentarium.
BACKGROUND: RNA interference (RNAi) provides an attractive tool to modulate biological systems, and ultimately, to treat human diseases. We describe early results from a Phase Ib, first-in-human safety and tolerability study of an RNAi-based therapy, NUC B1000, among patients with mild to moderate chronic HBV. METHODS: Three subjects received a single 5 mg DNA dose of NUC B1000 as part of a planned dose escalation study. RESULTS: All participants reported pharyngitis, chills, myalgia and fever approximately 4-7 h after dosing. All subjects were asymptomatic after a single antipyretic dose with no symptom recurrences. Measurements of interferon (IFN)-α and -γ, interleukin (IL)-10, 12 18, 8 and 6, and tumour necrosis factor-α performed before and after dosing revealed cytokine increases before study drug administration. After drug administration, IFN-γ and IL-10 increased in two patients; IL-8 increased in one. Most increases returned to pretreatment levels within 1 week. Two patients were subsequently successfully treated with entecavir indicating that NUC B1000 does not compromise subsequent antiviral therapy. CONCLUSIONS: Thus far, NUC B1000 appears safe and well-tolerated; safety and efficacy studies across a larger, more diverse patient spectrum using increasing doses are needed to determine its appropriate role in the antiviral armamentarium.
Authors: J Wu; S Liu; J Yu; G Zhou; D Rao; C M Jay; P Kumar; R Sanchez; N Templeton; N Senzer; P Maples; J Nemunaitis; F C Brunicardi Journal: Cancer Gene Ther Date: 2014-01-24 Impact factor: 5.987
Authors: Jana L McCaskill; Glenn A Marsh; Paul Monaghan; Lin-Fa Wang; Timothy Doran; Nigel A J McMillan Journal: PLoS One Date: 2013-05-14 Impact factor: 3.240