Search

Your search keyword '"SGS Life Science Services (SGS)"' showing total 3 results
Start Over Author "SGS Life Science Services (SGS)" Topic middle aged
3 results on '"SGS Life Science Services (SGS)"'

1. Safety and immunogenicity of a measles-vectored SARS-CoV-2 vaccine candidate, V591 / TMV-083, in healthy adults: results of a randomized, placebo-controlled Phase I study

Author

Odile Launay, Cécile Artaud, Marie Lachâtre, Mohand Ait-Ahmed, Jelle Klein, Liem Binh Luong Nguyen, Christine Durier, Bastiaan Jansen, Yvonne Tomberger, Nathalie Jolly, Anna Grossmann, Houda Tabbal, Jérémy Brunet, Marion Gransagne, Zaineb Choucha, Damien Batalie, Ana Delgado, Matthias Müllner, Roland Tschismarov, Pieter-Jan Berghmans, Annette Martin, Katrin Ramsauer, Nicolas Escriou, Christiane Gerke, CIC Cochin Pasteur (CIC 1417), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôtel-Dieu-Groupe hospitalier Broca-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Centre de Recherche Translationnelle - Center for Translational Science (CRT), Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Clinical Pharmacology Unit Antwerp [Antwerp, Belgium], SGS Life Science Services (SGS), SGS (SGS)-SGS (SGS), Institut National de la Santé et de la Recherche Médicale (INSERM), SGS (SGS), Themis Bioscience GmbH, Génétique Moléculaire des Virus à ARN - Molecular Genetics of RNA Viruses (GMV-ARN (UMR_3569 / U-Pasteur_2)), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Département de Santé Globale - Department Global Health, BIOASTER Microbiology Technology Institute [Lyon], Service développement de l'innovation - Innovation Office, Direction des Applications de la Recherche et des Relations industrielles - The Technology Transfer and Industrial Partnership Department (DARRI), Institut Pasteur [Paris] (IP)-Institut Pasteur [Paris] (IP), HT was supported by a post-doctoral fellowship from ANRS|Maladies Infectieuses Émergentes. The study was funded by Themis Bioscience GmbH, a subsidiary of Merck & Co. Inc., Kenilworth, NJ, USA, and by the Coalition for Epidemic Preparedness Innovations (CEPI) as part of the project 'Outbreak Response to Novel Coronavirus (COVID-19): Development of a vaccine against novel coronavirus SARS-CoV-2 using the clinical Phase III measles vector technology'., We thank all study participants for their time and support. We thank the staff at the Centre d'Investigation Clinique (CIC) Vaccinologie Cochin-Pasteur, the Centre de Ressources Biologiques (CRB), and the Pharmacie à Usage Interieur (PUI) at Hôpital Cochin/APHP, Paris France, at the Clinical Pharmacology Unit (CPU), Antwerp, Belgium, at SGS, Mechelen, Belgium, and at Institut Pasteur, who contributed with their work to make the clinical study possible. We are grateful to Sylvain Baize (Institut Pasteur) for advice for the T cell assays, Brigitte Blumen (Institut Pasteur) for technical assistance, and Kevin Russell, Deborah D. Brown, Eseng Lai (all MSD) and Bruno Hoen (Institut Pasteur) for critical review of the manuscript. We acknowledge Prof. Dr. Herwig Kollaritsch (Medical University of Vienna, Austria), Assoc. Prof. Dr. Laura Richert (University of Bordeaux, France), and Dr. Yves Van Laethem (CHU Saint-Pierre, Brussels, Belgium) for agreeing to be members of the Data Safety Monitoring Board., We further thank the CEPI project team for their continuous support and helpful discussions., and Escriou, Nicolas

Subjects
Adult, Male, Medicine (General), COVID-19 Vaccines, [SDV.BIO]Life Sciences [q-bio]/Biotechnology, Adolescent, Genetic Vectors, General Biochemistry, Genetics and Molecular Biology, Immunogenicity, Vaccine, R5-920, [SDV.IMM.VAC] Life Sciences [q-bio]/Immunology/Vaccinology, Double-Blind Method, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, vaccine, Humans, measles vector, SARS-CoV-2, COVID-19, Articles, General Medicine, Middle Aged, [SDV.BIO] Life Sciences [q-bio]/Biotechnology, Measles virus, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Medicine, Female, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, [SDV.IMM.VAC]Life Sciences [q-bio]/Immunology/Vaccinology
Abstract

International audience; Background V591 (TMV-083) is a live recombinant measles vector-based vaccine candidate expressing a pre-fusion stabilized SARS-CoV-2 spike protein.Methods We performed a randomized, placebo-controlled Phase I trial with an unblinded dose escalation and a dou- ble-blind treatment phase at 2 sites in France and Belgium to evaluate the safety and immunogenicity of V591. Ninety healthy SARS-CoV-2 sero-negative adults (18-55 years of age) were randomized into 3 cohorts, each compris- ing 24 vaccinees and 6 placebo recipients. Participants received two intramuscular injections of a low dose vaccine (1 £ 105 median Tissue Culture Infectious Dose [TCID50]), one or two injections of a high dose vaccine (1 £ 106 TCID50), or placebo with a 28 day interval. Safety was assessed by solicited and unsolicited adverse events. Immuno- genicity was measured by SARS-CoV-2 spike protein-binding antibodies, neutralizing antibodies, spike-specific T cell responses, and anti-measles antibodies. ClinicalTrials.gov, NCT04497298.Findings Between Aug 10 and Oct 13, 2020, 148 volunteers were screened of whom 90 were randomized. V591 showed a good safety profile at both dose levels. No serious adverse events were reported. At least one treatment- related adverse event was reported by 15 (20.8%) participants receiving V591 vs. 6 (33.3%) of participants receiving placebo. Eighty-one percent of participants receiving two injections of V591 developed spike-binding antibodies after the second injection. However, neutralizing antibodies were detectable on day 56 only in 17% of participants receiv- ing the low dose and 61% receiving the high dose (2 injections). Spike-specific T cell responses were not detected. Pre-existing anti-measles immunity had a statistically significant impact on the immune response to V591, which was in contrast to previous results with the measles vector-based chikungunya vaccine.Interpretation While V591 was generally well tolerated, the immunogenicity was not sufficient to support further development.

Published
2022

2. First-in-Human Study in Healthy Subjects with FR104, a Pegylated Monoclonal Antibody Fragment Antagonist of CD28

Author

Steven Ramael, Jean-Paul Soulillou, Tim Van Assche, Weirong Wang, Ian Gourley, Maryvonne Hiance, Didier Coquoz, Caroline Mary, Cécile Braudeau, Régis Josien, Nicolas Poirier, Gilles Blancho, Virginie Thepenier, Jos Lempoels, Bernard Vanhove, Nina Salabert, Ian Anderson, Centre de Recherche en Transplantation et Immunologie (U1064 Inserm - CRTI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Institut de transplantation urologie-néphrologie (ITUN), Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), OSE Immunotherapeutics [Nantes, France], Clinical Pharmacology Unit Antwerp [Antwerp, Belgium], SGS Life Science Services (SGS), SGS (SGS)-SGS (SGS), Janssen Research & Development [Spring House, PA, USA], Laboratoire d’Immunologie [CHU Nantes] (Centre d’Immunomonitorage Nantes Atlantique - CIMNA), Centre hospitalier universitaire de Nantes (CHU Nantes), Copexis S.A. [Pully, Switzerland], LabEx IGO 'Immunotherapy, Graft, Oncology' [Nantes], Le Bihan, Sylvie, LabEX IGO Immunothérapie Grand Ouest, and Nantes Université (Nantes Univ)

Subjects
Adult, Graft Rejection, Male, 0301 basic medicine, medicine.drug_class, Immunology, chemical and pharmacologic phenomena, Pharmacology, Monoclonal antibody, Autoimmune Diseases, Cohort Studies, Immunoglobulin Fab Fragments, 03 medical and health sciences, 0302 clinical medicine, CD28 Antigens, Clinical Protocols, Pharmacokinetics, medicine, Humans, Immunology and Allergy, Potency, Lymphocyte Count, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, biology, business.industry, Antagonist, Antibodies, Monoclonal, Organ Transplantation, Middle Aged, Healthy Volunteers, Immunity, Humoral, Blockade, 030104 developmental biology, Pharmacodynamics, biology.protein, Administration, Intravenous, Female, Immunotherapy, Antibody, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Immunosuppressive Agents, Keyhole limpet hemocyanin, Follow-Up Studies, 030215 immunology
Abstract

FR104 is a monovalent pegylated Fab′ Ab, antagonist of CD28, under development for treatment of transplant rejection and autoimmune diseases. In contrast to CD80/86 antagonists (CTLA4-Ig), FR104 selectively blunts CD28 costimulation while sparing CTLA-4 and PD-L1 coinhibitory signals. In the present work, FR104 has been evaluated in a first-in-human study to evaluate the safety, pharmacokinetics, pharmacodynamics, and potency of i.v. administrations in healthy subjects. Sixty-four subjects were randomly assigned to four single ascending dose groups, two double dose groups and four single ascending dose groups challenged with keyhole limpet hemocyanin. Subjects were followed up over a maximum of 113 d. Overall, the pharmacokinetics of FR104 after a single and double infusions was approximately linear at doses ≥0.200 mg/kg. CD28 receptor occupancy by FR104 was saturated at the first sampling time point (0.5 h) at doses above 0.02 mg/kg and returned to 50% in a dose-dependent manner, by day 15 (0.020 mg/kg) to 85 (1.500 mg/kg). FR104 was well tolerated, with no evidence of cytokine-release syndrome and no impact on blood lymphocyte subsets. Inhibition of anti-keyhole limpet hemocyanin Ab response was dose-dependent in FR104 recipients and was already apparent at a dose of 0.02 mg/kg. Abs to FR104 were detected in 22/46 (48%) of FR104 recipients and only 1/46 (2.2%) was detected during drug exposure. In conclusion, selective blockade of CD28 with FR104 was safe and well tolerated at the doses tested. The observed immunosuppressive activity indicated that FR104 has potential to show clinical activity in the treatment of immune-mediated diseases.

Published
2016

3. Clinical pharmacology of exogenously administered alkaline phosphatase

Author

J.G. van der Hoeven, Ferdinand T F Snellen, M. Bulitta, Philippe G. Jorens, Jaap E. Tulleken, Peter Pickkers, R. Lins, S. Ramael, Peter Rogiers, J. Meulenbelt, Herbert Spapen, Jan Bakker, Risk Assessment of Toxic and Immunomodulatory Agents, Dep IRAS, Department of Intensive Care Medicine (551), Radboud University Medical Center [Nijmegen], Department of Anesthesiology, Isala Klinieken, Department of Intensive Care, Antwerp University Hospital [Edegem] (UZA), Erasmus Medical Centre, Department of Critical Care Medicine and Clinical Pharmacology, Division of Intensive Care Centre, University Medical Centre Utrecht, Institute for Risk Assessment Sciences, Utrecht University, ICU Department, University Hospital, Intensive and Respiratory Care Unit, University Medical Centre, Clinical Pharmacology Unit Antwerp, SGS Life Science Services (SGS), SGS (SGS)-SGS (SGS), and CRM Biometrics GmbH

Subjects
Adult, Male, EXPRESSION, medicine.medical_specialty, Renal failure, Time Factors, Pharmacology, Loading dose, law.invention, Sepsis, Pharmacokinetics, Double-Blind Method, law, PHOSPHODIESTERASE ACTIVITY, Internal medicine, Intensive care, Alkaline phosphatase, medicine, Humans, Pharmacology (medical), Infusions, Intravenous, Volunteer, ComputingMilieux_MISCELLANEOUS, Aged, Inflammation, Clinical pharmacology, SEPSIS, business.industry, Tumor Necrosis Factor-alpha, Pharmacology. Therapy, Interleukins, SEPTIC SHOCK, General Medicine, Middle Aged, medicine.disease, ADENOSINE, Endotoxemia, Pathogenesis and modulation of inflammation [N4i 1], Clinical trial, Endocrinology, Pharmacodynamics, Female, business, Half-Life
Abstract

Contains fulltext : 79632.pdf (Publisher’s version ) (Closed access) PURPOSE: To evaluate the clinical pharmacology of exogenous alkaline phosphatase (AP). METHODS: Randomized, double-blind, placebo-controlled sequential protocols of (1) ascending doses and infusion duration (volunteers) and (2) fixed dose and duration (patients) were conducted at clinical pharmacology and intensive care units. A total of 103 subjects (67 male volunteers and 36 patients with severe sepsis) were administered exogenous, 10-min IV infusions (three ascending doses) or 24-72 h continuous (132.5-200 U kg(-1) 24 h(-1)) IV infusion with/without preceding loading dose and experimental endotoxemia for evaluations of pharmacokinetics, pharmacodynamics, safety parameters, antigenicity, inflammatory markers, and outcomes. RESULTS: Linearity and dose-proportionality were shown during 10-min infusions. The relatively short elimination half-life necessitated a loading dose to achieve stable enzyme levels. Pharmacokinetic parameters in volunteers and patients were similar. Innate immunity response was not significantly influenced by AP, while renal function significantly improved in sepsis patients. CONCLUSIONS: The pharmacokinetics of exogenous AP is linear, dose-proportional, exhibit a short half-life, and are not influenced by renal impairment or dialysis.

Published
2009

Catalog

Books, media, physical & digital resources
See catalog results