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901. MEDI8897 Prevents Serious RSV Disease in Healthy Preterm Infants

BACKGROUND: RSV is the principal cause of lower respiratory tract infection (LRTI) among infants, and a significant unmet need exists for RSV prevention in healthy infants. We have developed a highly potent, extended half-life monoclonal antibody (mAb), to protect infants for an entire RSV season us...

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Autores principales: Pamela Griffin, Mary, Yuan, Yuan, Takas, Therese, DeVincenzo, John, Domachowske, Joseph B, Simoes, Eric A, Khan, Anis, Esser, Mark T, Dubovsky, Filip, Villafana, Tonya L
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6808696/
http://dx.doi.org/10.1093/ofid/ofz359.060
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author Pamela Griffin, Mary
Yuan, Yuan
Takas, Therese
DeVincenzo, John
Domachowske, Joseph B
Simoes, Eric A
Khan, Anis
Esser, Mark T
Dubovsky, Filip
Villafana, Tonya L
author_facet Pamela Griffin, Mary
Yuan, Yuan
Takas, Therese
DeVincenzo, John
Domachowske, Joseph B
Simoes, Eric A
Khan, Anis
Esser, Mark T
Dubovsky, Filip
Villafana, Tonya L
author_sort Pamela Griffin, Mary
collection PubMed
description BACKGROUND: RSV is the principal cause of lower respiratory tract infection (LRTI) among infants, and a significant unmet need exists for RSV prevention in healthy infants. We have developed a highly potent, extended half-life monoclonal antibody (mAb), to protect infants for an entire RSV season using a single IM dose. Here we report the efficacy, safety, pharmacokinetics, and anti-drug antibody (ADA) responses for MEDI8897 in palivizumab-ineligible preterm infants born between 29 and 35 weeks gestation. METHODS: A total of 1,453 Infants were randomized 2:1 to receive a single 50 mg IM injection of MEDI8897 (n = 969) or placebo (n = 484) and followed for 360 days. Enrollment occurred just prior to the 2016 and 2017 RSV seasons in 23 northern and southern hemisphere countries. Blood was collected periodically. Infants with a medically attended (MA) LRTI (outpatient or inpatient) had nasal swabs obtained for central RSV testing by RT-PCR. Predefined clinical criteria were used for the case definition. RESULTS: A total of 1,417 (97.5%) subjects completed the 150-day efficacy follow-up period and 1,367 (94.1%) completed the study. In the MEDI8897 group, a 70.1% (95% CI: 52.3%, 81.2%; P < 0.0001) reduction in the incidence of medically attended RSV LRTI and a 78.4% (95% CI: 51.9%, 90.3%; P = 0.0002) reduction in the incidence of RSV LRTI hospitalization was achieved. These efficacy results were consistent when analyzed by hemisphere, RSV subtype, and subject demographics. Similar proportions of adverse events (86.8% placebo; 86.2% MEDI8897) and serious adverse events (16.9% placebo; 11.2% MEDI8897) were reported in study subjects. There were no significant hypersensitivity reactions with similar proportions reported for both groups (0.6% placebo; 0.5% MEDI8897). The incidence of ADA detected any time post baseline was low (3.8% placebo; 5.6% MEDI8897) with no impact on PK or safety. The occurrence of non-RSV LRTIs was similar for both groups indicating no replacement by other pathogens. CONCLUSION: In this large randomized study of RSV prophylaxis in healthy preterm infants, MEDI8897 immunoprophylaxis provided a significant reduction in RSV MA-LRTI and hospitalization. These results have promising implications for the future of RSV prophylaxis for all infants. This study was funded by AstraZeneca and sanofi pasteur. DISCLOSURES: All Authors: No reported Disclosures.
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spelling pubmed-68086962019-10-28 901. MEDI8897 Prevents Serious RSV Disease in Healthy Preterm Infants Pamela Griffin, Mary Yuan, Yuan Takas, Therese DeVincenzo, John Domachowske, Joseph B Simoes, Eric A Khan, Anis Esser, Mark T Dubovsky, Filip Villafana, Tonya L Open Forum Infect Dis Abstracts BACKGROUND: RSV is the principal cause of lower respiratory tract infection (LRTI) among infants, and a significant unmet need exists for RSV prevention in healthy infants. We have developed a highly potent, extended half-life monoclonal antibody (mAb), to protect infants for an entire RSV season using a single IM dose. Here we report the efficacy, safety, pharmacokinetics, and anti-drug antibody (ADA) responses for MEDI8897 in palivizumab-ineligible preterm infants born between 29 and 35 weeks gestation. METHODS: A total of 1,453 Infants were randomized 2:1 to receive a single 50 mg IM injection of MEDI8897 (n = 969) or placebo (n = 484) and followed for 360 days. Enrollment occurred just prior to the 2016 and 2017 RSV seasons in 23 northern and southern hemisphere countries. Blood was collected periodically. Infants with a medically attended (MA) LRTI (outpatient or inpatient) had nasal swabs obtained for central RSV testing by RT-PCR. Predefined clinical criteria were used for the case definition. RESULTS: A total of 1,417 (97.5%) subjects completed the 150-day efficacy follow-up period and 1,367 (94.1%) completed the study. In the MEDI8897 group, a 70.1% (95% CI: 52.3%, 81.2%; P < 0.0001) reduction in the incidence of medically attended RSV LRTI and a 78.4% (95% CI: 51.9%, 90.3%; P = 0.0002) reduction in the incidence of RSV LRTI hospitalization was achieved. These efficacy results were consistent when analyzed by hemisphere, RSV subtype, and subject demographics. Similar proportions of adverse events (86.8% placebo; 86.2% MEDI8897) and serious adverse events (16.9% placebo; 11.2% MEDI8897) were reported in study subjects. There were no significant hypersensitivity reactions with similar proportions reported for both groups (0.6% placebo; 0.5% MEDI8897). The incidence of ADA detected any time post baseline was low (3.8% placebo; 5.6% MEDI8897) with no impact on PK or safety. The occurrence of non-RSV LRTIs was similar for both groups indicating no replacement by other pathogens. CONCLUSION: In this large randomized study of RSV prophylaxis in healthy preterm infants, MEDI8897 immunoprophylaxis provided a significant reduction in RSV MA-LRTI and hospitalization. These results have promising implications for the future of RSV prophylaxis for all infants. This study was funded by AstraZeneca and sanofi pasteur. DISCLOSURES: All Authors: No reported Disclosures. Oxford University Press 2019-10-23 /pmc/articles/PMC6808696/ http://dx.doi.org/10.1093/ofid/ofz359.060 Text en © The Author(s) 2019. Published by Oxford University Press on behalf of Infectious Diseases Society of America. http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Abstracts
Pamela Griffin, Mary
Yuan, Yuan
Takas, Therese
DeVincenzo, John
Domachowske, Joseph B
Simoes, Eric A
Khan, Anis
Esser, Mark T
Dubovsky, Filip
Villafana, Tonya L
901. MEDI8897 Prevents Serious RSV Disease in Healthy Preterm Infants
title 901. MEDI8897 Prevents Serious RSV Disease in Healthy Preterm Infants
title_full 901. MEDI8897 Prevents Serious RSV Disease in Healthy Preterm Infants
title_fullStr 901. MEDI8897 Prevents Serious RSV Disease in Healthy Preterm Infants
title_full_unstemmed 901. MEDI8897 Prevents Serious RSV Disease in Healthy Preterm Infants
title_short 901. MEDI8897 Prevents Serious RSV Disease in Healthy Preterm Infants
title_sort 901. medi8897 prevents serious rsv disease in healthy preterm infants
topic Abstracts
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6808696/
http://dx.doi.org/10.1093/ofid/ofz359.060
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