Safety and efficacy of AK0529 in respiratory syncytial virus-infected infant patients : A phase 2 proof-of-concept trial
© 2023 Shanghai Ark Biopharmaceutical Ltd Co. Influenza and Other Respiratory Viruses published by John Wiley & Sons Ltd..
Background: Respiratory syncytial virus (RSV) infection is a cause of substantial morbidity and mortality in young children. There is currently no effective therapy available.
Methods: This was a Phase 2 study of the oral RSV fusion protein inhibitor AK0529 in infants aged 1-24 months, hospitalized with RSV infection. In Part 1, patients (n = 24) were randomized 2:1 to receive a single dose of AK0529 up to 4 mg/kg or placebo. In Part 2, patients (n = 48) were randomized 2:1 to receive AK0529 at 0.5, 1, or 2 mg/kg bid or placebo for 5 days. Sparse pharmacokinetic samples were assessed using population pharmacokinetics modelling. Safety, tolerability, viral load, and respiratory signs and symptoms were assessed daily during treatment.
Results: No safety or tolerability signals were detected for AK0529: grade ≥3 treatment-emergent adverse events occurring in 4.1% of patients in AK0529 and 4.2% in placebo groups, respectively, and none led to death or withdrawal from the study. In Part 2, targeted drug exposure was reached with 2 mg/kg bid. A numerically greater reduction in median viral load with 2 mg/kg bid AK0529 than with placebo at 96 h was observed. A -4.0 (95% CI: -4.51, -2.03) median reduction in Wang Respiratory Score from baseline to 96 h was observed in the 2 mg/kg group compared with -2.0 (95% CI: -3.42, -1.82) in the placebo group.
Conclusions: AK0529 was well tolerated in hospitalized RSV-infected infant patients. Treatment with AK0529 2 mg/kg bid was observed to reduce viral load and Wang Respiratory Score.
Clinical Trials Registration: NCT02654171.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:17 |
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| Enthalten in: |
Influenza and other respiratory viruses - 17(2023), 7 vom: 15. Juli, Seite e13176 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Huang, Li-Min [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 31.07.2023 Date Revised 31.07.2023 published: Electronic-eCollection ClinicalTrials.gov: NCT02654171 Citation Status MEDLINE |
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| doi: |
10.1111/irv.13176 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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NLM360025382 |
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| 100 | 1 | |a Huang, Li-Min |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Safety and efficacy of AK0529 in respiratory syncytial virus-infected infant patients |b A phase 2 proof-of-concept trial |
| 264 | 1 | |c 2023 | |
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| 500 | |a Date Revised 31.07.2023 | ||
| 500 | |a published: Electronic-eCollection | ||
| 500 | |a ClinicalTrials.gov: NCT02654171 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2023 Shanghai Ark Biopharmaceutical Ltd Co. Influenza and Other Respiratory Viruses published by John Wiley & Sons Ltd. | ||
| 520 | |a Background: Respiratory syncytial virus (RSV) infection is a cause of substantial morbidity and mortality in young children. There is currently no effective therapy available | ||
| 520 | |a Methods: This was a Phase 2 study of the oral RSV fusion protein inhibitor AK0529 in infants aged 1-24 months, hospitalized with RSV infection. In Part 1, patients (n = 24) were randomized 2:1 to receive a single dose of AK0529 up to 4 mg/kg or placebo. In Part 2, patients (n = 48) were randomized 2:1 to receive AK0529 at 0.5, 1, or 2 mg/kg bid or placebo for 5 days. Sparse pharmacokinetic samples were assessed using population pharmacokinetics modelling. Safety, tolerability, viral load, and respiratory signs and symptoms were assessed daily during treatment | ||
| 520 | |a Results: No safety or tolerability signals were detected for AK0529: grade ≥3 treatment-emergent adverse events occurring in 4.1% of patients in AK0529 and 4.2% in placebo groups, respectively, and none led to death or withdrawal from the study. In Part 2, targeted drug exposure was reached with 2 mg/kg bid. A numerically greater reduction in median viral load with 2 mg/kg bid AK0529 than with placebo at 96 h was observed. A -4.0 (95% CI: -4.51, -2.03) median reduction in Wang Respiratory Score from baseline to 96 h was observed in the 2 mg/kg group compared with -2.0 (95% CI: -3.42, -1.82) in the placebo group | ||
| 520 | |a Conclusions: AK0529 was well tolerated in hospitalized RSV-infected infant patients. Treatment with AK0529 2 mg/kg bid was observed to reduce viral load and Wang Respiratory Score | ||
| 520 | |a Clinical Trials Registration: NCT02654171 | ||
| 650 | 4 | |a Randomized Controlled Trial | |
| 650 | 4 | |a Clinical Trial, Phase II | |
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a AK0529 | |
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| 650 | 4 | |a respiratory syncytial virus (RSV) | |
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| 650 | 7 | |a ziresovir |2 NLM | |
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| 650 | 7 | |a Sulfones |2 NLM | |
| 650 | 7 | |a Quinazolines |2 NLM | |
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| 700 | 1 | |a Huang, Yi-Chuan |e verfasserin |4 aut | |
| 700 | 1 | |a Tai, Andrew |e verfasserin |4 aut | |
| 700 | 1 | |a Chi, Hsin |e verfasserin |4 aut | |
| 700 | 1 | |a Chieng, Chae-Hee |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Jinn-Li |e verfasserin |4 aut | |
| 700 | 1 | |a Goldbart, Aviv |e verfasserin |4 aut | |
| 700 | 1 | |a Tang, Swee-Ping |e verfasserin |4 aut | |
| 700 | 1 | |a Huang, Yhu-Chering |e verfasserin |4 aut | |
| 700 | 1 | |a George, Shane |e verfasserin |4 aut | |
| 700 | 1 | |a Alabaz, Derya |e verfasserin |4 aut | |
| 700 | 1 | |a Bentur, Lea |e verfasserin |4 aut | |
| 700 | 1 | |a Su, Siew-Choo |e verfasserin |4 aut | |
| 700 | 1 | |a de Bruyne, Jessie |e verfasserin |4 aut | |
| 700 | 1 | |a Karadag, Bulent |e verfasserin |4 aut | |
| 700 | 1 | |a Gu, Feng |e verfasserin |4 aut | |
| 700 | 1 | |a Zou, Gang |e verfasserin |4 aut | |
| 700 | 1 | |a Toovey, Stephen |e verfasserin |4 aut | |
| 700 | 1 | |a DeVincenzo, John P |e verfasserin |4 aut | |
| 700 | 1 | |a Wu, Jim Z |e verfasserin |4 aut | |
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