Intravenous Immunoglobulin Rich in Neutralising Antibodies to SARS-CoV-2 as a Passive Immunity Modality in Healthy Individuals at Risk of Infection With COVID-19: Study Protocol for an Open Label, Active Control Phase 1/2 Study.

Background The COVID-19 pandemic has demonstrated the fragility of our healthcare systems and the need for rapid development of effective care strategies. Global efforts to develop novel therapeutics have intensified, but in late November 2020, few are approved. There is an urgent need for novel therapeutics to limit further spread of COVID-19. Passive immunity by infusing neutralising anti-SARS-CoV-2 antibodies provides a method to prevent infection in individuals at heightened risk such as frontline health care workers. Convalescent plasma (CP) collected from donors who have recovered from an infectious disease can be pooled and fractionated into hyperimmune intravenous immunoglobulin (HIVIG), a concentrated formulation with enriched levels of pathogen-specific antibodies. HIVIG are established for therapeutic and prophylactic administration across many infectious diseases and possess many advantages over CP including consistent high titres of antiviral antibodies without ABO matching or risk of transfusion related acute lung injury (TRALI) or transfusion associated circulatory overload (TACO), lower infusion volume, simpler storage, longer shelf life, and easier administration. Method A parallel group, open-label, active control, phase 1/2 trial which allocates healthy adult healthcare workers never infected with SARS-CoV-2 to receive a single intravenous infusion of either CP or HIVIG. This clinical trial is the first to establish whether a HIVIG preparation concentrated with antibodies to SARS-CoV-2 is safe when administered to healthcare workers in the prevention of COVID-19, and to assess whether the anti-SARS-CoV-2 antibodies in the HIVIG are pharmacokinetically equivalent to those in unmodified CP.Discussion Trials to date suggest that allocation of limited CP may be optimised if used for prevention rather than treatment of COVID-19. This HIVIG (CovimmuneTM, Aegros Ltd.) is manufactured by a novel plasma fractionation technology (HaemaFracTM, Aegros Ltd.) which offers high purity and a greater protein yield from smaller batches of starting plasma than is possible with conventional fractionation techniques. If successful, this approach can be rapidly scaled up for implementation into clinical practice and contribute to the sustainability of healthcare systems during the current and future pandemics. The more prevention and treatment options available to address the COVID-19 pandemic, the stronger the position our society will hold. Trial registration Australia & New Zealand Clinical Trials Registry. Registration number: ACTRN12620001249943p. Date: 20/11/2020. https://www.anzctr.org.au/ACTRN12620001249943p.aspx