Icenticaftor, a CFTR Potentiator, in COPD: A Multicenter, Parallel-Group, Double-Blind Clinical Trial.

CFTR (cystic fibrosis transmembrane conductance regulator) dysfunction is associated with mucus accumulation and worsening chronic obstructive pulmonary disease (COPD) symptoms. The aim of this phase IIb dose-finding study was to compare a CFTR potentiator, icenticaftor (QBW251), with placebo in patients with COPD and chronic bronchitis. Patients with COPD on triple therapy for at least three months were randomized to six treatment arms (icenticaftor 450, 300, 150, 75, or 25 mg or placebo twice daily [b.

Ligelizumab impairs IgE-binding to plasmacytoid dendritic cells more potently than omalizumab and restores IFN-α production and FOXP3 Treg generation.

Background: Ligelizumab is an anti-IgE monoclonal antibody binding IgE with higher affinity than omalizumab that is under clinical investigation for several IgE-mediated diseases. We previously showed that omalizumab removes IgE bound to FcεRI on plasmacytoid dendritic cells (pDCs) and restores their ability to produce IFN-α and regulatory T cells (Tregs). The aim of this work is to investigate the capacity of ligelizumab to regulate functional properties of pDCs in comparison with omalizumab.

The rationale for development of ligelizumab in food allergy.

Food allergy (FA) is a growing healthcare problem worldwide and the rising prevalence in many countries can be attributed to lifestyle, environmental, and nutritional changes. Immunoglobulin E (IgE)-mediated FA is the most common form of FA affecting approximately 3%-10% of adults and 8% of children across the globe. Food allergen-induced immediate hypersensitivity reactions mediated by IgE and high-affinity IgE receptor (FcεRI) complexes on mast cells and basophils are a major hallmark of the disease.

Ligelizumab treatment for severe asthma: learnings from the clinical development programme.

Objective: Ligelizumab is a humanised IgG1 anti-IgE antibody that binds IgE with higher affinity than omalizumab. Ligelizumab had greater efficacy than omalizumab on inhaled and skin allergen provocation responses in mild allergic asthma. This multi-centre, randomised, double-blind study was designed to test ligelizumab in severe asthma patients not adequately controlled with high-dose inhaled corticoids plus long-acting β2-agonist.

Safety and efficacy of the cystic fibrosis transmembrane conductance regulator potentiator icenticaftor (QBW251).

Background: This is the first-in-human study of icenticaftor, an oral potentiator of the cystic fibrosis (CF) transmembrane conductance regulator (CFTR) channel. Restoration of CFTR activity has shown significant clinical benefits, but more studies are needed to address all CFTR mutations.

Methods: Safety, pharmacodynamics/pharmacokinetics of icenticaftor were evaluated in a randomized, double-blind, placebo-controlled study in healthy volunteers.

Omalizumab effectively protects against early and late allergic responses in asthma after 4 weeks.

Background: Omalizumab is licensed for therapy in severe allergic asthma with an effect demonstrated after 8 weeks or longer treatment. As new applications for omalizumab demand precise knowledge of the onset of effects, the objective of this study was to determine the time course of the early (EAR) and late allergic reaction (LAR).

Materials And Methods: Ten patients (IgE>300 IU/mL and <700 IU/mL) with a significant response to allergen challenge were treated with omalizumab according to the approved dosing table.

Pharmacokinetics, pharmacodynamics and safety of QGE031 (ligelizumab), a novel high-affinity anti-IgE antibody, in atopic subjects.

Background: Using a monoclonal antibody with greater affinity for IgE than omalizumab, we examined whether more complete suppression of IgE provided greater pharmacodynamic effects, including suppression of skin prick responses to allergen.

Objective: To explore the pharmacokinetics, pharmacodynamics and safety of QGE031 (ligelizumab), a novel high-affinity humanized monoclonal IgG1κ anti-IgE.

Methods: Preclinical assessments and two randomized, placebo-controlled, double-blind clinical trials were conducted in atopic subjects.

Exploratory Study of Tegaserod for Dyspepsia in Women Receiving PPIs for Heartburn.

BACKGROUND AND AIMS: Tegaserod is a selective serotonin receptor (5-HT(4)) agonist that relieves dysmotility symptoms associated with constipation. Here we explore its effects on functional dyspepsia symptoms and heartburn during continued proton pump inhibitor (PPI) treatment. METHODS: In this multicenter pilot study, following a 2-week screening/baseline period, women with functional dyspepsia and persisting heartburn treated with PPIs received add-on open-label tegaserod 6 mg twice daily (bid) for 4 weeks.

Tegaserod in patients with mechanical sensitivity and overlapping symptoms of functional heartburn and functional dyspepsia.

Background: While functional heartburn (FH) and functional dyspepsia (FD) are recognized clinical entities, symptoms often overlap across both disorders. Despite their frequency, little is known of the underlying pathophysiology of overlapping symptoms. This study evaluated the effect of the 5-HT(4) agonist, tegaserod, on visceral sensitivity and symptom improvement in patients with overlapping symptoms of FH and FD.

Heparin-binding epidermal growth factor-like growth factor, a v-Jun target gene, induces oncogenic transformation.

Jun is a transcription factor belonging to the activator protein 1 family. A mutated version of Jun (v-Jun) transduced by the avian retrovirus ASV17 induces oncogenic transformation in avian cell cultures and sarcomas in young galliform birds. The oncogenicity of Jun probably results from transcriptional deregulation of v-Jun-responsive target genes.

The DF-1 chicken fibroblast cell line: transformation induced by diverse oncogenes and cell death resulting from infection by avian leukosis viruses.

DF-1 is a continuous cell line of chicken embryo fibroblasts. The cells are free of endogenous sequences related to avian sarcoma and leukosis viruses and have normal fibroblastic morphology. DF-1 cells support the replication of avian retroviruses; diverse oncogenes induce foci of oncogenic transformation on monolayers of DF-1, and avian leukosis viruses of envelope subgroups B, D, and C induce cell death and form plaques.

Changes in cerebrospinal fluid and cerebrovascular endothelin concentrations during hypotension and hypertension in newborn piglets with induced sterile meningitis.

The effects of sterile meningitis on endothelin-1 (ET-1) and big ET-1 concentrations during hypotension and hypertension were studied in the cerebrospinal fluid and plasma of newborn piglets. Cerebrospinal fluid was obtained via cisterna magna puncture, and blood was obtained from the sagittal sinus vein and left subclavian artery. The study group consisted of 14 newborn piglets injected with 0.

Effect of group B streptococcal meningitis on retinal and choroidal blood flow in newborn pigs.

Purpose: To assess the effect of group B streptococcal (GBS) meningitis on retinal blood flow (RetBF) and choroidal blood flow (ChBF) autoregulation in sedated newborn piglets (1 to 5 days of age).

Methods: Fourteen study animals injected with 0.5 ml heat-killed GBS (10(9)) were compared to 10 control animals injected with 0.