Safety and Intranasal Retention of a Broad-Spectrum Anti-SARS-CoV-2 Monoclonal Antibody SA55 Nasal Spray in Healthy Volunteers: A Phase I Clinical Trial
Background: A broad-spectrum anti-SARS-CoV-2 monoclonal antibody (mAb), SA55, is highly effective against SARS-CoV-2 variants. This trial aimed at demonstrating the safety, tolerability, local drug retention and neutralizing activity, systemic exposure level, and immunogenicity of the SA55 nasal spr...
Saved in:
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2024-12-01
|
| Series: | Pharmaceutics |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1999-4923/17/1/43 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832587692355878912 |
|---|---|
| author | Chaoying Hu Yibo Zhou Xing Meng Jianhua Li Jinxia Chen Zhifang Ying Xiaoliang Sunney Xie Yaling Hu Yunlong Cao Ronghua Jin |
| author_facet | Chaoying Hu Yibo Zhou Xing Meng Jianhua Li Jinxia Chen Zhifang Ying Xiaoliang Sunney Xie Yaling Hu Yunlong Cao Ronghua Jin |
| author_sort | Chaoying Hu |
| collection | DOAJ |
| description | Background: A broad-spectrum anti-SARS-CoV-2 monoclonal antibody (mAb), SA55, is highly effective against SARS-CoV-2 variants. This trial aimed at demonstrating the safety, tolerability, local drug retention and neutralizing activity, systemic exposure level, and immunogenicity of the SA55 nasal spray in healthy individuals. Methods: This phase I, dose-escalation clinical trial combined an open-label design with a randomized, controlled, double-blind design. Healthy participants aged 18–65 years were enrolled and received a single dose of the SA55 nasal spray (1 mg or 2 mg) or multiple doses of SA55 nasal spray/placebo for 7 days (1 or 2 mg/dose, 3 or 6 doses/day). Safety monitoring was conducted throughout the study. Nasal swabs and venous blood samples were collected to analyze local drug concentration/neutralization, systemic exposure, and immunogenicity. Results: From 2 June to 11 August 2023, 80 participants were enrolled and received study intervention. The severity of adverse reactions (ADRs) reported during the study was mild in all cases, and all ADRs were laboratory test abnormalities without corresponding symptoms or vital signs. A total of 9 ADRs were reported, of which all were mild in severity. Overall ADR incidence rate was 16.67% (8/48) in single-dose groups and 4.17% (1/24) in multiple-dose groups. The nasal local drug concentration and neutralizing activity were generally stable within 4–8 h, with favorable neutralization activity against Omicron BF.7 and XBB strains. Conclusions: This study demonstrated favorable safety and tolerability of the SA55 nasal spray in healthy volunteers, exhibited satisfactory neutralizing activity against Omicron variants intranasally, and indicated low systemic toxicity risk. |
| format | Article |
| id | doaj-art-14daf9e60d7c402395974f346a5ce041 |
| institution | Kabale University |
| issn | 1999-4923 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj-art-14daf9e60d7c402395974f346a5ce0412025-01-24T13:45:41ZengMDPI AGPharmaceutics1999-49232024-12-011714310.3390/pharmaceutics17010043Safety and Intranasal Retention of a Broad-Spectrum Anti-SARS-CoV-2 Monoclonal Antibody SA55 Nasal Spray in Healthy Volunteers: A Phase I Clinical TrialChaoying Hu0Yibo Zhou1Xing Meng2Jianhua Li3Jinxia Chen4Zhifang Ying5Xiaoliang Sunney Xie6Yaling Hu7Yunlong Cao8Ronghua Jin9Phase I Clinical Trial Unit, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, ChinaPhase I Clinical Trial Unit, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, ChinaClinical Research and Development Center, Sinovac Biotech Co., Ltd., Beijing 100085, ChinaZhejiang Key Laboratory of Public Health Detection and Pathogenesis Research, Hangzhou 310051, ChinaClinical Research and Development Center, Sinovac Life Sciences Co., Ltd., Beijing 102601, ChinaRespiratory Virus Vaccine, National Institutes for Food and Drug Control, Beijing 100061, ChinaBiomedical Pioneering Innovation Center (BIOPIC), Peking University, Beijing 100871, ChinaClinical Research and Development Center, Sinovac Life Sciences Co., Ltd., Beijing 102601, ChinaBiomedical Pioneering Innovation Center (BIOPIC), Peking University, Beijing 100871, ChinaPhase I Clinical Trial Unit, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, ChinaBackground: A broad-spectrum anti-SARS-CoV-2 monoclonal antibody (mAb), SA55, is highly effective against SARS-CoV-2 variants. This trial aimed at demonstrating the safety, tolerability, local drug retention and neutralizing activity, systemic exposure level, and immunogenicity of the SA55 nasal spray in healthy individuals. Methods: This phase I, dose-escalation clinical trial combined an open-label design with a randomized, controlled, double-blind design. Healthy participants aged 18–65 years were enrolled and received a single dose of the SA55 nasal spray (1 mg or 2 mg) or multiple doses of SA55 nasal spray/placebo for 7 days (1 or 2 mg/dose, 3 or 6 doses/day). Safety monitoring was conducted throughout the study. Nasal swabs and venous blood samples were collected to analyze local drug concentration/neutralization, systemic exposure, and immunogenicity. Results: From 2 June to 11 August 2023, 80 participants were enrolled and received study intervention. The severity of adverse reactions (ADRs) reported during the study was mild in all cases, and all ADRs were laboratory test abnormalities without corresponding symptoms or vital signs. A total of 9 ADRs were reported, of which all were mild in severity. Overall ADR incidence rate was 16.67% (8/48) in single-dose groups and 4.17% (1/24) in multiple-dose groups. The nasal local drug concentration and neutralizing activity were generally stable within 4–8 h, with favorable neutralization activity against Omicron BF.7 and XBB strains. Conclusions: This study demonstrated favorable safety and tolerability of the SA55 nasal spray in healthy volunteers, exhibited satisfactory neutralizing activity against Omicron variants intranasally, and indicated low systemic toxicity risk.https://www.mdpi.com/1999-4923/17/1/43SARS-CoV-2monoclonal antibodySA55 nasal sprayphase I clinical trialbroad-spectrum neutralizing antibodyintranasal administration |
| spellingShingle | Chaoying Hu Yibo Zhou Xing Meng Jianhua Li Jinxia Chen Zhifang Ying Xiaoliang Sunney Xie Yaling Hu Yunlong Cao Ronghua Jin Safety and Intranasal Retention of a Broad-Spectrum Anti-SARS-CoV-2 Monoclonal Antibody SA55 Nasal Spray in Healthy Volunteers: A Phase I Clinical Trial Pharmaceutics SARS-CoV-2 monoclonal antibody SA55 nasal spray phase I clinical trial broad-spectrum neutralizing antibody intranasal administration |
| title | Safety and Intranasal Retention of a Broad-Spectrum Anti-SARS-CoV-2 Monoclonal Antibody SA55 Nasal Spray in Healthy Volunteers: A Phase I Clinical Trial |
| title_full | Safety and Intranasal Retention of a Broad-Spectrum Anti-SARS-CoV-2 Monoclonal Antibody SA55 Nasal Spray in Healthy Volunteers: A Phase I Clinical Trial |
| title_fullStr | Safety and Intranasal Retention of a Broad-Spectrum Anti-SARS-CoV-2 Monoclonal Antibody SA55 Nasal Spray in Healthy Volunteers: A Phase I Clinical Trial |
| title_full_unstemmed | Safety and Intranasal Retention of a Broad-Spectrum Anti-SARS-CoV-2 Monoclonal Antibody SA55 Nasal Spray in Healthy Volunteers: A Phase I Clinical Trial |
| title_short | Safety and Intranasal Retention of a Broad-Spectrum Anti-SARS-CoV-2 Monoclonal Antibody SA55 Nasal Spray in Healthy Volunteers: A Phase I Clinical Trial |
| title_sort | safety and intranasal retention of a broad spectrum anti sars cov 2 monoclonal antibody sa55 nasal spray in healthy volunteers a phase i clinical trial |
| topic | SARS-CoV-2 monoclonal antibody SA55 nasal spray phase I clinical trial broad-spectrum neutralizing antibody intranasal administration |
| url | https://www.mdpi.com/1999-4923/17/1/43 |
| work_keys_str_mv | AT chaoyinghu safetyandintranasalretentionofabroadspectrumantisarscov2monoclonalantibodysa55nasalsprayinhealthyvolunteersaphaseiclinicaltrial AT yibozhou safetyandintranasalretentionofabroadspectrumantisarscov2monoclonalantibodysa55nasalsprayinhealthyvolunteersaphaseiclinicaltrial AT xingmeng safetyandintranasalretentionofabroadspectrumantisarscov2monoclonalantibodysa55nasalsprayinhealthyvolunteersaphaseiclinicaltrial AT jianhuali safetyandintranasalretentionofabroadspectrumantisarscov2monoclonalantibodysa55nasalsprayinhealthyvolunteersaphaseiclinicaltrial AT jinxiachen safetyandintranasalretentionofabroadspectrumantisarscov2monoclonalantibodysa55nasalsprayinhealthyvolunteersaphaseiclinicaltrial AT zhifangying safetyandintranasalretentionofabroadspectrumantisarscov2monoclonalantibodysa55nasalsprayinhealthyvolunteersaphaseiclinicaltrial AT xiaoliangsunneyxie safetyandintranasalretentionofabroadspectrumantisarscov2monoclonalantibodysa55nasalsprayinhealthyvolunteersaphaseiclinicaltrial AT yalinghu safetyandintranasalretentionofabroadspectrumantisarscov2monoclonalantibodysa55nasalsprayinhealthyvolunteersaphaseiclinicaltrial AT yunlongcao safetyandintranasalretentionofabroadspectrumantisarscov2monoclonalantibodysa55nasalsprayinhealthyvolunteersaphaseiclinicaltrial AT ronghuajin safetyandintranasalretentionofabroadspectrumantisarscov2monoclonalantibodysa55nasalsprayinhealthyvolunteersaphaseiclinicaltrial |