학술논문
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 trialResearch in context
Document Type
article
Author
Joon Young Song; Won Suk Choi; Jung Yeon Heo; Eun Jin Kim; Jin Soo Lee; Dong Sik Jung; Shin-Woo Kim; Kyung-Hwa Park; Joong Sik Eom; Su Jin Jeong; Jacob Lee; Ki Tae Kwon; Hee Jung Choi; Jang Wook Sohn; Young Keun Kim; Byung Wook Yoo; In-Jin Jang; Maria Z. Capeding; François Roman; Thomas Breuer; Piotr Wysocki; Lauren Carter; Sushant Sahastrabuddhe; Manki Song; Naveena D'Cor; Hun Kim; Ji Hwa Ryu; Su Jeen Lee; Yong Wook Park; Hee Jin Cheong; Agathe Philippot; Francesca Solmi; Maria Angeles Ceregido; Byoung-Shik Shim; Sang Hwan Seo; Simone D'Souza; Patchara Thaisrivichai; Josefina Carlos; Edison Alberto; Sorachai Nitayaphan; Winai Ratanasuwan; Piroon Mootsikapun; Romanee Chaiwarith; Luong Chan Quang; Olena Karpenko; Tatiana Yurkiv; Vitalii Kutovyi; Angela Bartko; Olga Gyrina; Olga Barna; Mykhailo Pugach; Claire Thurlow; Simon Carson; Susan Smith; Mike Williams; Tiwini Hemi Senior; Tim Humphrey; Davitt Sheahan; Hokeun Park; Yoon Yeong Lee; Seung Gu Kang
Source
EClinicalMedicine, Vol 64, Iss , Pp 102140- (2023)
Subject
Language
English
ISSN
2589-5370
Abstract
Summary: 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.