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한빛사 논문

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EClinicalMedicine, Oct 2023, 64 102140 | https://doi.org/10.1016/j.eclinm.2023.102140 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.

Joon Young Song ^a, Won Suk Choi ^b, Jung Yeon Heo ^c, Eun Jin Kim ^c, Jin Soo Lee ^d, Dong Sik Jung ^e, Shin-Woo Kim ^f, Kyung-Hwa Park ^g, Joong Sik Eom ^h, Su Jin Jeong ⁱ, Jacob Lee^j, Ki Tae Kwon ^k, Hee Jung Choi ^l, Jang Wook Sohn ^m, Young Keun Kim ⁿ, Byung Wook Yoo ^o, In-Jin Jang ^p, Maria Z. Capeding ^q, François Roman^r, Thomas Breuer^r, Piotr Wysocki ^s, Lauren Carter ^t,u, Sushant Sahastrabuddhe ^v, Manki Song ^v, Naveena D'Cor ^v, Hun Kim ^w, Ji Hwa Ryu ^w, Su Jeen Lee ^w, Yong Wook Park ^w, Hee Jin Cheong ^aGBP510/AS03 study group^x

^aDivision of Infectious Diseases, Department of Internal Medicine, Korea University Guro Hospital, Korea University College of Medicine, Seoul, Republic of Korea

^bDivision of Infectious Diseases, Department of Internal Medicine, Korea University Ansan Hospital, Korea University College of Medicine, Ansan, Republic of Korea

^cDepartment of Infectious Diseases, Ajou University School of Medicine, Suwon, Republic of Korea

^dDivision of Infectious Diseases, Department of Internal Medicine, Inha University College of Medicine, Incheon, Republic of Korea

^eDivision of Infectious Diseases, Department of Internal Medicine, Dong-A University College of Medicine, Busan, Republic of Korea

^fDivision of Infectious Diseases, Department of Internal Medicine, Kyungpook National University Hospital, School of Medicine, Kyungpook National University, Daegu, Republic of Korea

^gDivision of Infectious Diseases, Department of Internal Medicine, Chonnam National University Medical School, Gwangju, Republic of Korea

^hDivision of Infectious Diseases, Department of Internal Medicine, Gil Medical Centre, Gachon University College of Medicine, Incheon, Republic of Korea

ⁱDivision of Infectious Diseases, Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea

^jDivision of Infectious Diseases, Department of Internal Medicine, Hallym University College of Medicine, Chuncheon, Republic of Korea

^kDivision of Infectious Diseases, Department of Internal Medicine, Kyungpook National University Chilgok Hospital, School of Medicine, Kyungpook National University, Daegu, Republic of Korea

^lDivision of Infectious Diseases, Department of Internal Medicine, Ewha Womans University Mokdong Hospital, Seoul, Republic of Korea

^mDivision of Infectious Diseases, Department of Internal Medicine, Korea University Anam Hospital, Korea University College of Medicine, Seoul, Republic of Korea

ⁿDivision of Infectious Diseases, Department of Internal Medicine, Yonsei University Wonju Severance Christian Hospital, Yonsei University Wonju College of Medicine, Wonju, Republic of Korea

^oDepartment of Family Medicine, Soon Chun Hyang University Hospital, Seoul, Republic of Korea

^pDepartment of Clinical Pharmacology and Therapeutics, College of Medicine, Seoul National University Hospital, Seoul, Republic of Korea

^qTropical Disease Foundation – San Francisco Multi-purpose Bldg, Laguna, 4000, Philippines

^rGlaxoSmithKline Vaccines, Wavre, Belgium

^sGlaxoSmithKline Vaccines, Warsaw, Poland

^tDepartment of Biochemistry, University of Washington, WA, USA

^uInstitute for Protein Design, University of Washington, WA, USA

^vInternational Vaccine Institute, Seoul, Republic of Korea

^wDepartment of R&D, SK Bioscience, Seongnam, Republic of Korea

^xFull list provided as Supplementary Material.

Corresponding author : Hee Jin Cheong

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.

논문정보

형식Research article
게재일2023년 10월 (BRIC 등록일 2023-09-17)
연구진국내(교신)+국외 연구진
분야 의약학 > 면역의학

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