A phase 3 trial of IV immunoglobulin for Alzheimer disease.

Objective: We tested biweekly infusions of IV immunoglobulin (IVIg) as a possible treatment for mild to moderate Alzheimer disease (AD) dementia.

Methods: In a phase 3, double-blind, placebo-controlled trial, we randomly assigned 390 participants with mild to moderate AD to receive placebo (low-dose albumin) or IVIg (Gammagard Liquid; Baxalta, Bannockburn, IL) administered IV at doses of 0.2 or 0.

Efficacy, Safety, and Pharmacokinetics of a Novel Human Immune Globulin Subcutaneous, 20 % in Patients with Primary Immunodeficiency Diseases in North America.

Patients with primary immunodeficiency disease (PIDD) typically require life-long intravenous (IV) or subcutaneous (SC) immunoglobulin (Ig) replacement therapy to prevent recurrent infections. The efficacy, safety, and pharmacokinetics of a highly concentrated (20 %) Ig preparation for SC administration (IGSC 20 %) were evaluated in a prospective trial in patients with PIDD. A total of 74 patients (aged 3-83 years) received 4327 IGSC 20 % infusions over a median of 380.

Demonstration of safety of intravenous immunoglobulin in geriatric patients in a long-term, placebo-controlled study of Alzheimer's disease.

Introduction: We present safety results from a study of Gammagard Liquid intravenous immunoglobulin (IGIV) in patients with probable Alzheimer's disease.

Methods: This was a placebo-controlled double-blind study. Subjects were randomized to 400 mg/kg (n = 127), 200 mg/kg (n = 135) IGIV, or to 0.

Efficacy and safety of protein C concentrate to treat purpura fulminans and thromboembolic events in severe congenital protein C deficiency.

Severe congenital protein C (PC) deficiency (SCPCD) is associated with disseminated intravascular coagulation (DIC), purpura fulminans (PF), and vascular thromboembolic events (TE), often leading to organ failure and death. PC replacement therapy offers a safe, effective treatment for thromboembolic complications of SCPCD and secondary prophylaxis for recurrent DIC, PF, and TEs. A prospective, multi-centre, open-label, phase 2/3 study was conducted to demonstrate the safety and efficacy of protein C concentrate for treatment of PF and acute TEs.

Hemostatic efficacy, safety, and pharmacokinetics of a recombinant von Willebrand factor in severe von Willebrand disease.

This phase 3 trial evaluated the safety and hemostatic efficacy of a recombinant von Willebrand factor (rVWF) for treatment of bleeds in severe von Willebrand disease (VWD). rVWF was initially administered together with recombinant factor VIII (rFVIII) and subsequently alone, as long as hemostatic factor VIII activity (FVIII : C) levels were maintained. Pharmacokinetics (PK) were evaluated in a randomized cross-over design (rVWF vs rVWF:rFVIII at 50 IU VWF:ristocetin cofactor activity [RCo]/kg).

Phase I/II randomized double-blind study of the safety and immunogenicity of a nonadjuvanted vero cell culture-derived whole-virus H9N2 influenza vaccine in healthy adults.

Studies on candidate pandemic vaccines against avian influenza viruses have focused on H5N1, but viruses of other subtypes, such as A/H9N2, are also considered to have pandemic potential. We investigated the safety and immunogenicity of two immunizations with one of five different antigen doses (ranging from 3.75 to 45 μg of hemagglutinin antigen) of a nonadjuvanted whole-virus G9 lineage H9N2 influenza virus vaccine in healthy adults aged 18 to 49 years.

Safety and immunogenicity of a vero cell culture-derived whole-virus influenza A(H5N1) vaccine in a pediatric population.

Background: Children are highly vulnerable to infection with novel influenza viruses. It is essential to develop candidate pandemic influenza vaccines that are safe and effective in the pediatric population.

Methods: Infants and children aged 6-35 months and 3-8 years, respectively, were randomized to receive 2 immunizations with a 7.

Single priming dose of meningococcal group C conjugate vaccine (NeisVac-C®) in infants.

Since the introduction of the meningococcal C conjugate (MCC) vaccine in the pediatric population in 1999, numerous clinical studies have confirmed the immunogenicity and safety of the NeisVac-C(®) vaccine, and several have observed a strong immune response after a single priming dose, which could be successfully boosted. Maximizing protection of infants with as few vaccine doses as possible would increase the general acceptability of the immunization strategies and support broader coverage without increasing vaccination costs. This was a randomized feasibility study of a single priming NeisVac-C(®) vaccine dose administered at 4 or 6 months of age, compared to the currently licensed two dose priming at 2 and 4 months of age, followed by a booster vaccination at 12-13 months of age.

Safety and immunogenicity of a novel multivalent OspA vaccine against Lyme borreliosis in healthy adults: a double-blind, randomised, dose-escalation phase 1/2 trial.

Background: Lyme borreliosis is caused by Borrelia burgdorferi sensu stricto in the USA and by several Borrelia species in Europe and Asia, but no human vaccine is available. We investigated the safety and immunogenicity of adjuvanted and non-adjuvanted vaccines containing protective epitopes from Borrelia species outer surface protein A (OspA) serotypes in healthy adults.

Methods: Between March 1, 2011, and May 8, 2012, we did a double-blind, randomised, dose-escalation phase 1/2 study at four sites in Austria and Germany.

Cell culture (Vero cell) derived whole-virus non-adjuvanted H5N1 influenza vaccine induces long-lasting cross-reactive memory immune response: homologous or heterologous booster response following two dose or single dose priming.

Background: Influenza pandemic preparedness involves priming of the population with pre-pandemic vaccines. Such vaccines should be well tolerated and induce a long-lasting immunological memory that can effectively be boosted with a single dose of pandemic vaccine once available. The presented studies assessed different prime-boost regimens with a Vero cell-derived whole virus non-adjuvanted H5N1 vaccine.

A non-adjuvanted whole-virus H1N1 pandemic vaccine is well tolerated and highly immunogenic in children and adolescents and induces substantial immunological memory.

This phase 1/2 open-label, randomized clinical study investigated the safety and immunogenicity of a non-adjuvanted, whole virus, Vero cell-derived H1N1 pandemic influenza vaccine (A/H1N1/California/07/2009) in children and adolescents (6 months to 17 years). Subjects were stratified by age (6-11 months, 12-35 months, 3-8 years, 9-17 years) to receive two vaccinations 21 days apart of either the 3.75 μg or 7.

Antibody persistence after two vaccinations with either FSME-IMMUN® Junior or ENCEPUR® Children followed by third vaccination with FSME-IMMUN® Junior.

Tick-borne encephalitis (TBE) vaccination strategies to induce optimal seroprotection in children are under constant evaluation. This multi-center, randomized, controlled, phase III clinical study examined antibody persistence in children aged 1-11 y following two prospectively administered doses of either the FSME-IMMUN® Junior or Encepur Children® vaccines, as well as investigating the immunogenicity, safety and vaccine interchangeability of a third vaccination with FSME-IMMUN(®) Junior. A high level of antibody persistence was observed in all subjects 6 mo after the first of two vaccinations with either pediatric TBE vaccine.

Pre-vaccination immunity and immune responses to a cell culture-derived whole-virus H1N1 vaccine are similar to a seasonal influenza vaccine.

Background: Immune responses to novel pandemic influenza vaccines may be influenced by previous exposure to antigenically similar seasonal strains.

Methods: An open-label, randomized, phase I/II study was conducted to assess the immunogenicity and safety of a non-adjuvanted, inactivated whole-virus H1N1 A/California/07/2009 vaccine. 408 subjects were stratified by age (18-59 and >60 years) and randomized 1:1 to receive two vaccinations with either 3.

A cell culture-derived influenza vaccine provides consistent protection against infection and reduces the duration and severity of disease in infected individuals.

Background: Current knowledge of the consistency of protection induced by seasonal influenza vaccines over the duration of a full influenza season is limited, and little is known about the clinical course of disease in individuals who become infected despite vaccination.

Methods: Data from a randomized double-blind placebo-controlled clinical trial undertaken in healthy young adults in the 2008-2009 influenza season were used to investigate the weekly cumulative efficacy of a Vero cell culture-derived influenza vaccine. In addition, the duration and severity of disease in vaccine and placebo recipients with cell culture-confirmed influenza infection were compared.

Clinical development of a Vero cell culture-derived seasonal influenza vaccine.

Background: Cell culture technologies have the potential to improve the robustness and flexibility of influenza vaccine supply and to substantially shorten manufacturing timelines. We investigated the safety, immunogenicity and efficacy of a Vero cell culture-derived seasonal influenza vaccine and utilized these studies to establish a serological correlate of vaccine protection.

Methods: Two multicenter, randomized, double-blind phase III trials were undertaken in the US during the 2008-2009 Northern hemisphere influenza season, in young (18-49 years) and older (50-64 years and ≥ 65 years) adult subjects.

Safety and immunogenicity of two different doses of a Vero cell-derived, whole virus clade 2 H5N1 (A/Indonesia/05/2005) influenza vaccine.

A successful vaccine development strategy for areas with clustered H5N1 events requires conduct of vaccine trials in potentially non-naïve subjects and evaluation of post-vaccination responsiveness. An open-label, randomized, phase I/II study therefore assessed the immunogenicity and safety of two different dose levels of an inactivated, non-adjuvanted, whole virus clade 2.1 (A/Indonesia/05/2005) H5N1 Vero cell-derived influenza vaccine in healthy adults (21-45 years) from a region where the virus has been circulating (Hong Kong) as well as Singapore.

Population pharmacokinetics of recombinant factor VIII: the relationships of pharmacokinetics to age and body weight.

Comparison of the pharmacokinetics (PK) of a coagulation factor between groups of patients can be biased by differences in study protocols, in particular between blood sampling schedules. This could affect clinical dose tailoring, especially in children. The aim of this study was to describe the relationships of the PK of factor VIII (FVIII) with age and body weight by a population PK model.

Safety and immunogenicity of an inactivated whole virus Vero cell-derived Ross River virus vaccine: a randomized trial.

Background: Ross River virus (RRV) is endemic in Australia and several South Pacific Islands. Approximately 5000 cases of RRV disease, which is characterized by debilitating polyarthritis, are recorded each year in Australia. This study describes the first clinical trial of a candidate RRV vaccine.

Prevention of tick-borne encephalitis by FSME-IMMUN vaccines: review of a clinical development programme.

The need for highly effective tick-borne encephalitis (TBE) vaccines has increased globally due to a variety of factors including climate, social, economic and demographic changes, which are thought to have promoted the expansion of the endemic region of TBE viruses. The first TBE vaccine, FSME-IMMUN Inject, was introduced in the 1970s and has been continually improved since then to enhance both its safety and immunogenicity. The current formulation was established in 2001 and is marketed as FSME-IMMUN.

Efficacy, safety, and immunogenicity of a Vero-cell-culture-derived trivalent influenza vaccine: a multicentre, double-blind, randomised, placebo-controlled trial.

Background: The use of cell-culture technologies for the manufacture of influenza vaccines might contribute to improved strain selection and robust vaccine supplies. We investigated the safety, immunogenicity, and protective efficacy of a Vero-cell-culture-derived influenza vaccine, and assessed the correlation between vaccine efficacy and haemagglutination inhibition antibody titre.

Methods: In a double-blind, placebo-controlled, phase 3 trial undertaken in 36 centres in the USA, healthy adults (aged 18-49 years) were randomly assigned in a 1:1 ratio to one injection of either placebo or Vero-cell-culture-derived influenza vaccine during the 2008-09 season.

Clinical evaluation to determine the appropriate paediatric formulation of a tick-borne encephalitis vaccine.

Two dose-finding studies and one open label safety study with a paediatric FSME-IMMUN formulation were conducted in children and adolescents aged 1-15 years (N=3697). The 1.2 microg antigen dose was identified as the optimal dose, inducing high seroconversion rates following the primary vaccination series.

Comparison of immunogenicity and safety between two paediatric TBE vaccines.

TBE vaccination strategies capable of inducing strong paediatric immunogenicity and acceptable reactogenicity are still under evaluation. This single-blind, multi-center, randomized, controlled, phase III clinical study compared the immunogenicity and safety of the two paediatric TBE vaccines available in Europe (FSME-IMMUN Junior and Encepur Children) following administration of two doses of either vaccine in 303 children aged 1-11 years. Regardless of immunological test or viral antigen used, immunological responses were consistently higher in children vaccinated with FSME-IMMUN Junior than those vaccinated with Encepur Children.

A cell culture (Vero)-derived H5N1 whole-virus vaccine induces cross-reactive memory responses.

Novel strategies are required to provide rapid vaccine coverage in the event of an influenza pandemic. A phase I/II dose finding/formulation study was performed with a whole-virus H5N1 clade 1 A/Vietnam vaccine (2-dose priming regimen) to evaluate safety and immunogenicity. Seventy-seven of 141 subjects in this study received a booster (12-17 months after priming) with a 7.

Seropersistence of tick-borne encephalitis antibodies, safety and booster response to FSME-IMMUN 0.5 ml in adults aged 18-67 years.

A clinical study was carried out to evaluate the persistence of tick-borne encephalitis (TBE) antibodies 2 and 3 years after a primary vaccination series (three-dose regimen), and to assess the antibody response to a booster vaccination with FSME-IMMUN. Volunteers (N = 347, 18-67 years) who had received two doses of either FSME-IMMUN or Encepur adults and a third vaccination with FSME-IMMUN were enrolled. Seropositivity rates were assessed by ELISA and neutralization test (NT).