This amendment included the following changes: changes made in response to the Food and Drug Administration feedback, including further definition of subject self assessment timing; clarification of reasons for and recording of antipyretic treatment, inclusion of a urinalysis sample on Day 3; modification of the analysis plan to include an analysis of the primary efficacy variable on the intent-to-treat (ITT) population as a secondary endpoint and some minor editorial changes, corrections, and clarifications.

This amendment included the following changes: clarification of inclusion criteria and exclusion criteria, prior and concomitant medications, and withdrawal of subjects; removal of the following exclusion criteria: immunized (intranasal or injected vaccine) against influenza in the 6 months before the study; incorporation of changes made to initiate the treatment part of this study (Part B) in a clinic; addition of an interim analysis and some minor editorial changes, corrections, and clarifications.

This amendment included the following changes: Incorporation of changes made to streamline the study by removing surveillance (Part A) and including additional testing for screen failures, to refine inclusion/exclusion criteria and to modify language regarding duration of the study to reflect the extension of the study into another season of influenza in the Northern Hemisphere; addition of assessment for confirmation of influenza A per rapid influenza diagnostic test (RIDT) following informed consent. Sites were instructed to take 2 images of each positive RIDT and to file the images as source documents; clarification that all subjects who signed informed consent had to have a virology assessment on their nasopharyngeal (NP) swab, irrespective of enrollment for treatment; exclusion of nasal steroid medications; clarification that screen failures had to undergo virology testing from NP swabs; clarification of the type and use of antipyretic and anti-inflammatory medications allowed; expansion of study duration from 5 to 18 months to obtain desired enrollment of approximately 500 subjects and some minor editorial changes, corrections, and clarifications.

This amendment included the following changes: Incorporation of changes made to the primary objective from an evaluation of symptom relief to an effect on viral activity. This led to a change in the primary endpoint to viral area under the curve (AUC), and to clinical symptoms becoming the key secondary endpoint. Analytical details were updated accordingly, specifying the dose-response relation of viral AUC following administration of JNJ 63623872 as primary analysis, as well as updating the analysis of the key secondary endpoint. A formal interim analysis was also added at the end of the 2015 2016 Northern Hemisphere season. The intention was to recruit the full 500 planned subjects, unless at the time of the interim analysis a statistically significant positive dose response relationship was concluded. Addition of a potential extension to a second Southern Hemisphere season and the associated increased study duration and some minor editorial changes, corrections, and clarifications.