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HCMV Therapeutic Antibody Safety Trial

HCMV 治疗性抗体安全性试验

基本信息

批准号：
10015670
负责人：
Lawrence Michael Kauvar
金额：
$ 29.97万
依托单位：
TRELLIS BIOSCIENCE, INC.
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-07-01 至 2021-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10015670
关键词：
Adult Affinity Antibodies Antiviral Agents B-Lymphocytes Binding Biological Sciences Bone Marrow Transplantation Child Chinese Hamster Ovary Cell Clinical Clinical Research Clinical Trials Cognitive Communicable Diseases Complex Congenital Abnormality Consultations Cytomegalovirus Delaware Development Disease Documentation Dose Drug Controls Drug Kinetics Epitopes Ethical Review Europe Fetus First Pregnancy Trimester Funding Grant Health Personnel Hospitalization Human Human Cloning Human Pathology Human Resources Immunoglobulins In Vitro Incidence Infection International Intravenous Japan Leadership Mammals Medical Medical Care Costs Modeling Monoclonal Antibodies Mothers Motor National Institute of Allergy and Infectious Disease Organ Organ Transplantation Passive Immunization Patients Phase Phase II Clinical Trials Population Positioning Attribute Pregnancy Private Sector Production Protocols documentation Publishing Quality Control Rattus Reporting Risk Safety Science Serotyping Services Site Small Business Innovation Research Grant Solid Specificity Technology Testing Therapeutic Agents Therapeutic Monoclonal Antibodies Therapeutic antibodies Tissues Toxic effect Toxicology Transplant Recipients Transplantation U-Series Cooperative Agreements Viral Virion Woman Work Writing cell bank cell type clinical development clinical lot cost cross reactivity deafness economic impact first-in-human healthy volunteer human model human monoclonal antibodies interest latent infection lead candidate medical complication neutralizing monoclonal antibodies operation phase I trial polyclonal human antibody prevent programs reactivation from latency side effect small molecule stillbirth transmission process

项目摘要

Abstract Human cytomegalovirus (HCMV) transmission from mother to fetus is implicated in ~15% of stillbirths and ~16,000 birth defects annually in the US. HCMV is also the major viral cause of medical complications associated with bone marrow and organ transplantation. Passive immunization using anti-HCMV enriched human immune globulin (HIG) has shown promising activity for both indications. HIG is a complex, variable product that may cause side effects from off-target antibody binding. A monoclonal antibody (mAb) offers qualitative advantages over HIG including potency, safety, production efficiency and quality control. Trellis Bioscience has discovered a high affinity native human mAb (TRL345) against the most conserved site on the HCMV virion (gB AD-2 Site I). TRL345 is a human IgG1kappa (G1m1,17 (z,a); Km3 allotype) monoclonal antibody cloned from human B lymphocytes. This mAb neutralized 15 out of 15 clinical isolates of all four major serotypes. It protected all of the specialized cell types relevant to human pathology. It was also fully protective in a model of human placental fragments grown as tissue explants ex vivo. This published work was completed under a Phase I/II SBIR grant. A Master Cell Bank has been developed that expresses TRL345 in CHO cells at a commercially useful level (1.74 g/L) at the 250L GMP scale. All IND-enabling analytical work has been completed, including GLP toxicology in rats and tissue reactivity profiling. With SBIR CRP funding, the first clinical lot has been manufactured yielding sufficient material for Phase 1 and 2 human clinical trials. We propose here to conduct a Phase 1 single ascending dose clinical trial in healthy volunteers.

摘要