Cancer Center Support Grant Supplement: Clinical Evaluation of a Q GRFT Nasal Spray for Prevention of SARS-CoV-2

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.