Trial ChiCTR2200057758
Publication Zhang Y, Nature, 2023
Dates: 2022-01-01 to 2022-02-28
Funding: Mixed (Yunnan Provincial Science and Technology Department China ; National Natural Science Foundation of China ; Yunnan Natural Science Foundation ; High-level Health Technical Personnel Project of Yunnan Province ; Spring City Plan: The High-level Talent Promotion and Training Project of Kunming ; Vaccines and placebo were provided by the Walvax Biotechnology Co., Ltd and the SinoVac Biotech Co., Ltd., Beijing, China. )
Conflict of interest: Yes

Methods
RCT
Location : Single center / China
Follow-up duration (months): 3
5 x 10^10 vp ChAdTS-S (n=50)
30 mcg RQ3013 (n=50)
25 mcg ZR202-CoV (n=50)
3 mcg CoronaVac(n=50)
Placebo (n=50)
Inclusion criteria
  • 18 to 59 years old, male or female
  • Two doses of inactivated COVID-19 vaccine CoronaVac were administered and the interval between two doses was 3-5 weeks
  • It is now in day 100 to day 270 after administering of the second dose of the inactivated COVID-19 vaccine CoronaVac
  • Healthy participants who are determined by medical history, physical examination, and clinical judgment of the investigator to be eligible for inclusion in the study
  • can follow the researchers’ guidance to accomplish the research process
  • capable of giving personal signed informed consent. Note: Healthy participants with preexisting stable disease, defined as disease not requiring significant change in therapy or hospitalisation for worsening disease during the 6 weeks before enrolment, can be included.
Exclusion criteria
  • History of SARS-CoV-2 infection
  • History of severe adverse reaction and/or allergic reaction associated with a vaccine or any vaccine components
  • Pregnancy or planned pregnancy
  • Breastfeeding
  • Medical history of uncontrolled common diseases, such as coronary heart disease, hypertension, diabetes, chronic respiratory disease, tumors
  • Severe psychiatric disorders
  • Receive treatment with immunosuppressants
  • Receipt of blood/plasma products or immunoglobulin from 60 days before enrolment or planned receipt throughout the study
  • Previous or current participation in other studies which could disturb the immunogenicity and safety assessment in this study
  • Participants who have any inapplicable factors according to the study protocol in the view of researcher.
Interventions
Intervention
1 IM dose of ChAdTS-S (5×1010 viral particles per 0.5 mL), 100-270 days after CoronaVac primary series.
1 IM dose of RQ3013 (30 mcg per 0.15 mL), 100-270 days after CoronaVac primary series.
1 IM dose of ZR202-CoV (25 mcg per 0.5mL), 100-270 days after CoronaVac primary series.
1 IM dose of CoronaVac (600 antigen units per 0.5 mL), 100-270 days after CoronaVac primary series.
Control
1 IM dose of placebo, 100-270 days after CoronaVac primary series.
Participants
Randomized
250 participants
Characteristics of participants
Type of participants: Adults
N=250
108 males
Children: 0
Pregnant women: 0
Immunocompromized patients: 0
Mean age:
Age range: NR
Description of participants
Adults aged 18-59, healthy or with stable pre-existing disease and with no history of SARS-CoV-2 infection, at a single center in China.
Primary outcome
In the register
1) Outcome：Neutralizing antibody titers; Measure time point of outcome：The 7th, 14th, 28th days after the third dose of vaccination; Measure method：Micro-cytopathic effect neutralization test (MCPENT) 2) Outcome：Incidence of adverse events; Measure time point of outcome：From the third dose of vaccine to 45 minutes, 0 to 14 days; Measure method：Clinical analysis 3) Outcome：Cellular immune response to SARS-CoV-2; Measure time point of outcome：The 7th, 14th, 28th, 90th and 180th days after the third dose of vaccination; Measure method：Enzyme-linked immunospot assay and flow cytometry analysis.
In the report
The geometric mean titres (GMTs) of neutralising antibodies against the wild-type, delta and omicron variants of live SARS-CoV-2 at day 0 (pre-vaccination), 7, 14, and 28 after boosting vaccination ; the occurrence of adverse events within 14 days after the booster vaccination.
Documents
available

Protocol

Yes. In English

Statistical plan

Yes

Data-sharing stated: Yes
Data accessibility: De-identified data are freely available from the corresponding author upon request. All codes associated with data analysis are freely available from the corresponding author upon request. E-mail addresses: weijia19631225@163.com (J. Wei), zijiezhang@ynu.edu.cn (Z. Zhang). *
Risk of bias
Overall
The overall risk of bias reported in the table corresponds to the highest risk of bias for the outcomes assessed for the systematic review
Some concerns
General comment In addition to the published article, the trial registry, protocol, statistical analysis plan and supplementary appendices were used in data extraction and assessment of risk of bias. The primary outcomes in the article reflect those in the registries. The article presented preliminary analyses for a study with ongoing follow-up. GMTs of serum SARS-CoV-2 receptor binding domain (RBD)-specific IgG were listed as a secondary outcome in the protocol, but were not reported in the paper. The trial (n = 250) achieved its target sample size (n = 250). This trial was updated on Mars 29th 2023, after publication of additional results of the trial.