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

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

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

Study Overview

• Status: Completed
• Conditions: COVID-19
• Intervention / Treatment: Biological: Adsorbed COVID-19 (inactivated) Vaccine; Biological: Placebo

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 Type: Interventional
• Enrollment (Actual): 12688
• Phase: Phase 3

Contacts and Locations

Study Locations

• Brazil
  • Rio De Janeiro, Brazil, 21710-232
    • Instituto de Infectologia Evandro Chagas - Fiocruz
  • DF
    • Brasilia, DF, Brazil, 71691-082
      • Universidade de Brasília
  • MG
    • Belo Horizonte, MG, Brazil, 30750-140
      • Universidade Federal De Minas Gerais
  • MS
    • Campo Grande, MS, Brazil, 79080-190
      • Hospital Universitário Maria Aparecida Pedrossian
  • Mount
    • Cuiabá, Mount, Brazil, 78048-902
      • Hospital Universitário Júlio Müller
  • PR
    • Curitiba, PR, Brazil, 80060-900
      • Hospital das Clinicas da Universidade Federal do Paraná
  • RS
    • Pelotas, RS, Brazil, 96020-360
      • Hospital Escola da Universidade Federal de Pelotas
    • Porto Alegre, RS, Brazil, 90619-900
      • Hospital Sao Lucas da Pontificia Universidade Catolica do Rio Grande do Sul
  • SP
    • Barretos, SP, Brazil, 14780-070
      • Hospital de Amor - Fundação Pio XII
    • Campinas, SP, Brazil, 13083-888
      • Hospital das Clínicas da Unicamp
    • Ribeirao Preto, SP, Brazil, 14015-069
      • Hospital Das Clinicas Da Faculdade De Medicina De Ribeirao Preto da Universidade de Sao Paulo
    • Sao Paulo, SP, Brazil, 05403 000
      • Centro de Pesquisas Clínicas do Instituto Central do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo
    • Sao Paulo, SP, Brazil, 01246-900
      • Instituto de Infectologia Emilio Ribas
    • Sao Paulo, SP, Brazil, 05652-900
      • Instituto Israelita de Ensino e Pesquisa Albert Einstein
    • São Caetano do Sul, SP, Brazil, 09521-160
      • Universidade Municipal de São Caetano do Sul
  • São Paulo
    • São José Do Rio Preto, São Paulo, Brazil, 15090-000
      • Faculdade de Medicina de São José do Rio Preto - FAMERP

Participation Criteria

Eligibility Criteria

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

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / 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 Names: 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 Names: 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Frequency of adverse events up to seven days after immunization	Frequency of adverse reaction in the seven days following each immunization per age group	Seven days after each immunization
Incidence of COVID-19 cases after two-doses immunization schedule	Number of virologically-confirmed symptomatic COVID-19 two weeks after second dose of vaccine	Two weeks after second dose up to one year after first dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Frequency of severe COVID-19 cases	Frequency of virologically-confirmed severe COVID-19 cases after receiving, at least, one dose of the vaccine	From first vaccination up to one year after first dose
Frequency of adverse events of special interest after immunization	Frequency of adverse events of special interest after receiving, at least, one dose of the vaccine	From first vaccination up to one year after first dose
Incidence of COVID-19 cases after two-doses immunization schedule according to previous exposure	Number of virologically-confirmed symptomatic COVID-19 two weeks after second dose of vaccine according to previous exposure to SARS-CoV-2	Two weeks after first dose up to one year after first dose
Incidence of COVID-19 cases after 14-days of first immunization	Number of virologically-confirmed symptomatic COVID-19 two weeks after first dose of vaccine, regardless the vaccination schedule was completed	Two weeks after last dose uup to one year after first dose
Combined incidence of SARS-CoV-2 infection	Number of virologically-confirmed and or serologically-confirmed SARS-CoV-2 infections two weeks after first dose of vaccine	Two weeks after second dose up to one year after first dose
Incidence of severe COVID-19 cases after two-doses immunization schedule	Number of virologically-confirmed severe COVID-19 two weeks after second dose of vaccine	Two weeks after second dose up to one year after first dose
Frequency of adverse events up to 28 days after immunization	Frequency of adverse reaction in the 28 days following each immunization per age group	28 days after each immunization
Seroconversion rate	Number of seroconversion responses to SARS-CoV-2 in the second week after each vaccination per age group in a subset of participants	Two weeks after each vaccination
Cell-mediated immune profile	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	Two and four weeks afer each vaccination
Seropositivity rate	Number of seropositive responses to SARS-CoV-2 in the second week after each vaccination per age group in a subset of participants	Two weeks after second vaccination

Collaborators and Investigators

• Sponsor: Butantan Institute
• Collaborators: Sinovac Life Sciences Co., Ltd.
• Investigators: Study Director: Ricardo Palacios, MD, PhD, Butantan Institute

Publications and helpful links

General Publications

• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): July 21, 2020
• Primary Completion (Actual): December 17, 2020
• Study Completion (Actual): February 17, 2022

Study Registration Dates

• First Submitted: June 30, 2020
• First Submitted That Met QC Criteria: June 30, 2020
• First Posted (Actual): July 2, 2020

Study Record Updates

• Last Update Posted (Actual): February 15, 2024
• Last Update Submitted That Met QC Criteria: February 14, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19
• Other Study ID Numbers: COV-02-IB

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No