Assessment of the immunogenicity and safety of varying doses of an MF59®-adjuvanted cell culture-derived A/H1N1 pandemic influenza vaccine in Japanese paediatric, adult and elderly subjects.

INTRODUCTION: Effective vaccination strategies are required to combat future influenza pandemics. Here we report the results of three independent clinical trials performed in Japan to assess the immunogenicity, tolerability and safety of varying doses of a cell culture-derived MF59(®)-adjuvanted A/H1N1 pandemic vaccine in healthy Japanese paediatric, adult and elderly subjects. METHODS: One hundred and twenty-three children (6 months-18 years), and 200 adults (19-60 years) were randomly assigned in a 1:1 ratio to receive two doses of vaccine containing either 7.5 µg antigen with a full (9.75 mg) adjuvant dose, or 3.75 µg antigen with a half (4.875 mg) adjuvant dose. One hundred elderly (≥ 61 years) subjects received only the low antigen/adjuvant vaccine formulation. Immunogenicity was assessed by haemagglutination inhibition assay at baseline and three weeks after the first and second vaccine doses on Days 22 and 43, respectively. Solicited and unsolicited adverse reactions were recorded for seven and 21 days post-immunization, respectively. RESULTS: In adult and elderly subjects, a single low antigen/adjuvant dose vaccination was sufficient to meet all of the three European licensure criteria established for influenza vaccines. One high, or two low antigen/adjuvant dose vaccinations were required to meet the licensure criteria in paediatric subjects. Both vaccine formulations were well tolerated, with the majority of adverse reactions mild to moderate in severity. None of the five serious adverse events reported throughout the three trials were considered to be vaccine-related by the investigators. CONCLUSION: The use of MF59 adjuvant allows for much reduced vaccine antigen content, and a single dose administration schedule in adults and the elderly. The production of pandemic vaccine using modern cell culture techniques is highly advantageous in terms of the quantity, quality, and rapidity of antigen production; these benefits, in combination with the use of MF59, maximize manufacturing capacity and global vaccine supply. These data support the suitability of the investigational vaccine for use in the Japanese paediatric, adult, and elderly populations.

Comparison of half and full doses of an MF59-adjuvanted cell culture-derived A/H1N1v vaccine in Japanese children.

INTRODUCTION: The substantial pandemic (A/H1N1v) influenza disease burden in children highlights the need for effective vaccination. We report the results of modern cell culture technology, lower doses of antigen, and different doses of MF59(R) adjuvant (Novartis Vaccines, Marburg, Germany), on the immunogenicity and safety profile in a healthy Japanese pediatric population. METHODS: A total of 123 children from 6 months to 19 years of age were randomly assigned in a 1:1 ratio to receive, at 21-day intervals, two doses of either 3.75 microg antigen with 50% of the standard MF59 dose (group A) or 7.5 microg antigen and 100% standard MF59 dose (group B). Antibody levels were measured by hemagglutinin inhibition (HI) and microneutralization assays on day 1 and on days 22 and 43 (3 weeks after the first and second vaccinations, respectively). Solicited adverse events were reported for 7 days after each injection and spontaneous events were reported throughout the study period. RESULTS: At 3 weeks after the first vaccination, seroprotective HI antibodies (titers >or=40) were observed in 56% and 78% of subjects from groups A and B, respectively; 100% in both groups exhibited HI titers >or=40 after the second dose. The reactogenicity profile was acceptable, with local and systemic reactions described as mainly mild to moderate in severity. Five serious adverse events were reported, but none related to the study vaccine. CONCLUSION: One dose of cell culture-derived A/H1N1v vaccine containing 7.5 microg antigen with the full MF59 adjuvant dose was immunogenic and well tolerated in healthy Japanese children, meeting all three European Union Committee for Medicinal Products for Human Use (EU CHMP) licensure criteria. Two doses of 3.75 microg antigen with 50% of the standard MF59 dose fulfilled these licensure criteria.

Efficacy and safety of aliskiren in Japanese hypertensive patients with renal dysfunction.

This 12-week, multicenter, open-label study assessed the efficacy, pharmacokinetics and safety of a once-daily aliskiren in Japanese hypertensive patients with renal dysfunction. Patients (n=40, aged 20-80 years) with mean sitting diastolic blood pressure (msDBP) >or=95 and <110 mm Hg and serum creatinine between >or=1.3 and <3.0 mg per 100 ml in males or between >or=1.2 and <3.0 mg per 100 ml in females were eligible. Patients began therapy with a once-daily morning oral dose of 75 mg of aliskiren. In patients with inadequate blood pressure control (msDBP >or=90 or mean sitting systolic blood pressure [msSBP] >or=140 mm Hg) and without safety concerns (serum potassium >5.5 mEq l(-1) or an increase in serum creatinine >or=20%), the aliskiren dose was increased to 150 mg and then to 300 mg in sequential steps starting from Week 2. Efficacy was assessed as change in msSBP/msDBP from baseline to the Week 8 endpoint (with the last observation carried forward). The mean reduction from baseline to Week 8 endpoint was 13.9+/-16.6 and 11.6+/-9.7 mm Hg for msSBP and msDBP, respectively. At the Week 8 endpoint, 65% patients had achieved blood pressure response (msDBP <90 or a 10 mm Hg decrease or msSBP <140 or a 20 mm Hg decrease) and 30% had achieved blood pressure control (msSBP <140 mm Hg and msDBP <90 mm Hg). Aliskiren was well tolerated with no new safety concerns in Japanese hypertensive patients with renal dysfunction.