Assessing the safety and pharmacokinetics of casirivimab and imdevimab (CAS+IMD) in a cohort of pregnant outpatients with COVID-19: results from an adaptive, multicentre, randomised, double-blind, phase 1/2/3 study

• Published in: BMJ open Vol. 14; no. 10; p. e087431
• Main Authors: Norton, Thomas D, Thakur, Mazhar, Ganguly, Samit, Ali, Shazia, Chao, Jesse, Waldron, Alpana, Xiao, Jing, Patel, Yogesh, Turner, Kenneth C, Davis, John D, Irvin, Susan C, Pan, Cynthia, Atmodjo-Watkins, Dominique, Hooper, Andrea T, Hamilton, Jennifer D, Subramaniam, Danise, Bocchini, Joseph A, Kowal, Bari, DiCioccio, A. Thomas, Bhore, Rafia, Geba, Gregory P, Cox, Edward, Braunstein, Ned, Dakin, Paula, Herman, Gary A
• Format: Journal Article
• Language: English
• Published: England British Medical Journal Publishing Group 08.10.2024; BMJ Publishing Group LTD; BMJ Publishing Group
• Subjects: Adult; Adults; Antibodies, Monoclonal, Humanized - pharmacokinetics; Antibodies, Monoclonal, Humanized - therapeutic use; Antibodies, Neutralizing; Antiviral Agents - administration & dosage; Antiviral Agents - adverse effects; Antiviral Agents - pharmacokinetics; Antiviral Agents - therapeutic use; Clinical outcomes; clinical trial; COVID-19; COVID-19 Drug Treatment; Double-Blind Method; Drug Combinations; Drug dosages; Female; Humans; Infections; Infectious Diseases; Menstruation; Monoclonal antibodies; Original Research; Pandemics; Pharmacokinetics; Pregnancy; Pregnancy Complications, Infectious - drug therapy; SARS-CoV-2; Severe acute respiratory syndrome coronavirus 2; Treatment Outcome; Womens health; Young Adult; COVID-19; clinical trial; pregnancy
• ISSN: 2044-6055; 2044-6055
• DOI: 10.1136/bmjopen-2024-087431

ObjectivePregnant women with COVID-19 are at elevated risk for severe outcomes, but clinical data on management of these patients are limited. Monoclonal antibodies, such as casirivimab plus imdevimab (CAS+IMD), have proven effective in treating non-pregnant adults with COVID-19, prompting further evaluation in pregnant women.MethodsA phase 3 portion of an adaptive, multicentre, randomised, double-blind, placebo-controlled trial evaluated the safety, clinical outcomes, pharmacokinetics and immunogenicity of CAS+IMD (1200 mg or 2400 mg) in the treatment of pregnant outpatients with COVID-19 (NCT04425629). Participants were enrolled between December 2020 and November 2021, prior to the emergence of Omicron-lineage variants against which CAS+IMD is not active. Safety was evaluated in randomised participants who received study drug (n=80); clinical outcomes were evaluated in all randomised participants (n=82). Only two pregnant participants received placebo, limiting conclusions regarding treatment effect. Infants born to pregnant participants were followed for developmental outcomes ≤1 year of age.ResultsIn pregnant participants, CAS+IMD was well tolerated, with no grade ≥2 hypersensitivity or infusion-related reactions reported. There were no participant deaths, and only one COVID-19–related medically attended visit. Although two pregnancies (3%) reported issues in the fetus/neonate, they were confounded by maternal history or considered to be due to an alternate aetiology. No adverse developmental outcomes in infants ≤1 year of age were considered related to in utero exposure to the study drug. CAS+IMD 1200 mg and 2400 mg rapidly and similarly reduced viral loads, with a dose-proportional increase in concentrations of CAS+IMD in serum. Pharmacokinetics were consistent with that reported in the general population. Immunogenicity incidence was low.ConclusionCAS+IMD treatment of pregnant outpatients with COVID-19 showed similar safety, clinical outcomes and pharmacokinetic profiles to that observed in non-pregnant adults. There was no evidence of an impact on developmental outcomes in infants ≤1 year of age.Trial registration numberNCT04425629.