Trial NCT04646590
Publication Dai L, N Engl J Med, 2022
Dates: 2020-12-12 to 2021-12-15
Funding: Mixed (The National Science and Technology Major Project; the National Natural Science Foundation of China; the Chinese Academy of Sciences; Anhui Zhifei Longcom Biopharmaceutical.)
Conflict of interest: Yes
| Methods | |
| RCT | |
| Location :
Multicenter / Uzbekistan, Indonesia, Pakistan, Ecuador, China. Follow-up duration (months): 12 | |
| 25 mcg ZF2001 (n = 14453) Placebo (adjuvant) (n = 14451) |
|
| Inclusion criteria | 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: thrombocytopenia, any coagulation dysfunction or receiving anti-coagulatory treatment, 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; 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.); 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. |
| Interventions | |
| Intervention
3 IM doses of 25 mcg ZF2001 vaccine, each 30 days apart |
|
| Control
3 IM doses of adjuvant placebo, each 30 days apart | |
| Participants | |
| Randomized 28904 participants | |
| Characteristics of participants Type of participants: Adults N=28904 19521 males Children: 0 Pregnant women: 0 Immunocompromized patients: 0 Mean age: Age range: 18-92 | |
| Description of participants Adults 18 years of age or older with no history of Covid-19, positive tests for SARS-CoV-2 exposure or vaccination, or of congenital or acquired immune deficiency or autoimmune disease at 32 clinical centers across Uzbekistan, Indonesia, Pakistan, Ecuador and China. | |
| Primary outcome | |
| In the register 1. The number of any severity of COVID-9 cases 14 days to one year after whole vaccination; 2. Adverse events from the first dose of vaccination until 30 days after full course of vaccination; 3. Serious adverse events from the first dose of vaccination until 12 months after full course of vaccination. | |
| In the report Real-time PCR–confirmed symptomatic Covid-19 occurring at least 7 days after the third dose. | |
| Variants description | |
Variants
| |
| Description Delta. Indirect evidence. To 15th December 2021, 626/738 outcome cases yielded genotyping results. Of these, 454/626 (72.5%) were Delta. | |
| Documents avalaible |
Protocol Yes. In English Statistical plan Yes Data-sharing stated:
Yes, With publication |
| Risk of bias Overall The overall risk of bias reported in the table corresponds to the highest risk of bias for the outcomes assessed for the systematic review |
Variant delta: Some concerns |
| General comment | In addition to the published article, the trial registry, protocol, statistical analysis plan and supplementary appendices were used in data extraction and assessment of risk of bias. The article presented interim analyses for a study with ongoing follow-up. There were no important differences between protocol/registry and published report in population, procedures, interventions or outcomes for efficacy and safety outcomes. The protocol and registry report immunogenicity outcomes, but none were reported in this paper. The trial (n = 28,904) achieved the target sample size reported in the article (n = 28,000), but not the target sample size in the registry (n = 29,000). |