Safety and Immunogenicity Study of Inactivated Vaccine for Prophylaxis of SARS CoV-2 Infection (COVID-19)

• ClinicalTrials.gov Identifier: NCT04352608
• Recruitment Status: Active, not recruiting
• First Posted: April 20, 2020
• Last Update Posted: August 4, 2020
• Sponsor: Sinovac Research and Development Co., Ltd.
• Information provided by (Responsible Party): Sinovac Biotech Co., Ltd ( Sinovac Research and Development Co., Ltd. )

Tracking Information

• First Submitted Date: April 14, 2020
• First Posted Date: April 20, 2020
• Last Update Posted Date: August 4, 2020
• Actual Study Start Date: April 16, 2020
• Actual Primary Completion Date: July 10, 2020 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 16, 2020)

• Safety indexes of adverse reactions [ Time Frame: From the beginning of the vaccination to 28 days after the whole schedule vaccination ]
  Occurence of adverse reactions post vaccination
• Immunogenicity indexes of neutralizing-antibody seroconversion rates for the emergency vaccination schedule （day 0,14） [ Time Frame: The 14th day after two doses of vaccination ]
  The seroconversion rates of neutralizing antibodies against 2019 novel coronavirus tested by micro-neutralization assay in serum
• Immunogenicity indexes of neutralizing-antibody seroconversion rates for the routine vaccination schedule (day 0,28) [ Time Frame: The 28th day after two doses of vaccination ]
  The seroconversion rates of neutralizing antibodies against 2019 novel coronavirus tested by micro-neutralization assay in serum

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: April 16, 2020)

• Safety indexes of adverse reactions [ Time Frame: 0~7 days after each dose injection ]
  Occurence of adverse reactions post vaccination
• Occurrence of abnormal changes of laboratory safety examinations (hemoglobin,WBCs, platelets, ALT, AST, total bilirubin, creatinine, creatine phosphokinase, urine protein, urine sugar, urinary erythrocyte) [ Time Frame: The 3rd day after each dose injection ]
  Safety index, abnormal changes will be defined as any one of the lab indexes experiencing changes out of clinical reference value range.
• Safety indexes of serious adverse events (SAEs） [ Time Frame: From the beginning of the vaccination to 6 months after two doses of vaccination ]
  Occurence of SAEs post vaccination
• Immunogenicity indexes of neutralizing-antibody seroconversion rates [ Time Frame: 7,14,21,42 days after the first dose injection for emergency vaccination schedule and 28,35,42 days after the first dose injection for the routine vaccination schedules ]
  The seroconversion rates of neutralizing antibodies against 2019 novel coronavirus tested by micro-neutralization assay in serum
• Immunogenicity indexes of IgG antibody seropositivity rates [ Time Frame: 7,14,21,28, 42 days after the first dose injection for emergency vaccination schedule and 28,35,42,56 days after the first dose injection for the routine vaccination schedule ]
  The seropositivity rates of IgG antibody tested by ELISA serum
• Immunogenicity indexes IgM antibody seropositivity rates [ Time Frame: 7,14,21,28, 42 days after the first dose injection for emergency vaccination schedule and 28,35,42,56 days after the first dose injection for the routine vaccination schedule ]
  The seropositivity rates of IgM antibody tested by ELISA serum
• Immunogenicity indexes of GMT of neutralizing-antibody [ Time Frame: 7,14,21,28, 42 days after the first dose injection for emergency vaccination schedule and 28,35,42,56 days after the first dose injection for the routine vaccination schedule ]
  The GMT of neutralizing antibody against 2019 novel coronavirus tested by micro-neutralization assay in serum
• Immunogenicity indexes of GMR of neutralizing-antibody [ Time Frame: 7,14,21,28, 42 days after the first dose injection for emergency vaccination schedule and 28,35,42,56 days after the first dose injection for the routine vaccination schedule ]
  The GMR of neutralizing antibody against 2019 novel coronavirus tested by micro-neutralization assay in serum

• Original Secondary Outcome Measures: Same as current

Current Other Pre-specified Outcome Measures (submitted: April 16, 2020)

• Immunogenicity indexes of cellular immune [ Time Frame: The 14th day after each dose vaccination ]
  specific cellular immune responses
• Immunogenicity indexes of neutralizing-antibody persistence [ Time Frame: 6 months after two doses of vaccination ]
  he seropositivity rates of neutralizing antibodies against 2019 novel coronavirus tested by micro-neutralization assay in serum
• Immunogenicity indexes of neutralizing-antibody GMT [ Time Frame: 6 months after two doses of vaccination ]
  The GMT of neutralizing antibody against 2019 novel coronavirus tested by micro-neutralization assay in serum
• Safety indexes-Seropositivity rates of antinuclear antibody [ Time Frame: The 7th day after each dose injection ]
  Seropositivity rates of antinuclear antibody in serum
• Safety indexes-Level of Inflammatory factors [ Time Frame: The 7th day after each dose injection ]
  Level of Inflammatory factors in serum

• Original Other Pre-specified Outcome Measures: Same as current

Descriptive Information

• Brief Title: Safety and Immunogenicity Study of Inactivated Vaccine for Prophylaxis of SARS CoV-2 Infection (COVID-19)
• Official Title: A Randomized, Double-Blinded, Placebo-Controlled, Phase Ⅰ/Ⅱ Clinical Trial, to Evaluate the Safety and Immunogenicity of the SARS-CoV-2 Inactivated Vaccine in Healthy Adults Aged 18~59 Years
• Brief Summary: This study is a randomized, double-blinded, and placebo controlled phase Ⅰ/Ⅱ clinical trial of the SARS-CoV-2 inactivated vaccine manufactured by Sinovac Research & Development Co., Ltd. The purpose of this study is to evaluate the safety and immunogenicity of the experimental vaccine in healthy adults aged 18~59 Years.
• Detailed Description: This study is a randomized, double-blinded, single-center, placebo-controlled phase Ⅰ/Ⅱ clinical trial in adults aged 18~59 years. The purpose of this study is to evaluate the immunogenicity and safety of the experimental SARS-CoV-2 inactivated vaccine. The experimental vaccine and placebo were both manufactured by Sinovac Research & Development Co., Ltd. A total of 744 subjects will be enrolled, with 144 at phase Ⅰ, and 600 at phase Ⅱ. Participant will be assigned to receive two doses of experimental vaccine or placebo on the schedule of day 0,14 or day 0,28.
• Study Type: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Prevention
• Condition: COVID-19

Intervention

• Biological: Two doses of medium dosage inactivated SARS-CoV-2 vaccine at the emergency vaccination schedule
  Two doses of medium dosage (600SU/0.5ml) experimental vaccine at the schedule of day 0,14
• Biological: Two doses of high dosage inactivated SARS-CoV-2 vaccine at the emergency vaccination schedule
  Two doses of high dosage (1200 SU/0.5ml) experimental vaccine at the schedule of day 0,14
• Biological: Two doses of placebo at the emergency vaccination schedule
  Two doses of placebo at the schedule of day 0,14
• Biological: Two doses of medium dosage inactivated SARS-CoV-2 vaccine at the routine vaccination schedule
  Two doses of medium dosage (600SU/0.5ml) experimental vaccine at the schedule of day 0,28
• Biological: Two doses of high dosage inactivated SARS-CoV-2 vaccine at the routine vaccination schedule
  Two doses of high dosage (1200 SU/0.5ml) experimental vaccine at the schedule of day 0,28
• Biological: Two doses of placebo at the routine vaccination schedule
  Two doses of placebo at the schedule of day 0,28

Study Arms

• Experimental: Emergency schedule & Medium dosage vaccine
  Two doses of medium dosage inactivated SARS-CoV-2 vaccine at the emergency vaccination schedule
  Intervention: Biological: Two doses of medium dosage inactivated SARS-CoV-2 vaccine at the emergency vaccination schedule
• Experimental: Emergency schedule & High dosage vaccine
  Two doses of high dosage inactivated SARS-CoV-2 vaccine at the emergency vaccination schedule
  Intervention: Biological: Two doses of high dosage inactivated SARS-CoV-2 vaccine at the emergency vaccination schedule
• Placebo Comparator: Emergency schedule & Placebo
  Two doses of placebo at the emergency vaccination schedule
  Intervention: Biological: Two doses of placebo at the emergency vaccination schedule
• Experimental: Routine schedule & Medium dosage vaccine
  Two doses of medium dosage inactivated SARS-CoV-2 vaccine at the routine vaccination schedule
  Intervention: Biological: Two doses of medium dosage inactivated SARS-CoV-2 vaccine at the routine vaccination schedule
• Experimental: Routine schedule & High dosage vaccine
  Two doses of high dosage inactivated SARS-CoV-2 vaccine at the routine vaccination schedule
  Intervention: Biological: Two doses of high dosage inactivated SARS-CoV-2 vaccine at the routine vaccination schedule
• Placebo Comparator: Routine schedule & Placebo
  Two doses of placebo at the routine vaccination schedule
  Intervention: Biological: Two doses of placebo at the routine vaccination schedule

• Publications *: Zhang Y, Zeng G, Pan H, Li C, Hu Y, Chu K, Han W, Chen Z, Tang R, Yin W, Chen X, Hu Y, Liu X, Jiang C, Li J, Yang M, Song Y, Wang X, Gao Q, Zhu F. Safety, tolerability, and immunogenicity of an inactivated SARS-CoV-2 vaccine in healthy adults aged 18-59 years: a randomised, double-blind, placebo-controlled, phase 1/2 clinical trial. Lancet Infect Dis. 2021 Feb;21(2):181-192. doi: 10.1016/S1473-3099(20)30843-4. Epub 2020 Nov 17.

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: April 16, 2020): 744
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: December 13, 2020
• Actual Primary Completion Date: July 10, 2020 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Healthy adults aged 18-59 years;
• Proven legal identity;
• Participants should be capable of understanding the informed consent form, and such form should be signed prior to enrolment ;

Exclusion Criteria:

• Travel history / residence history of Wuhan city and surrounding areas, or other communities with case reports within 14 days;
• History of contact with a SARS-CoV-2 infection (positive in nucleic acid test) within 14 days;
• Have contacted patients with fever or respiratory symptoms from Wuhan and surrounding areas, or from communities with case reports within 14 days;
• Have contacted patients with fever or respiratory symptoms from Wuhan and surrounding areas, or from communities with case reports within 14 days;
• Self-reported history of SARS;
• Self-reported history of new coronavirus infection;
• Positive in serum antibodies (IgG or IgM) screening of COVID-19;
• Positive in nasopharyngeal swabs or anal swabs through RT-PCR;
• Women who are breastfeeding, pregnant or planning to become pregnant during the study period;
• BMI≥35 kg/m2;
• History of asthma, history of allergy to the vaccine or vaccine components, or serious adverse reactions to the vaccine, such as urticaria, dyspnea, and angioedema;
• Congenital malformations or developmental disorders, genetic defects, severe malnutrition, etc.;
• Autoimmune disease or immunodeficiency / immunosuppression;
• Suffering from severe chronic diseases, severe cardiovascular diseases, hypertension and diabetes that cannot be controlled by drugs, liver and kidney diseases, malignant tumors, etc.;
• Severe neurological disease (epilepsy, convulsions or convulsions) or mental illness;
• Thyroid disease or history of thyroidectomy, spleenlessness, functional spleenlessness, spleenlessness or splenectomy resulting from any condition;
• Diagnosed abnormal blood coagulation function (eg, lack of blood coagulation factors, blood coagulopathy, abnormal platelets) or obvious bruising or blood coagulation;
• Immunosuppressive therapy, cytotoxic therapy, inhaled corticosteroids (excluding allergic rhinitis corticosteroid spray therapy, acute non-complicated dermatitis superficial corticosteroid therapy) in the past 6 months;
• Abnormal laboratory test results in the physical examination such as clinically significant abnormal hematology and biochemistry beyond the reference value range (only applicable to Phase I clinical trials);
• History of alcohol or drug abuse;
• Receipt of blood products within in the past 3 months;
• Receipt of other investigational drugs in the past 30 days;
• Receipt of attenuated live vaccines in the past 14 days;
• Receipt of inactivated or subunit vaccines in the past 7 days;
• Attacks of acute diseases or chronic diseases in the past 7 days;
• Axillary temperature >37.0°C;
• According to the investigator's judgment, the subject has any other factors that are not suitable for participating in the clinical trial.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 59 Years (Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: China

Administrative Information

• NCT Number: NCT04352608
• Other Study ID Numbers: PRO-nCOV-1001
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

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

• IPD Sharing Statement: Not Provided
• Responsible Party: Sinovac Biotech Co., Ltd ( Sinovac Research and Development Co., Ltd. )
• Study Sponsor: Sinovac Research and Development Co., Ltd.
• Collaborators: Not Provided

Investigators

• Principal Investigator: Fengcai Zhu, Doctor; Jiangsu Provincial Center for Disease Control and Prevention

• PRS Account: Sinovac Biotech Co., Ltd
• Verification Date: April 2020