The safety and efficacy of quadrivalent live attenuated influenza vaccine in Japanese children aged 2-18 years: Results of two phase 3 studies.

BACKGROUND: Quadrivalent live attenuated influenza vaccine (Q/LAIV) has not been assessed in Japanese children. OBJECTIVES: Evaluate safety and efficacy of Q/LAIV in Japanese children. PATIENTS/METHODS: Two phase 3 studies were conducted in the 2014-2015 influenza season. Study 1 was an open-label, uncontrolled single arm, multicenter study of Q/LAIV safety in subjects aged 2-6 years. Study 2 was a randomized, double-blind, placebo-controlled multicenter study of Q/LAIV safety and efficacy; subjects aged 7-18 years were randomized 2:1 to receive Q/LAIV or placebo. Primary efficacy endpoint was laboratory-confirmed symptomatic influenza infection caused by vaccine-matched strains; secondary endpoint evaluated efficacy against all strains regardless of match. Both studies reported solicited symptoms, adverse events (AEs), and serious AEs. RESULTS: In Study 1, 100 subjects received Q/LAIV. In Study 2, 1301 subjects received Q/LAIV (n = 868) or placebo (n = 433). Treatment-emergent AEs occurred in 42% of subjects in Study 1, and in 24.3% of subjects in the Q/LAIV arm and in 25.9% of subjects in the placebo arm in Study 2. In Study 2, a single infection by a vaccine-matched strain was reported in the placebo arm, resulting in a vaccine efficacy estimate of 100% (95% CI: -1875.3, 100.0); efficacy for all strains regardless of match to the vaccine was 27.5% (95% CI: 7.4, 43.0). CONCLUSIONS: Quadrivalent live attenuated influenza vaccine did not meet its primary efficacy endpoint as only a single infection by a vaccine-matched strain was detected; however, efficacy for the secondary endpoint, all strains regardless of match, was achieved. Q/LAIV was generally well tolerated in the Japanese pediatric population.

SAFETY AND TOLERABILITY OF VANDETANIB IN JAPANESE PATIENTS WITH MEDULLARY THYROID CANCER: A PHASE I/II OPEN-LABEL STUDY.

OBJECTIVE: In a phase III trial, Western patients with medullary thyroid cancer (MTC) treated with the oral multikinase inhibitor vandetanib showed significantly improved progression-free survival (PFS) and objective response rate (ORR) compared with placebo. The biology of MTC and pharmacokinetics (PK) are similar for Japanese and Western patients; therefore, similar clinical benefit is anticipated in the Japanese population. This study evaluated the safety and tolerability of vandetanib in Japanese patients with unresectable locally advanced or metastatic MTC. METHODS: This was a phase I/II, open-label, nonrandomized study. Patients received vandetanib (300 mg daily) until objective disease progression. The primary endpoints were safety and tolerability. Secondary endpoints included efficacy and PK. Final data analysis was conducted once all patients with measurable baseline disease had been followed to progression, or for 56 weeks. RESULTS: Fourteen patients received vandetanib. All patients experienced at least one adverse event (AE), and 7 patients (50%) experienced grade ≥3 AEs. Common AEs included diarrhea (79%), hypertension (64%), and rash (43%). Four patients reported a total of five serious AEs (SAEs). Eleven patients (79%) had dose interruptions, and 8 patients (57%) had dose reductions. One patient discontinued treatment because of an SAE (interstitial lung disease). No patients met the prespecified criterion for QTc prolongation. The ORR was 38% and PFS at 12 months was 85%. CONCLUSION: Safety and efficacy data were comparable to those previously reported, and AEs were generally manageable by standard clinical practice or dose modifications. Overall, vandetanib was considered to be beneficial for Japanese MTC patients. ABBREVIATIONS: AE = adverse event CI = confidence interval Css,max = maximum steady-state plasma concentration DCR = disease control rate EGFR = epidermal growth factor receptor ILD = interstitial lung disease MTC = medullary thyroid cancer ORR = objective response rate PFS = progression-free survival PK = pharmacokinetics RECIST = Response Evaluation Criteria in Solid Tumors RET = re-arranged during transfection SAE = serious adverse event VEGFR = vascular endothelial growth factor receptor.

Simeprevir (TMC435) once daily with peginterferon-α-2b and ribavirin in patients with genotype 1 hepatitis C virus infection: The CONCERTO-4 study.

AIM: The efficacy and safety of simeprevir in combination with peginterferon-α-2b and ribavirin (PEG IFN-α-2b/RBV) were investigated in patients infected with hepatitis C virus (HCV) genotype 1 who were treatment-naïve or had previously received interferon (IFN)-based therapy. METHODS: CONCERTO-4 (NCT01366638) was an open-label, non-comparative, multicenter study of once-daily simeprevir (TMC435) 100 mg in combination with PEG IFN-α-2b/RBV in treatment-naïve and -experienced patients (prior relapsers or non-responders to IFN-based therapy) with chronic HCV genotype 1 infection. Twelve-week combination treatment was followed by 24/48-week response-guided PEG IFN-α-2b/RBV therapy for treatment-naïve patients and prior relapsers, and 48-week PEG IFN-α-2b/RBV therapy for prior non-responders. Patients were followed for 72 weeks after treatment initiation. The proportions of patients with sustained viral response (SVR; undetectable HCV RNA) at treatment end and 12 weeks after the last treatment (SVR12) were among the major efficacy end-points. Safety, including adverse events (AE), was monitored. RESULTS: Of the 79 patients treated, the proportion achieving SVR12 was highest among treatment-naïve patients (91.7%) and prior relapsers (100%) versus 38.5% of prior non-responders. All treatment-naïve patients and prior non-responders who achieved SVR12 also achieved SVR at treatment end and 24 weeks after last dose; 96.6% of prior relapsers achieved both end-points. Most AE were of grade 1 or 2 severity. Grade 3 AE occurred in 17 patients, most frequently neutropenia (6.3%). CONCLUSION: Simeprevir combined with PEG IFN-α-2b/RBV was effective in patients infected with HCV genotype 1, both for initial treatment of naïve patients and for retreatment of patients in whom previous IFN-based therapy had failed.