Covid-19 Living Data

Trial NCT05069129
Publication Al Kaabi N, Nat Commun, 2022
Dates: 2021-10-23 to 2021-11-08
Funding: Private (The trial was funded by Lanzhou Institute of Biological Products Co., Ltd (LIBP) of Sinopharm and Beijing Institute of Biological Products Co., Ltd (BIBP) of Sinopharm. National Vaccine and Serum Institute (NVSI) of Sinopharm and China National Biotec Group Co., Ltd. (CNBG) of Sinopharm designed the trial, performed the analyses, and interpreted the data.)
Conflict of interest: Yes

Methods
	RCT
	Location : Single center / United Arab Emirates Follow-up duration (months): 1
	20 mcg NVSI-06-08, prime 4–6 months earlier (n = 299) 6.5 U BBIBP-CorV, prime 4–6 months earlier (n = 301) 20 mcg NVSI-06-08, prime 7-9 months earlier (n = 297) 6.5 U BBIBP-CorV, prime 7-9 months earlier (n = 303) 20 mcg NVSI-06-08, prime >9 months earlier (n = 300) 6.5 U BBIBP-CorV, prime >9 months earlier (n = 300)
Inclusion criteria	Aged 18 years and above Judged by the investigator that the health condition is well after inquiry and physical examination Vaccinated with 2 doses of Sinopharm CNBG’s inactivated COVID-19 vaccine Female subjects who are not nursing or pregnant at the time of enrolment (negative urine pregnancy test) and have no family planning within the first 6 months after enrollment. Effective contraceptive measures have been taken within 2 weeks before inclusion During the whole follow-up period of the study, be able and willing to complete the whole prescribed study plan With self ability to understand the study procedures, the informed consent & voluntarily sign an informed consent form and is able to comply with the requirements of the clinical study protocol.
Exclusion criteria	Confirmed cases, suspected cases or asymptomatic cases of COVID-19 With a history of SARS and MERS infection (self-report, on-site inquiry) Has vaccinated with any other vaccines rather than one or more doses of Sinopharm CNBG inactivated COVID-19 vaccine Axillary temperature ≥37.3 C (forehead temperature ≥37.8 C) Previous severe allergic reactions to vaccination (such as acute allergic reactions, urticaria, dyspnea, angioneurotic edema or abdominal pain) Allergy to known components of recombinant COVID-19 vaccine (e.g., aluminum and histidine) Severe respiratory diseases severe liver and kidney diseases hypertension (systolic blood pressure 150 mmHg, diastolic blood pressure 90 mmHg) diabetic complications malignant tumors various acute diseases or acute attacks of chronic diseases Has been diagnosed with congenital or acquired immunodeficiency, HIV infection, lymphoma, leukemia or other autoimmune diseases Has a history of convulsions, epilepsy, encephalopathy long-term alcohol and drug abuse history of thyroidectomy history of infectious diseases mental illness or family history (direct) With Congenital malformation or developmental disorder, genetic defect, severe malnutrition, etc. Has a history of coagulation dysfunction (e.g. coagulation factors deficiency and coagulation diseases) Asplenia or splenectomy, functional asplenia caused by any situation Receving anti-TB (tuberculosis) therapy Received immunoenhancement or inhibitor therapy within 3 months (continuous oral or IV administration for more than 14 days) Received other vaccines within 14 days before vaccination Received blood products within 3 months before vaccination Received other investigational drugs within 6 months before vaccination Plans to move before the end of the study or leave the local area for a long time during the scheduled study visits Other circumstances judged by investigators that are not suitable for this clinical trial.
Interventions
	Intervention 1 IM dose of 20 mcg NVSI-06-08 booster, 4-6 months after prime vaccination with 2 IM doses of BBIBP-CorV 1 IM dose of 20 mcg NVSI-06-08 booster, 7-9 months after prime vaccination with 2 IM doses of BBIBP-CorV 1 IM dose of 20 mcg NVSI-06-08 booster, >9 months after prime vaccination with 2 IM doses of BBIBP-CorV
	Control 1 IM dose of 6.5 U BBIBP-CorV booster, 4-6 months after prime vaccination with 2 IM doses of BBIBP-CorV1 IM dose of 6.5 U BBIBP-CorV booster, 7-9 months after prime vaccination with 2 IM doses of BBIBP-CorV1 IM dose of 6.5 U BBIBP-CorV booster, >9 months after prime vaccination with 2 IM doses of BBIBP-CorV
Participants
	Randomized 1833 participants
	Characteristics of participants Type of participants: Healthy adults N=1833 1633 males Children: 0 Pregnant women: 0 Immunocompromized patients: 0 Mean age: Age range: 20-60
	Description of participants Healthy adults that were HIV-negative and with no previous history of COVID-19 in a single centre in the United Arab Emirates.
Primary outcome
	In the register 1) The incidence and serverity of any adverse reactions [ Time Frame: within 30 minutes after vaccination ]; 2) The incidence and serverity of solicited adverse events [ Time Frame: within 30 minutes after vaccination ]; 3) The incidence and serverity of solicited adverse reactions [ Time Frame: within 0-7 days after vaccination ]; 4) The incidence and severity of unsolicited adverse reactions [ Time Frame: within 0-7 days after vaccination ]; 5) The incidence and serverity of solicited adverse reactions [ Time Frame: within 8-30 days after vaccination ]; 6) The incidence and serverity of solicited adverse events [ Time Frame: within 8-30 days after vaccination ]; 7) The incidence of SAE observed [ Time Frame: after vaccination and up to 6 months after full course of immunization. ]; 8) The incidence of AESI observed [ Time Frame: after vaccination and up to 6 months after full course of immunization ]; 9) GMT of subject's anti- SARS-CoV-2 neutralizing antibody [ Time Frame: 15th day after vaccination ]; 10) GMT of subject's anti- SARS-CoV-2 neutralizing antibody [ Time Frame: 30th day after vaccination ]; 11) Rate of 4-fold rise of anti- SARS-CoV-2 neutralizing antibody [ Time Frame: 15th day after vaccination ]; 12) Rate of 4-fold rise of anti- SARS-CoV-2 neutralizing antibody [ Time Frame: 30th day after vaccination ].
	In the report 1) Neutralizing response on 15 days and 30 days after booster vaccination, by evaluation of the geometric mean titers (GMTs) of neutralizing antibodies and the corresponding fourfold rise rate (i.e., post-/pre-boost ≥4) against SARS-CoV-2 prototype strain. Neutralizing antibody titers were measured using live-virus neutralization assay; 2) Occurrence and severity of any adverse reactions within 30 days post-boost
Documents available	Protocol Yes. In English Statistical plan Yes Data-sharing stated: Yes, from 1 month to 1 year after the completion of the study Data accessibility: The individual participant data will be shared after de-identification. The clinical trial is still ongoing, and the data will be available from 1 month to 1 year after the completion of the study. Researchers who provide a scientifically sound proposal will be allowed access to the individual participant data. Proposals should be directed to the corresponding author Qi Ming Li (liqiming189@163.com). The proposals will be reviewed and approved by the funder, investigator, and collaborators on the basis of scientific merit. To gain access, data requestors will need to sign a data access agreement.
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 and its supplement, the study registry, protocol & SAP were used in data extraction and risk of bias assessment. The study report is a preliminary analysis at 1-month follow-up. The target sample size (N=1800) specified in the registry was achieved. The primary outcomes in the article reflect those in the registries. Most adverse events data are reported for the intervention and control strata pooled comparison, not per arm. There is no change from the trial registration in the intervention and control treatments.