Covid-19 Living Data

Trial NCT05249816
Publication Toback S, medRxiv, 2023
Dates: 2022-03-18 to 2022-06-09
Funding: Private (Cogna Technology Solutions LLC, Abu Dhabi, UAE; and Novavax, Inc., Gaithersburg, MD, US)
Conflict of interest: Yes

Methods
	RCT
	Location : Multicenter / UAE Follow-up duration (months): 28
	NVX-CoV2373 = (n=499) BBIBP-CorV = (n=501)
Inclusion criteria	Adults ≥ 18 years of age, inclusive, at screening. Willing and able to give informed consent prior to study enrollment and to comply with study procedures. Females of childbearing potential (defined as any female who has experienced menarche) who is NOT surgically sterile (i.e., hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or postmenopausal (defined as amenorrhea at least 12 consecutive months), must agree to either be heterosexually inactive OR consistently use a medically acceptable method of contraception, from enrollment and to 3 months after the last vaccination. Is medically stable, as determined by the investigator (based on review of health status, vital signs [to include body temperature], medical history, and targeted physical examination [to include body weight]). Vital signs must be within medically acceptable ranges as determined by the investigator prior to the first vaccination. Agrees to not participate in any other SARS-CoV-2 prevention or treatment trials for the duration of the study. NOTE: For participants who become hospitalized with COVID-19, participation in investigational treatment studies is permitted. Has previously received a documented complete two dose series of the BBIBP-CorV vaccine with the second dose having been given at least 180 days prior to study vaccination OR has previously received a documented complete two dose series of the BBIBP-CorV vaccine and a third dose booster of BBIBP-CorV vaccine, with the third dose having been given at least 90 days prior to study vaccination.
Exclusion criteria	Participation in research involving receipt of investigational products (drug/biologic/device) within 90 days prior to first study vaccination. Has previously received a primary series vaccination or booster dose of any COVID- 19 vaccine other than BBIBP-CorV. Received influenza vaccination within 14 days prior to first study vaccination, or any other vaccine (including COVID-19) within 30 days prior to first study vaccination. Any known allergies to products contained in the investigational product Any history of anaphylaxis to any prior vaccine. Autoimmune or immunodeficiency disease/condition (iatrogenic or congenital) requiring ongoing immunomodulatory therapy. NOTE: Stable endocrine disorders (eg, thyroiditis, pancreatitis), including stable diabetes mellitus with no history of diabetic ketoacidosis are NOT excluded. Chronic administration (defined as > 14 continuous days) of immunosuppressant, systemic glucocorticoids, or other immune-modifying drugs within 90 days prior to first study vaccination. NOTE: An immunosuppressant dose of glucocorticoid is defined as a systemic dose ≥ 10 mg of prednisone per day or equivalent. The use of topical or intranasal glucocorticoids is permitted. Topical tacrolimus and ocular cyclosporin are permitted. Use of inhaled glucocorticoids is prohibited. Received immunoglobulin, blood-derived products, or immunosuppressant drugs within 90 days prior to first study vaccination. Active cancer (malignancy) on therapy within 3 years prior to first study vaccination (with the exception of adequately treated non-melanomatous skin carcinoma or lentigo maligna and uterine cervical carcinoma in situ without evidence of disease, at the discretion of the investigator). Participants who are breastfeeding, pregnant, or who plan to become pregnant prior to the end of study. Suspected or known history of alcohol abuse or drug addiction within 2 years prior to the first study vaccine dose that, in the opinion of the investigator, might interfere with protocol compliance. Any other condition that, in the opinion of the investigator, would pose a health risk to the participant if enrolled or could interfere with evaluation of the study vaccine or interpretation of study results (including neurologic or psychiatric conditions likely to impair the quality of safety reporting). Study team member or immediate family member of any study team member (inclusive of Sponsor, CRO, and study site personnel involved in the conduct or planning of the study)
Interventions
	Intervention 1 IM dose of NVX-CoV2373 6 months after 2 doses prime vaccination with BBIBP-CorV or 3 months after first booster dose with BBIBP-CorV
	Control 1 IM dose of BBIBP-CorV 6 months after 2 doses prime vaccination with BBIBP-CorV or 3 months after first booster dose with BBIBP-CorV
Participants
	Randomized 1000 participants
	Characteristics of participants Type of participants: Healthy volunteers N=1000 841 males Children: 0 Pregnant women: 0 Immunocompromized patients: 0 Mean age: Age range: 20.0-65.0
	Description of participants Healthy adult volunteers who had received a complete 2 doses series of BBIBP-CorV vaccine with or without a a third dose booster of BBIBP-CorV vaccine in 2 centres in UAE
Primary outcome
	In the register 1.Utilizing ratio of IgG GMTs and difference in seroconversion rates to compare IgG antibody responses between the vaccines. [ Time Frame: On Day 14. ] Comparative IgG antibody responses on Day 14, summarized in terms of the ratio of IgG GMTs and difference in seroconversion rates (SCR; defined as ≥ 4-fold increase from baseline booster dose) between the vaccines. Non-inferiority will be demonstrated if: The lower bound of the two-sided 95% CI on the ratio of the GMTS (GMTNVX-CoV2373/GMTBBIBP-CorV) is ≥ 0.6667, AND The lower bound of the two-sided 95% CI on the difference between the SCRs (SCRNVX-CoV2373 - SCR BBIBP-CorV) is ≥ 10%. 2.Utilizing Case Report Forms and safety follow up via telephone to measure and assess incidence, duration, and severity of solicited local and systemic adverse events (AEs) [ Time Frame: For 7 days following each vaccination. ] All safety analyses will be summarized descriptively by vaccine group using the Safety Analysis Set. To compare the overall safety, the two-sided 95% CIs for the difference of incidence of solicited AEs for 7 days following each vaccination. Recording of solicited and unsolicited AEs may be conducted by electronic data capture (EDC)/reporting. All AEs will be followed until resolution or until clinically stable. 3.Utilizing Case Report Forms to measure and assess Incidence, duration, severity, and relationship of unsolicited AEs [ Time Frame: Through 28 days after the last vaccination. ] All safety analyses will be summarized descriptively by vaccine group using the Safety Analysis Set. 1085BUnsolicited AEs will be coded by preferred term and system organ class using MedDRA and summarized by vaccine group as well as by severity and relationship to booster vaccine. Unsolicited AEs through 28 days after the booster vaccination. Recording of solicited and unsolicited AEs may be conducted by electronic data capture (EDC)/reporting. All AEs will be followed until resolution or until clinically stable. 4.Utilizing Case Report Forms to measure incidence and relationship of medically attended adverse events (MAAEs), adverse events of special interest (AESIs) (predefined list), and serious adverse events (SAEs) throughout the study. [ Time Frame: Throughout the study. Note: Beginning on Day 29, only MAAEs related to the vaccine will be recorded. ] To compare the overall safety of a single booster injection of NVX-CoV2373 with Matrix-M adjuvant with a single booster injection of BBIBP-CorV in participants previously vaccinated with a primary two-dose series of the BBIBP-CorV vaccine. Recording of solicited and unsolicited AEs may be conducted by electronic data capture (EDC)/reporting. All AEs will be followed until resolution or until clinically stable.
	In the report The primary objective of this study was to assess the safety and immune response of a single booster dose of NVX-CoV2373 in comparison to a single booster dose of BBIBP-CorV. Immunogenicity was assessed by anti-Spike (anti-S) IgG antibodies and neutralizing antibodies against SARS-CoV-2 to ancestral (Wuhan) strain on days 0, 14, 28 and 180.
Documents available	Protocol NR Statistical plan * Data-sharing stated: Unclear Data accessibility: Study information is available at https://clinicaltrials.gov/ct2/show/NCT05249816, and requests will be considered. Corresponding author: Seth Toback stoback@novavax.com
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 all available versions of the pre-print , the study registry was used in data extraction and risk of bias assessment. The target sample size specified in the registry was achieved (n=1000). This study included participants with only prime vaccination and participants with first booster dose: two prior doses 185 participants (18.5%), three prior doses 813 participants (81.3%) and missing info 2 participants (0.2%). The article presented interim analyses for a study with ongoing follow-up. There were no important differences between protocol/registry and published report in population, procedures, interventions or outcomes