Clinical trial NCT04612972: Efficacy, Safety and Immunogenicity of Inactivated SARS-CoV-2 Vaccines (Vero Cell) to Prevent COVID-19 in Healthy Adult Population In Peru Healthy Adult Population In Peru
Official title: Ensayo Clínico de Fase III, Aleatorio, Doble Ciego y Controlado Con Placebo Paralelo, Para Evaluar la Seguridad y la Eficacia Protectora de la Vacuna Inactivada Contra el SARS-CoV-2 en la Población Sana de 18 años o más, en Perú
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: COVID-19
Lead sponsor: Universidad Peruana Cayetano Heredia
Sponsor class: OTHER
Collaborators: name: National University of San Marcos, Peru
First posted: 2020-11-03
Enrollment: 12000
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Arm 1:Investigational vaccine 1:

Inactivated SARS-CoV-2 vaccine (Vero cell) Manufacturer: Wuhan Institute of Biological Products Co., Ltd. Wuhan Institute of Virology, Chinese Academy of Sciences Specification: 200WU/dose for per human use, 0.5 mL/ dose

Arm 2: Investigational vaccine 2:

Inactivated SARS-CoV-2 vaccine (Vero cell) Manufacturer: Beijing Institute of Biological Products Co., Ltd. Specification: 4μg/dose for per human use, 0.5 mL/ dose

Arm 3: Placebo Product name: Placebo/Aluminum Adjuvant of Inactivated SARS-CoV-2 vaccine Active Ingredient: None; Virus Contents: None Adjuvant: aluminum hydroxide Manufacturer: Wuhan Institute of Biological Products Co., Ltd. Specification: 0.5 mL/ dose, 0.5mL for per human use
Primary purpose: PREVENTION

Brief summary: 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.

Detailed description: 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

Eligibility criteria: 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.

Primary outcomes:
measure: Proportion of confirmed Covid-19 cases in the two vaccine groups and the placebo group.
timeFrame: One year beginning on day 14 after the second dose of immunization
Secondary outcomes:
measure: Proportion of severe cases of SARS CoV 2 pneumonia and deaths in the two vaccine groups and the placebo group.
timeFrame: One year beginning on day 14 after the second dose of immunization
measure: Incidence of any adverse reactions/events
timeFrame: 12 months
Other outcomes:
measure: Comparison of levels of neutralizing antibodies in infected versus non infected participants
timeFrame: After 14 days after 2 doses of immunization
measure: Number of ADE/VED cases
timeFrame: 28days after full course of immunization.
measure: 4-fold growth rate, GMT and GMI of anti-SARS-CoV-2 neutralizing antibody at day 28
timeFrame: 28days after full course of immunization.
measure: GMT of anti-SARS-CoV-2 neutralizing antibody at 6 and 12 months
timeFrame: 6th month and 12th month after 2 doses of immunization.
Locations:
city: San Martin De Porres
country: Peru
facility: Av. Honorio Delgado 430, Urb. Ingeniería
state: Lima
Study officials:
affiliation: Universidad Peruana Cayetano Heredia
name: Coralith Garcia, MD
role: PRINCIPAL_INVESTIGATOR
References: