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Effect of 2 Inactivated SARS-CoV-2 Vaccines on Symptomatic COVID-19 Infection in AdultsA Randomized Clinical Trial

Educational Objective
To identify the key insights or developments described in this article
1 Credit CME
Key Points

Question  What is the efficacy of 2 inactivated SARS-CoV-2 vaccines for prevention of symptomatic COVID-19?

Findings  This prespecified interim analysis of a randomized clinical trial included 40 382 participants who received at least 1 dose of a 2-dose inactivated vaccine series developed from either SARS-CoV-2 WIV04 (5 µg/dose) or HB02 (4 µg/dose) strains or an aluminum hydroxide–only control, with a primary end point of the incidence of symptomatic COVID-19 at least 14 days after the second injection. The efficacy for the 2 vaccines, compared with an aluminum hydroxide–only control, was 72.8% in the WIV04 group and 78.1% in the HB02 group; both comparisons were statistically significant.

Meaning  Two inactivated SARS-CoV-2 vaccines demonstrated efficacy against symptomatic COVID-19 compared with an aluminum hydroxide–only control.

Abstract

Importance  Although effective vaccines against COVID-19 have been developed, additional vaccines are still needed.

Objective  To evaluate the efficacy and adverse events of 2 inactivated COVID-19 vaccines.

Design, Setting, and Participants  Prespecified interim analysis of an ongoing randomized, double-blind, phase 3 trial in the United Arab Emirates and Bahrain among adults 18 years and older without known history of COVID-19. Study enrollment began on July 16, 2020. Data sets used for the interim analysis of efficacy and adverse events were locked on December 20, 2020, and December 31, 2020, respectively.

Interventions  Participants were randomized to receive 1 of 2 inactivated vaccines developed from SARS-CoV-2 WIV04 (5 µg/dose; n = 13 459) and HB02 (4 µg/dose; n = 13 465) strains or an aluminum hydroxide (alum)–only control (n = 13 458); they received 2 intramuscular injections 21 days apart.

Main Outcomes and Measures  The primary outcome was efficacy against laboratory-confirmed symptomatic COVID-19 14 days following a second vaccine dose among participants who had no virologic evidence of SARS-CoV-2 infection at randomization. The secondary outcome was efficacy against severe COVID-19. Incidence of adverse events and reactions was collected among participants who received at least 1 dose.

Results  Among 40 382 participants randomized to receive at least 1 dose of the 2 vaccines or alum-only control (mean age, 36.1 years; 32 261 [84.4%] men), 38 206 (94.6%) who received 2 doses, contributed at least 1 follow-up measure after day 14 following the second dose, and had negative reverse transcriptase–polymerase chain reaction test results at enrollment were included in the primary efficacy analysis. During a median (range) follow-up duration of 77 (1-121) days, symptomatic COVID-19 was identified in 26 participants in the WIV04 group (12.1 [95% CI, 8.3-17.8] per 1000 person-years), 21 in the HB02 group (9.8 [95% CI, 6.4-15.0] per 1000 person-years), and 95 in the alum-only group (44.7 [95% CI, 36.6-54.6] per 1000 person-years), resulting in a vaccine efficacy, compared with alum-only, of 72.8% (95% CI, 58.1%-82.4%) for WIV04 and 78.1% (95% CI, 64.8%-86.3%) for HB02 (P < .001 for both). Two severe cases of COVID-19 occurred in the alum-only group and none occurred in the vaccine groups. Adverse reactions 7 days after each injection occurred in 41.7% to 46.5% of participants in the 3 groups; serious adverse events were rare and similar in the 3 groups (WIV04: 64 [0.5%]; HB02: 59 [0.4%]; alum-only: 78 [0.6%]).

Conclusions and Relevance  In this prespecified interim analysis of a randomized clinical trial, treatment of adults with either of 2 inactivated SARS-CoV-2 vaccines significantly reduced the risk of symptomatic COVID-19, and serious adverse events were rare. Data collection for final analysis is pending.

Trial Registration  ClinicalTrials.gov Identifier: NCT04510207; Chinese Clinical Trial Registry: ChiCTR2000034780

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CME Disclosure Statement: Unless noted, all individuals in control of content reported no relevant financial relationships. If applicable, all relevant financial relationships have been mitigated.

Article Information

Corresponding Author: Xiaoming Yang, MD, China National Biotec Group Company Limited, B2 Shuangqiao Rd, Chaoyang District, Beijing, China (yangxiaoming@sinopharm.com); An Pan, PhD, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Rd, Qiaokou District, Wuhan, China (panan@hust.edu.cn).

Accepted for Publication: May 12, 2021.

Published Online: May 26, 2021. doi:10.1001/jama.2021.8565

Author Contributions: Dr Pan had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Drs Al Kaabi and Yuntao Zhang and Mr Xia contributed equally to the study.

Concept and design: Al Kaabi, Yuntao Zhang, Xia, Y. Yang, Xiaoming Yang.

Acquisition, analysis, or interpretation of data: Xia, Al Qahtani, Abdulrazzaq, Al Nusair, Hassany, Jawad, Abdalla, Al Mazrouei, Al Karam, Li, Xuqin Yang, W. Wang, Lai, Chen, Huang, Q. Wang, T. Yang, Liu, Ma, Abdelhadi, Khan, Saifuddin Fasihuddin, You, Xie, Y. Zhao, Jiang, G. Zhao, Yanbo Zhang, Mahmoud, ElTantawy, Xiao, Koshy, Zaher, H. Wang, Duan, Pan, Xiaoming Yang.

Drafting of the manuscript: Yuntao Zhang, Xia, Y. Yang, G. Zhao, Yanbo Zhang, Pan.

Critical revision of the manuscript for important intellectual content: Al Kaabi, Xia, Al Qahtani, Abdulrazzaq, Al Nusair, Hassany, Jawad, Abdalla, Al Mazrouei, Al Karam, Li, Xuqin Yang, W. Wang, Lai, Chen, Huang, Q. Wang, T. Yang, Liu, Ma, Abdelhadi, Khan, Saifuddin Fasihuddin, You, Xie, Y. Zhao, Jiang, Mahmoud, ElTantawy, Xiao, Koshy, Zaher, H. Wang, Duan, Xiaoming Yang.

Statistical analysis: Xia, Jiang, G. Zhao, Yanbo Zhang.

Obtained funding: Yuntao Zhang, Li, W. Wang, Y. Zhao, Xiaoming Yang.

Administrative, technical, or material support: Xia, Abdelhadi, Xiao, Koshy, H. Wang, Duan, Xiaoming Yang.

Supervision: Xia, Abdelhadi, Xiaoming Yang.

Conflict of Interest Disclosures: Drs Xiaoming Yang, Yuntao Zhang, and Duan and Ms Y. Yang, Ms Y. Zhao, Ms H.Wang, and Mr Li reported receiving grants from the Ministry of Science and Technology of the People’s Republic of China (2020YFC0842100) during the conduct of the study. Dr Yuntao Zhang, Ms Y Yang, Ms Xuqin Yang, Mr Lai, Ms Q. Wang, Mr T. Yang, Mr Liu, and Dr Xiaoming Yang are employees of the China National Biotec Group Company Limited; Mr Li, Mr Chen and Drs Huang and Duan are employees of the Wuhan Institute of Biological Products Co, Ltd; and Mr W. Wang, Mr Ma, Ms Y. Zhao, and Ms H. Wang are employees of the Beijing Institute of Biological Products Co, Ltd—all companies that developed the vaccine and sponsored the trial. Drs Jiang and G. Zhao are employees of the Beijing Key-Tech Statistical Consulting Co, Ltd, and received fees from the China National Biotec Group Company Limited to conduct the data analysis. Drs Al Kaabi, Abdalla, Hussein, Al Mazrouei, Al Karam, Hussain, and Khan and Mr Fasihuddin reported being an employee of Abu Dhabi Health Services Company. Drs Mahmoud and Zaher, Mr ElTantawy, Mr Xiao, and Mr Koshy reported being an employee of the G42 Healthcare. Ms H. Wang reported receiving grants from the Beijing Municipal Science & Technology Commission during the conduct of the study and having a patent for 202010575098.9 pending, a patent for 202010537733.4 pending, a patent for 202010537730.0 pending, a patent for 202110052921.2 pending, and a patent for 202110052933.5 pending. Drs Xiaoming Yang and Duan and Mr Li have a patent for 202010559132.3 pending. No other disclosures were reported.

Funding/Support: This study was supported by the National Key Research and Development Project of China (2020YFC0842100). The vaccine was developed and the study was sponsored by the Wuhan Institute of Biological Products Co. Ltd., the Beijing Institute of Biological Products Co, Ltd, both of which belong to the China National Biotec Group Company Limited.

Role of the Funder/Sponsor: The Wuhan Institute of Biological Products Co. Ltd, the Beijing Institute of Biological Products Co. Ltd, both belong to the China National Biotec Group Company Limited, were the study sponsors and designed the trial, provided the study product, and oversaw all trial operations. The sponsors used contract clinical research organizations to coordinate interactions with regulatory authorities and oversee clinical site operations. Data were collected by the clinical site research staff, managed by a blinded contract research organization data management team, monitored by a contract research organization, and overseen by the sponsor and an independent data and safety monitoring board. The interim analysis was performed by an independent statistician who was not involved in the trial after the data were collected, checked, and locked for the specific groups before unblinding. Manuscript preparation was performed by the study authors and the decision to submit the manuscript for publication was made by the study authors.

Additional Contributions: We are grateful for all investigators at the United Arab Emirates, Bahrain, Egypt, and Jordan who contributed to the site work of the trials. We thank all the participants in the trial and members of the data and safety monitoring board. The members in the data and safety monitoring board included Jielai Xia, PhD (Air Force Medical University); Xuanyi Wang, PhD (Fudan University); and Xingwang Li, PhD (Capital Medical University). The members have expertise in infectious disease prevention and treatment, vaccine and drug development, epidemiology, and statistics. The members in the end point assessment committee in the Middle East included Jameela Alsalman, MD (Department of Health of Bahrain [chair]); Dala Al Mansoori, MD (Tawam Hospital, Abu Dhabi Health Services Company at the United Arab Emirates); and Bassam Mahboub, MD (Health Authority of Dubai, the United Arab Emirates). The members in the end point assessment committee in China included Jingui Wang, MSc (Peking University First Hospital [chair]); Jinming Li, PhD (National Center for Clinical Laboratories, National Health Commission of People’s Republic of China); Bin Cao, PhD (China-Japan Friendship Hospital); Jianxing Qiu, PhD (Peking University First Hospital); and Bassam Mahboub, MD (Health Authority of Dubai, the United Arab Emirates). All members of the data and safety monitoring board and end point assessment committee reported no conflict of interest with the companies who developed the vaccines, and received remuneration for their work.

Data Sharing Statement: See Supplement 4.

AMA CME Accreditation Information

Credit Designation Statement: The American Medical Association designates this Journal-based CME activity activity for a maximum of 1.00  AMA PRA Category 1 Credit(s)™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Successful completion of this CME activity, which includes participation in the evaluation component, enables the participant to earn up to:

  • 1.00 Medical Knowledge MOC points in the American Board of Internal Medicine's (ABIM) Maintenance of Certification (MOC) program;;
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  • 1.00 Lifelong Learning points in the American Board of Pathology’s (ABPath) Continuing Certification program; and
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It is the CME activity provider's responsibility to submit participant completion information to ACCME for the purpose of granting MOC credit.

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