Human Monoclonal Antibodies Neutralizing Cytomegalovirus (CMV) for Prophylaxis of CMV Disease: Report of a Phase I Trial in Bone Marrow Transplant Recipients
Autor: | Thomas F. Schulz, L. Ostberg, P. Grass, Christoph Huber, M. Scriba, K. Larcher, Dietger Niederwieser, Herbert Tilg, M. Mach, M. P. Dierich, W. E. Aulitzky, A. C. Stern, J. Martindale |
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Jazyk: | angličtina |
Rok vydání: | 2017 |
Předmět: |
Adult
Male medicine.medical_specialty Adolescent medicine.drug_class medicine.medical_treatment Congenital cytomegalovirus infection Cytomegalovirus Phases of clinical research Enzyme-Linked Immunosorbent Assay Monoclonal antibody Gastroenterology Pharmacokinetics Betaherpesvirinae Internal medicine medicine Humans Immunology and Allergy Bone Marrow Transplantation biology business.industry Immunization Passive Antibodies Monoclonal Middle Aged biology.organism_classification medicine.disease Autotransplantation Infectious Diseases medicine.anatomical_structure Cytomegalovirus Infections Immunology biology.protein Drug Evaluation Female Bone marrow Antibody business Half-Life |
Popis: | The safety and pharmacokinetics of the two neutralizing human IgG1 monoclonal antibodies to cytomegalovirus (CMV) SDZ 89-104 and 89-109 in bone marrow transplant (BMT) recipients was assessed in an open phase I trial. Thirteen patients, 8 seropositive and 5 seronegative for CMV, were treated with allogeneic or autologous bone marrow transplantation. SDZ 89-104 was given to 5 and SDZ 89-109 to 8 patients. Patients were divided into high- and low-dose groups. A fixed prestudy dose of 0.1 mg/kg was given 4 days before BMT. On days 3, 17, 31, 45, 59, and 73, patients were treated with either 0.5 or 2 mg/kg of the respective antibody. Results indicate that doses of 2 mg/kg of SDZ 89-104 or SDZ 89-109 in alternating weeks can be safely administered to BMT patients. Serum trough levels measured by antiidiotype ELISA were approximately 10 micrograms/ml after administration of 0.5 mg/kg and approximately 50 micrograms/ml after treatment with 2 mg/kg of SDZ 89-104 or SDZ 89-109. High serum levels defined by antiidiotype ELISA techniques closely paralleled increased neutralizing activity. Serum half-lives calculated from these data were approximately 6 days. |
Databáze: | OpenAIRE |
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