EFFECTIVENESS, SAFETY AND IMMUNOGENICITY OF THE HALF DOSE OF THE VACCINE ChadOx1 nCoV-19 (AZD1222) for COVID-19

SARS-CoV-2 Clinical Trial

Official title:

EFFECTIVENESS, SAFETY AND IMMUNOGENICITY OF THE HALF DOSE OF THE VACCINE ChadOx1 nCoV-19 (AZD1222) for COVID-19

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05059106
• Other study ID #: FUES02
• Status: Recruiting
• Phase: Phase 2/Phase 3
• Start date: June 1, 2021
• Est. completion date: October 30, 2022

Study information

• Verified date: September 2021
• Source: Federal University of Espirito Santo
• Contact: Valéria Valim, PhD
• Phone: +5527999874665
• Email: val.valim[@]gmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study is clinical trial (intervention study with external comparison group) to test vaccination with reduced dose (half dose) of ChAdOx1 nCoV-19 (AZD1222), in a 2-dose schedule with an interval of 8 weeks, including all adults aged 18 to 49 years from Viana city - Espírito Santo (ES)/Brazil, on the incidence of new cases over 12 months following treatment, compared to an external group from same state and adjusted for socio-demographic and epidemiological variables.

Description:

This study is clinical trial (intervention study with external comparison group) to test vaccination with reduced dose (half dose) of ChAdOx1 nCoV-19 (AZD1222), in a 2-dose schedule with an interval of 8 weeks, including all adults aged 18 to 49 years from Viana city - Espírito Santo (ES)/Brazil, on the incidence of new cases over 12 months following treatment, compared to an external group from same state and adjusted for socio-demographic and epidemiological variables. Cellular and humoral immunity will be studied in a representative sub-sample compared to an external reference group (cohort of health workers) vaccinated with standard dose. The outcomes will be evaluated at 28 days after the second dose and follow-up after 6 months and 12 months. The main outcome will be to decrease in 60% the incidence of new cases over 6 months after receiving the vaccine. The clinical epidemiological variables will be obtained from e-SUS VS, e-SUS notifica and datasus: number of cases, number of deaths with specific ICD for covid-19, number of hospital admissions for covid-19; number of ICU admissions for the treatment of SARS, total number of tests (RT-PCR) performed and positive. The cellular and humoral immune response will be assessed by viral neutralization assay (neutralizing antibody test), serological assay by chemiluminescence, determination of specific IgM and IgG profiles, measurement of systemic soluble factors (chemokines, cytokines and growth factors), stimulation antigen-specific peripheral blood mononuclear cells in vitro and investigation of memory T and B lymphocytes and intracytoplasmic cytokines. It is estimated to include 29,637 people in the study, to reach 85% vaccination cover of individuals aged 18-49 years. The subsample size immunogenicity test is 600 individuals from the eligible population, estimating losses of 15% and study power of 90%, alpha error of 1%. The hypothesis of the study is that the reduction in the incidence of covid-19 and the cellular and humoral immune response achieved with a half dose will be similar to the reduction expected with the standard dose.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 29637
• Est. completion date: October 30, 2022
• Est. primary completion date: June 1, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 49 Years

Eligibility

Inclusion Criteria:

• residents of Viana, Espírito Santo, aged between 18 and 49 years

Exclusion Criteria:

• Pregnant women;

• History of severe allergic reaction (anaphylaxis) to any previously administered vaccine;

• Having received another vaccine in the last 14 days;

• Belonging to a priority risk group for vaccination, as per the PNI recommendations;

• Have fever or flu-like symptoms;

• Have previously received any vaccine for covid-19 at any time;

• Recent diagnosis of covid-19 with onset of symptoms 28 days before vaccination;

• Disorders of coagulation and use of anticoagulants.

Related Conditions & MeSH terms

• COVID-19
• SARS-CoV-2

Intervention

Biological:
• Half dose of ChAdOx1 nCoV-19 (AZD1222)
Vaccination with reduced dose (half dose) of ChAdOx1 nCoV-19 (AZD1222), in a 2-dose schedule with an interval of 8 weeks, including all adults aged 18 to 49 years, from non-priority groups, from Viana city - Espírito Santo (ES)/Brazil.
• Standard dose of ChAdOx1 nCoV-19 (AZD1222)
Vaccination with standad dose of ChAdOx1 nCoV-19 (AZD1222), in a 2-dose schedule with an interval of 8 weeks, in external cohort of health workers aged 18 to 49 years.

Locations

Country	Name	City	State
Brazil	Federal University of Espirito Santo	Vitória	Espirito Santo

Sponsors (5)

Lead Sponsor	Collaborator
Federal University of Espirito Santo	Escola Nacional de Saúde Pública Sérgio Arouca/Fiocruz, Escola Superior de Ciências da Santa Casa de Misericórdia de Vitória, Instituto René Rachou/Fiocruz, Programa de Computação Científica/Fiocruz

Country where clinical trial is conducted

Brazil, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Adverse events	All adverse events will be followed up to establish severity and causal correlation. There will be surveillance of deaths and will be reported to the ethics committee.	14 months
Primary	Incidence of new cases	Incidence of new cases over 12 months following treatment	12 months
Secondary	Number of deaths	Number of deaths with specific ICD for covid-19	12 months
Secondary	number of hospital admissions	number of hospital admissions for covid-19	12 months
Secondary	number of intensive care unit (ICU) admissions	number of intensive care unit (ICU) admissions for the treatment of SARS	12 months
Secondary	number of tests (RT-PCR)	number of tests (RT-PCR) performed and positive	12 months
Secondary	Viral Neutralization Assay	Neutralizing antibody titers will be expressed by the ability of antibodies to neutralize up to 50% the number of plaques (PRNT50). Title > 1:50 will be considered positive.	4 and 8 months
Secondary	serological assay	Serological test by chemiluminescence. Results are expressed in U/mL and data interpretation will be done as follows: <0.8 U/mL = non-reactive sample; =0.8 U/mL = reactive sample.	8 and 10 months
Secondary	IgM	Determination of specific IgM profile. Results will be expressed in fluorescence intensity or pg/ml.	8 and 10 months
Secondary	IgG	Determination of specific IgG profile. Results will be expressed in fluorescence intensity or pg/ml.	8 and 10 months
Secondary	systemic soluble factors	Dosage of soluble systemic factors (chemokines, cytokines and growth factors). Results will be expressed in pg/ml.	8 and 10 months
Secondary	Antigen-specific stimulation of peripheral blood mononuclear cells	Antigen-specific stimulation of peripheral blood mononuclear cells in vitro. The results will be expressed in percentage positive frequency for a specific cell phenotype.	10 and 12 months
Secondary	Lymphocyte investigation	Investigation of memory T and B lymphocytes. The results will be expressed in percentage positive frequency for a specific cell phenotype.	10 and 12 months
Secondary	Cytokine investigation	Investigation of intracytoplasmic cytokines. The results will be expressed in percentage positive frequency for a specific cell phenotype.	10 and 12 months