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Immunogenicity and safety of SARS-CoV-2 recombinant protein nanoparticle vaccine GBP510 adjuvanted with AS03: interim results of a randomised, active-controlled, observer-blinded, phase 3 trial
- Title
- Immunogenicity and safety of SARS-CoV-2 recombinant protein nanoparticle vaccine GBP510 adjuvanted with AS03: interim results of a randomised, active-controlled, observer-blinded, phase 3 trial
- Authors
- Song; Joon Young; Choi; Won Suk; Heo; Jung Yeon; Kim; Eun Jin; Lee; Jin Soo; Jung; Dong Sik; Shin-Woo; Park; Kyung-Hwa; Eom; Joong Sik; Jeong; Su Jin; Jacob; Kwon; Ki Tae; Hee Jung; Sohn; Jang Wook; Young Keun; Yoo; Byung Wook; Jang; In-Jin; Capeding; Maria Z.; Roman; François; Breuer; Thomas; Wysocki; Piotr; Carter; Lauren; Sahastrabuddhe; Sushant; Manki; D'Cor; Naveena; Hun; Ryu; Ji Hwa; Su Jeen; Yong Wook; Cheong; Hee Jin; Philippot; Agathe; Solmi; Francesca; Ceregido; Maria Angeles; Shim; Byoung-Shik; Seo; Sang Hwan; D'Souza; Simone; Thaisrivichai; Patchara; Carlos; Josefina; Alberto; Edison; Nitayaphan; Sorachai; Ratanasuwan; Winai; Mootsikapun; Piroon; Chaiwarith; Romanee; Chan Quang; Luong; Karpenko; Olena; Yurkiv; Tatiana; Kutovyi; Vitalii; Bartko; Angela; Gyrina; Olga; Barna; Pugach; Mykhailo; Thurlow; Claire; Carson; Simon; Smith; Susan; Williams; Mike; Hemi Senior; Tiwini; Humphrey; Tim; Sheahan; Davitt; Hokeun; Yoon Yeong; Kang; Seung Gu
- Ewha Authors
- 최희정
- SCOPUS Author ID
- 최희정
- Issue Date
- 2023
- Journal Title
- eClinicalMedicine
- ISSN
- 2589-5370
- Citation
- eClinicalMedicine vol. 64
- Keywords
- COVID-19; Immunogenicity; Nanoparticle vaccine; Recombinant protein vaccine; Safety; SARS-CoV-2
- Publisher
- Elsevier Ltd
- Indexed
- SCIE; SCOPUS
- Document Type
- Article
- Abstract
- Background: GBP510 vaccine contains self-assembling, recombinant nanoparticles displaying SARS-CoV-2 spike receptor-binding domains. We report interim phase 3 immunogenicity results for GBP510 adjuvanted with AS03 (GBP510/AS03) compared with ChAdOx1-S (Vaxzevria, AstraZeneca) in healthy adults aged ≥18 years, up to 6 months after the second dose. Methods: This was a randomised, active-controlled, observer-blinded, parallel group, phase 3 study, conducted at 38 sites across six countries (South Korea, Philippines, Thailand, Vietnam, Ukraine and New Zealand). Cohort 1 (no history of SARS-CoV-2 infection/COVID-19 vaccination) was randomised 2:1 to receive two doses of GBP510/AS03 or ChAdOx1-S (immunogenicity and safety), while Cohort 2 (regardless of baseline serostatus) was randomised 5:1 (safety). Primary objectives were to demonstrate superiority in geometric mean titre (GMT) and non-inferiority in seroconversion rate (SCR; ≥4-fold rise from baseline) of GBP510/AS03 vs. ChAdOx1-S for neutralising antibodies against the ancestral strain by live-virus neutralisation assay. Secondary objectives included assessment of safety and reactogenicity (long-term 6 months cut-off date: 09 August 2022). This study was registered on ClinicalTrials.gov (NCT05007951). Findings: Between 30 August 2021 and 11 January 2022, a total of 4913 participants were screened and 4036 participants (1956 in Cohort 1 and 2080 in Cohort 2) who met eligibility criteria were enrolled and randomised to receive 2 doses of GBP510/AS03 (n = 3039) or ChAdOx1-S (n = 997). Most participants were Southeast Asian (81.5%) and aged 18–64 years (94.7%). The primary objectives assessed in per-protocol set included 877 participants in GBP510/AS03 and 441 in ChAdOx1-S group: at 2 weeks after the second vaccination, the GMT ratio (GBP510/AS03/ChAdOx1-S) in per-protocol set was 2.93 (95% CI 2.63–3.27), demonstrating superiority (95% CI lower limit >1) of GBP510/AS03; the between-group SCR difference of 10.8% (95% CI 7.68–14.32) also satisfied the non-inferiority criterion (95% CI lower limit > −5%). Neutralizing antibody titres sustained higher for the GBP510/AS03 group compared to the ChAdOx1-S group through 6 months after the second vaccination. In Safety analysis (Cohort 1 & 2), the proportion of participants with adverse events (AEs) after any vaccination was higher with GBP510/AS03 vs. ChAdOx1-S for solicited local AEs (56.7% vs. 49.2%), but was similar for solicited systemic AEs (51.2% vs. 53.5%) and unsolicited AEs (13.3% vs. 14.6%) up to 28 days after the second vaccination. No safety concerns were identified during follow-up for 6 months after the second vaccination. Interpretation: Our interim findings suggested that GBP510/AS03 met the superiority criterion for neutralising antibodies and non-inferiority criterion for SCR compared with ChAdOx1-S, and showed a clinically acceptable safety profile. Funding: This work was supported, in whole or in part, by funding from CEPI and the Bill & Melinda Gates Foundation Investments INV-010680 and INV-006462. The Bill & Melinda Gates Foundation supported this project for the generation of IND-enabling data and CEPI supported this clinical study. © 2023
- DOI
- 10.1016/j.eclinm.2023.102140
- Appears in Collections:
- 의과대학 > 의학과 > Journal papers
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