A phase I study to evaluate safety, pharmacokinetics, and pharmacodynamics of respiratory syncytial virus neutralizing monoclonal antibody MK‐1654 in healthy Japanese adults
Abstract Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infection among all infants worldwide and remains a significant cause of morbidity and mortality. To address this unmet medical need, MK‐1654, a half‐life extended RSV neutralizing monoclonal antibody, is in c...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2022-07-01
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| Series: | Clinical and Translational Science |
| Online Access: | https://doi.org/10.1111/cts.13290 |
| _version_ | 1828747761066967040 |
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| author | Yuji Orito Naoyuki Otani Yuki Matsumoto Katsukuni Fujimoto Nobuyuki Oshima Brian M. Maas Luzelena Caro Antonios O. Aliprantis Kara S. Cox Osamu Tokumaru Masaaki Kodama Hideo Kudo Hiromitsu Imai Naoto Uemura |
| author_facet | Yuji Orito Naoyuki Otani Yuki Matsumoto Katsukuni Fujimoto Nobuyuki Oshima Brian M. Maas Luzelena Caro Antonios O. Aliprantis Kara S. Cox Osamu Tokumaru Masaaki Kodama Hideo Kudo Hiromitsu Imai Naoto Uemura |
| author_sort | Yuji Orito |
| collection | DOAJ |
| description | Abstract Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infection among all infants worldwide and remains a significant cause of morbidity and mortality. To address this unmet medical need, MK‐1654, a half‐life extended RSV neutralizing monoclonal antibody, is in clinical development for the prevention of RSV disease in infants. This was a phase I, randomized, placebo‐controlled, single‐site, double‐blind trial of MK‐1654 in 44 healthy Japanese adults. The safety, tolerability, pharmacokinetics, antidrug antibodies (ADAs), and serum neutralizing antibody (SNA) titers against RSV were evaluated for 1 year after a single intramuscular (i.m.) or intravenous (i.v.) dose of MK‐1654 or placebo in five groups (100 mg i.m., 300 mg i.m., 300 mg i.v., 1000 mg i.v., or placebo). MK‐1654 was generally well‐tolerated in Japanese adults. There were no serious drug‐related adverse events (AEs) reported in any MK‐1654 recipient and no discontinuations due to any AEs in the study. The half‐life of MK‐1654 ranged from 76 to 91 days across dosing groups. Estimated bioavailability was 86% for 100 mg i.m. and 77% for 300 mg i.m. One participant out of 33 (3.0%) developed detectable ADA with no apparent associated AEs. The RSV SNA titers increased in a dose‐dependent manner among participants who received MK‐1654. These data support the development of MK‐1654 for use in Japanese infants. |
| first_indexed | 2024-04-14T04:47:01Z |
| format | Article |
| id | doaj.art-e40accb32f454104982f83fe7c931136 |
| institution | Directory Open Access Journal |
| issn | 1752-8054 1752-8062 |
| language | English |
| last_indexed | 2024-04-14T04:47:01Z |
| publishDate | 2022-07-01 |
| publisher | Wiley |
| record_format | Article |
| series | Clinical and Translational Science |
| spelling | doaj.art-e40accb32f454104982f83fe7c9311362022-12-22T02:11:26ZengWileyClinical and Translational Science1752-80541752-80622022-07-011571753176310.1111/cts.13290A phase I study to evaluate safety, pharmacokinetics, and pharmacodynamics of respiratory syncytial virus neutralizing monoclonal antibody MK‐1654 in healthy Japanese adultsYuji Orito0Naoyuki Otani1Yuki Matsumoto2Katsukuni Fujimoto3Nobuyuki Oshima4Brian M. Maas5Luzelena Caro6Antonios O. Aliprantis7Kara S. Cox8Osamu Tokumaru9Masaaki Kodama10Hideo Kudo11Hiromitsu Imai12Naoto Uemura13MSD K.K. Tokyo JapanOita University Oita JapanMSD K.K. Tokyo JapanMSD K.K. Tokyo JapanMSD K.K. Tokyo JapanMerck and Co., Inc. Rahway New Jersey USAMerck and Co., Inc. Rahway New Jersey USAMerck and Co., Inc. Rahway New Jersey USAMerck and Co., Inc. Rahway New Jersey USAOita University Oita JapanOita University Oita JapanOita University Oita JapanOita University Oita JapanOita University Oita JapanAbstract Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infection among all infants worldwide and remains a significant cause of morbidity and mortality. To address this unmet medical need, MK‐1654, a half‐life extended RSV neutralizing monoclonal antibody, is in clinical development for the prevention of RSV disease in infants. This was a phase I, randomized, placebo‐controlled, single‐site, double‐blind trial of MK‐1654 in 44 healthy Japanese adults. The safety, tolerability, pharmacokinetics, antidrug antibodies (ADAs), and serum neutralizing antibody (SNA) titers against RSV were evaluated for 1 year after a single intramuscular (i.m.) or intravenous (i.v.) dose of MK‐1654 or placebo in five groups (100 mg i.m., 300 mg i.m., 300 mg i.v., 1000 mg i.v., or placebo). MK‐1654 was generally well‐tolerated in Japanese adults. There were no serious drug‐related adverse events (AEs) reported in any MK‐1654 recipient and no discontinuations due to any AEs in the study. The half‐life of MK‐1654 ranged from 76 to 91 days across dosing groups. Estimated bioavailability was 86% for 100 mg i.m. and 77% for 300 mg i.m. One participant out of 33 (3.0%) developed detectable ADA with no apparent associated AEs. The RSV SNA titers increased in a dose‐dependent manner among participants who received MK‐1654. These data support the development of MK‐1654 for use in Japanese infants.https://doi.org/10.1111/cts.13290 |
| spellingShingle | Yuji Orito Naoyuki Otani Yuki Matsumoto Katsukuni Fujimoto Nobuyuki Oshima Brian M. Maas Luzelena Caro Antonios O. Aliprantis Kara S. Cox Osamu Tokumaru Masaaki Kodama Hideo Kudo Hiromitsu Imai Naoto Uemura A phase I study to evaluate safety, pharmacokinetics, and pharmacodynamics of respiratory syncytial virus neutralizing monoclonal antibody MK‐1654 in healthy Japanese adults Clinical and Translational Science |
| title | A phase I study to evaluate safety, pharmacokinetics, and pharmacodynamics of respiratory syncytial virus neutralizing monoclonal antibody MK‐1654 in healthy Japanese adults |
| title_full | A phase I study to evaluate safety, pharmacokinetics, and pharmacodynamics of respiratory syncytial virus neutralizing monoclonal antibody MK‐1654 in healthy Japanese adults |
| title_fullStr | A phase I study to evaluate safety, pharmacokinetics, and pharmacodynamics of respiratory syncytial virus neutralizing monoclonal antibody MK‐1654 in healthy Japanese adults |
| title_full_unstemmed | A phase I study to evaluate safety, pharmacokinetics, and pharmacodynamics of respiratory syncytial virus neutralizing monoclonal antibody MK‐1654 in healthy Japanese adults |
| title_short | A phase I study to evaluate safety, pharmacokinetics, and pharmacodynamics of respiratory syncytial virus neutralizing monoclonal antibody MK‐1654 in healthy Japanese adults |
| title_sort | phase i study to evaluate safety pharmacokinetics and pharmacodynamics of respiratory syncytial virus neutralizing monoclonal antibody mk 1654 in healthy japanese adults |
| url | https://doi.org/10.1111/cts.13290 |
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