Clinical trial NCT04646590: A Phase III Clinical Trial to Determine the Safety and Efficacy of ZF2001 for Prevention of COVID-19
Official title: A Phase III Randomized, Double-blind, Placebo-controlled Clinical Trial in 18 Years of Age and Above to Determine the Safety and Efficacy of ZF2001, a Recombinant Novel Coronavirus Vaccine (CHO Cell) for Prevention of COVID-19
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Prevention of COVID-19
Safety and Efficacy
Lead sponsor: Anhui Zhifei Longcom Biologic Pharmacy Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2020-11-30
Enrollment: 28904
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: A randomized, double-blind, placebo-controlled international multicenter clinical trial design will be adopted. A total of 29,000 subjects aged 18 years and above are planned to be recruited, including 750 subjects aged 18-59 years and 250 subjects aged 60 years and above in China; 21,000 subjects aged 18-59 years and 7,000 subjects aged 60 years and above will be recruited outside China. Safety and immunogenicity will be evaluated among the Chinese subjects, and efficacy, immunogenicity and safety will be evaluated among the subjects outside China. Among them, 750 subjects aged 18-59 and 250 subjects aged 60 and above from outside China and all subjects from China will be selected as the immunogenicity subgroup for immunogenicity bridging study. The IgG levels of SARS-COV-2 neutralizing antibody and RBD protein binding antibody will be detected by blood sampling before vaccination, 14 days and 6 months after full course of vaccination to evaluate the immunogenicity and immune persistence.

Detailed description: After signing the informed consent form, the volunteers aged 18 years and above will receive the relevant examinations after an inquiry by investigator of the medical history (including COVID-19 history), recent medication(vaccine) history, allergy history and concomitant medications, and demographic data collection by the investigators, including physical examination (skin and mucous membranes, lymph nodes, head, neck, chest, abdomen, spine/limbs), novel Coronavirus (SARS-COV-2) nucleic acid test and antibody test, urine pregnancy (women of childbearing age) test, and vital signs (blood pressure, axillary/oral temperature, pulse) evaluation.

Screening eligible subjects will be 1:1 randomly assigned to the experimental group and the placebo control group, and vaccinated as per the 0, 1, 2 month immunization schedule.

All adverse events (AEs) up to 30 minutes after each dose of vaccination, all AEs from 0 to 7 days (including both solicited and unsolicited), and all AES from 8 to 30 days (unsolicited) will be collected; All serious adverse events (SAEs) will be collected from the first dose of vaccination to 12 months after the whole vaccination.

The incidence rate and efficacy of any severity of COVID-9 of any severity 14 days after whole vaccination.

Blood samples (5ml) will be collected before the first dose of vaccination and 14 days and 6 months after the whole course of vaccination to detect neutralizing antibody of SARS-COV-2 and protein binding antibody IgG of receptor binding region (RBD) .

Eligibility criteria: Inclusion Criteria:

* Population aged 18 years and above;
* Subjects voluntarily participate in the study and sign the informed consent form; and are able to provide valid identification, and understand and comply with the requirements of the trial protocol;
* Female subjects of childbearing age agree to use effective contraceptive measures from the beginning of the study to 2 months after full course of vaccination.

Exclusion Criteria:

* Suspected or confirmed as fever(axillary temperature ≥37.3°C / oral temperature ≥37.5°C) within 72 hours before the enrollment, or axillary temperature ≥37.3°C / oral temperature ≥37.5°C at the day of screening;
* Diastolic blood pressure ≥ 100mmhg and / or systolic blood pressure ≥ 150mmhg;
* Patients with previous history of a COVID-19;
* Detection of SARS-COV-2 nucleic acid or antibody is positive;
* Those who are suffering from the following diseases:

  1. With thrombocytopenia, any coagulation dysfunction or receiving anti-coagulatory treatment
  2. Congenital or acquired immune deficiency or autoimmune disease history; no spleen, or history of splenic surgery and trauma, or receiving immunomodulator treatment within 6 months, e.g., immunosuppressive dose of glucocorticoids (reference dose: equivalent to 20mg/ day of prednisone, over 1 week); Or monoclonal antibodies; Or thymosin; Or interferon etc.; However, topical application (such as ointment, eye drops, inhalers or nasal sprays) is permitted;
  3. Symptoms related to acute respiratory tract infection (such as sneezing, nasal congestion, runny nose, cough, sore throat, loss of taste, chills, shortness of breath, etc.);
  4. Cancer patients (except basal cell carcinoma).
* With a history of serious allergy to any vaccine or any composition of Investigational product (including: aluminum preparations), such as allergic shock, allergic throat edema, allergic purpura, thrombocytopenic purpura, localized allergic necrosis reaction (Arthus reaction), dyspnea and angioneuroedema;
* Inoculated with subunit vaccine and inactivated vaccine within 14 days before the first dosing of investigational vaccine, or inoculated with attenuated live vaccine within 30 days;
* Previous receiving blood transfusion or blood relevant products (including immunoglobulin) within 3 months, or planning to receive such products from the starting of study to \<6 months after the whole-course inoculation;
* Have participated in or are participating in other covid-19 related clinical trials;
* Women in breastfeeding period or in pregnant period (including women at childbearing age with positive result of urine pregnancy test);
* Considered by investigators as any disease or state possibly making the subject at unacceptable risk; not conforming to the requirements of study protocol; interference of assessment of reactions of vaccine.

Primary outcomes:
measure: The endpoint of efficacy study
timeFrame: 14 days to one year after whole vaccination
measure: The endpoint of safety study
timeFrame: From the first dose of vaccination until 30 days after full course of vaccination
measure: The endpoint of safety study
timeFrame: From the first dose of vaccination until 12 months after full course of vaccination
Secondary outcomes:
measure: The endpoint of efficacy study
timeFrame: Up to one year after the vaccination
measure: Endpoint of immunogenicity and immune persistence study
timeFrame: At 14 days and 6 months after full course of vaccination
Other outcomes:
Locations:
city: Changsha
country: China
facility: Hunan Provincial Center for Disease Control and Prevention
state: Hunan
city: Guayaquil
country: Ecuador
facility: Biodimed Guayaquil Clinical Research Center
state: Guayas
city: Quito
country: Ecuador
facility: Biodimed Alemania Clinical Research Center
state: Pichincha
city: Quito
country: Ecuador
facility: Biodimed Eloy Alfaro Clinical Research Center
state: Pichincha
city: Jakarta
country: Indonesia
facility: Fkui-Rscm
state: Daerah Khusus Ibukota Jakarta
city: Bandung
country: Indonesia
facility: FK Unpad/RSHS
state: Jawa Barat
city: Faisalabad
country: Pakistan
facility: Aziz Fatimah Hospital
state: Punjab
city: Lahore
country: Pakistan
facility: Avicenna Hospital
state: Punjab
city: Lahore
country: Pakistan
facility: Central Park Teaching Hospital
state: Punjab
city: Lahore
country: Pakistan
facility: National Hospital & Medical Center
state: Punjab
city: Lahore
country: Pakistan
facility: University of Health Sciences
state: Punjab
city: Rawalpindi
country: Pakistan
facility: Al-Shifa Trust Eye Hospital
state: Punjab
city: Karachi
country: Pakistan
facility: Indus Hospital and Health Network
state: Sindh
city: Islamabad
country: Pakistan
facility: Shaheed Zulfiqar Ali Bhutto Medical University
city: Tashkent
country: Uzbekistan
facility: Family Hospital No.15
city: Tashkent
country: Uzbekistan
facility: GUVD Poliklinika
city: Tashkent
country: Uzbekistan
facility: IIV Markaziy Poliklinika
city: Tashkent
country: Uzbekistan
facility: Toshkent viloyat IIV Poliklinika
Study officials:
affiliation: Hunan Provincial Center for Disease Control and Prevention
name: Fangjun Li, Bachelor
role: PRINCIPAL_INVESTIGATOR
References:
citation: Dai L, Gao L, Tao L, Hadinegoro SR, Erkin M, Ying Z, He P, Girsang RT, Vergara H, Akram J, Satari HI, Khaliq T, Sughra U, Celi AP, Li F, Li Y, Jiang Z, Dalimova D, Tuychiev J, Turdikulova S, Ikram A, Flores Lastra N, Ding F, Suhardono M, Fadlyana E, Yan J, Hu Z, Li C, Abdurakhmonov IY, Gao GF; ZF2001 Global Trial Group. Efficacy and Safety of the RBD-Dimer-Based Covid-19 Vaccine ZF2001 in Adults. N Engl J Med. 2022 Jun 2;386(22):2097-2111. doi: 10.1056/NEJMoa2202261. Epub 2022 May 4.