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1.
Open Forum Infectious Diseases ; 9(Supplement 2):S159, 2022.
Article in English | EMBASE | ID: covidwho-2189552

ABSTRACT

Background. Adintrevimab is a fully human IgG1 monoclonal antibody engineered to have potent and broad neutralization against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and other SARS-like CoVs with pandemic potential. Adintrevimab is being assessed in two separate phase 2/3 clinical trials: the EVADE trial for prevention of COVID-19 in both post-exposure and preexposure settings and the STAMP trial for treatment of COVID-19. Here we report higher doses being evaluated in a healthy volunteer study given that emerging variants may have varying susceptibilities to adintrevimab. Previous results 300 mg IM, 600 mg IM, and 500 mg IV cohorts have been reported. Methods. This is an ongoing Phase 1, randomized, placebo (PBO)-controlled, single ascending-dose study of adintrevimab administered intramuscularly (IM) or intravenously (IV) to healthy adults aged 18-50 years with no current SARS-CoV-2 infection. Participants were randomized 8:2 in 3 high dose cohorts (N=10/cohort: n=8 adintrevimab, n=2 PBO): adintrevimab 1200 mg IM, 1200 mg IV, and 4500 mg IV. Safety, tolerability, and pharmacokinetics (PK) were assessed up to 21 days post dose. Results. Overall, 30 participants received adintrevimab (n=24) or PBO (n=6). Blinded safety data for all cohorts and PK for 1200 mg IV are reported. Through 21 days post dose all doses were well-tolerated, with no study drug-related adverse events (AEs), serious AEs, injection site reactions, or hypersensitivity reactions reported. The observed PK profile of the 1200 mg IV dose included Cmax of 423+/-105 mug/ml. Comparison of 500 mg and 1200 mg IV doses indicate dose proportionality of Cmax and exposure (AUC Day 21). Conclusion. A single dose of adintrevimab, up to 4500 mg, was well tolerated. These preliminary safety data and PK support potential use of higher doses of adintrevimab as needed to address emerging SARS-CoV-2 variants.

2.
Open Forum Infectious Diseases ; 8(SUPPL 1):S420, 2021.
Article in English | EMBASE | ID: covidwho-1746398

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).

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