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Principal Investigator: Robert L. Ferris
Organization: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
Fiscal Year: 2020
Award: $1,197,257
Funding agency: National Cancer Institute
The current approaches of using protective barriers, social distancing and increased hand hygiene to prevent SARS-CoV-2 transmission have economic consequences and variable efficacy at reducing the spread of SARS-CoV-2. Therefore, curtailing the acquisition of SARS-CoV-2 infection via chemoprophylactic strategies is a high priority. SARS-CoV-2 transmission occurs predominantly through oral and nasal routes leading to high viral replication in the oropharynx and nasopharynx. We hypothesize that prophylactic use of antivirals against SARS-CoV-2 via a nasal spray can lead to virus inactivation at the sites of viral entry and replication. Our network of collaborators has shown that the broad spectrum oligomannose-binding lectins, Griffithsin (GRFT) and Q-GRFT, inhibit viral entry of all coronaviruses tested, including SARS-CoV, MERS-CoV and SARS-CoV2. Moreover, delivery of these antiviral lectins to the upper respiratory tract provides significant protection from SARS-CoV, MERS-CoV and paramyxovirus Nipah virus in animal models. Therefore, the PREVENT COVID clinical program is designed to establish the feasibility of this approach by demonstrating that nasal administration of Q-GRFT is safe and acceptable and also ascertain whether levels of Q-GRFT in upper respiratory tract samples are adequate to provide protection from SARS-CoV-2 based on pharmacodynamic assessments of the respiratory tract fluids. Three specific aims are proposed to advance the Q-GRFT nasal spray from bench to the clinic. Aim 1 will collate the results of preclinical studies of Q-GRFT along with chemical composition and manufacturing information related to the Q-GRFT nasal formulation to support the development of the Investigator’s Brochure, which will support the filing of an investigator-initiated Investigational New Drug (IND) Application to the US Food and Drug Administration. In Aim 2, pilot studies will be conducted to collect matrices from human volunteers (nasal swabs, nasal washes, saliva samples, pharyngeal swabs and gargle solutions) for development of analytical and biological methods to guide the development of validated assays for the quantification of Q-GRFT in the upper respiratory tract samples obtained from participants in the phase 1 study. In Aim 3, a Phase 1 randomized, placebo-controlled study (PREVENT COVID-101) of the Q-GRFT nasal spray in 45 healthy volunteers will be conducted. Healthy adults ages 18-45 will be randomized 2:1 to receive the Q-GRFT vs identical placebo. Participants will use the spray once, followed by a safety assessment 24 hours later. If safe and acceptable, a second period of daily administration for 14 days will commence. Follow up safety assessments will be conducted after 14 daily applications and the final safety assessment will occur 28 days after initiation of the daily use dosing period. The primary study objective will be to evaluate safety. Secondary objectives include user perceptions and acceptability, assessment of the level of Q-GRFT in respiratory tract samples and the impact of product use on taste and smell. Ultimately, the success of PREVENT COVID program will lead to a safe nasal spray, which can be further evaluated in an efficacy trial to study prevention of coronavirus infection.
Terms: <2019 novel coronavirus><2019-nCoV><21+ years old><Active Follow-up><Address><Adult><Adult Human><Age><Aging><Animal Model><Animal Models and Related Studies><Antiviral Agents><Antiviral Drugs><Antivirals><Area><Assay><Basic Research><Basic Science><Binding><Bio-Informatics><Bioassay><Bioinformatics><Biologic Assays><Biological><Biological Assay><Biology><Biometrics><Biometry><Biostatistics><Body Tissues><Booklets><Breast Cancer><Brochures><CCSG><COVID><Cancer Biology><Cancer Burden><Cancer Center Support Grant><Cancer Patient><Cancer Survivor><Cancers><Catchment Area><Chemicals><Climate><Clinical><Clinical Data><Clinical Evaluation><Clinical Protocols><Clinical Research><Clinical Sciences><Clinical Study><Clinical Testing><CoV disease><Collaborations><Community Outreach><Comprehensive Cancer Center><Coronaviridae><Coronaviridae Infections><Coronavirus><Coronavirus Infections><Cytometry><Data><Decision Making><Development><Diagnosis><Direct Costs><Discipline><Dose><Economics><Education><Education and Outreach><Educational Achievement><Educational Status><Educational aspects><Ensure><Faculty><Food and Drug Administration><Formulation><Funding><Goals><Gustation><Hand><Head and Neck Cancer><Health><Hour><Human Volunteers><Hygiene><Immune Monitoring><Immunologic Monitoring><Immunological Monitoring><Immunomonitoring><Infection><Instruction and Outreach><Investigational Drugs><Investigational New Drug Application><Investigational New Drugs><Investigators><Journals><Laboratories><Lead><Leadership><Learning><Lectin><Liquid substance><MERS corona virus><MERS coronavirus><MERS virus><MERS-CoV><Magazine><Malignant Head and Neck Neoplasm><Malignant Melanoma><Malignant Neoplasms><Malignant Ovarian Neoplasm><Malignant Ovarian Tumor><Malignant Tumor><Malignant Tumor of the Lung><Malignant Tumor of the Ovary><Malignant neoplasm of lung><Malignant neoplasm of ovary><Medicine><Mentors><Meteorological Climate><Methods><Middle East 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documentation><Publishing><Pulmonary Body System><Pulmonary Cancer><Pulmonary Organ System><Pulmonary malignant Neoplasm><QOL><Quality of life><Randomized><Research><Research Peer Review><Research Personnel><Research Resources><Research Support><Researchers><Resource Sharing><Resources><Respiratory System><Respiratory System, Nose, Nasal Passages><Respiratory Tracts><Respiratory tract structure><Rhinopharynx><Route><SARS Virus><SARS corona virus><SARS coronavirus><SARS-Associated Coronavirus><SARS-CoV><SARS-CoV-2><SARS-CoV2><SARS-Related Coronavirus><SARS-associated coronavirus 2><SARS-coronavirus-2><SARS-related coronavirus 2><Safety><Saliva><Sampling><Secure><Services><Severe Acute Respiratory Syndrome Virus><Severe Acute Respiratory Syndrome corona virus><Severe Acute Respiratory Syndrome coronavirus><Severe acute respiratory syndrome coronavirus 2><Sham Treatment><Sight><Site><Smell><Smell Perception><Social Distance><Strategic Planning><Swab><System><Taste><Taste Perception><Testing><Therapeutic><Tissue imaging><Tissues><Training and Outreach><Translational Research><Translational Science><Transmission><Tutoring and Outreach><UPCI><USFDA><United States Food and Drug Administration><Universities><University of Pittsburgh Cancer Institute><Upper respiratory tract><Viral><Viral Inactivation><Virus Inactivation><Virus Replication><Vision><Wuhan coronavirus><acronyms><active followup><adiposity><adulthood><ages><animal facility><anti-cancer research><anti-viral agents><anti-viral drugs><anti-virals><anticancer research><base><bench bed side><bench bedside><bench to bed side><bench to bedside><bench to clinic><biobehavior><biobehavioral><cancer epidemiology><cancer genomics><cancer immunology><cancer microenvironment><cancer prevention><cancer proteomics><cancer research><cell imaging><cellular imaging><climatic><clinical care><clinical test><corona virus><corona virus disease><coronavirus disease><corpulence><corpulency><corpulentia><data management><design><designing><developmental><educational level><efficacy trial><fluid><follow up><follow-up><followed up><followup><gustatory perception><gustatory processing><gustatory response><head/neck cancer><healthy volunteer><heavy metal Pb><heavy metal lead><imaging facilities><imaging in vivo><improved><in vivo imaging><innovate><innovation><innovative><liquid><lung cancer><malignancy><malignant breast neoplasm><malignant breast tumor><malignant head and neck tumor><melanoma><member><model of animal><model organism><nasopharnygeal><neoplasm immunology><neoplasm/cancer><obese><obese people><obese person><obese population><odor perception><olfactory perception><oncogenomics><oncology program><oral pharyngeal><ovarian cancer><pharmacokinetics and pharmacodynamics><phase 1 study><pilot study><pre-clinical study><preclinical study><prevent><preventing><programs><prophylactic><randomisation><randomization><randomized placebo controlled study><randomly assigned><recruit><research 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