Evaluation of Full Versus Fractional Dose of COVID-19 Vaccine Given as a Booster for the Prevention of COVID-19 in Adults in Mongolia.

Phase 3

Completed

Conditions: COVID-19

Interventions: Biological: Tozinameran - Standard Dose
Biological: Tozinameran - Fractional Dose

Registration Number: NCT05265065

Lead Sponsor: Murdoch Childrens Research Institute

Brief Summary: This clinical trial is a single-blind, randomised study to determine the reactogenicity and immunogenicity of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) vaccine (Pfizer-BioNTech) as booster dose in adults, who have previously received either Sinopharm (BBIBP-CorV®), AstraZeneca (ChAdOx1-S, or Vaxzevria®) or Sputnik V (Gam-COVID-Vac®) as their primary doses 6 to 9 months earlier. Both standard and fractional doses will be tested.

Participants are healthy adults aged 18 years or older, with no upper age limit. Procedures will be implemented to ensure participants of all ages (aged 18 and above) are included and that there is an even age distribution (\<50 and ≥50 years) in each group. There will be a total of 6 groups (Sinopharm-standard dose Pfizer, Sinopharm-fractional dose Pfizer, AstraZeneca-standard dose Pfizer, AstraZeneca-fractional dose Pfizer, Sputnik - standard dose Pfizer, Sputnik - fractional dose Pfizer), with 200 participants per group for Sinopharm and 100 for AstraZeneca and Sputnik.

Detailed Description: As per brief summary

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 601

Inclusion Criteria

Have completed two doses of Sinopharm, AstraZeneca or Sputnik vaccines with the recommended schedule 6 months prior to the date of enrolment
Willing and able to give written informed consent
Aged 18 years or above
Willing to complete the follow-up requirements of the study

Exclusion Criteria

Received 3 doses of COVID-19 vaccine
Received 2 doses of COVID-19 less than 6 months prior to the start of the trial
Currently on immunosuppressive medication or anti-cancer chemotherapy
HIV infection
Congenital immune deficiency syndrome
Has received immunoglobulin or other blood products in the 3 months prior to vaccination
Study staff and their relatives
Have a history of a severe allergic reaction to any COVID-19 vaccines or have a medical exception to receiving further COVID-19 vaccines

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Standard Pfizer-BioNTech booster group	Tozinameran - Standard Dose	Biological/Vaccine: Tozinameran - Standard Dose Other Names: BNT162b2 Comirnaty Pfizer Covid-19 vaccine Tozinameran is a single-stranded, 5'-capped messenger RNA (mRNA) produced using a cellfree in vitro transcription from the corresponding DNA templates, encoding the viral spike (S) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Dose - 30 µg in 0.3 ml. Liquid for injection. Single dose.
Fractional Pfizer-BioNTech booster group	Tozinameran - Fractional Dose	Biological/Vaccine: Tozinameran - Standard Dose Other Names: BNT162b2 Comirnaty Pfizer Covid-19 vaccine Tozinameran is a single-stranded, 5'-capped messenger RNA (mRNA) produced using a cellfree in vitro transcription from the corresponding DNA templates, encoding the viral spike (S) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Dose - 15 µg in 0.3 ml. Liquid for injection. Single dose.

Primary Outcome Measures

Name	Time	Method
Seroresponse	28-days post booster vaccination	Serum samples collected at 28-days post booster vaccination from all groups will be evaluated for SARS-CoV-2 specific IgG antibodies using IgG ELISA. The primary endpoint is the seroresponse rate at the Day-28 visit. The seroresponse rate at the individual level is defined as either a ≥4-fold rise in binding antibodies at the Day-28 visit compared to baseline (pre-vaccination) with a titre of \<200 BAU/ml, a ≥2-fold rise among participants with a baseline (pre-vaccination) titre of \>200 BAU/ml, or a ≥4-times the lower limit of detection if baseline levels are lower than the limit of detection.
Solicited Grade 3 or 4 Local or Systemic Reaction	7 days post booster vaccination	Questionnaire to document solicited reactions is developed specifically for this study. Data will be reported as the proportion of participants who report grade 3 or 4 reactions by each intervention arm. Solicited reactions such as pain, tenderness, erythema/redness, induration, swelling, fever, nausea, vomiting, headache, fatigue/malaise, myalgia, arthralgia, diarrhea, enlarged lymph nodes will be collected from the participants 7 days post-vaccination.

Secondary Outcome Measures

Name	Time	Method
Seroresponse by Priming Vaccine Strata	28-days post booster vaccination	Serum samples collected at 28-days post booster vaccination from all groups will be evaluated for SARS-CoV-2 specific IgG antibodies using IgG ELISA. The primary endpoint is the seroresponse rate at the Day-28 visit. The seroresponse rate at the individual level is defined as either a ≥4-fold rise in binding antibodies at the Day-28 visit compared to baseline (pre-vaccination) with a titre of \<200 BAU/ml, a ≥2-fold rise among participants with a baseline (pre-vaccination) titre of \>200 BAU/ml, or a ≥4-times the lower limit of detection if baseline levels are lower than the limit of detection. Priming strata (previously COVID vaccination): AstraZeneca (ChAdOx1-S, or Vaxzevria®); Sinopharm (BBIBP-CorV®); Sputnik V (Gam-COVID-Vac®)
SARS-CoV-2 Specific IgG Antibodies at Day-28	28-days post booster vaccination	Serum samples collected at 28-days post booster vaccination from all groups will be evaluated for SARS-CoV-2 specific IgG antibodies using IgG ELISA.
SARS-CoV-2 Specific IgG Antibodies at Day-28 by Priming Vaccine Strata	28-days post booster vaccination	Serum samples collected at 28-days post booster vaccination from all groups will be evaluated for SARS-CoV-2 specific IgG antibodies using IgG ELISA. Priming strata (previously COVID vaccination): AstraZeneca (ChAdOx1-S, or Vaxzevria®); Sinopharm (BBIBP-CorV®); Sputnik V (Gam-COVID-Vac®)
SARS-CoV-2 Specific IgG Antibodies at Baseline (Pre Booster), 28- Days, 6- and 12-months Post Booster Vaccination.	Baseline (pre booster), 28 days, 6- and 12-months post booster vaccination	Serum samples collected at baseline (pre booster), 28 days, 6- and 12-months post booster vaccination from all groups will be evaluated for SARS-CoV-2 specific IgG antibodies using IgG CMIA. Data will be reported as binding antibody units (BAU)/mL and presented as geometric mean concentration (GMC) and 95% confidence intervals (CI).
SARS-CoV-2 Specific Neutralising Antibodies at Baseline (Pre Booster), 28 Days-, 6- and 12-months Post Booster Vaccination Measured by Surrogate Virus Neutralization Test (sVNT).	Baseline (pre booster), 28 days-, 6- and 12-months post booster vaccination	Serum samples collected at baseline (pre booster), 28 days-, 6- and 12-months post booster vaccination from all groups will be evaluated for SARS-CoV-2 specific neutralising antibodies using the GenScript® cPass surrogate virus neutralization test (sVNT) for both wild-type and Omicron variant. Neutralising antibody response will be reported as percentage (%) inhibition of receptor binding domain-angiotensin-converting enzyme 2 (RBD-ACE2) binding relative to a positive control.
SARS-CoV-2 Specific Neutralising Antibodies at Baseline (Pre Booster), 28 Days-, 6- and 12-months Post Booster Vaccination Measured by SARS-CoV-2 Microneutralisation Assay	Baseline (pre booster), 28 days-, 6- and 12-months post booster vaccination	A subset of samples (20%) from all four timepoints will be assessed using a SARS-CoV-2 microneutralisation assay to both the wild type (vaccine) strain and for two SARS-CoV-2 Variants of concern. Neutralizing antibody will be reported as endpoint titre.
Interferon Gamma (IFNγ) Concentrations in International Units (IU)/mL	Baseline (pre booster), 28 days-, 6- and 12-months post booster vaccination	Applicable to the subset participants with additional blood collection. Interferon gamma (IFNγ) concentrations as a measurement of cellular immunity will be assessed on a subset of the participants from each group. QuantiFERON Human IFN-γ SARS-CoV-2 (Qiagen) will be used to stimulate IFN-γ production in peripheral blood mononuclear cells (PBMCs) and then IFN-γ production will be measured using ELISA (enzyme-linked immunosorbent assay). Data will be presented as GMC and 95% CI.
Number of IFNγ Producing Cells/Million PBMCs	Baseline (pre booster), 28 days-, 6- and 12-months post booster vaccination	Applicable to the subset participants with additional blood collection. IFNγ producing cells as a measurement of cellular immunity will be assessed on a subset of the participants (40%) from each group. IFN-γ Enzyme-Linked ImmunoSpot (Elispot) assay will be performed on isolated peripheral blood mononuclear cells (PBMCs). Data will be reported as number of IFNγ producing cells/million and presented using means and 95% CI.
Frequency of Cytokine-expressing T Cells	Assessed at 4 time-points (baseline, 28 days, 6 months, and 12 months)	Frequency of cytokine-expressing T cells will be assessed on a subset of participants (40%) using flow cytometry (intracellular staining) on PBMCs samples. Data will be reported as frequency (%) of cytokine-expressing T cells presented as means and 95% CI.
Cellular Immunity: Multiplex Cytokine Assays - Reported as Cytokine Concentrations in pg/ml and Presented as GMC and 95% CI	Baseline (pre booster), 28 days-, 6- and 12-months post booster vaccination	Cytokine concentrations following PBMCs stimulation will be assessed on a subset of participants (40%) using multiplex cytokine assays.Data will be reported as cytokine concentrations in pg/ml and presented as GMC and 95% CI.IFN-γ Elispot, intracellular cytokine assays (flow cytometry) and multiplex cytokine assays will be performed on isolated PBMCs.
Incidence of Unsolicited Adverse Events (AE)	28 days-post booster vaccination	All unsolicited AE will be collected for 28 days post booster vaccination. Data will be presented as proportion of participants who report unsolicited AE.
Incidence of Medically Attended Adverse Events	3 months post booster vaccination	All participants with medically attended AE will be collected for 3 months post booster vaccination. Data will be presented as proportion of participants who report unsolicited AE.
Incidence of Serious Adverse Events (SAE)	12 months post booster vaccination	SAE will be collected throughout the follow-up period of 12 months post booster vaccination. Data will be presented as a proportion of participants who report unsolicited SAE.
Incidence of PCR Confirmed COVID-19 Infection	Up to 12 months post booster vaccination	Confirmed COVID-19 infections will be documented throughout the follow-up period, by clinical severity.