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

Phase 2
Conditions
SARS-CoV-2
Interventions
Biological: Standard dose of ChAdOx1 nCoV-19 (AZD1222)
Biological: Half dose of ChAdOx1 nCoV-19 (AZD1222)
Registration Number
NCT05059106
Lead Sponsor
Federal University of Espirito Santo
Brief 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.

Detailed 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 & Eligibility

Status
UNKNOWN
Sex
All
Target Recruitment
29637
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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
SEQUENTIAL
Arm && Interventions
GroupInterventionDescription
Group 2Standard dose of ChAdOx1 nCoV-19 (AZD1222)Standad dose of ChAdOx1 nCoV-19 (AZD1222) in a 2-dose schedule with an interval of 8 weeks.
Group 1Half dose of ChAdOx1 nCoV-19 (AZD1222)Half dose of ChAdOx1 nCoV-19 (AZD1222) ) in a 2-dose schedule with an interval of 8 weeks.
Primary Outcome Measures
NameTimeMethod
Incidence of new cases12 months

Incidence of new cases over 12 months following treatment

Secondary Outcome Measures
NameTimeMethod
Viral Neutralization Assay4 and 8 months

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.

serological assay8 and 10 months

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.

Antigen-specific stimulation of peripheral blood mononuclear cells10 and 12 months

Antigen-specific stimulation of peripheral blood mononuclear cells in vitro. The results will be expressed in percentage positive frequency for a specific cell phenotype.

Lymphocyte investigation10 and 12 months

Investigation of memory T and B lymphocytes. The results will be expressed in percentage positive frequency for a specific cell phenotype.

number of hospital admissions12 months

number of hospital admissions for covid-19

Number of deaths12 months

Number of deaths with specific ICD for covid-19

number of intensive care unit (ICU) admissions12 months

number of intensive care unit (ICU) admissions for the treatment of SARS

number of tests (RT-PCR)12 months

number of tests (RT-PCR) performed and positive

IgM8 and 10 months

Determination of specific IgM profile. Results will be expressed in fluorescence intensity or pg/ml.

IgG8 and 10 months

Determination of specific IgG profile. Results will be expressed in fluorescence intensity or pg/ml.

systemic soluble factors8 and 10 months

Dosage of soluble systemic factors (chemokines, cytokines and growth factors). Results will be expressed in pg/ml.

Cytokine investigation10 and 12 months

Investigation of intracytoplasmic cytokines. The results will be expressed in percentage positive frequency for a specific cell phenotype.

Trial Locations

Locations (1)

Federal University of Espirito Santo

🇧🇷

Vitória, Espirito Santo, Brazil

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