Clinical trial NCT05069129: 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
Official title: 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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: COVID-19 Pneumonia
Coronavirus Infections
Keywords: COVID-19
Lead sponsor: National Vaccine and Serum Institute, China
Sponsor class: INDUSTRY
Collaborators: name: China National Biotec Group Company Limited
name: Lanzhou Institute of Biological Products Co., Ltd
name: Beijing Insitute of Biological Products Co., Ltd
First posted: 2021-10-06
Enrollment: 1848
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: The incidence and serverity of any adverse reactions
timeFrame: within 30 minutes after vaccination
measure: The incidence and serverity of solicited adverse events
timeFrame: within 30 minutes after vaccination
measure: The incidence and serverity of solicited adverse reactions
timeFrame: within 0-7 days after vaccination
measure: The incidence and severity of unsolicited adverse reactions
timeFrame: within 0-7 days after vaccination
measure: The incidence and serverity of solicited adverse reactions
timeFrame: within 8-30 days after vaccination
measure: The incidence and serverity of solicited adverse events
timeFrame: within 8-30 days after vaccination
measure: The incidence of SAE observed
timeFrame: after vaccination and up to 6 months after full course of immunization.
measure: The incidence of AESI observed
timeFrame: after vaccination and up to 6 months after full course of immunization
measure: GMT of subject's anti- SARS-CoV-2 neutralizing antibody
timeFrame: 15th day after vaccination
measure: GMT of subject's anti- SARS-CoV-2 neutralizing antibody
timeFrame: 30th day after vaccination
measure: Rate of 4-fold rise of anti- SARS-CoV-2 neutralizing antibody
timeFrame: 15th day after vaccination
measure: Rate of 4-fold rise of anti- SARS-CoV-2 neutralizing antibody
timeFrame: 30th day after vaccination
Secondary outcomes:
measure: Rate of GMT of subject's anti-SARS-CoV-2 IgG antibody
timeFrame: before vaccination
measure: Rate of GMT of subject's anti-SARS-CoV-2 IgG antibody
timeFrame: 30th day after the full course of vaccination
measure: Rate of 4-fold rise of anti- SARS-CoV-2 neutralizing antibody
timeFrame: before vaccination
measure: Rate of 4-fold rise of anti- SARS-CoV-2 neutralizing antibody
timeFrame: 30th day after the full course of vaccination
measure: GMI of subject's anti-SARS-CoV-2 IgG antibody
timeFrame: before vaccination
measure: GMI of subject's anti-SARS-CoV-2 IgG antibody
timeFrame: 30th day after the full course of vaccination
measure: Proportion of neutralizing antibody titer ≥ 1: 16, ≥ 1: 32 and ≥ 1: 64
timeFrame: before vaccination
measure: Proportion of neutralizing antibody titer ≥ 1: 16, ≥ 1: 32 and ≥ 1: 64
timeFrame: 30th day after the full course of vaccination
measure: Rate of Anti-SAR-CoR-2 neutralizing antibody
timeFrame: the 3th month, 6th month, 12th month, 18 month and 24th month after the full course of vaccination
measure: Rate of GMT of IgG antibody
timeFrame: the 3th month, 6th month, 12th month, 18 month and 24th month after the full course of vaccination
measure: Rate of the titer of neutralizing antibody ≥ 1: 16, ≥ 1: 32 and ≥ 1: 64
timeFrame: the 3th month, 6th month, 12th month, 18 month and 24th month after the full course of vaccination
measure: Rate of Anti-SAR-CoR-2 neutralizing antibody
timeFrame: the 6th month, 12th month after the full course of vaccination
measure: Rate of GMT of IgG antibody
timeFrame: the 6th month, 12th month after the full course of vaccination
measure: Rate of the titer of neutralizing antibody ≥ 1: 16, ≥ 1: 32 and ≥ 1: 64
timeFrame: the 6th month, 12th month after the full course of vaccination
Other outcomes:
measure: The vaccine efficay of recombinant COVID-19 vaccine (CHO cells) against COVID-19, severe cases and deaths
timeFrame: 14th day after vaccination
measure: Anti-SARS-CoV-2 neutralizing antibody
timeFrame: 3th month, 6th month, 9th month and 12th month after full course of immunization
measure: Anti-SARS-CoV-2 GMT of IgG antibody
timeFrame: 3th month, 6th month, 9th month and 12th month after full course of immunization
measure: Proportion of neutralizing antibody titer ≥ 1: 16, ≥ 1: 32 and ≥ 1: 64
timeFrame: 3th month, 6th month, 9th month and 12th month after full course of immunization
measure: 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
timeFrame: 15th day after full course of immunization
measure: To evaluate the vaccine efficacy of recombinant COVID-19 vaccine (CHO cells，NVSI-06-08) against different variants after sequential vaccination at different schedules
timeFrame: 15th day after full course of immunization
Locations:
city: Seha
country: United Arab Emirates
facility: Sheikh Khalifa Medical City
state: Abu Dhab
Study officials:
References:
citation: 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.