A randomized phase 2 study on demeclocycline in patients with mild-to-moderate COVID-19

• Published in: Scientific reports Vol. 13; no. 1; p. 13809
• Main Authors: Iwahori, Kota, Nii, Takuro, Yamaguchi, Norihiko, Kawasaki, Takahiro, Okamura, Satomi, Hashimoto, Kazuki, Matsuki, Takanori, Tsujino, Kazuyuki, Miki, Keisuke, Osa, Akio, Goya, Sho, Abe, Kinya, Mori, Masahide, Takeda, Yoshito, Yamada, Tomomi, Kida, Hiroshi, Kumanogoh, Atsushi
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 23.08.2023; Nature Publishing Group; Nature Portfolio
• Subjects: 631/250/255/2514; 631/326/596/4130; Antiviral agents; CD4 antigen; Clinical trials; COVID-19; Demeclocycline; Humanities and Social Sciences; Immunomodulation; Inflammation; Interleukin 6; Lymphocytes; Lymphocytes T; multidisciplinary; Patients; Registration; Science; Science (multidisciplinary); Severe acute respiratory syndrome coronavirus 2; Tetracyclines
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-023-41051-2

Tetracyclines exhibit anti-viral, anti-inflammatory, and immunomodulatory activities via various mechanisms. The present study investigated the efficacy and safety of demeclocycline in patients hospitalized with mild-to-moderate COVID-19 via an open-label, multicenter, parallel-group, randomized controlled phase 2 trial. Primary and secondary outcomes included changes from baseline (day 1, before the study treatment) in lymphocytes, cytokines, and SARS-CoV-2 RNA on day 8. Seven, seven, and six patients in the control, demeclocycline 150 mg daily, and demeclocycline 300 mg daily groups, respectively, were included in the modified intention-to-treat population that was followed until day 29. A significant change of 191.3/μL in the number of CD4 +  T cells from day 1 to day 8 was observed in the demeclocycline 150 mg group (95% CI 5.1/μL–377.6/μL) (p = 0.023), whereas that in the control group was 47.8/μL (95% CI − 151.2/μL to 246.8/μL), which was not significant (p = 0.271). The change rates of CD4 +  T cells negatively correlated with those of IL-6 in the demeclocycline-treated groups (R = − 0.807, p = 0.009). All treatment-emergent adverse events were of mild-to-moderate severity. The present results indicate that the treatment of mild-to-moderate COVID-19 patients with demeclocycline elicits immune responses conducive to recovery from COVID-19 with good tolerability. Trial registration : This study was registered with the Japan Registry of Clinical Trials (Trial registration number: jRCTs051200049; Date of the first registration: 26/08/2020).