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Clinical Trial of Efficacy and Safety of Sinovac's Adsorbed COVID-19 (Inactivated) Vaccine in Healthcare Professionals

Phase 3
Completed
Conditions
COVID-19
Interventions
Biological: Placebo
Biological: Adsorbed COVID-19 (inactivated) Vaccine
Registration Number
NCT04456595
Lead Sponsor
Butantan Institute
Brief Summary

This is a phase III clinical trial to assess efficacy and safety of the Adsorbed COVID-19 (inactivated) vaccine manufactured by Sinovac in health care professionals

Detailed Description

This is a phase III clinical trial to assess efficacy and safety of the Adsorbed COVID-19 (inactivated) vaccine manufactured by Sinovac in health care professionals.

The study will be double-blind placebo-controlled trial with participants randomly allocated 1:1 to placebo and vaccine arms.

The immunization schedule is two doses intramuscular injections (deltoid) with a 14-days interval.

For efficacy, the study aims to detect COVID-19 cases, defined as symptomatic SARS-CoV-2 infections, after the second week post-immunization schedule.

For safety and immunogenicity, participants are categorized in two age groups, Adults (18-59 years) and Elderly (60 years and above). Safety database aims to detect adverse reactions with frequency of 1:1000 or higher in adults and 1:500 in elderly.

All participants will be followed up to 12 months. Interim preliminary efficacy analysis can be triggered by reaching the target number of 61 cases. Primary efficacy analysis requires 151 cases.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
12688
Inclusion Criteria
  1. Adults 18 years of age or older;
  2. Healthcare professionals who work in direct contact care of people with possible or confirmed COVID-19 cases;
  3. Agree with periodic contacts by phone or electronic means, and home visits;
  4. Show voluntary intention to participate in the study, documented by the informed consent form signed by participant.
Exclusion Criteria
  1. For females: Pregnancy (confirmed by positive beta-hCG test), breastfeeding or intent to engage in sexual relations with reproductive intent without use of birth control methods in the three months following vaccination;
  2. Evidence of uncontrolled neurological, cardiac, pulmonary, hepatic or renal disease, according to anamnesis or physical examination. Significant changes in treatment or hospitalizations due to worsening of the condition in the last three months are indicators of uncontrolled disease;
  3. Diseases with impaired immune system including: neoplasms (except basal cell carcinoma), congenital or acquired immunodeficiencies and autoimmune diseases not controlled according to anamnesis or physical examination. Significant changes in treatment or hospitalizations due to worsening of the condition in the last three months are indicators of uncontrolled disease;
  4. Behavioral, cognitive or psychiatric disease that, in the opinion of the principal investigator or his or her representative physician, affects the participant's ability to understand and cooperate with all study protocol requirements;
  5. Any alcohol or drug abuse over the 12 months prior to enrollment in the study that has caused medical, professional or family problems, indicated by clinical history;
  6. History of severe allergic reactions or anaphylaxis to the study vaccine or to components thereof;
  7. History of asplenia;
  8. Participation in another clinical trial with an investigational product in the six months prior to enrollment in the study or planned participation in another clinical trial within the two years following enrollment;
  9. Previous participation in a study to evaluate a COVID-19 vaccine or prior exposure to a COVID-19 vaccine;
  10. Use of immunosuppressant therapy regimens within the six months prior to enrollment in the study for planned use within the two years following enrollment. Immunosuppressant therapy regimens include: antineoplastic chemotherapy, radiation therapy and immunosuppressants to induce transplant tolerance, among others.
  11. Use of immunosuppressive doses of corticosteroids within the three months prior to the enrollment in the study and planned use of immunosuppressive doses of corticoids within the three months following enrollment in the study. Immunosuppressive doses of corticosteroids will be considered the equivalent prednisone 20 mg/day for adults, for longer than one week. Continued use of topical or nasal corticosteroids is not considered an immunosuppressant;
  12. Received blood products (transfusions or immunoglobulins) within the three months prior to enrollment in the study, or planned administration of blood products or immunoglobulins within the two years following enrollment in the study;
  13. Suspected or confirmed fever within the 72 hours prior to vaccination or axillary temperature greater than 37.8 °C* on the day of vaccination (enrollment may be postponed until participant has gone 72 hours without fever);
  14. Possible or confirmed case of COVID-19 on the day of vaccination (vaccination can be postponed until the participant completes 72 hours without symptoms or the diagnosis is ruled out);
  15. Received live attenuated virus vaccine or inactivated vaccine within the 28 days or 14 days, respectively, prior to enrollment in the study, or immunization planned within the 28 days after enrollment in the study;
  16. History of bleeding disorder (e.g. factor deficiency, coagulopathy or platelet disorder), or prior history of significant bleeding or bruising following IM injections or venipuncture
  17. Any other condition that, in the opinion of the principal investigator or his/her representative physician, could put the safety/rights of potential participants at risk or prevent them from complying with this protocol.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Adult - PlaceboPlaceboParticipants aging 18-59 years receiving two doses with 14-days interval of placebo
Elderly - PlaceboPlaceboParticipants aging 60 years or above receiving two doses with 14-days interval of placebo
Elderly - VaccineAdsorbed COVID-19 (inactivated) VaccineParticipants aging 60 years or above receiving two doses with 14-days interval of Adsorbed COVID-19 (inactivated) Vaccine
Adult - VaccineAdsorbed COVID-19 (inactivated) VaccineParticipants aging 18-59 years receiving two doses with 14-days interval of Adsorbed COVID-19 (inactivated) Vaccine
Primary Outcome Measures
NameTimeMethod
Frequency of adverse events up to seven days after immunizationSeven days after each immunization

Frequency of adverse reaction in the seven days following each immunization per age group

Incidence of COVID-19 cases after two-doses immunization scheduleTwo weeks after second dose up to one year after first dose

Number of virologically-confirmed symptomatic COVID-19 two weeks after second dose of vaccine

Secondary Outcome Measures
NameTimeMethod
Frequency of severe COVID-19 casesFrom first vaccination up to one year after first dose

Frequency of virologically-confirmed severe COVID-19 cases after receiving, at least, one dose of the vaccine

Seroconversion rateTwo weeks after each vaccination

Number of seroconversion responses to SARS-CoV-2 in the second week after each vaccination per age group in a subset of participants

Combined incidence of SARS-CoV-2 infectionTwo weeks after second dose up to one year after first dose

Number of virologically-confirmed and or serologically-confirmed SARS-CoV-2 infections two weeks after first dose of vaccine

Frequency of adverse events up to 28 days after immunization28 days after each immunization

Frequency of adverse reaction in the 28 days following each immunization per age group

Incidence of COVID-19 cases after two-doses immunization schedule according to previous exposureTwo weeks after first dose up to one year after first dose

Number of virologically-confirmed symptomatic COVID-19 two weeks after second dose of vaccine according to previous exposure to SARS-CoV-2

Incidence of COVID-19 cases after 14-days of first immunizationTwo weeks after last dose uup to one year after first dose

Number of virologically-confirmed symptomatic COVID-19 two weeks after first dose of vaccine, regardless the vaccination schedule was completed

Incidence of severe COVID-19 cases after two-doses immunization scheduleTwo weeks after second dose up to one year after first dose

Number of virologically-confirmed severe COVID-19 two weeks after second dose of vaccine

Frequency of adverse events of special interest after immunizationFrom first vaccination up to one year after first dose

Frequency of adverse events of special interest after receiving, at least, one dose of the vaccine

Cell-mediated immune profileTwo and four weeks afer each vaccination

Number of cell-mediated immune response against SARS-CoV-2 in the week two and four after the second vaccination per age group in a subset of participants

Seropositivity rateTwo weeks after second vaccination

Number of seropositive responses to SARS-CoV-2 in the second week after each vaccination per age group in a subset of participants

Trial Locations

Locations (16)

Hospital das Clínicas da UNICAMP

🇧🇷

Campinas, SP, Brazil

Faculdade de Medicina de São José do Rio Preto - FAMERP

🇧🇷

São José Do Rio Preto, São Paulo, Brazil

Hospital Universitário Júlio Müller

🇧🇷

Cuiabá, Mount, Brazil

Universidade de Brasília

🇧🇷

Brasilia, DF, Brazil

Hospital Universitário Maria Aparecida Pedrossian

🇧🇷

Campo Grande, MS, Brazil

Hospital São Lucas da Pontificia Universidade Catolica do Rio Grande do Sul

🇧🇷

Porto Alegre, RS, Brazil

Universidade Federal de Minas Gerais

🇧🇷

Belo Horizonte, MG, Brazil

Hospital de Amor - Fundação Pio XII

🇧🇷

Barretos, SP, Brazil

Hospital das Clínicas da Universidade Federal do Paraná

🇧🇷

Curitiba, PR, Brazil

Hospital Escola da Universidade Federal de Pelotas

🇧🇷

Pelotas, RS, Brazil

Instituto Israelita de Ensino e Pesquisa Albert Einstein

🇧🇷

Sao Paulo, SP, Brazil

Instituto de Infectologia Emílio Ribas

🇧🇷

Sao Paulo, SP, Brazil

Universidade Municipal de São Caetano do Sul

🇧🇷

São Caetano do Sul, SP, Brazil

Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo

🇧🇷

Ribeirao Preto, SP, Brazil

Centro de Pesquisas Clínicas do Instituto Central do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo

🇧🇷

Sao Paulo, SP, Brazil

Instituto de Infectologia Evandro Chagas - Fiocruz

🇧🇷

Rio De Janeiro, Brazil

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