Phase 1 Trial of a Therapeutic Anti-Yellow Fever Virus Human Antibody
Copyright © 2020 Massachusetts Medical Society..
BACKGROUND: Insufficient vaccine doses and the lack of therapeutic agents for yellow fever put global health at risk, should this virus emerge from sub-Saharan Africa and South America.
METHODS: In phase 1a of this clinical trial, we assessed the safety, side-effect profile, and pharmacokinetics of TY014, a fully human IgG1 anti-yellow fever virus monoclonal antibody. In a double-blind, phase 1b clinical trial, we assessed the efficacy of TY014, as compared with placebo, in abrogating viremia related to the administration of live yellow fever vaccine (YF17D-204; Stamaril). The primary safety outcomes were adverse events reported 1 hour after the infusion and throughout the trial. The primary efficacy outcome was the dose of TY014 at which 100% of the participants tested negative for viremia within 48 hours after infusion.
RESULTS: A total of 27 healthy participants were enrolled in phase 1a, and 10 participants in phase 1b. During phase 1a, TY014 dose escalation to a maximum of 20 mg per kilogram of body weight occurred in 22 participants. During phases 1a and 1b, adverse events within 1 hour after infusion occurred in 1 of 27 participants who received TY014 and in none of the 10 participants who received placebo. At least one adverse event occurred during the trial in 22 participants who received TY014 and in 8 who received placebo. The mean half-life of TY014 was approximately 12.8 days. At 48 hours after the infusion, none of the 5 participants who received the starting dose of TY014 of 2 mg per kilogram had detectable YF17D-204 viremia; these participants remained aviremic throughout the trial. Viremia was observed at 48 hours after the infusion in 2 of 5 participants who received placebo and at 72 hours in 2 more placebo recipients. Symptoms associated with yellow fever vaccine were less frequent in the TY014 group than in the placebo group.
CONCLUSIONS: This phase 1 trial of TY014 did not identify worrisome safety signals and suggested potential clinical benefit, which requires further assessment in a phase 2 trial. (Funded by Tysana; ClinicalTrials.gov number, NCT03776786.).
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2020 |
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| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:383 |
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| Enthalten in: |
The New England journal of medicine - 383(2020), 5 vom: 30. Juli, Seite 452-459 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Low, Jenny G [VerfasserIn] |
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| Links: |
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| Themen: |
Antibodies, Monoclonal, Humanized |
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| Anmerkungen: |
Date Completed 17.08.2020 Date Revised 22.10.2020 published: Print ClinicalTrials.gov: NCT03776786 Citation Status MEDLINE |
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| doi: |
10.1056/NEJMoa2000226 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM313021546 |
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| 245 | 1 | 0 | |a Phase 1 Trial of a Therapeutic Anti-Yellow Fever Virus Human Antibody |
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| 500 | |a Date Completed 17.08.2020 | ||
| 500 | |a Date Revised 22.10.2020 | ||
| 500 | |a published: Print | ||
| 500 | |a ClinicalTrials.gov: NCT03776786 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2020 Massachusetts Medical Society. | ||
| 520 | |a BACKGROUND: Insufficient vaccine doses and the lack of therapeutic agents for yellow fever put global health at risk, should this virus emerge from sub-Saharan Africa and South America | ||
| 520 | |a METHODS: In phase 1a of this clinical trial, we assessed the safety, side-effect profile, and pharmacokinetics of TY014, a fully human IgG1 anti-yellow fever virus monoclonal antibody. In a double-blind, phase 1b clinical trial, we assessed the efficacy of TY014, as compared with placebo, in abrogating viremia related to the administration of live yellow fever vaccine (YF17D-204; Stamaril). The primary safety outcomes were adverse events reported 1 hour after the infusion and throughout the trial. The primary efficacy outcome was the dose of TY014 at which 100% of the participants tested negative for viremia within 48 hours after infusion | ||
| 520 | |a RESULTS: A total of 27 healthy participants were enrolled in phase 1a, and 10 participants in phase 1b. During phase 1a, TY014 dose escalation to a maximum of 20 mg per kilogram of body weight occurred in 22 participants. During phases 1a and 1b, adverse events within 1 hour after infusion occurred in 1 of 27 participants who received TY014 and in none of the 10 participants who received placebo. At least one adverse event occurred during the trial in 22 participants who received TY014 and in 8 who received placebo. The mean half-life of TY014 was approximately 12.8 days. At 48 hours after the infusion, none of the 5 participants who received the starting dose of TY014 of 2 mg per kilogram had detectable YF17D-204 viremia; these participants remained aviremic throughout the trial. Viremia was observed at 48 hours after the infusion in 2 of 5 participants who received placebo and at 72 hours in 2 more placebo recipients. Symptoms associated with yellow fever vaccine were less frequent in the TY014 group than in the placebo group | ||
| 520 | |a CONCLUSIONS: This phase 1 trial of TY014 did not identify worrisome safety signals and suggested potential clinical benefit, which requires further assessment in a phase 2 trial. (Funded by Tysana; ClinicalTrials.gov number, NCT03776786.) | ||
| 650 | 4 | |a Clinical Trial, Phase I | |
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Randomized Controlled Trial | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 7 | |a Antibodies, Monoclonal, Humanized |2 NLM | |
| 650 | 7 | |a TY014 |2 NLM | |
| 650 | 7 | |a Yellow Fever Vaccine |2 NLM | |
| 700 | 1 | |a Ng, Justin H J |e verfasserin |4 aut | |
| 700 | 1 | |a Ong, Eugenia Z |e verfasserin |4 aut | |
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| 700 | 1 | |a Budigi, Yadunanda |e verfasserin |4 aut | |
| 700 | 1 | |a Sasisekharan, Ram |e verfasserin |4 aut | |
| 700 | 1 | |a Ooi, Eng-Eong |e verfasserin |4 aut | |
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