Clinical trial NCT04456595: Clinical Trial of Efficacy and Safety of Sinovac's Adsorbed COVID-19 (Inactivated) Vaccine in Healthcare Professionals
Official title: Double-Blind, Randomized, Placebo-Controlled Phase III Clinical Trial to Evaluate Efficacy and Safety in Healthcare Professionals of the Adsorbed COVID-19 (Inactivated) Vaccine Manufactured by Sinovac
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: COVID-19
Lead sponsor: Butantan Institute
Sponsor class: OTHER_GOV
Collaborators: name: Sinovac Life Sciences Co., Ltd.
First posted: 2020-07-02
Enrollment: 12688
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Incidence of COVID-19 cases after two-doses immunization schedule
timeFrame: Two weeks after second dose up to one year after first dose
measure: Frequency of adverse events up to seven days after immunization
timeFrame: Seven days after each immunization
Secondary outcomes:
measure: Incidence of COVID-19 cases after two-doses immunization schedule according to previous exposure
timeFrame: Two weeks after first dose up to one year after first dose
measure: Incidence of COVID-19 cases after 14-days of first immunization
timeFrame: Two weeks after last dose uup to one year after first dose
measure: Combined incidence of SARS-CoV-2 infection
timeFrame: Two weeks after second dose up to one year after first dose
measure: Incidence of severe COVID-19 cases after two-doses immunization schedule
timeFrame: Two weeks after second dose up to one year after first dose
measure: Frequency of adverse events up to 28 days after immunization
timeFrame: 28 days after each immunization
measure: Frequency of severe COVID-19 cases
timeFrame: From first vaccination up to one year after first dose
measure: Frequency of adverse events of special interest after immunization
timeFrame: From first vaccination up to one year after first dose
measure: Seroconversion rate
timeFrame: Two weeks after each vaccination
measure: Cell-mediated immune profile
timeFrame: Two and four weeks afer each vaccination
measure: Seropositivity rate
timeFrame: Two weeks after second vaccination
Other outcomes:
Locations:
city: Brasilia
country: Brazil
facility: Universidade de Brasília
state: DF
city: Belo Horizonte
country: Brazil
facility: Universidade Federal de Minas Gerais
state: MG
city: Cuiabá
country: Brazil
facility: Hospital Universitário Júlio Müller
state: Mount
city: Campo Grande
country: Brazil
facility: Hospital Universitário Maria Aparecida Pedrossian
state: MS
city: Curitiba
country: Brazil
facility: Hospital das Clínicas da Universidade Federal do Paraná
state: PR
city: Pelotas
country: Brazil
facility: Hospital Escola da Universidade Federal de Pelotas
state: RS
city: Porto Alegre
country: Brazil
facility: Hospital São Lucas da Pontificia Universidade Catolica do Rio Grande do Sul
state: RS
city: Barretos
country: Brazil
facility: Hospital de Amor - Fundação Pio XII
state: SP
city: Campinas
country: Brazil
facility: Hospital das Clínicas da UNICAMP
state: SP
city: Ribeirao Preto
country: Brazil
facility: Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo
state: SP
city: Sao Paulo
country: Brazil
facility: Instituto de Infectologia Emílio Ribas
state: SP
city: Sao Paulo
country: Brazil
facility: Centro de Pesquisas Clínicas do Instituto Central do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo
state: SP
city: Sao Paulo
country: Brazil
facility: Instituto Israelita de Ensino e Pesquisa Albert Einstein
state: SP
city: São Caetano do Sul
country: Brazil
facility: Universidade Municipal de São Caetano do Sul
state: SP
city: São José Do Rio Preto
country: Brazil
facility: Faculdade de Medicina de São José do Rio Preto - FAMERP
state: São Paulo
city: Rio De Janeiro
country: Brazil
facility: Instituto de Infectologia Evandro Chagas - Fiocruz
Study officials:
affiliation: Butantan Institute
name: Ricardo Palacios, MD, PhD
role: STUDY_DIRECTOR
References:
citation: Palacios R, Patino EG, de Oliveira Piorelli R, Conde MTRP, Batista AP, Zeng G, Xin Q, Kallas EG, Flores J, Ockenhouse CF, Gast C. Double-Blind, Randomized, Placebo-Controlled Phase III Clinical Trial to Evaluate the Efficacy and Safety of treating Healthcare Professionals with the Adsorbed COVID-19 (Inactivated) Vaccine Manufactured by Sinovac - PROFISCOV: A structured summary of a study protocol for a randomised controlled trial. Trials. 2020 Oct 15;21(1):853. doi: 10.1186/s13063-020-04775-4.
citation: Luan N, Li T, Wang Y, Cao H, Yin X, Lin K, Liu C. Th2-Oriented Immune Serum After SARS-CoV-2 Vaccination Does Not Enhance Infection In Vitro. Front Immunol. 2022 Apr 8;13:882856. doi: 10.3389/fimmu.2022.882856. eCollection 2022.