Clinical Trial on Sequential Immunization of Recombinant COVID-19 Vaccine (CHO Cells,NVSI-06-08) and Inactivated COVID-19 Vaccine (Vero Cells) in Population Aged 18 Years and Above

A Randomized, Controlled Phase I and Sequential Study to Evaluate the Safety and Immunogenicity Following Immunization of GEN2-Recombinant COVID-19 Vaccine (CHO Cells,NVSI-06-08) and Inactivated COVID-19 Vaccine (Vero Cells) in Population Aged 18 Years and Above

This is randomized, blinded and controlled design. Among the randomly selected subjects who have been vaccinated with two doses of Inactivated COVID-19 vaccine (Vero cell), based on a step-wise approach, the subjects will receive one dose of recombinant COVID-19 vaccine sequentially at different shedules of 4-6 months, 7-9 months and >9 months after two doses of vaccination, and the subjects vaccinated at different schedules will be randomly assigned to different sequential immunization groups. At the same time, each sequential immunization group will be matched with a control group with the inactivated COVID-19 vaccine (vero cells) as the booster dose.

Study Overview

• Status: Recruiting
• Conditions: Coronavirus Infections; COVID-19 Pneumonia
• Intervention / Treatment: Biological: Recombinant COVID-19 Vaccine (CHO cell，NVSI-06-08); Biological: Inactivated COVID-19 vaccine (Vero cells); Biological: 3 doses Recombinant COVID-19 Vaccine (CHO cell，NVSI-06-08)

• Study Type: Interventional
• Enrollment (Anticipated): 1848
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United Arab Emirates
  • Abu Dhab
    • Seha, Abu Dhab, United Arab Emirates, 519000
      • Recruiting
      • Sheikh Khalifa Medical City

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age range: populations aged 18 years and above;
• Judged by the investigator that the health condition is well after inquiry and physical examination;
• Vaccinated with 2 doses of CNBG inactivated COVID-19 vaccine according to the product insert（sequential clinical trial group）
• Never vaccinated COVID-19 vaccine（safety observation group）;
• Female subjects who are not nursing or pregnant at the time of enrolment (negative urine pregnancy test) and have no family planning within the first 3 months after enrolment. Effective contraceptive measures have been taken within 2 weeks before inclusion.
• During the whole follow-up period of the study, be able and willing to complete the whole prescribed study plan; Self has ability to understand the study procedures, the informed consent & voluntarily sign an informed consent form and is able to comply with the requirements of the clinical study protocol.

Exclusion Criteria:

• Confirmed cases, suspected cases or asymptomatic cases of COVID-19;
• With a history of SARS and MERS infection (self-report, on-site inquiry);
• Has vaccinated with any vaccine other than one or more doses of CNBG inactivated COVID-19 vaccine;
• Axillary temperature ≥ 37.3 ℃ (forehead temperature ≥ 37.8 ℃);
• Previous severe allergic reactions to vaccination (such as acute allergic reactions, urticaria, dyspnea, angioneurotic edema or abdominal pain) or allergy to known components of recombinant COVID-19 vaccine;
• Allergic to any component of the study vaccine (e.g. aluminum, histidine, etc.)
• Known or suspected diseases include：Severe respiratory diseases, severe liver and kidney diseases, hypertension (systolic blood pressure ≥ 150 mmHg, diastolic blood pressure ≥ 90 mmHg), diabetic complications, malignant tumors, various acute diseases or acute attacks of chronic diseases;
• Has been diagnosed with congenital or acquired immunodeficiency, HIV infection, lymphoma, leukemia or other autoimmune diseases;
• Has a history of convulsions, epilepsy, encephalopathy，long term history of alcohol and drug abuse, history of thyroidectomy, infectious diseasesor mental illness or family history（lineal）;
• With Congenital malformation or developmental disorder, genetic defect, severe malnutrition, etc.;
• Has a history of coagulation dysfunction (e.g. coagulation factors deficiency and coagulation diseases);
• Absence of spleen or splenectomy, functional absence of spleen caused by any condition
• Anti -TB (TB) treatment is under way.
• Patients receiving immunoenhancement or inhibitor therapy within 3 months (continuous oral or IV administration for more than 14 days);
• Received blood products before within 3 months before vaccination;
• Received other investigational drugs within 6 months before vaccination;
• Plan to move before the end of the study or leave the local area for a long time during the scheduled study visit
• Other circumstances judged by investigators that are not suitable for this clinical trial

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Subject last vaccination time is within 4-6 months（sequential clinical trial group）; Subject have been vaccinated with two doses of Inactivated COVID-19 vaccine (Vero cell).The last vaccination time is within 4-6 months	Biological: Recombinant COVID-19 Vaccine (CHO cell，NVSI-06-08); Intramuscular injection of Recombinant COVID-19 Vaccine (CHO cell，NVSI-06-08) in the deltoid muscle of the upper arm; Biological: Inactivated COVID-19 vaccine (Vero cells); Intramuscular injection of Inactivated COVID-19 vaccine (Vero cells) in the deltoid muscle of the upper arm
EXPERIMENTAL: Subject last vaccination time is within 7-9 months（sequential clinical trial group）; Subject have been vaccinated with two doses of Inactivated COVID-19 vaccine (Vero cell).The last vaccination time is within 91-180 days 7-9 months	Biological: Recombinant COVID-19 Vaccine (CHO cell，NVSI-06-08); Intramuscular injection of Recombinant COVID-19 Vaccine (CHO cell，NVSI-06-08) in the deltoid muscle of the upper arm; Biological: Inactivated COVID-19 vaccine (Vero cells); Intramuscular injection of Inactivated COVID-19 vaccine (Vero cells) in the deltoid muscle of the upper arm
EXPERIMENTAL: Subject last vaccination time more than 9 months（sequential clinical trial group）; Subject have been vaccinated with two doses of Inactivated COVID-19 vaccine (Vero cell).The last vaccination time more than 9 months	Biological: Recombinant COVID-19 Vaccine (CHO cell，NVSI-06-08); Intramuscular injection of Recombinant COVID-19 Vaccine (CHO cell，NVSI-06-08) in the deltoid muscle of the upper arm; Biological: Inactivated COVID-19 vaccine (Vero cells); Intramuscular injection of Inactivated COVID-19 vaccine (Vero cells) in the deltoid muscle of the upper arm
EXPERIMENTAL: Safety Observation Group; Subject have been vaccinated with three doses of Recombinant COVID-19 Vaccine (CHO Cells,NVSI-06-08) on 0，30，60 days	Biological: 3 doses Recombinant COVID-19 Vaccine (CHO cell，NVSI-06-08); Intramuscular injection of Recombinant COVID-19 Vaccine (CHO cell，NVSI-06-08) in the deltoid muscle of the upper arm on 0，30，60 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The incidence and severity of unsolicited adverse reactions	within 0-7 days after vaccination
The incidence and serverity of any adverse reactions	within 30 minutes after vaccination
The incidence and serverity of solicited adverse events	within 30 minutes after vaccination
The incidence and serverity of solicited adverse reactions	within 0-7 days after vaccination
The incidence and serverity of solicited adverse reactions	within 8-30 days after vaccination
The incidence and serverity of solicited adverse events	within 8-30 days after vaccination
The incidence of SAE observed	after vaccination and up to 6 months after full course of immunization.
The incidence of AESI observed	after vaccination and up to 6 months after full course of immunization
GMT of subject's anti- SARS-CoV-2 neutralizing antibody	15th day after vaccination
GMT of subject's anti- SARS-CoV-2 neutralizing antibody	30th day after vaccination
Rate of 4-fold rise of anti- SARS-CoV-2 neutralizing antibody	15th day after vaccination
Rate of 4-fold rise of anti- SARS-CoV-2 neutralizing antibody	30th day after vaccination

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of GMT of subject's anti-SARS-CoV-2 IgG antibody		before vaccination
Rate of GMT of subject's anti-SARS-CoV-2 IgG antibody		30th day after the full course of vaccination
Rate of 4-fold rise of anti- SARS-CoV-2 neutralizing antibody		before vaccination
Rate of 4-fold rise of anti- SARS-CoV-2 neutralizing antibody		30th day after the full course of vaccination
GMI of subject's anti-SARS-CoV-2 IgG antibody		before vaccination
GMI of subject's anti-SARS-CoV-2 IgG antibody		30th day after the full course of vaccination
Proportion of neutralizing antibody titer ≥ 1: 16, ≥ 1: 32 and ≥ 1: 64		before vaccination
Proportion of neutralizing antibody titer ≥ 1: 16, ≥ 1: 32 and ≥ 1: 64		30th day after the full course of vaccination
Rate of Anti-SAR-CoR-2 neutralizing antibody	only sequential clinical trial group	the 3th month, 6th month, 12th month, 18 month and 24th month after the full course of vaccination
Rate of GMT of IgG antibody	only sequential clinical trial group	the 3th month, 6th month, 12th month, 18 month and 24th month after the full course of vaccination
Rate of the titer of neutralizing antibody ≥ 1: 16, ≥ 1: 32 and ≥ 1: 64	only sequential clinical trial group	the 3th month, 6th month, 12th month, 18 month and 24th month after the full course of vaccination
Rate of Anti-SAR-CoR-2 neutralizing antibody	only Safety Observation Group	the 6th month, 12th month after the full course of vaccination
Rate of GMT of IgG antibody	only Safety Observation Group	the 6th month, 12th month after the full course of vaccination
Rate of the titer of neutralizing antibody ≥ 1: 16, ≥ 1: 32 and ≥ 1: 64	only Safety Observation Group	the 6th month, 12th month after the full course of vaccination

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
The vaccine efficay of recombinant COVID-19 vaccine (CHO cells) against COVID-19, severe cases and deaths		14th day after vaccination
Anti-SARS-CoV-2 neutralizing antibody		3th month, 6th month, 9th month and 12th month after full course of immunization
Anti-SARS-CoV-2 GMT of IgG antibody		3th month, 6th month, 9th month and 12th month after full course of immunization
Proportion of neutralizing antibody titer ≥ 1: 16, ≥ 1: 32 and ≥ 1: 64		3th month, 6th month, 9th month and 12th month after full course of immunization
The vaccine efficacy of recombinant COVID-19 vaccine (CHO cells，NVSI-06-08) against COVID-19, severe cases and deaths aged 18 years and above		15th day after full course of immunization
To evaluate the vaccine efficacy of recombinant COVID-19 vaccine (CHO cells，NVSI-06-08) against different variants after sequential vaccination at different schedules	only sequential clinical trial group	15th day after full course of immunization

Collaborators and Investigators

• Sponsor: National Vaccine and Serum Institute, China
• Collaborators: China National Biotec Group Company Limited; Lanzhou Institute of Biological Products Co., Ltd; Beijing Insitute of Biological Products Co., Ltd

Publications and helpful links

General Publications

• Kaabi NA, Yang YK, Du LF, Xu K, Shao S, Liang Y, Kang Y, Su JG, Zhang J, Yang T, Hussein S, ElDein MS, Yang SS, Lei W, Gao XJ, Jiang Z, Cong X, Tan Y, Wang H, Li M, Mekki HM, Zaher W, Mahmoud S, Zhang X, Qu C, Liu DY, Zhang J, Yang M, Eltantawy I, Hou JW, Lei ZH, Xiao P, Wang ZN, Yin JL, Mao XY, Zhang J, Qu L, Zhang YT, Yang XM, Wu G, Li QM. Safety and immunogenicity of a hybrid-type vaccine booster in BBIBP-CorV recipients in a randomized phase 2 trial. Nat Commun. 2022 Jun 27;13(1):3654. doi: 10.1038/s41467-022-31379-0.

Study record dates

Study Major Dates

• Study Start (ACTUAL): October 14, 2021
• Primary Completion (ANTICIPATED): December 1, 2023
• Study Completion (ANTICIPATED): February 1, 2024

Study Registration Dates

• First Submitted: October 3, 2021
• First Submitted That Met QC Criteria: October 5, 2021
• First Posted (ACTUAL): October 6, 2021

Study Record Updates

• Last Update Posted (ACTUAL): February 1, 2023
• Last Update Submitted That Met QC Criteria: January 30, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Keywords: COVID-19
• Additional Relevant MeSH Terms: Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19; Coronavirus Infections; Physiological Effects of Drugs; Immunologic Factors; Vaccines
• Other Study ID Numbers: CNBG-REC-2021003

Drug and device information, study documents

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