Abstract Background ADG20 is a fully human IgG1 monoclonal antibody engineered to have high potency and broad neutralization against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and other SARS-like CoVs with pandemic potential by binding to a highly conserved epitope in the receptor-binding domain (RBD) of the spike protein. The Fc region of ADG20 has been modified to provide an extended half-life. ADG20 is in clinical development for the treatment and prevention of COVID-19. Methods This is an ongoing Phase 1, randomized, placebo (PBO)-controlled, single ascending-dose study of ADG20 administered intramuscularly (IM) or intravenously (IV) to healthy adults aged 18–50 years with no evidence of prior or current SARS-CoV-2 infection. Participants were randomized 8:2 in 3 cohorts (N=10/cohort: n=8 ADG20, n=2 PBO): ADG20 300 mg IM, 500 mg IV, and 600 mg IM. Safety, tolerability, PK, and sVNA titers were assessed up to 3 months post dose. Serum ADG20 concentrations were measured with a validated hybrid ligand binding liquid chromatography–mass spectrometry (MS)/MS assay. sVNA titers against authentic SARS-CoV-2 were determined by a plaque reduction neutralization assay. Results Overall, 30 participants received ADG20 (n=24) or PBO (n=6). Blinded safety data for all cohorts and PK/sVNA titer data for the 300 mg IM cohort are reported. Through a minimum of 10 weeks post dose, no study drug-related adverse events (AEs), serious AEs, injection site reactions, or hypersensitivity reactions were reported. The observed preliminary PK profile was dose proportional, consistent with an extended half-life monoclonal antibody, and well predicted by translational physiologically-based PK modeling. The measured 50% sVNA titer (MN50; geometric mean [coefficient of variation, %]) was 1382 (32.7%) 13 days after a single 300 mg IM dose. These values are within the range of peak serum neutralizing antibody titers reported for COVID-19 mRNA vaccines. Conclusion A single dose of ADG20, up to 600 mg IM, was well tolerated. Preliminary PK and sVNA titer profiles support the ongoing Phase 2/3 trials of ADG20 at a 300 mg IM dose for the prevention of COVID-19 (EVADE: NCT04859517) and treatment of ambulatory patients with mild to moderate COVID-19 (STAMP: NCT04805671). Disclosures Helen Paguntalan, MD , Adagio Therapeutics, Inc. (Scientific Research Study Investigator) Zoltán Magyarics, MD, PhD , Adagio Therapeutics, Inc. (Consultant) Lynn E. Connolly, MD, PhD , Adagio Therapeutics, Inc. (Employee) Ellie Hershberger, PharmD , Adagio Therapeutics, Inc. (Employee) Kristin Narayan, PhD , Adagio Therapeutics, Inc. (Employee) Deepali Gupta, BS , Adagio Therapeutics, Inc. (Employee) Paul G. Ambrose, PharmD , Adagio Therapeutics, Inc. (Employee) Frank Engler, PhD , Adagio Therapeutics, Inc. (Independent Contractor) Ed Campanaro, BSN, MSHS , Adagio Therapeutics, Inc. (Employee) Anita F. Das, PhD , Adagio Therapeutics, Inc. (Consultant) Pete Schmidt, MD , Adagio Therapeutics, Inc. (Employee)
【초록키워드】 Treatment, SARS-CoV-2, coronavirus, pandemic, Trial, Safety, Therapeutics, neutralization, SARS-COV-2 infection, monoclonal antibody, Variation, Moderate COVID-19, Randomized, Cohort, RBD, adverse event, Mild, Placebo, epitope, single dose, binding, Evidence, Ligand, Concentration, dose, phase, Phase 1, hypersensitivity reaction, Support, acute respiratory syndrome, COVID-19 mRNA vaccines, Tolerability, Reactions, profile, injection, participant, clinical development, serious AEs, Fc region, intravenously, Serum neutralizing antibody, plaque reduction neutralization, Administered, employee, consultant, SARS-like CoV, human IgG1, prevention of COVID-19, Result, predicted, conserved, Inc, healthy, reported, the spike protein, the receptor-binding domain, were measured, translational, AEs, Ambrose, ambulatory patient, BSN, Ellie, Frank, geometric, intramuscularly, PK modeling, were assessed, 【제목키워드】 COVID-19, Safety, prevention, titer, Phase 1, profile, being, Result, Assessing, Developed, Extended,