First-in-human study of two anti-SARS CoV-2 antibodies in health volunteers

NIH Pandemic-Era Grants

Pandemic Era Grants

2021

↗ Live URL (may be dead)

Document text

Principal Investigator: Luis J Montaner
Organization: WISTAR INSTITUTE
Fiscal Year: 2021
Award: $1,571,599
Funding agency: National Institute of Allergy and Infectious Diseases

Project Summary
The Coronavirus Disease 2019 (COVID-19) pandemic is currently gripping the world without a known cure or
prevention. Aside from the health consequences, the necessary decrease in human activity has resulted in
economic losses without modern precedent, especially in the developing world where health care and sanitation
were not sufficient even prior to the pandemic. Innumerable efforts are being undertaken to develop vaccines to
SARS-CoV-2 and it is likely that antibodies will be essential for protection.
COVID-19 antibody therapy in the form of polyclonal plasma from convalescent individuals is currently being
explored as a therapeutic option and has been granted an emergency use authorization (EUA) by the FDA.
Monoclonal antibodies may prove to be particularly useful in preventing SARS-CoV-2 infection in populations
who may not mount protective immune responses to vaccination (e.g. advanced age, immunocompromise) and
for post-exposure prophylaxis in individuals at high risk to develop severe COVID-19.
C135 and C144 are recombinant, fully human mAbs that specifically bind SARS-CoV-2 spike protein receptor
binding domain (RBD) and exhibit exceptional neutralizing activity in vitro against SARS-CoV-2. Two one-amino
acid mutations have been introduced to prolong half-life and allow dose sparing. The C135-LS and C144-LS
combination has shown remarkable activity in both prophylaxis and therapy experiments in several relevant
animal models in both prophylaxis and treatment experiments. These preclinical data support the clinical evahe
from SARS-CoV-2 and accelerate viral clearance and disease resolution in SARS-CoV-2-infected individuals.
The proposed study is a first-in-human, open label, single dose, dose-escalation phase 1 trial to evaluate the
safety and pharmacokinetics of the C135-LS and C144-LS combination in healthy volunteers.

Terms: <2019 novel corona virus><2019 novel coronavirus><2019-nCoV><2019-nCoV S protein><2019-nCoV spike glycoprotein><2019-nCoV spike protein><Amino Acid Substitution><Amino Acids><Animal Model><Animal Models and Related Studies><Animals><Antibodies><Antibody Therapy><Antigens><Antiviral Agents><Antiviral Drugs><Antivirals><Asparagine><Binding><Biological><COVID crisis><COVID epidemic><COVID pandemic><COVID-19><COVID-19 S protein><COVID-19 antibody><COVID-19 crisis><COVID-19 epidemic><COVID-19 global health crisis><COVID-19 global pandemic><COVID-19 health crisis><COVID-19 infection><COVID-19 pandemic><COVID-19 public health crisis><COVID-19 spike glycoprotein><COVID-19 spike protein><COVID-19 virus><COVID19><COVID19 S protein><COVID19 crisis><COVID19 epidemic><COVID19 global health crisis><COVID19 global pandemic><COVID19 health crisis><COVID19 infection><COVID19 pandemic><COVID19 public health crisis><COVID19 spike glycoprotein><COVID19 spike protein><COVID19 virus><CV-19><CV19><Clinical><Clinical Evaluation><Clinical Testing><Clinical Treatment Moab><CoV-2><CoV2><Cricetinae><Data><Disease><Disorder><Dose><Drug Kinetics><Economics><Elderly><Exhibits><FDA EUA><FDA Emergency Use Authorization><Fc domain><Food and Drug Administration EUA><Food and Drug Administration Emergency Use Authorization><Genetic Alteration><Genetic Change><Genetic defect><Grant><Half-Life><Hamsters><Hamsters Mammals><Health><Healthcare><Hu-mABs><Human Activities><IV Infusion><Immune><Immune response><Immunes><Immunocompromised><Immunocompromised Host><Immunocompromised Patient><Immunological response><Immunosuppressed Host><In Vitro><Individual><Infection><Intravenous><Intravenous infusion procedures><L-Asparagine><L-Serine><Leucine><Methionine><Mice><Mice Mammals><Modernization><Molecular Interaction><Monoclonal Antibodies><Murine><Mus><Mutation><Outcome><Participant><Pathology><Pattern><Pharmacokinetics><Phase><Phase I Study><Play><Population><Populations at Risk><Position><Positioning Attribute><Prevention><Prophylactic treatment><Prophylaxis><Randomized Controlled Trials><Recombinants><Resistance><Resolution><Role><SARS corona virus 2><SARS-CoV-2><SARS-CoV-2 S protein><SARS-CoV-2 antibody><SARS-CoV-2 epidemic><SARS-CoV-2 global health crisis><SARS-CoV-2 global pandemic><SARS-CoV-2 infection><SARS-CoV-2 pandemic><SARS-CoV-2 spike glycoprotein><SARS-CoV-2 spike protein><SARS-CoV2><SARS-CoV2 S protein><SARS-CoV2 antibody><SARS-CoV2 epidemic><SARS-CoV2 infection><SARS-CoV2 pandemic><SARS-CoV2 spike glycoprotein><SARS-CoV2 spike protein><SARS-associated corona virus 2><SARS-associated coronavirus 2><SARS-coronavirus-2><SARS-coronavirus-2 epidemic><SARS-coronavirus-2 pandemic><SARS-related corona virus 2><SARS-related coronavirus 2><SARSCoV2><Safety><Sanitation><Serine><Severe Acute Respiratory Distress Syndrome CoV 2><Severe Acute Respiratory Distress Syndrome Corona Virus 2><Severe Acute Respiratory Distress Syndrome Coronavirus 2><Severe Acute Respiratory Syndrome CoV 2><Severe Acute Respiratory Syndrome CoV 2 epidemic><Severe Acute Respiratory Syndrome CoV 2 pandemic><Severe Acute Respiratory Syndrome-associated coronavirus 2><Severe Acute Respiratory Syndrome-related coronavirus 2><Severe acute respiratory syndrome associated corona virus 2><Severe acute respiratory syndrome corona virus 2><Severe acute respiratory syndrome coronavirus 2><Severe acute respiratory syndrome coronavirus 2 S protein><Severe acute respiratory syndrome coronavirus 2 epidemic><Severe acute respiratory syndrome coronavirus 2 infection><Severe acute respiratory syndrome coronavirus 2 pandemic><Severe acute respiratory syndrome coronavirus 2 spike glycoprotein><Severe acute respiratory syndrome coronavirus 2 spike protein><Severe acute respiratory syndrome related corona virus 2><Site><Sterility><Subcutaneous Injections><Therapeutic><Universities><Vaccination><Vaccines><Variant><Variation><Viral><World Health><Wuhan coronavirus><advanced age><aminoacid><anti-viral agents><anti-viral drugs><anti-virals><antibody against COVID-19><antibody against SARS-CoV-2><antibody against SARS-CoV2><antibody against coronavirus disease 2019><antibody against severe acute respiratory syndrome coronavirus 2><antibody based therapies><antibody to COVID-19><antibody to SARS-CoV-2><antibody to SARS-CoV2><antibody to coronavirus disease 2019><antibody to severe acute respiratory syndrome coronavirus 2><antibody treatment><antibody-based therapeutics><antibody-based treatment><clinical candidate><clinical development><clinical test><convalescent plasma><corona virus disease 2019><corona virus disease 2019 epidemic><corona virus disease 2019 pandemic><coronavirus disease 2019><coronavirus disease 2019 S protein><coronavirus disease 2019 antibody><coronavirus disease 2019 crisis><coronavirus disease 2019 epidemic><coronavirus disease 2019 global health crisis><coronavirus disease 2019 global pandemic><coronavirus disease 2019 health crisis><coronavirus disease 2019 infection><coronavirus disease 2019 pandemic><coronavirus disease 2019 public health crisis><coronavirus disease 2019 spike glycoprotein><coronavirus disease 2019 spike protein><coronavirus disease 2019 virus><coronavirus disease crisis><coronavirus disease epidemic><coronavirus disease pandemic><design><designing><elders><emergency use authorization><experiment><experimental research><experimental study><first in man><first-in-human><genome mutation><geriatric><hCoV19><health care><healthy volunteer><high risk><host response><humAbs><human mAbs><human monoclonal antibodies><human monoclonals><human study><immune system response><immunogen><immunoresponse><immunosuppressed patient><in vitro activity><in vivo><infected with COVID-19><infected with COVID19><infected with SARS-CoV-2><infected with SARS-CoV2><infected with coronavirus disease 2019><infected with severe acute respiratory syndrome coronavirus 2><intravenous infusion><late life><later life><life-threatening COVID><life-threatening COVID-19><life-threatening SARS-CoV-2><life-threatening coronavirus disease><life-threatening coronavirus disease 2019><life-threatening severe acute respiratory syndrome coronavirus 2><mAbs><model of animal><model organism><nCoV2><neutralizing mAb><neutralizing monoclonal antibodies><non-human primate><nonhuman primate><older adult><older person><open label><open label study><pandemic><pandemic disease><phase 1 study><phase 1 trial><phase I trial><pre-clinical><preclinical><pressure><prevent><preventing><receptor binding><receptor bound><research clinical testing><resistant><senior citizen><serious COVID><serious COVID-19><serious SARS-CoV-2><serious coronavirus disease><serious coronavirus disease 2019><serious severe acute respiratory syndrome coronavirus 2><severe COVID><severe COVID-19><severe COVID19><severe SARS-CoV-2><severe acute respiratory syndrome coronavirus 2 antibody><severe acute respiratory syndrome coronavirus 2 global health crisis><severe acute respiratory syndrome coronavirus 2 global pandemic><severe coronavirus disease><severe coronavirus disease 19><severe coronavirus disease 2019><severe severe acute respiratory syndrome coronavirus 2><social role><sterile><subcutaneous><subdermal><subdermal injection><volunteer>