Pharmacokinetics, Efficacy, and Safety of a SARS-CoV-2 Antibody Treatment in Pediatric Participants: An Open-Label Addendum of a Placebo-Controlled, Randomized Phase 2/3 Trial
Abstract Introduction Bamlanivimab and etesevimab (BAM + ETE) are monoclonal antibodies (mAbs) effective in reducing COVID-19-related hospitalizations and all-cause mortality in adult participants at increased risk for severe disease. We present pharmacokinetic (PK), efficacy, and safety results fro...
| Main Authors: | , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Adis, Springer Healthcare
2023-06-01
|
| Series: | Infectious Diseases and Therapy |
| Subjects: | |
| Online Access: | https://doi.org/10.1007/s40121-023-00832-y |
| _version_ | 1797752612045455360 |
|---|---|
| author | Himanshu P. Upadhyaya Jenny Y. Chien Amanda J. Long Martin S. Bohm Nicole L. Kallewaard Lisa F. Macpherson Dipak R. Patel Matthew M. Hufford Constance J. Krull Jocelyn Y. Ang Peter Chen William J. Muller Jeffrey A. Potts Timothy Quinn Mark Williams BLAZE-1 Investigators |
| author_facet | Himanshu P. Upadhyaya Jenny Y. Chien Amanda J. Long Martin S. Bohm Nicole L. Kallewaard Lisa F. Macpherson Dipak R. Patel Matthew M. Hufford Constance J. Krull Jocelyn Y. Ang Peter Chen William J. Muller Jeffrey A. Potts Timothy Quinn Mark Williams BLAZE-1 Investigators |
| author_sort | Himanshu P. Upadhyaya |
| collection | DOAJ |
| description | Abstract Introduction Bamlanivimab and etesevimab (BAM + ETE) are monoclonal antibodies (mAbs) effective in reducing COVID-19-related hospitalizations and all-cause mortality in adult participants at increased risk for severe disease. We present pharmacokinetic (PK), efficacy, and safety results from pediatric participants (< 18 years of age) with COVID-19 who were treated with BAM + ETE. Methods In an addendum to the phase 2/3 BLAZE-1 clinical trial (NCT04427501), pediatric participants received open-label weight-based dosing (WBD, n = 94) based on exposure-matching to the authorized dose of BAM + ETE in adult participants. For efficacy and safety assessments, placebo (n = 14) and BAM + ETE (n = 20)-treated adolescent participants (> 12 to < 18 years of age) from the BLAZE-1 trial were included in the overall pediatric population (N = 128). All participants had mild to moderate COVID-19 upon enrollment and ≥ 1 risk factor for severe COVID-19. The primary objective was to characterize the PK of BAM and ETE in the WBD population. Results The median age of the participants was 11.2 years, 46.1% were female, 57.9% were Black/African American, and 19.7% were Hispanic/Latino. The area under the curve for BAM and ETE in the WBD population was similar to that previously observed in adults. There were no COVID-19-related hospitalizations or deaths. All adverse events (AE) except one were mild or moderate, with one participant reporting a serious AE. Conclusion WBD in pediatric participants achieved similar drug exposures compared to adult participants that received the authorized BAM + ETE dose. The pediatric efficacy and safety data were consistent with adults receiving mAbs for COVID-19. Trial Registration Number NCT04427501. |
| first_indexed | 2024-03-12T17:06:59Z |
| format | Article |
| id | doaj.art-4a8e4f959324473bb550800f3098224f |
| institution | Directory Open Access Journal |
| issn | 2193-8229 2193-6382 |
| language | English |
| last_indexed | 2024-03-12T17:06:59Z |
| publishDate | 2023-06-01 |
| publisher | Adis, Springer Healthcare |
| record_format | Article |
| series | Infectious Diseases and Therapy |
| spelling | doaj.art-4a8e4f959324473bb550800f3098224f2023-08-06T11:21:11ZengAdis, Springer HealthcareInfectious Diseases and Therapy2193-82292193-63822023-06-011271861187310.1007/s40121-023-00832-yPharmacokinetics, Efficacy, and Safety of a SARS-CoV-2 Antibody Treatment in Pediatric Participants: An Open-Label Addendum of a Placebo-Controlled, Randomized Phase 2/3 TrialHimanshu P. Upadhyaya0Jenny Y. Chien1Amanda J. Long2Martin S. Bohm3Nicole L. Kallewaard4Lisa F. Macpherson5Dipak R. Patel6Matthew M. Hufford7Constance J. Krull8Jocelyn Y. Ang9Peter Chen10William J. Muller11Jeffrey A. Potts12Timothy Quinn13Mark Williams14BLAZE-1 InvestigatorsEli Lilly and CompanyEli Lilly and CompanyEli Lilly and CompanyEli Lilly and CompanyEli Lilly and CompanyEli Lilly and CompanyEli Lilly and CompanyEli Lilly and CompanyEli Lilly and CompanyChildren’s Hospital of MichiganCedars–Sinai Medical CenterAnn & Robert H. Lurie Children’s Hospital of Chicago and Northwestern University Feinberg School of MedicineGreat Lakes Research GroupSky Clinical Research Network GroupEli Lilly and CompanyAbstract Introduction Bamlanivimab and etesevimab (BAM + ETE) are monoclonal antibodies (mAbs) effective in reducing COVID-19-related hospitalizations and all-cause mortality in adult participants at increased risk for severe disease. We present pharmacokinetic (PK), efficacy, and safety results from pediatric participants (< 18 years of age) with COVID-19 who were treated with BAM + ETE. Methods In an addendum to the phase 2/3 BLAZE-1 clinical trial (NCT04427501), pediatric participants received open-label weight-based dosing (WBD, n = 94) based on exposure-matching to the authorized dose of BAM + ETE in adult participants. For efficacy and safety assessments, placebo (n = 14) and BAM + ETE (n = 20)-treated adolescent participants (> 12 to < 18 years of age) from the BLAZE-1 trial were included in the overall pediatric population (N = 128). All participants had mild to moderate COVID-19 upon enrollment and ≥ 1 risk factor for severe COVID-19. The primary objective was to characterize the PK of BAM and ETE in the WBD population. Results The median age of the participants was 11.2 years, 46.1% were female, 57.9% were Black/African American, and 19.7% were Hispanic/Latino. The area under the curve for BAM and ETE in the WBD population was similar to that previously observed in adults. There were no COVID-19-related hospitalizations or deaths. All adverse events (AE) except one were mild or moderate, with one participant reporting a serious AE. Conclusion WBD in pediatric participants achieved similar drug exposures compared to adult participants that received the authorized BAM + ETE dose. The pediatric efficacy and safety data were consistent with adults receiving mAbs for COVID-19. Trial Registration Number NCT04427501.https://doi.org/10.1007/s40121-023-00832-yBamlanivimabCOVID-19EtesevimabMonoclonal antibodiesPediatricPharmacokinetics |
| spellingShingle | Himanshu P. Upadhyaya Jenny Y. Chien Amanda J. Long Martin S. Bohm Nicole L. Kallewaard Lisa F. Macpherson Dipak R. Patel Matthew M. Hufford Constance J. Krull Jocelyn Y. Ang Peter Chen William J. Muller Jeffrey A. Potts Timothy Quinn Mark Williams BLAZE-1 Investigators Pharmacokinetics, Efficacy, and Safety of a SARS-CoV-2 Antibody Treatment in Pediatric Participants: An Open-Label Addendum of a Placebo-Controlled, Randomized Phase 2/3 Trial Infectious Diseases and Therapy Bamlanivimab COVID-19 Etesevimab Monoclonal antibodies Pediatric Pharmacokinetics |
| title | Pharmacokinetics, Efficacy, and Safety of a SARS-CoV-2 Antibody Treatment in Pediatric Participants: An Open-Label Addendum of a Placebo-Controlled, Randomized Phase 2/3 Trial |
| title_full | Pharmacokinetics, Efficacy, and Safety of a SARS-CoV-2 Antibody Treatment in Pediatric Participants: An Open-Label Addendum of a Placebo-Controlled, Randomized Phase 2/3 Trial |
| title_fullStr | Pharmacokinetics, Efficacy, and Safety of a SARS-CoV-2 Antibody Treatment in Pediatric Participants: An Open-Label Addendum of a Placebo-Controlled, Randomized Phase 2/3 Trial |
| title_full_unstemmed | Pharmacokinetics, Efficacy, and Safety of a SARS-CoV-2 Antibody Treatment in Pediatric Participants: An Open-Label Addendum of a Placebo-Controlled, Randomized Phase 2/3 Trial |
| title_short | Pharmacokinetics, Efficacy, and Safety of a SARS-CoV-2 Antibody Treatment in Pediatric Participants: An Open-Label Addendum of a Placebo-Controlled, Randomized Phase 2/3 Trial |
| title_sort | pharmacokinetics efficacy and safety of a sars cov 2 antibody treatment in pediatric participants an open label addendum of a placebo controlled randomized phase 2 3 trial |
| topic | Bamlanivimab COVID-19 Etesevimab Monoclonal antibodies Pediatric Pharmacokinetics |
| url | https://doi.org/10.1007/s40121-023-00832-y |
| work_keys_str_mv | AT himanshupupadhyaya pharmacokineticsefficacyandsafetyofasarscov2antibodytreatmentinpediatricparticipantsanopenlabeladdendumofaplacebocontrolledrandomizedphase23trial AT jennyychien pharmacokineticsefficacyandsafetyofasarscov2antibodytreatmentinpediatricparticipantsanopenlabeladdendumofaplacebocontrolledrandomizedphase23trial AT amandajlong pharmacokineticsefficacyandsafetyofasarscov2antibodytreatmentinpediatricparticipantsanopenlabeladdendumofaplacebocontrolledrandomizedphase23trial AT martinsbohm pharmacokineticsefficacyandsafetyofasarscov2antibodytreatmentinpediatricparticipantsanopenlabeladdendumofaplacebocontrolledrandomizedphase23trial AT nicolelkallewaard pharmacokineticsefficacyandsafetyofasarscov2antibodytreatmentinpediatricparticipantsanopenlabeladdendumofaplacebocontrolledrandomizedphase23trial AT lisafmacpherson pharmacokineticsefficacyandsafetyofasarscov2antibodytreatmentinpediatricparticipantsanopenlabeladdendumofaplacebocontrolledrandomizedphase23trial AT dipakrpatel pharmacokineticsefficacyandsafetyofasarscov2antibodytreatmentinpediatricparticipantsanopenlabeladdendumofaplacebocontrolledrandomizedphase23trial AT matthewmhufford pharmacokineticsefficacyandsafetyofasarscov2antibodytreatmentinpediatricparticipantsanopenlabeladdendumofaplacebocontrolledrandomizedphase23trial AT constancejkrull pharmacokineticsefficacyandsafetyofasarscov2antibodytreatmentinpediatricparticipantsanopenlabeladdendumofaplacebocontrolledrandomizedphase23trial AT jocelynyang pharmacokineticsefficacyandsafetyofasarscov2antibodytreatmentinpediatricparticipantsanopenlabeladdendumofaplacebocontrolledrandomizedphase23trial AT peterchen pharmacokineticsefficacyandsafetyofasarscov2antibodytreatmentinpediatricparticipantsanopenlabeladdendumofaplacebocontrolledrandomizedphase23trial AT williamjmuller pharmacokineticsefficacyandsafetyofasarscov2antibodytreatmentinpediatricparticipantsanopenlabeladdendumofaplacebocontrolledrandomizedphase23trial AT jeffreyapotts pharmacokineticsefficacyandsafetyofasarscov2antibodytreatmentinpediatricparticipantsanopenlabeladdendumofaplacebocontrolledrandomizedphase23trial AT timothyquinn pharmacokineticsefficacyandsafetyofasarscov2antibodytreatmentinpediatricparticipantsanopenlabeladdendumofaplacebocontrolledrandomizedphase23trial AT markwilliams pharmacokineticsefficacyandsafetyofasarscov2antibodytreatmentinpediatricparticipantsanopenlabeladdendumofaplacebocontrolledrandomizedphase23trial AT blaze1investigators pharmacokineticsefficacyandsafetyofasarscov2antibodytreatmentinpediatricparticipantsanopenlabeladdendumofaplacebocontrolledrandomizedphase23trial |