PMID- 36852998 OWN - NLM STAT- MEDLINE DCOM- 20230320 LR - 20230324 IS - 1098-6596 (Electronic) IS - 0066-4804 (Print) IS - 0066-4804 (Linking) VI - 67 IP - 3 DP - 2023 Mar 16 TI - Safety, Tolerability, and Pharmacokinetics of Anti-SARS-CoV-2 Immunoglobulin Intravenous (Human) Investigational Product (COVID-HIGIV) in Healthy Adults: a Randomized, Controlled, Double-Blinded, Phase 1 Study. PG - e0151422 LID - 10.1128/aac.01514-22 [doi] LID - e01514-22 AB - Anti-SARS-CoV-2 immunoglobulin (human) investigational product (COVID-HIGIV) is a purified immunoglobulin preparation containing SARS-CoV-2 polyclonal antibodies. This single-center clinical trial aimed to characterize the safety and pharmacokinetics of COVID-HIGIV in healthy, adult volunteers. Participants were enrolled to receive one of three doses of COVID-HIGIV (100, 200, 400 mg/kg) or placebo in a 2:2:2:1 randomization scheme. Between 24 December 2020 and 27 July 2021, 28 participants met eligibility and were randomized with 27 of these 28 (96.4%) being administered either COVID-HIGIV (n = 23) or placebo (n = 4). Only one SAE was observed, and it occurred in the placebo group. A total of 18 out of 27 participants (66.7%) reported 50 adverse events (AEs) overall. All COVID-HIGIV-related adverse events were mild or moderate in severity and transient. The most frequent AEs (>5% of participants) reported in the safety population were headache (n = 6, 22.2%), chills (n = 3, 11.1%), increased bilirubin (n = 2, 7.4%), muscle spasms (n = 2, 7.4%), seasonal allergies (n = 2, 7.4%), pyrexia (n = 2, 7.4%), and oropharyngeal pain (n = 2, 7.4%). Using the SARS-CoV-2 binding IgG immunoassay (n = 22, specific for pharmacokinetics), the geometric means of Cmax (AU/mL) for the three COVID-HIGIV dose levels (low to high) were 7.69, 17.02, and 33.27 AU/mL; the average values of T(max) were 7.09, 7.93, and 5.36 h, respectively. The half-life of COVID-HIGIV per dose level was 24 d (583 h), 31 d (753 h), and 26 d (619 h) for the 100 mg/kg, 200 mg/kg, and 400 mg/kg groups, respectively. The safety and pharmacokinetics of COVID-HIGIV support its development as a single-dose regimen for postexposure prophylaxis or treatment of COVID-19. FAU - Liu, Sean T H AU - Liu STH AUID- ORCID: 0000-0002-3842-6838 AD - Division of Infectious Diseases, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA. FAU - Mirceta, Mila AU - Mirceta M AD - Emergent BioSolutions Canada, Inc., Winnipeg, Manitoba, Canada. FAU - Lin, Grace AU - Lin G AD - Emergent BioSolutions Canada, Inc., Winnipeg, Manitoba, Canada. FAU - Anderson, Deborah M AU - Anderson DM AD - Emergent BioSolutions Canada, Inc., Winnipeg, Manitoba, Canada. FAU - Broomes, Tarashon AU - Broomes T AD - Division of Infectious Diseases, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA. FAU - Jen, Alina AU - Jen A AD - Division of Infectious Diseases, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA. FAU - Abid, Ashley AU - Abid A AD - Division of Infectious Diseases, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA. FAU - Reich, David AU - Reich D AD - Division of Infectious Diseases, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA. FAU - Hall, Christine AU - Hall C AD - Emergent BioSolutions Canada, Inc., Winnipeg, Manitoba, Canada. FAU - Aberg, Judith A AU - Aberg JA AUID- ORCID: 0000-0001-8162-0284 AD - Division of Infectious Diseases, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA. LA - eng SI - ClinicalTrials.gov/NCT04661839 PT - Clinical Trial, Phase I PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, U.S. Gov't, Non-P.H.S. DEP - 20230228 PL - United States TA - Antimicrob Agents Chemother JT - Antimicrobial agents and chemotherapy JID - 0315061 RN - 0 (Antibodies, Viral) RN - 0 (Immunoglobulin G) SB - IM MH - Humans MH - Adult MH - *COVID-19 MH - SARS-CoV-2 MH - Antibodies, Viral MH - Immunoglobulin G MH - Administration, Intravenous MH - Double-Blind Method PMC - PMC10019156 OTO - NOTNLM OT - COVID-19 OT - antiviral pharmacology OT - hyperimmune immunoglobulin COIS- The authors declare a conflict of interest. Emergent is receiving funding from the U.S. Department of Defense's Joint Program Executive Office for Chemical, Biological, Radiological and Nuclear Defense (JPEO-CBRND), in collaboration with the Defense Health Agency, under Other Transaction number W911QY-20-9-0013, for the development of COVID-HIGIV, a countermeasure to SARS-CoV-2. The U.S. Government is authorized to reproduce and distribute reprints for Governmental purposes notwithstanding any copyright notation thereon. The views and conclusions contained herein are those of the authors and should not be interpreted as necessarily representing the official policies or endorsements, either expressed or implied, of the U.S. Government. J.A.A. serves on advisory boards for GSK/ViiV and Merck. J.A.A. is on a data safety monitoring board for Kintor Pharmaceuticals. D.M.A., C.H., G.L., and M.M. were employees of Emergent BioSolutions during the conduct of this study. D.M.A., C.H., and M.M. own shares of Emergent BioSolutions. C.H. holds a pending patent: '63/403,074 Hyperimmune Globulins for Treatment and Prevention of COVID-19'. S.T.H.L. has received consulting fees from Synairgen. EDAT- 2023/03/01 06:00 MHDA- 2023/03/21 06:00 PMCR- 2023/02/28 CRDT- 2023/02/28 09:04 PHST- 2023/03/01 06:00 [pubmed] PHST- 2023/03/21 06:00 [medline] PHST- 2023/02/28 09:04 [entrez] PHST- 2023/02/28 00:00 [pmc-release] AID - 01514-22 [pii] AID - aac.01514-22 [pii] AID - 10.1128/aac.01514-22 [doi] PST - ppublish SO - Antimicrob Agents Chemother. 2023 Mar 16;67(3):e0151422. doi: 10.1128/aac.01514-22. Epub 2023 Feb 28.