Effect of Different SARS-CoV-2 Vaccine Schedules and Vaccination Intervals on Reactogenicity and Humoral Immunogenicity

SARS-CoV2 Infection Clinical Trial

Official title:

Comparison of Different BNT162b2 and ChAdOx1-S COVID-19 Vaccination Intervals and Combinations on Reactogenicity and Humoral Immunogenicity in Adults

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05076227
• Other study ID #: HelCoVac
• Status: Completed
• Start date: January 30, 2021
• Est. completion date: March 27, 2022

Study information

• Verified date: December 2022
• Source: University of Witten/Herdecke
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Investigation of the reactogenicity and immunogenicity of homologous and heterologous vaccine combinations with regard to the formation of SARS-CoV-2 antispike antibodies in health care workers after basic immunization and boost vaccination

Description:

The basic immunizations (first and second vaccination) were performed from January to June 2021 using the m-RNA vaccine BNT162b2 (BioNTech/Pfizer, B)9 and the vector-based vaccine ChAdOx1-S (AstraZeneca, A). BNT162b2 was used to boost vaccine all study population. The time interval between the basic immunisation and the boost vaccination varied.

Four vaccine-groups could be distinguished:

Group 1 received BNT162b2 with the second vaccination 3 weeks after the first vaccination.

Vaccinees of groups 2 and 3 received AZD1222/ChAdOx1-S as first vaccination and could choose after 12 weeks whether second vaccination with BNT162b2 or AZD1222/ChAdOx1-S should be carried out. This results in homologous (first: AZD1222/ChAdOx1-S, second: AZD1222/ChAdOx1-S) and heterologous (first: AZD1222/ChAdOx1-S, second: BNT162b2) vaccine combinations.

Group 4 received BNT162b2 with the second vaccination 6 weeks after first vaccination.

Blood samples were collected at six time points: four weeks, three and six months after completion of the basic immunization, immediately before boost vaccination, four weeks and three months after boost vaccination.

Reactogenicity after first, second, and boost vaccination was assessed using questionnaires to determine vaccine-induced adverse drug reactions (ADR) within seven days after the respective vaccinations.

In addition, demographic data (age, gender, occupational group, allergies) were collected, local and systemic vaccination reactions are differentiated and the need for medication and inability to work as a result of vaccination reactions are prospectively recorded.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1206
• Est. completion date: March 27, 2022
• Est. primary completion date: March 27, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• hospital staff who received COVID-19 vaccination

Exclusion Criteria:

• lack of a written informed consent

Related Conditions & MeSH terms

• COVID-19
• Hypersensitivity
• Immunisation Reaction
• SARS-CoV2 Infection
• Tolerance

Intervention

Drug:
• IM injection of vaccination (mRNA vaccination)
mRNA vaccination
• IM injection of vaccination (vector based vaccination)
vector based vaccination

Locations

Country	Name	City	State
Germany	Helios Hospital Hildesheim	Hildesheim	Niedersachsen

Sponsors (1)

Lead Sponsor	Collaborator
Serge Thal

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Difference between the four cohorts regarding the antibody of the viral spike protein 4 weeks after second vaccination	The descriptive data are described by frequencies (%/n) and the continuous data by corresponding position parameters (median, interquartile range). The confirmatory analysis is performed using the Wilcoxon or Kruskal-Wallis test.; The Bonferroni correction is applied accordingly.	4 weeks after second vaccination
Primary	Difference between the four cohorts regarding the antibody of the viral spike protein 3 months after second vaccination	The descriptive data are described by frequencies (%/n) and the continuous data by corresponding position parameters (median, interquartile range). The confirmatory analysis is performed using the Wilcoxon or Kruskal-Wallis test.; The Bonferroni correction is applied accordingly.	3 months after second vaccination
Primary	Difference between the four cohorts regarding the antibody of the viral spike protein 6 months after second vaccination	The descriptive data are described by frequencies (%/n) and the continuous data by corresponding position parameters (median, interquartile range). The confirmatory analysis is performed using the Wilcoxon or Kruskal-Wallis test.; The Bonferroni correction is applied accordingly.	6 months after second vaccination
Primary	Difference between the four cohorts regarding the antibody of the viral spike protein directly before boost vaccination	The descriptive data are described by frequencies (%/n) and the continuous data by corresponding position parameters (median, interquartile range). The confirmatory analysis is performed using the Wilcoxon or Kruskal-Wallis test.; The Bonferroni correction is applied accordingly.	directly before boost vaccination
Primary	Difference between the four cohorts regarding the antibody of the viral spike protein 4 weeks after boost vaccination	The descriptive data are described by frequencies (%/n) and the continuous data by corresponding position parameters (median, interquartile range). The confirmatory analysis is performed using the Wilcoxon or Kruskal-Wallis test.; The Bonferroni correction is applied accordingly.	4 weeks after boost vaccination
Primary	Difference between the four cohorts regarding the antibody of the viral spike protein 3 months after boost vaccination	The descriptive data are described by frequencies (%/n) and the continuous data by corresponding position parameters (median, interquartile range). The confirmatory analysis is performed using the Wilcoxon or Kruskal-Wallis test.; The Bonferroni correction is applied accordingly.	3 months after boost vaccination
Secondary	Do the four cohorts differ in terms of reactogenicity (systemic and/or local vaccine reactions) after the first vaccination?	For the secondary endpoints, frequencies (%/n) for categorical data and corresponding measures of location (median, interquartile range) for continuous data are used descriptively. The analysis is performed using appropriate tests such as Fisher's exact test, Chi² test, Mann-Whitney U test or Kruskal-Wallis test.	immediately after first vaccination
Secondary	Do the four cohorts differ in terms of reactogenicity (systemic and/or local vaccine reactions) after the second vaccination?	For the secondary endpoints, frequencies (%/n) for categorical data and corresponding measures of location (median, interquartile range) for continuous data are used descriptively. The analysis is performed using appropriate tests such as Fisher's exact test, Chi² test, Mann-Whitney U test or Kruskal-Wallis test.	immediately after second vaccination
Secondary	Do the four cohorts differ in terms of reactogenicity (systemic and/or local vaccine reactions) after the boost vaccination?	For the secondary endpoints, frequencies (%/n) for categorical data and corresponding measures of location (median, interquartile range) for continuous data are used descriptively. The analysis is performed using appropriate tests such as Fisher's exact test, Chi² test, Mann-Whitney U test or Kruskal-Wallis test.	immediately after third (boost) vaccination
Secondary	Differences between the 4 groups after first vaccination regarding a. the individual local vaccination reactions? b. the individual systemic vaccination reactions? c. the number or percentage of vaccination reactions?	For the secondary endpoints, frequencies (%/n) for categorical data and corresponding measures of location (median, interquartile range) for continuous data are used descriptively. The analysis is performed using appropriate tests such as Fisher's exact test, Chi² test, Mann-Whitney U test or Kruskal-Wallis test.	immediately after first vaccination
Secondary	Differences between the 4 groups after second vaccination regarding a. the individual local vaccination reactions? b. the individual systemic vaccination reactions? c. the number or percentage of vaccination reactions?	For the secondary endpoints, frequencies (%/n) for categorical data and corresponding measures of location (median, interquartile range) for continuous data are used descriptively. The analysis is performed using appropriate tests such as Fisher's exact test, Chi² test, Mann-Whitney U test or Kruskal-Wallis test.	immediately after second vaccination
Secondary	Differences between the 4 groups after boost vaccination regarding a. the individual local vaccination reactions? b. the individual systemic vaccination reactions? c. the number or percentage of vaccination reactions?	For the secondary endpoints, frequencies (%/n) for categorical data and corresponding measures of location (median, interquartile range) for continuous data are used descriptively. The analysis is performed using appropriate tests such as Fisher's exact test, Chi² test, Mann-Whitney U test or Kruskal-Wallis test.	immediately after boost vaccination
Secondary	Is there a difference between the four cohorts regarding the severity of vaccination reactions?	For the secondary endpoints, frequencies (%/n) for categorical data and corresponding measures of location (median, interquartile range) for continuous data are used descriptively. The analysis is performed using appropriate tests such as Fisher's exact test, Chi² test, Mann-Whitney U test or Kruskal-Wallis test.	immediately after first vaccination
Secondary	Is there a difference between the four cohorts regarding the severity of vaccination reactions?	For the secondary endpoints, frequencies (%/n) for categorical data and corresponding measures of location (median, interquartile range) for continuous data are used descriptively. The analysis is performed using appropriate tests such as Fisher's exact test, Chi² test, Mann-Whitney U test or Kruskal-Wallis test.	immediately after second vaccination
Secondary	Is there a difference between the four cohorts regarding the severity of vaccination reactions?	For the secondary endpoints, frequencies (%/n) for categorical data and corresponding measures of location (median, interquartile range) for continuous data are used descriptively. The analysis is performed using appropriate tests such as Fisher's exact test, Chi² test, Mann-Whitney U test or Kruskal-Wallis test.	immediately after boost vaccination
Secondary	Do the four cohorts differ with respect to the temporal occurrence of vaccination reactions?	For the secondary endpoints, frequencies (%/n) for categorical data and corresponding measures of location (median, interquartile range) for continuous data are used descriptively. The analysis is performed using appropriate tests such as Fisher's exact test, Chi² test, Mann-Whitney U test or Kruskal-Wallis test.	immediately after first vaccination
Secondary	Do the four cohorts differ with respect to the temporal occurrence of vaccination reactions?	For the secondary endpoints, frequencies (%/n) for categorical data and corresponding measures of location (median, interquartile range) for continuous data are used descriptively. The analysis is performed using appropriate tests such as Fisher's exact test, Chi² test, Mann-Whitney U test or Kruskal-Wallis test.	immediately after second vaccination
Secondary	Is there a difference between the four cohorts regarding the use of medication due to vaccination reactions?	For the secondary endpoints, frequencies (%/n) for categorical data and corresponding measures of location (median, interquartile range) for continuous data are used descriptively. The analysis is performed using appropriate tests such as Fisher's exact test, Chi² test, Mann-Whitney U test or Kruskal-Wallis test.	first and second vaccination
Secondary	Do the four cohorts differ with regard to the need for a certificate of incapacity for work due to vaccination reactions?	For the secondary endpoints, frequencies (%/n) for categorical data and corresponding measures of location (median, interquartile range) for continuous data are used descriptively. The analysis is performed using appropriate tests such as Fisher's exact test, Chi² test, Mann-Whitney U test or Kruskal-Wallis test.	immediately after first vaccination
Secondary	Are there differences regarding the job groups and the vaccination week days?	For the secondary endpoints, frequencies (%/n) for categorical data and corresponding measures of location (median, interquartile range) for continuous data are used descriptively. The analysis is performed using appropriate tests such as Fisher's exact test, Chi² test, Mann-Whitney U test or Kruskal-Wallis test.	immediately after first vaccination
Secondary	Do the four cohorts differ with regard to the need for a certificate of incapacity for work due to vaccination reactions?	For the secondary endpoints, frequencies (%/n) for categorical data and corresponding measures of location (median, interquartile range) for continuous data are used descriptively. The analysis is performed using appropriate tests such as Fisher's exact test, Chi² test, Mann-Whitney U test or Kruskal-Wallis test.	immediately after second vaccination
Secondary	Are there differences regarding the job groups and the vaccination week days?	For the secondary endpoints, frequencies (%/n) for categorical data and corresponding measures of location (median, interquartile range) for continuous data are used descriptively. The analysis is performed using appropriate tests such as Fisher's exact test, Chi² test, Mann-Whitney U test or Kruskal-Wallis test.	immediately after second vaccination
Secondary	Do the four cohorts differ with regard to the need for a certificate of incapacity for work due to vaccination reactions?	For the secondary endpoints, frequencies (%/n) for categorical data and corresponding measures of location (median, interquartile range) for continuous data are used descriptively. The analysis is performed using appropriate tests such as Fisher's exact test, Chi² test, Mann-Whitney U test or Kruskal-Wallis test.	immediately after boost vaccination
Secondary	Are there differences regarding the job groups and the vaccination week days?	For the secondary endpoints, frequencies (%/n) for categorical data and corresponding measures of location (median, interquartile range) for continuous data are used descriptively. The analysis is performed using appropriate tests such as Fisher's exact test, Chi² test, Mann-Whitney U test or Kruskal-Wallis test.	immediately after boost vaccination
Secondary	Are there differences within the cohorts regarding vaccination reactions in subjects with a known allergy?	For the secondary endpoints, frequencies (%/n) for categorical data and corresponding measures of location (median, interquartile range) for continuous data are used descriptively. The analysis is performed using appropriate tests such as Fisher's exact test, Chi² test, Mann-Whitney U test or Kruskal-Wallis test.	immediately after first vaccination
Secondary	Are there differences within the total population regarding vaccination reactions in subjects with a known allergy?	For the secondary endpoints, frequencies (%/n) for categorical data and corresponding measures of location (median, interquartile range) for continuous data are used descriptively. The analysis is performed using appropriate tests such as Fisher's exact test, Chi² test, Mann-Whitney U test or Kruskal-Wallis test.	immediately after first vaccination
Secondary	Are there differences within the cohorts regarding vaccination reactions in subjects with a known allergy?	For the secondary endpoints, frequencies (%/n) for categorical data and corresponding measures of location (median, interquartile range) for continuous data are used descriptively. The analysis is performed using appropriate tests such as Fisher's exact test, Chi² test, Mann-Whitney U test or Kruskal-Wallis test.	immediately after second vaccination
Secondary	Are there differences within the total population regarding vaccination reactions in subjects with a known allergy?	For the secondary endpoints, frequencies (%/n) for categorical data and corresponding measures of location (median, interquartile range) for continuous data are used descriptively. The analysis is performed using appropriate tests such as Fisher's exact test, Chi² test, Mann-Whitney U test or Kruskal-Wallis test.	immediately after second vaccination
Secondary	Is there a correlation within cohorts or within the overall population at four weeks regarding the level of antibody and the a. Extent of vaccine response (local, systemic, local & systemic, none)? b. Gender? c. Age? d. BMI?	For the secondary endpoints, frequencies (%/n) for categorical data and corresponding measures of location (median, interquartile range) for continuous data are used descriptively. Spearman's correlation is calculated.	4 weeks after second vaccination
Secondary	Do the variables listed above have an influence on the level of antibody?	For the secondary endpoints, frequencies (%/n) for categorical data and corresponding measures of location (median, interquartile range) for continuous data are used descriptively. To investigate a potential influence of the variables, a logistic regression is performed if necessary.	4 weeks after second vaccination
Secondary	Is there a correlation within cohorts or within the overall population at 3 months regarding the level of antibody and the a. Extent of vaccine response (local, systemic, local & systemic, none)? b. Gender? c. Age? d. BMI?	For the secondary endpoints, frequencies (%/n) for categorical data and corresponding measures of location (median, interquartile range) for continuous data are used descriptively. Spearman's correlation is calculated.	3 months after second vaccination
Secondary	Do the variables listed above have an influence on the level of antibody?	For the secondary endpoints, frequencies (%/n) for categorical data and corresponding measures of location (median, interquartile range) for continuous data are used descriptively. To investigate a potential influence of the variables, a logistic regression is performed if necessary.	3 months after second vaccination
Secondary	Is there a correlation within cohorts or within the overall population at 6 months regarding the level of antibody and the a. Extent of vaccine response (local, systemic, local & systemic, none)? b. Gender? c. Age? d. BMI?	For the secondary endpoints, frequencies (%/n) for categorical data and corresponding measures of location (median, interquartile range) for continuous data are used descriptively. Spearman's correlation is calculated.	6 months after second vaccination
Secondary	Do the variables listed above have an influence on the level of antibody?	For the secondary endpoints, frequencies (%/n) for categorical data and corresponding measures of location (median, interquartile range) for continuous data are used descriptively. To investigate a potential influence of the variables, a logistic regression is performed if necessary.	6 months after second vaccination
Secondary	Is there a correlation within cohorts or within the overall population directly before the boost regarding the level of antibody and the a. Extent of vaccine response (local, systemic, local & systemic, none)? b. Gender? c. Age? d. BMI?	For the secondary endpoints, frequencies (%/n) for categorical data and corresponding measures of location (median, interquartile range) for continuous data are used descriptively.	directly before boost vaccination
Secondary	Do the variables listed above have an influence on the level of antibody?	For the secondary endpoints, frequencies (%/n) for categorical data and corresponding measures of location (median, interquartile range) for continuous data are used descriptively.	directly before boost vaccination
Secondary	Is there a correlation within cohorts or within the overall population at 4 weeks after boost regarding the level of antibody and the a. Extent of vaccine response (local, systemic, local & systemic, none)? b. Gender? c. Age? d. BMI?	For the secondary endpoints, frequencies (%/n) for categorical data and corresponding measures of location (median, interquartile range) for continuous data are used descriptively.	4 weeks after boost vaccination
Secondary	Do the variables listed above have an influence on the level of antibody?	For the secondary endpoints, frequencies (%/n) for categorical data and corresponding measures of location (median, interquartile range) for continuous data are used descriptively.	4 weeks after boost vaccination
Secondary	Is there a correlation within cohorts or within the overall population at 3 months after boost regarding the level of antibody and the a. Extent of vaccine response (local, systemic, local & systemic, none)? b. Gender? c. Age? d. BMI?	For the secondary endpoints, frequencies (%/n) for categorical data and corresponding measures of location (median, interquartile range) for continuous data are used descriptively.	3 months after boost vaccination
Secondary	Do the variables listed above have an influence on the level of antibody?	For the secondary endpoints, frequencies (%/n) for categorical data and corresponding measures of location (median, interquartile range) for continuous data are used descriptively.	3 months after boost vaccination
Secondary	Is there a statistically significant or clinically relevant difference between the (drop in) antibodies at three months from baseline within the four cohorts?	For the secondary endpoints, frequencies (%/n) for categorical data and corresponding measures of location (median, interquartile range) for continuous data are used descriptively. The analysis is performed using appropriate tests such as Fisher's exact test, Chi² test, Mann-Whitney U test or Kruskal-Wallis test.	3 months after second vaccination
Secondary	Is there a statistically significant or clinically relevant difference between the (drop in) antibodies at six months from baseline within the four cohorts?	For the secondary endpoints, frequencies (%/n) for categorical data and corresponding measures of location (median, interquartile range) for continuous data are used descriptively. The analysis is performed using appropriate tests such as Fisher's exact test, Chi² test, Mann-Whitney U test or Kruskal-Wallis test.	6 months after second vaccination
Secondary	Is there a statistically significant or clinically relevant difference between the (drop in) antibodies at three months from baseline between the four cohorts?	For the secondary endpoints, frequencies (%/n) for categorical data and corresponding measures of location (median, interquartile range) for continuous data are used descriptively. The analysis is performed using appropriate tests such as Fisher's exact test, Chi² test, Mann-Whitney U test or Kruskal-Wallis test.	3 months after second vaccination
Secondary	Is there a statistically significant or clinically relevant difference between the (drop in) antibodies at six months from baseline between the four cohorts?	For the secondary endpoints, frequencies (%/n) for categorical data and corresponding measures of location (median, interquartile range) for continuous data are used descriptively. The analysis is performed using appropriate tests such as Fisher's exact test, Chi² test, Mann-Whitney U test or Kruskal-Wallis test.	6 months after second vaccination
Secondary	Are there any subjects within the study follow-up period who had proven SARS Cov2 infection? (Comparison between groups)	For the secondary endpoints, frequencies (%/n) for categorical data and corresponding measures of location (median, interquartile range) for continuous data are used descriptively. The analysis is performed using appropriate tests such as Fisher's exact test, Chi² test, Mann-Whitney U test or Kruskal-Wallis test.	until end of study
Secondary	Is there a correlation within the overall population between the level of antibody and detected SARS Cov2 infection?	For the secondary endpoints, frequencies (%/n) for categorical data and corresponding measures of location (median, interquartile range) for continuous data are used descriptively.	3 months and 6 months after second vaccination, directly before boost vaccination and 4 weeks and 3 months after boost vaccination