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Safety and Efficacy of AK0529 in Respiratory Syncytial Virus-Infected Infant Patients: a Phase 2 Proof-of-Concept Trial
  • +18
  • Li-Ming Huang,
  • Andreas Schibler,
  • Yi-Chuan Huang,
  • Andrew Tai,
  • Hsin Chi,
  • Chae-Hee Chieng,
  • Jinn-Li Wang,
  • Aviv Goldbart,
  • Swee-Ping Tang,
  • YC Huang,
  • Shane George,
  • Derya Alabaz,
  • Siew-Choo Su,
  • Jessie de Bruyne,
  • Bulent Karadag,
  • Lea Bentur,
  • Feng Gu,
  • Gang Zou,
  • Stephen Toovey,
  • John Devincenzo,
  • Jim Wu
Li-Ming Huang
National Taiwan University College of Medicine

Corresponding Author:lmhuang@ntu.edu.tw

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Andreas Schibler
Wesley Medical Research Ltd
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Yi-Chuan Huang
Chang Gung Memorial Hospital Kaohsiung Branch
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Andrew Tai
Women's and Children's Hospital Adelaide
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Hsin Chi
Mackay Memorial Hospital
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Chae-Hee Chieng
Sibu Hospital
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Jinn-Li Wang
Taipei Municipal Wan-Fang Hospital
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Aviv Goldbart
Soroka Medical Center
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Swee-Ping Tang
Hospital Selayang
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YC Huang
Chang Gung Memorial Hospital Linkou Main Branch
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Shane George
Gold Coast University Hospital
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Derya Alabaz
Cukurova University Faculty of Medicine
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Siew-Choo Su
Tengku Ampuan Rahimah Hospital
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Jessie de Bruyne
University of Malaya Medical Centre
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Bulent Karadag
Marmara University
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Lea Bentur
Ruth Rappaport Children's Hospital
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Feng Gu
Ark Biopharmaceutical
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Gang Zou
Ark Biopharmaceutical
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Stephen Toovey
Ark Biopharmaceutical
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John Devincenzo
Le Bonheur Children's Medical Center
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Jim Wu
Ark Biopharmaceutical
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Abstract

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 five days. Sparse pharmacokinetic samples were assessed using population pharmacokinetics modelling. Safety, tolerability, viral load, signs and symptoms were assessed daily during treatment. Results. No safety or tolerability signals were detected for AK0529: grade ≥3 treatment-emergent adverse events occurred 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 hours was observed. A -4.0 (95% CI: -4.51, -2.03) median reduction in RSV signs and symptom score from baseline to 96 hours 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 infants. Treatment with AK0529 2 mg/kg bid was observed to reduce viral load and clinical signs and symptoms.
17 Oct 2022Submitted to Influenza and other respiratory viruses
17 Oct 2022Submission Checks Completed
17 Oct 2022Assigned to Editor
31 Oct 2022Reviewer(s) Assigned
07 Apr 2023Review(s) Completed, Editorial Evaluation Pending
11 Apr 2023Editorial Decision: Revise Major
25 May 20231st Revision Received
30 May 2023Submission Checks Completed
30 May 2023Assigned to Editor
06 Jun 2023Reviewer(s) Assigned
10 Jun 2023Review(s) Completed, Editorial Evaluation Pending
05 Jul 2023Editorial Decision: Accept