Kandel R, Hartshorn KL

Kandel R, Hartshorn KL. of nasopharyngeal virus illness, quantified using quantitative PCR (98%) and 50% cells culture infective dose (TCID50) (100%) assays. Maximum viral weight, duration of viral dropping, influenza symptom scores, mucus weight, and inflammatory biomarkers were also reduced. Serum PK was linear having a half-life of 23 days. No MHAA4549A-treated subjects developed anti-drug antibodies. In conclusion, MHAA4549A was well tolerated and shown statistically significant and considerable antiviral activity in an IAV challenge model. (This study has been I-BRD9 authorized at ClinicalTrials.gov under identifier “type”:”clinical-trial”,”attrs”:”text”:”NCT01980966″,”term_id”:”NCT01980966″NCT01980966.) I-BRD9 effectiveness studies in mouse and ferret IAV lethal models shown that MHAA4549A offered significant safety over that of control-treated animals, even with administration at 72 h postinoculation (11). This demonstration of proof of activity led to an assessment of the security, pharmacokinetics, and effectiveness in clinical studies. In two phase 1 studies, MHAA4549A was shown to be well tolerated in healthy volunteers without IAV illness (15). Prior to screening effectiveness in the prospective human population, individuals hospitalized with severe influenza, proof of activity was assessed in this phase 2, dose-ranging, challenge study to determine the security, effectiveness, and pharmacokinetics (PK) of MHAA4549A in healthy subjects inoculated with IAV. (This study was presented in part like a poster in the 2015 Keystone Symposia Conference on Viral Immunity, Breckenridge, CO, 11 to 16 January 2015 [16].) RESULTS Subject demographics. Key subject demographics for randomized and intent-to-treat infected (ITTI) populations are summarized in Table 1. In the randomized human population, gender, ethnicity, and time between challenge disease and administration of study drug were balanced across the organizations. The median age of the subjects was 28 years, and 92% were white. The median age and body mass index (BMI) of subjects in the 1,200-mg MHAA4549A group were numerically higher than those of the additional organizations. To reflect anticipated dosing practice and allow a window to test efficacy, the protocol specified that subjects were to become treated between 24 and 36 h postinoculation (Fig. 1A), which is also typically the exponential phase of viral replication. The median time between hCIT529I10 inoculation and 1st dose for those subjects was 27.8 h. Within the ITTI human population, related baseline demographics were observed (Table 1). TABLE 1 Subject demographics and baseline characteristics (randomized and ITTI populations) = 32= 20= 20= 21= 8= 101????Age (yr), median (range)27.5 (20C43)26.5 (20C37)31.5 (19C45)28.0 (18C44)24.5 (20C43)28.0 (18C45)????Male, no. (%)21 (65.6)10 (50.0)14 (70.0)11 (52.4)6 (75.0)42 (61.4)????White colored, no. (%)30 (93.8)19 (95.0)18 (90.0)19 (90.5)7 (87.5)93 (92.1)????BMI (kg/m2), median (range)23.80 (19.8C30.3)22.62 (20.7C28.6)24.93 (19.2C31.9)23.61 (18.3C29.7)24.15 (19.8C28.9)23.83 (18.3C31.9)????Temp (C), median (range)36.65 (35.5C37.9)36.60 (35.7C37.3)36.70 (35.6C37.3)36.65 (35.7C37.6)36.75 (36.3C37.5)35.65 (35.5C37.9)????Inoculation to first dose, median time (h) (range)27.62 (24.4C30.2)27.40 (24.5C29.5)27.91 (26.4C30.0)27.44 (25.5C37.5)29.69 (28.9C30.7)27.75 (24.4C37.5)ITTI subjects= 21= 11= 13= 14= 2= 61????Age (yr), median (range)28.0 (20C43)25.0 (23C36)32.0 (19C44)28.0 (18C44)27.5 (26C29)27.0 (18C44)????Male, no. (%)14 (66.7)4 (36.4)11 (84.6)8 (57.1)2 (100.0)39 (63.9)????White colored, no. (%)21 (100.0)11 (100.0)11 (84.6)13 (92.9)2 (100.0)58 (95.1)????BMI (kg/m2), median (range)23.57 (19.8C28.3)22.59 (20.7C27.5)25.75 (19.2C31.9)23.98 (18.3C28.3)27.75 (26.6C28.9)24.07 (18.3C31.9)????Temp (C), median (range)36.60 (35.9C37.4)36.60 (35.7C37.3)36.50 (35.7C37.1)36.65 (35.7C37.6)36.70 (36.6C36.8)36.60 (35.7C37.6)????Inoculation to first dose, median time (h) (range)27.78 (24.7C30.2)27.50 (24.5C29.3)28.38 (26.9C30.0)27.34 (25.9C37.5)29.30 (29.1C29.5)27.85 (24.5C37.5) Open in a separate window Open in a separate window FIG 1 Study design (A) and disposition of study subjects (B). Disposition of study populations. One hundred randomized subjects were inoculated with concern disease and received study medications intravenously (i.v.) (Fig. 1B). The ITTI human population included a total of 61 subjects: I-BRD9 11 subjects in the 400-mg MHAA4549A group, 13 in the 1,200-mg MHAA4549A group, 14 in the 3,600-mg MHAA4549A group, 2 in the oseltamivir group, and 21 in the placebo group. Security. A total of 207.