This is a multicenter, randomized, double blind, parallel placebo controlled, phase 3 clinical trial to evaluate the protective efficacy, safety and immunogenicity of inactivated SARS-CoV-2 vaccines in healthy population 18 years old and above.
Product characteristics:
WIBP:
The inactivated SARS CoV 2 Vaccine (Vero cell) is prepared by inoculating Verda Reno cells
(Vero cell) with SARS CoV 2 WIV04 strain, culturing, harvesting, inactivating, clarifying,
concentrating, second inactivating, purifying and adding aluminum hydroxide adjuvant BIBP:
The inactivated SARS CoV 2 Vaccine (Vero cell) is prepared by inoculating Verda Reno cells
(Vero cell) with SARS CoV 2 HB02 strain, culturing, harvesting, inactivating, clarifying,
concentrating, purifying and adding aluminum hydroxide adjuvant. After vaccination, the body
can produce immune response to prevent diseases caused by SARS CoV 2.
Primary objective To evaluate the protective efficacy of inactivated SARS CoV 2 Vaccine (Vero
Cell) after full course of immunization in preventing diseases caused by the SARS CoV 2 in
healthy subjects aged 18 years old and above.
Study design:
This clinical trial is conducted in randomized, blind, placebo-controlled design. Total
sample size is 12,000, which are randomly allocated into investigational vaccine 1,
investigational vaccine 2 and placebo control group. Subjects with compatible symptoms, will
be excluded.
Immunization schedule: 2-doses of investigational vaccine or placebo are inoculated to the
deltoid muscle of the upper arm according to the Day 0 and day 21 (window for both days + 7
days), immunization schedule.
Safety observation After each dose of vaccination, the subject is observed for 30 minutes on
site, and local and systemic adverse events are collected. Within 0-30 21/28 days, the local
and systemic reactions of the subjects are actively followed up and recorded on the.
telephone follow-up contact form. Serious adverse events (SAE) will be daily monitored within
12 months after vaccination, and followed up, recorded and reported as required.
Observation of efficacy After the subjects are enrolled in the group, the monitoring of
SARS-CoV-2 infection cases will begin Planned and active follow-up is carried out on the
subjects, and a monitoring network is established in local medical and health institutions to
monitor SARS-CoV-2 infection-like cases in the subjects. Those diagnosed as suspected cases
by clinicians will be studied as epidemiological case, including nasopharyngeal swabs, sputum
and/or other lower respiratory secretions, venous blood in acute and convalescent stages are
collected. SARS-CoV-2 nucleic acid will be tested by RT-PCR method, and/or viral gene
sequencing. Subjects with positive nucleic acid, or/and convalescent serum antibodies
increased 4 fold or more than acute phase serum are confirmed cases of COVID-19. (refer to
case monitoring operation manual).
The incidence of confirmed SARS-CoV-2 disease in the three groups of study samples is
calculated and the epidemiological protection rate and confidence interval of SARS-CoV-2
inactivated vaccines against SARS-CoV-2 disease are analyzed.
Immunogenicity observation:
Immunogenicity (antibody response to inactivated SARS-CoV-2 vaccine / placebo) will be
evaluated in subjects V00001-V12000 on 14 days after 2nd dose (day 35) and 360 days after 2nd
dose (day 381). Subgroups of 1200 participants will be registered on 28 days after 2nd dose
(days 49), 180 days after 2nd dose ( day 201), to better precise the peak of neutralizing
antibodies
Case definition:
Cases will be further classified as:
Asymptomatic cases: No symptoms developed for 14 consecutive days after positive PCR testing.
Confirmed cases: On the basis of the clarification of the suspected case, the COVID-19 PCR
diagnosis is positive, or IgG antibodies in convalescent sera four times higher than
baseline.
Confirmed mild COVID-19 cases: The clinical symptoms were mild, and there was no sign of
pneumonia on imaging.
Confirmed moderate COVID-19 cases: Showing fever and respiratory symptoms with radiological
findings of pneumonia.
Confirmed severe COVID-19 cases: Confirmed COVID-19 case meeting any one of the following
criteria:
- Respiratory distress (RR≥30 breaths/min);
- Oxygen saturation≤93% at rest;
- Arterial partial pressure of oxygen (PaO2)/ fraction of inspired oxygen (FiO2)≦300mmHg
(1mmHg=0.133kPa);
- The clinical symptoms progressively worsened, and the chest imaging showed >50% obvious
lesion progression within 24-48 hours.
Confirmed Critical COVID-19 cases: Confirmed COVID-19 case meeting any one of the following
criteria:
- Respiratory failure and requiring mechanical ventilation;
- Shock;
- With other organ failure that requires ICU care;
- Death
Biological: Inactivated SARS CoV 2 vaccine (Vero cell) Wuhan/Beijing/Placebo
This clinical trial is conducted in randomized, blind, placebo controlled design Total sample size is 12 000, which are randomly allocated into investigational vaccine 1, investigational vaccine 2 and placebo control group.
Inclusion Criteria:
- Age range: Healthy subjects aged 18 years old and above
- By asking for medical history and physical examination, the investigator judged that
the health condition is well
- Female subjects of childbearing age are not nursing or pregnant at the time of
enrolment (negative urine pregnancy test), and do not plan to become pregnant within
the first 3 months after enrolment . Effective contraceptive measures have been taken
within 2 weeks before inclusion and continued for at least three month s after last
dose
- During the whole follow up period of the study, be able and willing to complete the
whole prescribed study plan.
- With self ability to understand the research procedures, with informed consent,
voluntarily sign an informed consent form, and be able to comply with the requirements
of the clinical study protocol.
Exclusion Criteria:
- SARS CoV 2 Infection Confirmed Cases, Suspected Cases or Asymptomatic Infection
- SARS CoV 2 Nucleic acid test positive
- Have a history of SARS , MERS infection (self report, on site inquiry
- Fever (axillary temperature > 37.0 ℃), dry cough, fatigue, nasal obstruction, runny
nose, pharyngeal pain, myalgia, diarrhea, shortness of breath and dyspnea occurred
within 14 days before vaccination
- Axillary body temperature > 37.0 ℃ before vaccination
- Previous severe allergic reactions to vaccination (such as acute allergic reactions,
urticaria, dyspnea, angioneurotic edema or abdominal pain) or allergy to known
ingredients of inactivated SARS CoV 2 vaccine have occurred.
- Have a history of convulsion, epilepsy, encephalopathy or mental illness or family
history
- Congenital malformations or developmental disorders, genetic defects, severe
malnutrition, etc.
- Severe liver and kidney diseases, uncontrollable hypertension (systolic blood pressure
≥ 140 mmHg, diastolic blood pressure ≥ 90 mmHg), diabetic complications, malignant
tumors, various acute diseases or acute attack period of chronic diseases
- Has been diagnosed with congenital or acquired immune deficiency, HIV infection,
lymphoma, leukemia or other autoimmune diseases
- Diseases known or suspected include severe respiratory diseases, severe cardiovascular
diseases, liver and kidney diseases, and malignant tumors. - Hist ory of coagulation
dysfunction (e.g. Coagulation factor deficiency, coagulation disease)
- Receiving anti TB therapy
- Patients receiving immunotherapy or inhibitor therapy within 3 months (continuous oral
or infusion for more than 14
- Live attenuated va ccine is inoculated within 1 month before this vaccination , other
vaccines are inoculated within 14 days before this vaccination
- Received blood products within 3 months before this vaccination
- Received other research drugs within 6 months before this vacc ination
- Investigator judged other circumstances that are not suitable for this clinical trial.
Av. Honorio Delgado 430, Urb. Ingeniería
San Martin De Porres, Lima, Peru
Coralith Garcia, MD, Principal Investigator
Universidad Peruana Cayetano Heredia