Date: 2014-05-20
Type of information: Presentation of results at a congress
phase: 2
Announcement: presentation of results at the American Thoracic Society 2014 International Conference in San Diego
Company: Gilead (USA)
Product: GS-5806
Action
mechanism: GS-5806 is an oral small molecule antiviral fusion inhibitor being evaluated for the treatment of respiratory syncytial virus (RSV). GS-5806 is believed to block RSV replication by inhibiting RSV F-mediated fusion of RSV RNA.
Disease: respiratory syncytial virus infection
Therapeutic area: Infectious diseases
Country:
Trial
details: The Phase 2 Challenge Study was a double-blind, placebo-controlled challenge study designed to assess the effect of GS-5806 on AUC RSV viral load (primary endpoint), as well as on mucus weight and total symptom score (secondary endpoints). In the study, 140 healthy adults (ages 18-45) were admitted into a clinical research quarantine unit where they received a clinical strain of RSV intranasally and were then monitored for 12 days. Once RSV-positive or five days after inoculation, whichever occurred first, patients were randomized within seven sequential cohorts. Patients in the first four cohorts were randomized 1:1 to receive GS-5806 (50 mg on Day 1 and 25 mg on Days 2-5) or matching placebo for five days. Following a pre-specified interim efficacy analysis at the conclusion of Cohorts 1-4, an adaptive phase (Cohorts 5-7) began, in which different GS-5806 dosing regimens (Cohort 5: Day 1: 50 mg; Days 2-3: 25 mg daily; Cohort 6: Day 1: 100 mg; Cohort 7: Day 1: 10 mg; Days 2-5: 5 mg daily) were evaluated.
Latest
news: * On May 20, 2014, Gilead Sciences announced results from a placebo-controlled, Phase 2a challenge study in healthy adult patients intranasally infected with respiratory syncytial virus (RSV). The study of GS-5806, an investigational oral RSV fusion inhibitor, achieved its primary and secondary endpoints of lower viral load (the amount of virus detected in the nasal wash), improvements in total mucus weight (the amount of mucus produced by the nose) and also symptom diary score compared to placebo. Detailed results from this study (Poster #1008) have been presented during a poster discussion session at the American Thoracic Society 2014 International Conference in San Diego. The primary efficacy analysis focused on the pre-specified quarantine phase of the study (Cohorts 1-4) of healthy volunteers with demonstrated RSV infection before treatment. Among 54 patients in Cohorts 1-4 (GS-5806: n=27; placebo: n=27), GS-5806 treatment resulted in a 99.9 percent reduction in the viral load (expressed as log transformed viral load area under the curve of 250.7 log10 plaque forming unit equivalents (PFUe*) hour/mL versus 757.7 log10 PFUe*hour/mL. Mean total mucus weight after treatment and mean change from baseline total symptom diary score (daily reporting of symptoms such as stuffy nose, cough and sore throat) also were significantly lower for GS-5806-treated patients. Mean total mucus weight during the five days after the first dose was 6.9 g for GS-5806 compared to 15.1 g for placebo-treated patients, a treatment difference of 8.2 g (p=0.028). Adjusted mean AUC of change in symptom diary score from after first dose through Day 12 was -20.2 for patients treated with GS-5806 compared to 204.9 score*hour for placebo-treated patients, a difference of 225.1 score*hour (p=0.005). There were no serious adverse events in the study. All adverse events were mild or moderate in severity, with the exception of one patient who received placebo. Grade 1 pulmonary function decrease was the only treatment-emergent adverse event experienced by two or more patients in either treatment group.
