PrEP-001 prophylactic effect against rhinovirus and influenza virus - RESULTS of 2 randomized trials

• Published in: Antiviral research Vol. 153; pp. 70 - 77
• Main Authors: Malcolm, Bruce Albert, Aerts, Caroline Anne, Dubois, Kristof Johan, Geurts, Frederik Joris, Marien, Kris, Rusch, Sarah, Van Dijck, Alex Henri, Verloes, Rene, Vingerhoets, Johan
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.05.2018
• Subjects: Administration, Intranasal; Drug-Related Side Effects and Adverse Reactions - epidemiology; Drug-Related Side Effects and Adverse Reactions - pathology; Healthy Volunteers; Humans; Immunologic Factors - administration & dosage; Immunologic Factors - adverse effects; Influenza A Virus, H3N2 Subtype - immunology; Influenza, Human - pathology; Influenza, Human - prevention & control; Innate immune response; Nasal; Nasal Mucosa - immunology; Picornaviridae Infections - pathology; Picornaviridae Infections - prevention & control; Placebos - administration & dosage; Poly I-C - administration & dosage; Poly I-C - adverse effects; Poly I:C; Powders - administration & dosage; Powders - adverse effects; Prophylaxis; Randomized Controlled Trials as Topic; Rhinovirus - immunology; Treatment Outcome; Upper respiratory viral infections; Viral disease; Upper respiratory viral infections; Nasal; Poly I:C; Innate immune response; Viral disease; Prophylaxis
• ISSN: 0166-3542; 1872-9096; 1872-9096
• DOI: 10.1016/j.antiviral.2018.03.005

PrEP-001 Nasal Powder, a proprietary formulation of polyriboinosinic and polyribocytidylic acid effectively elicits a cellular innate immune response in nasal epithelium. The aim of these 2 studies was to investigate the safety and efficacy of PrEP-001 prophylaxis against rhinovirus (HRV-A16) and influenza-A (H3N2-IAV). Healthy subjects randomly received 2 doses of PrEP-001 or placebo, 48 and 24 h pre-challenge with 10 TCID50 of HRV-A16 (Study 1) or H3N2-IAV (Study 2). In Study 1, PrEP-001 reduced median total symptom score from 38.5 to 4.5 (p = 0.004), median symptom duration from 6.0 to 1.7 days and median mucus production from 15 g to 3 g. The percentage of subjects classified as ill was reduced 3-fold (placebo 73%, PrEP-001 23%, p = 0.002). In Study 2, PrEP-001 reduced median total symptom score from 8.0 to 4.1 (p = 0.021), median symptom duration from 4.6 to 3.7 days and median mucus production from 3.6 g to 1.5 g. The percentage of subjects classified as ill was reduced 2-fold (placebo 48%, PrEP-001 24%, p = 0.064). PrEP-001 reduced peak viral shedding in both studies, as assessed by qRT-PCR of nasal lavage. Seroconversion rates were comparable between placebo and PrEP-001 (Study 1: 77% [both arms]; Study 2: placebo 73%, PrEP-001 80%). PrEP-001 was well-tolerated, with no clinically significant adverse events. PrEP-001 reduced the number of individuals with clinical illness and attenuated severity and duration of HRV-A16 and H3N2-IAV infections without compromising seroconversion, and was well-tolerated. This supports further evaluation of PrEP-001 as a potential pan-viral prophylaxis for upper respiratory tract infections. Study 1, HRV-A16 study: EudraCT Number 2012-005579-14 (study conducted before ClinicalTrials.gov registration required). Study 2, H3N2-IAV study: EudraCT Number 2015-002895-26 and ClinicalTrials.gov: NCT03220048.