Covid-19 Living Data

Trial NCT05158855
Publication Sung J, Vaccines, 2022
Dates: 2022-02-12 to 2022-02-12
Funding: Mixed (Innovation and Technology Fund and the Institutional Development Scheme—Research Infrastructure Grant from the Hong Kong Research Grants Council ; employees of DreamTec Cytokines Limited were co-authors.)
Conflict of interest: Yes

Methods
	RCT
	Location : Single center / China Follow-up duration (months): 1.2
	Spores Recombinant inactivated B. subtilis booster (after 2 doses of either BNT162b2 or BBIBP) (n = 9) 1 capsule wild-type B. subtilis spores (after 2 doses of either BNT162b2 or BBIBP) (n = 7)
Inclusion criteria	Healthy adults 18 to 65 years of age who were previously administrated with 2 doses of vaccine of any brand (either BNT162b2 or BBIBP COVID-19 vaccine was available in Macau) at least 6 months ago.
Exclusion criteria	known infection with SARS-CoV-2 virus human immunodeficiency virus hepatitis C virus or hepatitis B virus an immunocompromising condition a history of autoimmune disease a previous clinical diagnosis of COVID-19 the receipt of medications intended to prevent COVID-19 a positive nasal-swab result on a SARS-CoV-2 nucleic acid amplification test within 24 h before the receipt of trial booster or placebo.
Interventions
	Intervention Boost: 3 oral doses of 5x10^10 spores, on 3 consecutive days, 180 days after prime vaccination (with 2 doses of either BNT162b2 or BBIBP)
	Control Boost: 3 oral doses of 1 capsule of spores, on 3 consecutive days, 180 days after prime vaccination (with 2 doses of either BNT162b2 or BBIBP)
Participants
	Randomized 16 participants
	Characteristics of participants Type of participants: Healthy adults N=16 0 males Children: 0 Pregnant women: 0 Immunocompromized patients: 0 Mean age: Age range: NR
	Description of participants Healthy adult volunteers that were HIV-negative and SARS-CoV-2 infection-free in a single centre in China.
Primary outcome
	In the register 1) To assess the safety of the engineered Bacillus subtilis spore coat extract [Time Frame: 3 months]: To measure the weight changes in kilograms and number of incidence of adverse event from the beginning of the administration to 30 days after the administration. 2) Concentration of Neutralizing IgG antibody against Receptor binding domain of spike protein of SARS-CoV2 [Time Frame: 3 months]: To measure the concentration of Neutralizing IgG antibody against Receptor binding domain of spike protein of SARS-CoV2 before the administration and 14, 28 days after the administration.
	In the report During the blood sampling period, primary safety end points were assessed, including not only local reactions and systemic events, but also unsolicited adverse events and serious adverse events; All participants were observed for 1 h after the administration of booster or placebo to identify any immediate adverse events. Furthermore, 5 mL blood samples were drawn on days 0, 14, 35 and 49 for safety and immunogenicity assessments.
Documents available	Protocol NR Statistical plan * Data-sharing stated: Yes Data accessibility: The data presented in this study are available on request from the corresponding author. The data are not publicly available due to privacy issue. Corresponding author Keith Wai-Yeung Kwong: keithkwong@dreamtec.hk
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 study registry was used in data extraction and risk of bias assessment. This was a human pilot study with a very small sample size (only 9 vs 7 in each arm), which raises concerns about the ability of the randomisation process to control for confounding. Target sample size calculation was not discussed. The trial (n = 16) did not achieve the target sample size in the original (prospective) registration (n = 30). The trial registry was for an open-label single-arm study in 12-85 year-old participants whereas the reported trial was a randomized, placebo-controlled, observer-blinded study in 18-65 year-olds. There is no change from the trial registration in the intervention and control treatments. The cited study by the same author regarding the booster preparation was retracted: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9623846.