Safety, efficacy and pharmacokinetics of palivizumab in off-label neonates, infants, and young children at risk for serious respiratory syncytial virus infection: a multicenter phase II clinical trial

Masaaki Mori; Kanako Yoshizaki; Shinichi Watabe; Mika Ishige; Akinari Hinoki; Takuya Kondo; Tomoaki Taguchi; Hisaya Hasegawa; Tomoko Hatata; Naoyuki Tanuma; Kosuke Kirino; Akihiro Hirakawa; Takuya Naruto; Minoru Imai; Ryuji Koike; Kenichiro Hosoi; Satoshi Kusuda

doi:10.1016/j.lanwpc.2023.100847

Safety, efficacy and pharmacokinetics of palivizumab in off-label neonates, infants, and young children at risk for serious respiratory syncytial virus infection: a multicenter phase II clinical trial

Lancet Reg Health West Pac. 2023 Jul 26:39:100847. doi: 10.1016/j.lanwpc.2023.100847. eCollection 2023 Oct.

Authors

Masaaki Mori^{1

2}, Kanako Yoshizaki³, Shinichi Watabe³, Mika Ishige⁴, Akinari Hinoki⁵, Takuya Kondo⁶, Tomoaki Taguchi⁶, Hisaya Hasegawa⁷, Tomoko Hatata⁸, Naoyuki Tanuma⁹, Kosuke Kirino¹⁰, Akihiro Hirakawa¹¹, Takuya Naruto¹², Minoru Imai¹³, Ryuji Koike^{13

14}, Kenichiro Hosoi¹⁵, Satoshi Kusuda¹⁵

Affiliations

¹ Department of Pediatrics, Tokyo Medical and Dental University Medical Hospital, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan.
² Division of Rheumatology and Allergology, Department of Internal Medicine, St. Marianna University School of Medicine, Kawasaki, Japan.
³ Department of Pediatrics, Kurashiki Central Hospital, 1-1-1 Miwa, Kurashiki, Okayama 710-8602, Japan.
⁴ Department of Pediatrics and Child Health, Nihon University School of Medicine, 1-6 Kanda Surugadai, Chiyoda-ku, Tokyo 101-8309, Japan.
⁵ Department of Rare/Intractable Cancer Analysis Research, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan.
⁶ Department of Pediatric Surgery, Kyushu University Hospital, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
⁷ Division of Neonatal Intensive Care, Tokyo Women's Medical University, Adachi Medical Center, 4-33-1 Kohoku, Adachi-ku, Tokyo 123-8558, Japan.
⁸ Department of Pediatric Surgery, Nagano Children's Hospital, 3100 Toyoshina, Azumino, Nagano 399-8288, Japan.
⁹ Department of Pediatrics, Tokyo Metropolitan Fuchu Medical Center for the Disabled, 2-9-2 Musashidai, Fuchu, Tokyo 183-8553, Japan.
¹⁰ Department of Data Science, Clinical Research Center, National Center for Child Health and Development, 2-10-1 Ohkura, Setagaya-ku, Tokyo 157-0074, Japan.
¹¹ Department of Clinical Biostatistics, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan.
¹² Clinical Research Institute, Kanagawa Children's Medical Center, 2-138-4 Mutsukawa, Minami-ku, Yokohama 232-8555, Japan.
¹³ Medical Innovation Promotion Center, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan.
¹⁴ Clinical Research Center, Tokyo Medical and Dental University Hospital, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan.
¹⁵ Department of Pediatrics, Faculty of Medicine, Kyorin University, 6-20-2 Shinkawa, Mitaka, Tokyo 181-8611, Japan.

Abstract

Background: Pediatric patients with certain rare diseases are at increased risk of severe respiratory syncytial virus (RSV) infection. However, the prophylactic use of anti-RSV antibody (palivizumab) in these patients is not indicated at present in Japan.

Methods: This first-in-the-world multicenter, uncontrolled, open-label, phase II clinical trial was carried out between 28 July 2019 and 24 September 2021 at seven medical institutions in Japan to investigate the efficacy, safety, and pharmacokinetics of palivizumab in 23 subjects recruited from among neonates, infants, or children aged 24 months or younger who had any of the following conditions: pulmonary hypoplasia, airway stenosis, congenital esophageal atresia, inherited metabolic disease, or neuromuscular disease. At least four continuous doses of palivizumab were administered intramuscularly at 15 mg/kg at intervals of 30 days.

Findings: Twenty-three enrolled subjects completed the study. No subject required hospitalization for RSV. Adverse events (AE) did not notably differ from the event terms described in the latest interview form. Five severe AEs required unplanned hospitalization, but resolved without RSV infection. Therapeutically effective concentrations of palivizumab were maintained throughout the study period.

Interpretation: Palivizumab might be well tolerated and effective in preventing serious respiratory symptoms and hospitalization due to severe RSV infection, indicating the prophylactic use in the pediatric patients included in this study.

Funding: Japan Agency for Medical Research and Development (AMED), grant numbers 19lk0201097h0001 (to MM), 20lk0201097h0002 (to MM), 21lk0201097h0003 (to MM), and 22lk0201097h0004 (to MM). AMED did not have any role in the execution of this study, analysis and interpretation of the data, or the decision to submit the results.

Keywords: Airway stenosis; Congenital esophageal atresia; Efficacy; Inherited metabolic disease; Neuromuscular disease; Palivizumab; Pediatric patient; Pulmonary hypoplasia; Respiratory syncytial virus infection.