دورية أكاديمية
Anti-SARS-CoV-2 glyco-humanized polyclonal antibody XAV-19: phase II/III randomized placebo-controlled trial shows acceleration to recovery for mild to moderate patients with COVID-19.
| العنوان: | Anti-SARS-CoV-2 glyco-humanized polyclonal antibody XAV-19: phase II/III randomized placebo-controlled trial shows acceleration to recovery for mild to moderate patients with COVID-19. |
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| المؤلفون: | Poulakou G; 3rd Department of Internal Medicine, Medical School, Sotiria General Hospital, National and Kapodistrian University of Athens, Athens, Greece., Royer PJ; Xenothera, Nantes, France., Evgeniev N; Department of Medical Oncology, Complex Oncology Center, Russe, Bulgaria., Evanno G; Xenothera, Nantes, France., Shneiker F; Xenothera, Nantes, France., Marcelin AG; Sorbonne Université, Institut National de la Santé et de la Recherche Médicale (INSERM) 1136, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Assistance Publique-Hôpitaux de Paris (AP-HP), Pitié Salpêtrière Hospital, Department of Virology, Paris, France., Vanhove B; Xenothera, Nantes, France., Duvaux O; Xenothera, Nantes, France., Marot S; Sorbonne Université, Institut National de la Santé et de la Recherche Médicale (INSERM) 1136, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Assistance Publique-Hôpitaux de Paris (AP-HP), Pitié Salpêtrière Hospital, Department of Virology, Paris, France., Calvez V; Sorbonne Université, Institut National de la Santé et de la Recherche Médicale (INSERM) 1136, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Assistance Publique-Hôpitaux de Paris (AP-HP), Pitié Salpêtrière Hospital, Department of Virology, Paris, France. |
| المصدر: | Frontiers in immunology [Front Immunol] 2024 Apr 17; Vol. 15, pp. 1330178. Date of Electronic Publication: 2024 Apr 17 (Print Publication: 2024). |
| نوع المنشور: | Journal Article; Clinical Trial, Phase II; Randomized Controlled Trial; Research Support, Non-U.S. Gov't; Multicenter Study; Clinical Trial, Phase III |
| اللغة: | English |
| بيانات الدورية: | Publisher: Frontiers Research Foundation] Country of Publication: Switzerland NLM ID: 101560960 Publication Model: eCollection Cited Medium: Internet ISSN: 1664-3224 (Electronic) Linking ISSN: 16643224 NLM ISO Abbreviation: Front Immunol Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: [Lausanne : Frontiers Research Foundation] |
| مواضيع طبية MeSH: | SARS-CoV-2*/immunology , COVID-19*/immunology , COVID-19*/therapy , Antibodies, Viral*/immunology , Antibodies, Viral*/therapeutic use , COVID-19 Drug Treatment* , Antibodies, Neutralizing*/immunology , Antibodies, Neutralizing*/therapeutic use, Humans ; Male ; Female ; Middle Aged ; Double-Blind Method ; Aged ; Adult ; Treatment Outcome ; Severity of Illness Index |
| مستخلص: | Introduction: XAV-19 is a glyco-humanized swine polyclonal antibody targeting SARS-CoV-2 with high neutralizing activity. The safety and clinical efficacy of XAV-19 were investigated in patients with mild to moderate COVID-19. Methods: This phase II/III, multicentric, randomized, double-blind, placebo-controlled clinical trial was conducted to evaluate the safety and clinical efficacy of XAV-19 in patients with a seven-point WHO score of 2 to 4 at randomization, i.e., inpatients with COVID-19 requiring or not requiring low-flow oxygen therapy, and outpatients not requiring oxygen (EUROXAV trial, NCT04928430). Adult patients presenting in specialized or emergency units with confirmed COVID-19 and giving their consent to participate in the study were randomized to receive 150 mg of XAV-19 or placebo. The primary endpoint was the proportion of patients with aggravation within 8 days after treatment, defined as a worsening of the seven-point WHO score of at least one point between day 8 and day 1 (inclusion). The neutralization activity of XAV-19 against variants circulating during the trial was tested in parallel. Results: From March 2021 to October 2022, 279 patients received either XAV-19 (N = 140) or placebo (N = 139). A slow enrollment and a low rate of events forced the termination of the premature trial. XAV-19 was well tolerated. Underpowered statistics did not allow the detection of any difference in the primary endpoint between the two groups or in stratified groups. Interestingly, analysis of the time to improvement (secondary endpoint) showed that XAV-19 significantly accelerated the recovery for patients with a WHO score of 2 or 3 (median at 7 days vs. 14 days, p = 0.0159), and even more for patients with a WHO score of 2 (4 days vs. 14 days, p = 0.0003). The neutralizing activity against Omicron and BA.2, BA.2.12.1, BA.4/5, and BQ.1.1 subvariants was shown. Discussion: In this randomized placebo- controlled trial with premature termination, reduction of aggravation by XAV-19 at day 8 in patients with COVID-19 was not detectable. However, a significant reduction of the time to improvement for patients not requiring oxygen was observed. XAV-19 maintained a neutralizing activity against SARS-CoV-2 variants. Altogether, these data support a possible therapeutic interest for patients with mild to moderate COVID-19 requiring anti-SARS-CoV-2 neutralizing antibodies. Clinical Trial Registration: https://clinicaltrials.gov/, identifier NCT04928430; https://www.clinicaltrialsregister.eu/about.html (EudraCT), identifier 2020-005979-12. Competing Interests: Authors P-JR, GE, FS, BV, and OD are employees of the company Xenothera. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision. (Copyright © 2024 Poulakou, Royer, Evgeniev, Evanno, Shneiker, Marcelin, Vanhove, Duvaux, Marot and Calvez.) |
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| فهرسة مساهمة: | Keywords: (glyco-humanized) polyclonal antibody; COVID-19; SARS-CoV-2 variants; XAV-19; clinical trial |
| سلسلة جزيئية: | ClinicalTrials.gov NCT04928430 |
| المشرفين على المادة: | 0 (Antibodies, Viral) 0 (Antibodies, Neutralizing) |
| تواريخ الأحداث: | Date Created: 20240502 Date Completed: 20240502 Latest Revision: 20240614 |
| رمز التحديث: | 20240615 |
| مُعرف محوري في PubMed: | PMC11061480 |
| DOI: | 10.3389/fimmu.2024.1330178 |
| PMID: | 38694503 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1664-3224 |
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| DOI: | 10.3389/fimmu.2024.1330178 |