Trial NCT04352608
Publication Zhang Y, Lancet Infect Dis, 2020
Dates: 03/05/2020 to 05/05/2020
Funding: Mixed (National Key Research and Development Program, Beijing Science and Technology Program)
Conflict of interest: Yes
| Methods | |
| RCT | |
| Location :
Single center / China Follow-up duration (months): 1.41 | |
| • 3 μg at d0/14 (n = 120) • 6 μg at d0/14 (n = 120) • Placebo d0/14 (n = 60) • 3 μg at d0/28 (n = 120) • 6 μg at d0/28 (n = 120) • Placebo d0/28 (n = 60) | |
| Inclusion criteria | Healthy adults aged 18-59 years; Proven legal identity; Participants should be capable of understanding the informed consent form, and such form should be signed prior to enrolment |
| Exclusion criteria | Travel history / residence history of Wuhan city and surrounding areas, or other communities with case reports within 14 days; History of contact with a SARS-CoV-2 infection (positive in nucleic acid test) within 14 days; Have contacted patients with fever or respiratory symptoms from Wuhan and surrounding areas, or from communities with case reports within 14 days; Have contacted patients with fever or respiratory symptoms from Wuhan and surrounding areas, or from communities with case reports within 14 days; Self-reported history of SARS; Self-reported history of new coronavirus infection; Positive in serum antibodies (IgG or IgM) screening of COVID-19; Positive in nasopharyngeal swabs or anal swabs through RT-PCR; Women who are breastfeeding, pregnant or planning to become pregnant during the study period; BMI≥35 kg/m2; History of asthma, history of allergy to the vaccine or vaccine components, or serious adverse reactions to the vaccine, such as urticaria, dyspnea, and angioedema; Congenital malformations or developmental disorders, genetic defects, severe malnutrition, etc.; Autoimmune disease or immunodeficiency / immunosuppression; Suffering from severe chronic diseases, severe cardiovascular diseases, hypertension and diabetes that cannot be controlled by drugs, liver and kidney diseases, malignant tumors, etc.; Severe neurological disease (epilepsy, convulsions or convulsions) or mental illness; Thyroid disease or history of thyroidectomy, spleenlessness, functional spleenlessness, spleenlessness or splenectomy resulting from any condition; Diagnosed abnormal blood coagulation function (eg, lack of blood coagulation factors, blood coagulopathy, abnormal platelets) or obvious bruising or blood coagulation; Immunosuppressive therapy, cytotoxic therapy, inhaled corticosteroids (excluding allergic rhinitis corticosteroid spray therapy, acute non-complicated dermatitis superficial corticosteroid therapy) in the past 6 months; Abnormal laboratory test results in the physical examination such as clinically significant abnormal hematology and biochemistry beyond the reference value range (only applicable to Phase I clinical trials); History of alcohol or drug abuse; Receipt of blood products within in the past 3 months; Receipt of other investigational drugs in the past 30 days; Receipt of attenuated live vaccines in the past 14 days; Receipt of inactivated or subunit vaccines in the past 7 days; Attacks of acute diseases or chronic diseases in the past 7 days; Axillary temperature >37.0°C; According to the investigator's judgment, the subject has any other factors that are not suitable for participating in the clinical trial |
| Interventions | |
| Intervention
2 IM doses of 3μg per dose, on days 0, 14 2 IM doses of 6μg per dose, on days 0, 14 2 IM doses of 3μg per dose, on days 0, 28 2 IM doses of 6μg per dose, on days 0, 28 |
|
| Control
2 IM doses of 0.5 mL aluminum hydroxid per dose, on days 0, 142 IM doses of 0.5 mL aluminum hydroxid per dose, on days 0, 14 | |
| Participants | |
| Randomized 600 participants | |
| Characteristics of participants Type of participants: Healthy volunteers N=600 283 males Children: 0 Pregnant women: 0 Immunocompromized patients: 0 Mean age: 42.1 Age range: NR | |
| Description of participants Healthy SARS-CoV-2 serology/DNA negative adults in a single centre in China | |
| Primary outcome | |
| In the register 1) Safety indexes of adverse reactions [ Time Frame: From the beginning of the vaccination to 28 days after the whole schedule vaccination]; 2) Immunogenicity indexes of neutralizing-antibody seroconversion rates for the emergency vaccination schedule （day 0,14） [ Time Frame: The 14th day after two doses of vaccination]; 3) Immunogenicity indexes of neutralizing-antibody seroconversion rates for the routine vaccination schedule (day 0,28) [ Time Frame: The 28th day after two doses of vaccination ] | |
| In the report 1) Any adverse reactions within 28 days after each dose of study drug; 2) Seroconversion of neutralising antibodies to live SARS-CoV-2 at day 14 after the last dose in the days 0 and 14 vaccination cohort, or day 28 after the last dose in the days 0 and 28 vaccination cohort | |
| Documents avalaible |
Protocol NR Statistical plan * Data-sharing stated:
Yes, The data will be available immediately after publication and finalisation of the complete clinical study report for at least 6 months |
| 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 |
Some concerns |
| General comment | In addition to the published article, the trial registry was used in data extraction and assessment of risk of bias. Study protocol and statistical analysis plan were not available at the time of data extraction. The published article reports on phases 1 and 2 of the trial. Phase 2 achieved the target sample size specified in the trial registry. There were no major differences in population, interventions, or outcomes between the published article and registry. Phase 2 reported on 6 arms where randomization was carried out for high dose vaccine versus low dose vaccine versus placebo but not for shorter versus longer interval duration between doses. |