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

• ClinicalTrials.gov Identifier: NCT04456595
• Recruitment Status: Unknown
• First Posted: July 2, 2020
• Last Update Posted: February 11, 2021
• Sponsor: Butantan Institute
• Collaborator: Sinovac Life Sciences Co., Ltd.
• Information provided by (Responsible Party): Butantan Institute

Study Description

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

Condition or disease	Intervention/treatment	Phase
COVID-19	Biological: Adsorbed COVID-19 (inactivated) Vaccine; Biological: Placebo	Phase 3

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 12688 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Prevention
• 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
• Actual Study Start Date: July 21, 2020
• Actual Primary Completion Date: December 17, 2020
• Estimated Study Completion Date: February 2022

Arms and Interventions

Arm	Intervention/treatment
Experimental: Adult - Vaccine; Participants aging 18-59 years receiving two doses with 14-days interval of Adsorbed COVID-19 (inactivated) Vaccine	Biological: Adsorbed COVID-19 (inactivated) Vaccine; Adsorbed COVID-19 (inactivated) Vaccine manufactured by Sinovac; Other Name: CoronaVac
Experimental: Elderly - Vaccine; Participants aging 60 years or above receiving two doses with 14-days interval of Adsorbed COVID-19 (inactivated) Vaccine	Biological: Adsorbed COVID-19 (inactivated) Vaccine; Adsorbed COVID-19 (inactivated) Vaccine manufactured by Sinovac; Other Name: CoronaVac
Placebo Comparator: Adult - Placebo; Participants aging 18-59 years receiving two doses with 14-days interval of placebo	Biological: Placebo; Placebo of Adsorbed COVID-19 (inactivated) Vaccine manufactured by Sinovac
Placebo Comparator: Elderly - Placebo; Participants aging 60 years or above receiving two doses with 14-days interval of placebo	Biological: Placebo; Placebo of Adsorbed COVID-19 (inactivated) Vaccine manufactured by Sinovac

Outcome Measures

Primary Outcome Measures :

1. Incidence of COVID-19 cases after two-doses immunization schedule [ Time Frame: Two 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
2. Frequency of adverse events up to seven days after immunization [ Time Frame: Seven days after each immunization ]
   Frequency of adverse reaction in the seven days following each immunization per age group

Secondary Outcome Measures :

1. Incidence of COVID-19 cases after two-doses immunization schedule according to previous exposure [ Time Frame: Two 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
2. Incidence of COVID-19 cases after 14-days of first immunization [ Time Frame: Two 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
3. Combined incidence of SARS-CoV-2 infection [ Time Frame: Two 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
4. Incidence of severe COVID-19 cases after two-doses immunization schedule [ Time Frame: Two 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
5. Frequency of adverse events up to 28 days after immunization [ Time Frame: 28 days after each immunization ]
   Frequency of adverse reaction in the 28 days following each immunization per age group
6. Frequency of severe COVID-19 cases [ Time Frame: From 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
7. Frequency of adverse events of special interest after immunization [ Time Frame: From 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
8. Seroconversion rate [ Time Frame: Two 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
9. Cell-mediated immune profile [ Time Frame: Two 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
10. Seropositivity rate [ Time Frame: Two 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

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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.

Contacts and Locations

Locations

Brazil

Universidade de Brasília

Brasilia, DF, Brazil, 71691-082

Universidade Federal de Minas Gerais

Belo Horizonte, MG, Brazil, 30750-140

Hospital Universitário Júlio Müller

Cuiabá, Mount, Brazil, 78048-902

Hospital Universitário Maria Aparecida Pedrossian

Campo Grande, MS, Brazil, 79080-190

Hospital das Clínicas da Universidade Federal do Paraná

Curitiba, PR, Brazil, 80060-900

Hospital Escola da Universidade Federal de Pelotas

Pelotas, RS, Brazil, 96020-360

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

Porto Alegre, RS, Brazil, 90619-900

Hospital de Amor - Fundação Pio XII

Barretos, SP, Brazil, 14780-070

Hospital das Clínicas da UNICAMP

Campinas, SP, Brazil, 13083-888

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

Ribeirao Preto, SP, Brazil, 14015-069

Instituto de Infectologia Emílio Ribas

Sao Paulo, SP, Brazil, 01246-900

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

Sao Paulo, SP, Brazil, 05403 000

Instituto Israelita de Ensino e Pesquisa Albert Einstein

Sao Paulo, SP, Brazil, 05652-900

Universidade Municipal de São Caetano do Sul

São Caetano do Sul, SP, Brazil, 09521-160

Faculdade de Medicina de São José do Rio Preto - FAMERP

São José Do Rio Preto, São Paulo, Brazil, 15090-000

Instituto de Infectologia Evandro Chagas - Fiocruz

Rio De Janeiro, Brazil, 21710-232

Sponsors and Collaborators

Butantan Institute

Sinovac Life Sciences Co., Ltd.

Investigators

• Study Director: Ricardo Palacios, MD, PhD; Butantan Institute

More Information

Publications:

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.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Butantan Institute
• ClinicalTrials.gov Identifier: NCT04456595
• Other Study ID Numbers: COV-02-IB
• First Posted: July 2, 2020
• Last Update Posted: February 11, 2021
• Last Verified: February 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

COVID-19; Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases