tetano
Editor, Senior Moderator
BMJ Open
. 2024 Oct 8;14(10):e087431.
doi: 10.1136/bmjopen-2024-087431. 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
Thomas D Norton[SUP] 1 [/SUP], Mazhar Thakur[SUP] 2 [/SUP], Samit Ganguly[SUP] 2 [/SUP], Shazia Ali[SUP] 2 [/SUP], Jesse Chao[SUP] 2 [/SUP], Alpana Waldron[SUP] 2 [/SUP], Jing Xiao[SUP] 2 [/SUP], Yogesh Patel[SUP] 2 [/SUP], Kenneth C Turner[SUP] 2 [/SUP], John D Davis[SUP] 2 [/SUP], Susan C Irvin[SUP] 2 [/SUP], Cynthia Pan[SUP] 2 [/SUP], Dominique Atmodjo-Watkins[SUP] 2 [/SUP], Andrea T Hooper[SUP] 2 [/SUP], Jennifer D Hamilton[SUP] 2 [/SUP], Danise Subramaniam[SUP] 2 [/SUP], Joseph A Bocchini[SUP] 3 [/SUP], Bari Kowal[SUP] 2 [/SUP], A Thomas DiCioccio[SUP] 2 [/SUP], Rafia Bhore[SUP] 2 [/SUP], Gregory P Geba[SUP] 2 [/SUP], Edward Cox[SUP] 2 [/SUP], Ned Braunstein[SUP] 2 [/SUP], Paula Dakin[SUP] 2 [/SUP], Gary A Herman[SUP] 2 [/SUP]
Affiliations
Objective: Pregnant 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.
Methods: A 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.
Results: In 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.
Conclusion: CAS+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 number: NCT04425629.
Keywords: COVID-19; clinical trial; pregnancy.
. 2024 Oct 8;14(10):e087431.
doi: 10.1136/bmjopen-2024-087431. 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
Thomas D Norton[SUP] 1 [/SUP], Mazhar Thakur[SUP] 2 [/SUP], Samit Ganguly[SUP] 2 [/SUP], Shazia Ali[SUP] 2 [/SUP], Jesse Chao[SUP] 2 [/SUP], Alpana Waldron[SUP] 2 [/SUP], Jing Xiao[SUP] 2 [/SUP], Yogesh Patel[SUP] 2 [/SUP], Kenneth C Turner[SUP] 2 [/SUP], John D Davis[SUP] 2 [/SUP], Susan C Irvin[SUP] 2 [/SUP], Cynthia Pan[SUP] 2 [/SUP], Dominique Atmodjo-Watkins[SUP] 2 [/SUP], Andrea T Hooper[SUP] 2 [/SUP], Jennifer D Hamilton[SUP] 2 [/SUP], Danise Subramaniam[SUP] 2 [/SUP], Joseph A Bocchini[SUP] 3 [/SUP], Bari Kowal[SUP] 2 [/SUP], A Thomas DiCioccio[SUP] 2 [/SUP], Rafia Bhore[SUP] 2 [/SUP], Gregory P Geba[SUP] 2 [/SUP], Edward Cox[SUP] 2 [/SUP], Ned Braunstein[SUP] 2 [/SUP], Paula Dakin[SUP] 2 [/SUP], Gary A Herman[SUP] 2 [/SUP]
Affiliations
- PMID: 39384241
- DOI: 10.1136/bmjopen-2024-087431
Objective: Pregnant 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.
Methods: A 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.
Results: In 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.
Conclusion: CAS+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 number: NCT04425629.
Keywords: COVID-19; clinical trial; pregnancy.