All biotherapeutics have the potential to induce an immunogenic response and generate anti-drug antibodies (ADAs), especially when administered as multiple doses over prolonged periods. However, a clinically meaningful effect of ADAs can be difficult to identify to communicate the impact of immunogenicity on drug exposure, safety and efficacy outcomes in product labels in a way that is useful for health care providers. The immunogenicity working Group, IQ Consortium (Clinical Pharmacology Leadership Group) has conducted a survey to understand the current practices in analyzing immunogenicity data generated during clinical development and its impact on pharmacokinetics, clinically relevant pharmacodynamic biomarkers, safety, and efficacy outcome measures.
View Article and Find Full Text PDFJ Pharmacokinet Pharmacodyn
January 2025
Brain amyloid beta neuritic plaque accumulation is associated with an increased risk of progression to Alzheimer's disease (AD) [Pfeil, J., et al. in Neurobiol Aging 106: 119-129, 2021].
View Article and Find Full Text PDFPrimary hyperparathyroidism is rare in children. A germline mutation is identified in half of all children with primary hyperparathyroidism (70% of newborns and infants, and 40% of children and adolescents). The clinical manifestations of primary hyperparathyroidism in children are highly variable (often absent in newborns, rather severe and symptomatic in children and adolescents) and depend on the genetic cause, as well as the severity, rapidity of onset and duration of hypercalcemia.
View Article and Find Full Text PDFBackground: In this phase Ib/II open-label study, tumor immune suppression was targeted in patients with advanced refractory solid tumors and patients with recurrent/refractory non-small cell lung cancer (NSCLC) using galunisertib with nivolumab.
Methods: Eligible patients were ≥ 18 years old, had an Eastern Cooperative Oncology Group performance status ≤ 1, and were treatment-naive for anti-programmed cell death-1, its ligand, or transforming growth factor β receptor 1 kinase inhibitors. Phase Ib was an open-label, dose-escalation assessment of the safety and tolerability of galunisertib with nivolumab in patients with advanced refractory solid tumors.
Alzheimers Dement (N Y)
June 2023
Purpose: X-linked hypophosphatemia (XLH) is a rare, chronic, genetic condition characterized by renal phosphate wasting and abnormal bone and teeth mineralization. It represents a challenging and multifaceted disease that causes wide-ranging impacts on patients' lives. In this context, a scientific committee has designed a support initiative for patients treated for XLH: the aXess program.
View Article and Find Full Text PDFIsolated ACTH deficiency (IAD) is a life-threatening condition, particularly in the neonatal period, while a main consequence of undiagnosed isolated ACTH deficiency in survivors is cognitive impairment. is involved in the differentiation and proliferation of corticotropic cells and mutations are responsible for more than 60% of neonatal cases of IAD. We describe a new variant of the main transcript (NM 005149.
View Article and Find Full Text PDFUnlabelled: There is little scientific evidence regarding the safety of GHRT in LGG, where GH deficiency is common.
Purpose: to compare the recurrence rate in children with midline LGG, depending on whether or not they have received GHRT, in order to assess its impact on the risk of tumor recurrence.
Methods: This bicentric retrospective study included 124 patients under the age of 18 who were diagnosed with a midline low-grade glial tumor between 1998 and 2016.
Introduction: An Alzheimer's disease (AD) dementia disease progression model was developed based on the integrated Alzheimer's Disease Rating Scale (iADRS).
Methods: Data from 3483 placebo participants in six AD trials were used to develop the disease progression model with NONMEM (version 7.4.
Objectives: Ever since the first research on barriers to physical activity (PA) highlighting fear of hypoglycemia as a major barrier, many studies have attempted to understand their demographic and behavioural determinants. However, no research has been conducted on whether these perceived barriers toward PA are based on real-life-experienced adverse glycemic effects of exercise.
Methods: Sixty-two adults and 53 children/adolescents living with type 1 diabetes, along with their parents, completed the Barriers to Physical Activity in Type 1 Diabetes-1 (BAPAD-1) questionnaire on barriers to PA.
Am J Gastroenterol
December 2021
Case: Introduction:Fecal calprotectin is a known inflammatory marker used to evaluate patients with Inflammatory Bowel Disease (IBD). In fact, ACG Clinical Guideline for management of Crohn's disease recommend fecal calprotectin (FC) as a helpful test to distinguish IBD versus functional disorder such as Irritable Bowel Syndrome. Studies have also shown association of fecal calprotectin with colon cancer.
View Article and Find Full Text PDFHereditary hypophosphatemia with increased FGF23 levels are rare inherited metabolic diseases characterized by low serum phosphate because of impaired renal tubular phosphate reabsorption. The most common form is X-linked hypophosphatemia (XLH), secondary to a mutation in the PHEX gene. In children, XLH is often manifested by rickets, delayed development of gait, lower limb deformities, growth retardation, craniosynostosis, and spontaneous dental abscesses.
View Article and Find Full Text PDFBackground: Preclinical data suggest that vascular endothelial growth factor (VEGF) and transforming growth factor (TGF)-β signaling interact to stimulate angiogenesis and suppress antitumor immune responses. Thus, combined inhibition of both pathways may offer greater antitumor activity compared with VEGF-targeted antiangiogenic monotherapy against hepatocellular carcinoma (HCC).
Methods: This is a multicenter, open-label, phase 1b study of galunisertib, an inhibitor of TGF-β receptor 1, and ramucirumab, an anti-VEGF receptor 2 antibody, in patients with advanced HCC aiming to define the maximum tolerated dose (MTD).
Objective: To assess the respiratory function and sleep characteristics of obese adults and children.
Methods: All patients with non-syndromic, severe obesity (BMI ≥3 z-scores for children and ≥40.00kg/m for adults), referred for pulmonary function tests at Lille University Hospital, were retrospectively included.
Background: We assessed the safety, efficacy, and pharmacokinetics of the transforming growth factor beta (TGFβ) receptor inhibitor galunisertib co-administered with the anti-programmed death-ligand 1 (PD-L1) antibody durvalumab in recurrent/refractory metastatic pancreatic cancer previously treated with ≤2 systemic regimens.
Methods: This was a two-part, single-arm, multinational, phase Ib study. In a dose-finding phase, escalating oral doses of galunisertib were co-administered on days 1-14 with fixed-dose intravenous durvalumab 1500 mg on day 1 every 4 weeks (Q4W), followed by an expansion cohort phase.
In the last update of the RECIST criteria in 2009, it was proposed that the number of target lesions to be followed over time for response-to-treatment assessment be reduced from 10 to 5 lesions maximum, with up to 2 per organ. We explored the impact of reducing the number of target lesion on the assessment of drug effect in a randomised phase III clinical trial using a tumour growth inhibition (TGI) model. Tumour size measurements from 441 (out of 456) patients were used to build two datasets for which observations were the sum of longest diameters of all measurable lesions (ALL dataset) or following the RECIST 1.
View Article and Find Full Text PDFPurpose: SEQUOIA compared efficacy and safety of adding pegilodecakin (PEG), a pegylated recombinant human interleukin (IL)-10, with folinic acid, fluorouracil, and oxaliplatin (FOLFOX) in patients following progression on first-line gemcitabine-containing therapy with metastatic pancreatic ductal adenocarcinoma (PDAC).
Patients And Methods: SEQUOIA, a randomized, global phase III study, compared FOLFOX with PEG + FOLFOX as second line in gemcitabine-refractory PDAC. Patients were randomly assigned 1:1 (PEG + FOLFOX:FOLFOX) and stratified by prior gemcitabine and region.
Introduction: Checkpoint inhibitors (CPIs) have been approved to treat metastatic NSCLC. Pegilodecakin + CPI suggested promising efficacy in phase 1 IVY, providing rationale for randomized phase 2 trials CYPRESS 1 and CYPRESS 2.
Methods: CYPRESS 1 (N = 101) and CYPRESS 2 (N = 52) included Eastern Cooperative Oncology Group performance status of 0 to 1 and first-line/second-line metastatic NSCLC, respectively, without known EGFR/ALK mutations.
Aim: To describe the demographic characteristics, risk factors, and presenting features of children with symptomatic nutritional rickets in France.
Methods: This is a retrospective study of 38 children diagnosed with nutritional rickets from 1998 to 2019.
Results: We observed a higher frequency of rickets in males (74 vs.
Purpose Galunisertib, a TGF-β inhibitor, has demonstrated antitumor effects in preclinical and radiographic responses in some patients with malignant glioma. This Phase 1b/2a trial investigated the clinical benefit of combining galunisertib with temozolomide-based radiochemotherapy (TMZ/RTX) in patients with newly diagnosed malignant glioma (NCT01220271). Methods This is an open-label, 2-arm Phase 1b/2a study (N = 56) of galunisertib (intermittent dosing: 14 days on/14 days off per cycle of 28 days) in combination with TMZ/RTX (n = 40), versus a control arm (TMZ/RTX, n = 16).
View Article and Find Full Text PDFPurpose: To evaluate the exposure-overall survival (OS) relationship in patients with advanced pancreatic cancer treated with galunisertib plus gemcitabine (GG) or gemcitabine plus placebo (GP).
Methods: Galunisertib 300 mg/day was given orally as intermittent dosing and gemcitabine as per label. Galunisertib exposure metrics for each patient in the GG arm (n = 99) of a phase 2 study of pancreatic cancer were calculated.