PHASE 1 CLINICAL TRIALS OF A Q-GRIFFITHSIN NASAL SPRAY FOR SARS-CoV-2 PROPHYLAXIS

ABSTRACT

Background: The currently approved vaccines do not induce sterilizing immunity against SAR-CoV-2 infection, and immunity wanes over time. A robust broad spectrum topical prophylaxis strategy could protect vulnerable populations in the face of continuous evolution of SARS-CoV-2. The algal antiviral lectin Griffithsin (GRFT), and an engineered oxidation-resistant variant Q-GRFT have robust entry inhibitory activity against SARS-CoV variants of concern, in addition to other respiratory viruses with pandemic potential. We designed a nasal spray to deliver Q-GRFT to the upper respiratory tract mucosa for on-demand use as a broad-spectrum prophylactic. Two clinical trials (Phase 1a and 1b) were conducted to assess safety, tolerability, and pharmacokinetics of Q-GRFT nasal spray in healthy adults. Method(s) Healthy adult volunteers were enrolled in a Phase 1a double blinded, randomized study to receive a single dose of either intranasal Q-GRFT (3.0 mg, 2 sprays per nostril) or placebo at 21 ratio. Following a safety review, the Phase 1b study was initiated. Eleven volunteers in Group 1 received 3.0 mg dose once daily, for 7 days. After a safety review, 11 volunteers in Group 2 received a total of 6.0 mg Q-GRFT (3.0 mg twice daily for 7 days). Topical Q-GRFT concentrations were measured by ELISA in collected nasal and nasopharyngeal fluids. Drug levels in plasma were assayed to determine systemic exposure. Viral microneutralization cytopathic effect (CPE) assays were performed against SARS-CoV-2 Omicron BA-5 and MERS-CoV. Result(s) Eighteen adults (24-54 years;Males 58.3%, Females 41.7%;12 Q-GRFT, 6 Placebo), and 22 adults (aged 23-59 years;Males 52.4%, Females 47.6%) were enrolled in Phase 1a and 1b, respectively. In Phase 1a, a single dose of Q-GRFT maintained quantifiable levels in nasal passages and nasopharynx for up to 24 hours. Similarly, Q-GRFT was quantifiable in nasal and nasopharyngeal regions in the Phase 1b study. No dose accumulation effect or systemic exposure was observed. Nasal and nasopharyngeal swab eluates inhibited SARS-CoV-2 Omicron BA.5 and MERS-CoV in CPE assays. Q-GRFT did not modify olfactory sensation. No severe adverse events were reported. Thus, the nasal spray was deemed safe. Conclusion(s) Intranasal Q-GRFT was safe and enhanced mucosal SARSCoV-2 inhibitory activity in human volunteers. The results support further development of Q-GRFT as a broad-spectrum prophylactic against coronaviruses to curb ongoing infections, and for future pandemic preparedness.