DISCUSSION
nausea, myalgia, fever, fatigue, vomiting, rash, pain, pyrexia, muscle spasms, headache, oropharyngeal pain, chills, arthralgia
SEASONAL ALLERGIES, ADVERSE REACTIONS, EVENT, DISEASE, STERILE, MUSCULOSKELETAL AND CONNECTIVE TISSUE DISORDER, INFUSION REACTION
Study EBS-CVH-003 was a phase 1 single-center, double-blind, randomized, placebo-controlled study to assess the safety and pharmacokinetics of COVID-HIGIV following intravenous administration in healthy adult participants. The most frequent AEs (>5% of participants) reported in the safety population were headache (22.2%), chills (11.1%), increased bilirubin (7.4%), muscle spasms (7.4%), seasonal allergies (7.4%), pyrexia (7.4%), and oropharyngeal pain (7.4%). Of these common AEs, headache, increased bilirubin, and muscle spasms were considered related to COVID-HIGIV by the investigator at the time of the event. AEs related to musculoskeletal and connective tissue disorders (arthralgia, back pain, muscle spasms, and myalgia) were frequently reported in the COVID-HIGIV groups (5 participants; 21.7% of those receiving COVID-HIGIV), but none was observed in placebo participants. These frequently observed AEs were expected for a human IGIV product. AEs were more commonly reported for the highest COVID-HIGIV dose level (400 mg/kg). Most related AEs were of mild intensity and self-limited (observed in 9 of 13 participants experiencing related AEs; 69.2%), indicative of an overall favorable safety profile for COVID-HIGIV.The PK results for COVID-HIGIV obtained in this study were similar to the PK of other human IGIV products manufactured by Emergent and other commercial IGIV products (A limitation of this study was that the pseudoviral neutralizing antibody assay was not suitable for evaluating PK parameters for COVID-HIGIV due to its reduced sensitivity to antibody concentrations below 60 AU/mL. Such a high lower limit of quantitation (LLOQ) brings into question the utility of this assay for future evaluations of serum-neutralizing antibody concentrations. Further assay optimization would be necessary to be able to quantify PK parameters of neutralizing S-protein antibodies at lower concentrations in participants who are SARS-CoV-2 antibody negative at baseline. Future studies with COVID-HIGIV in participants that are antibody positive at baseline may be a feasible approach to generate PK data for SARS-CoV-2 neutralizing antibodies using this assay, as there would likely not be a limitation due to the LLOQ. Another limitation of the study was that mean age of the participants was 30.6 years of age with a range of 19 to 56 years. This may not be the target patient population if COVID-HIGIV will be used as a treatment for persons at high risk for severe disease. The high-risk population is typically greater than 65 years old.COVID-HIGIV is a sterile liquid preparation of the purified IgG fraction of human plasma containing polyclonal antibodies to SARS-CoV-2. COVID-HIGIV is being developed for postexposure prophylaxis and treatment of COVID-19. Given the reduced efficacy of some MAbs against emerging variants (The safety of human immunoglobulins is well established, and the most common types of adverse reactions to IGIV and hyperimmune products are nonanaphylactic infusion reactions (self-limiting), such as abdominal or back pain, fever, headache, chills, rash, fatigue, nausea, or vomiting. The incidence of adverse reactions associated with IGIVs is in the range of 1 to 15%, typically ≤5% (