Safety, pharmacokinetics, and immunogenicity of the combination of the broadly neutralizing anti-HIV-1 antibodies 3BNC117 and 10-1074 in healthy adults: A randomized, phase 1 study.
<h4>Background</h4>Additional forms of pre-exposure prophylaxis are needed to prevent HIV-1 infection. 3BNC117 and 10-1074 are broadly neutralizing anti-HIV-1 antibodies that target non-overlapping epitopes on the HIV-1 envelope. We investigated the safety, tolerability, pharmacokinetics...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2019-01-01
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| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0219142 |
| _version_ | 1817994989208076288 |
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| author | Yehuda Z Cohen Allison L Butler Katrina Millard Maggi Witmer-Pack Rebeka Levin Cecilia Unson-O'Brien Roshni Patel Irina Shimeliovich Julio C C Lorenzi Jill Horowitz Stephen R Walsh Shu Lin Joshua A Weiner Anna Tse Alicia Sato Chelsey Bennett Bryan Mayer Kelly E Seaton Nicole L Yates Lindsey R Baden Allan C deCamp Margaret E Ackerman Michael S Seaman Georgia D Tomaras Michel C Nussenzweig Marina Caskey |
| author_facet | Yehuda Z Cohen Allison L Butler Katrina Millard Maggi Witmer-Pack Rebeka Levin Cecilia Unson-O'Brien Roshni Patel Irina Shimeliovich Julio C C Lorenzi Jill Horowitz Stephen R Walsh Shu Lin Joshua A Weiner Anna Tse Alicia Sato Chelsey Bennett Bryan Mayer Kelly E Seaton Nicole L Yates Lindsey R Baden Allan C deCamp Margaret E Ackerman Michael S Seaman Georgia D Tomaras Michel C Nussenzweig Marina Caskey |
| author_sort | Yehuda Z Cohen |
| collection | DOAJ |
| description | <h4>Background</h4>Additional forms of pre-exposure prophylaxis are needed to prevent HIV-1 infection. 3BNC117 and 10-1074 are broadly neutralizing anti-HIV-1 antibodies that target non-overlapping epitopes on the HIV-1 envelope. We investigated the safety, tolerability, pharmacokinetics, and immunogenicity of the intravenous administration of the combination of 3BNC117 and 10-1074 in healthy adults.<h4>Methods</h4>This randomized, double-blind, placebo-controlled, single center, phase 1 study enrolled healthy adults aged 18-65 years to receive one infusion of 3BNC117 immediately followed by 10-1074 at 10 mg/kg, three infusions of 3BNC117 followed by 10-1074 at 3 mg/kg or 10 mg/kg every 8 weeks, or placebo infusions. The primary outcomes were safety and pharmacokinetics. This trial is registered with ClinicalTrials.gov, number NCT02824536.<h4>Findings</h4>Twenty-four participants were enrolled in a 3:1 ratio to receive the study products or placebo. The combination of 3BNC117 and 10-1074 was safe and generally well tolerated. There were no serious adverse events considered related to the infusions. The mean elimination half-lives of 3BNC117 and 10-1074 were 16.4 ± 4.6 days and 23.0 ± 5.4 days, respectively, similar to what was observed in previous studies in which each antibody was administered alone. Anti-drug antibody responses were rare and without evidence of related adverse events or impact on elimination kinetics.<h4>Interpretation</h4>Single and repeated doses of the combination of 3BNC117 and 10-1074 were well tolerated in healthy adults. These data support the further development of the combination of 3BNC117 and 10-1074 as a long-acting injectable form of pre-exposure prophylaxis for the prevention of HIV-1 infection. |
| first_indexed | 2024-04-14T02:00:27Z |
| format | Article |
| id | doaj.art-b4f6a55fa3004a4ca5d76ce1d1d48b8b |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-14T02:00:27Z |
| publishDate | 2019-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-b4f6a55fa3004a4ca5d76ce1d1d48b8b2022-12-22T02:18:52ZengPublic Library of Science (PLoS)PLoS ONE1932-62032019-01-01148e021914210.1371/journal.pone.0219142Safety, pharmacokinetics, and immunogenicity of the combination of the broadly neutralizing anti-HIV-1 antibodies 3BNC117 and 10-1074 in healthy adults: A randomized, phase 1 study.Yehuda Z CohenAllison L ButlerKatrina MillardMaggi Witmer-PackRebeka LevinCecilia Unson-O'BrienRoshni PatelIrina ShimeliovichJulio C C LorenziJill HorowitzStephen R WalshShu LinJoshua A WeinerAnna TseAlicia SatoChelsey BennettBryan MayerKelly E SeatonNicole L YatesLindsey R BadenAllan C deCampMargaret E AckermanMichael S SeamanGeorgia D TomarasMichel C NussenzweigMarina Caskey<h4>Background</h4>Additional forms of pre-exposure prophylaxis are needed to prevent HIV-1 infection. 3BNC117 and 10-1074 are broadly neutralizing anti-HIV-1 antibodies that target non-overlapping epitopes on the HIV-1 envelope. We investigated the safety, tolerability, pharmacokinetics, and immunogenicity of the intravenous administration of the combination of 3BNC117 and 10-1074 in healthy adults.<h4>Methods</h4>This randomized, double-blind, placebo-controlled, single center, phase 1 study enrolled healthy adults aged 18-65 years to receive one infusion of 3BNC117 immediately followed by 10-1074 at 10 mg/kg, three infusions of 3BNC117 followed by 10-1074 at 3 mg/kg or 10 mg/kg every 8 weeks, or placebo infusions. The primary outcomes were safety and pharmacokinetics. This trial is registered with ClinicalTrials.gov, number NCT02824536.<h4>Findings</h4>Twenty-four participants were enrolled in a 3:1 ratio to receive the study products or placebo. The combination of 3BNC117 and 10-1074 was safe and generally well tolerated. There were no serious adverse events considered related to the infusions. The mean elimination half-lives of 3BNC117 and 10-1074 were 16.4 ± 4.6 days and 23.0 ± 5.4 days, respectively, similar to what was observed in previous studies in which each antibody was administered alone. Anti-drug antibody responses were rare and without evidence of related adverse events or impact on elimination kinetics.<h4>Interpretation</h4>Single and repeated doses of the combination of 3BNC117 and 10-1074 were well tolerated in healthy adults. These data support the further development of the combination of 3BNC117 and 10-1074 as a long-acting injectable form of pre-exposure prophylaxis for the prevention of HIV-1 infection.https://doi.org/10.1371/journal.pone.0219142 |
| spellingShingle | Yehuda Z Cohen Allison L Butler Katrina Millard Maggi Witmer-Pack Rebeka Levin Cecilia Unson-O'Brien Roshni Patel Irina Shimeliovich Julio C C Lorenzi Jill Horowitz Stephen R Walsh Shu Lin Joshua A Weiner Anna Tse Alicia Sato Chelsey Bennett Bryan Mayer Kelly E Seaton Nicole L Yates Lindsey R Baden Allan C deCamp Margaret E Ackerman Michael S Seaman Georgia D Tomaras Michel C Nussenzweig Marina Caskey Safety, pharmacokinetics, and immunogenicity of the combination of the broadly neutralizing anti-HIV-1 antibodies 3BNC117 and 10-1074 in healthy adults: A randomized, phase 1 study. PLoS ONE |
| title | Safety, pharmacokinetics, and immunogenicity of the combination of the broadly neutralizing anti-HIV-1 antibodies 3BNC117 and 10-1074 in healthy adults: A randomized, phase 1 study. |
| title_full | Safety, pharmacokinetics, and immunogenicity of the combination of the broadly neutralizing anti-HIV-1 antibodies 3BNC117 and 10-1074 in healthy adults: A randomized, phase 1 study. |
| title_fullStr | Safety, pharmacokinetics, and immunogenicity of the combination of the broadly neutralizing anti-HIV-1 antibodies 3BNC117 and 10-1074 in healthy adults: A randomized, phase 1 study. |
| title_full_unstemmed | Safety, pharmacokinetics, and immunogenicity of the combination of the broadly neutralizing anti-HIV-1 antibodies 3BNC117 and 10-1074 in healthy adults: A randomized, phase 1 study. |
| title_short | Safety, pharmacokinetics, and immunogenicity of the combination of the broadly neutralizing anti-HIV-1 antibodies 3BNC117 and 10-1074 in healthy adults: A randomized, phase 1 study. |
| title_sort | safety pharmacokinetics and immunogenicity of the combination of the broadly neutralizing anti hiv 1 antibodies 3bnc117 and 10 1074 in healthy adults a randomized phase 1 study |
| url | https://doi.org/10.1371/journal.pone.0219142 |
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