Trial NCT04412538
Publication Che Y, Clin Infect Dis, 2020
Dates: 01//06/2020 to 30/06/2020
Funding: Public/non profit (The National Key R&D Program of China, the Program of Chinese Academy of Medicine Science, and the Major Science and Technology Special Projects of Yunnan Province)
Conflict of interest: *
| Methods | |
| RCT | |
| Location :
Multicenter / China Follow-up duration (months): 1.41 | |
| • Medium dose at d0/14 (n = 150) • High dose at d0/14 (n = 150) • Placebo d0/14 (n = 75) • Medium dose at d0/28 (n = 150) • High dose at d0/28 (n = 150) • Placebo d0/28 (n = 75) | |
| Inclusion criteria | Healthy adults aged 18 to 59 years (including boundary values), both men and women; Proven legal identity; Participants should understand the contents of the informed consent form, the vaccine in this trial, voluntarily sign the informed consent form, and be capable of using thermometers, scales, and filling in diary cards and contact cards as required; Participants should be able to communicate well with investigators, understand and comply with the requirements of this trial; Axillary temperature ≤37.0 ℃ |
| Exclusion criteria | Contraindications for vaccination; History of allergy to vaccines or drugs; Immunization with any vaccine within 1 month; History of abnormal clinical manifestations and serious diseases to be excluded, including but not limited to nervous system, cardiovascular system, blood and lymphatic system, immune system, kidney, liver, gastrointestinal tract, respiratory system, metabolism, bones and other system diseases, and a history of malignant tumors; Those who developed acute disease within 2 weeks, or had symptoms of fever or upper respiratory tract infection within 7 days; Those who have a hereditary bleeding tendency or coagulation dysfunction, or a history of thrombosis or bleeding disorders; Surgical removal of spleen or other important organs for any reason; Those who have undergone surgery within 3 months before signing the informed consent, or those who plan to perform surgery during the trial or within 3 months after the end of the trial (including cosmetic surgery, dental and oral surgery). Those who donated or lost blood (≥400 mL) in the past 3 months, who received blood transfusion or use of blood products, or who planned blood donation during the trial; Receipt of other investigational or unregistered products (drugs, vaccines, biological product or devices) in the past 3 months, or plan to use other investigational or unregistered products during the study; Receipt of immunosuppressive therapy within 6 months before signing the informed consent form, such as long-term systemic glucocorticoid therapy (with systemic glucocorticoid therapy for more than 2 weeks within 6 months, such as prednisone or similar drugs) ), but local administration (such as ointment, eye drops, inhalation, or nasal spray) is allowed. The local administration should not exceed the dosage recommended in the instructions or have any signs of systemic exposure; The comprehensive physical examination does not meet the health standards, mainly including: (1) Those with abnormal vital signs (Pulse <55 beats per minute or> 100 beats per minute at rest, Systolic blood pressure ≥140mmHg or Diastolic blood pressure ≥90mmHg, breathing> 20 beats per minute or <12 beats per minute). (2) Those who tested positive for human immunodeficiency virus (HIV) antibody, hepatitis B surface antigen, hepatitis B e antigen, hepatitis C virus antibody, or Treponema pallidum antibody (tp-trust); Participants who have a positive pregnancy test, or are breastfeeding, or plan to become pregnant, or plan to donate sperm or eggs from the screening to 12 months after the second vaccination; Positive in SARS-CoV-2 nucleic acid screening or antibodies (IgG or IgM) screening; History of severe acute respiratory syndrome (SARS) or Middle East respiratory syndrome (MERS) or other coronavirus infection (HCoV-229E, HCoV-OC43, HCoV-NL63, HCoV-HKU1); History of contact with confirmed or suspected cases infected with SARS-CoV-2 within 1 month; Any other situations judged by investigators as not suitable for participating in this study. |
| Interventions | |
| Intervention
2 IM doses of 100-EU KMS-1 per dose on days 0, 14 2 IM doses of 150-EU KMS-1 per dose on days 0, 14 2 IM doses of 100-EU KMS-1 per dose on days 0, 28 2 IM doses of 150-EU KMS-1 per dose on days 0, 28 |
|
| Control
2 IM doses of 0.5 mL adjuvant in saline per dose on days 0, 142 IM doses of 0.5 mL adjuvant in saline per dose on days 0, 28 | |
| Participants | |
| Randomized 750 participants | |
| Characteristics of participants Type of participants: Healthy volunteers N=750 283 males Children: 0 Pregnant women: 0 Immunocompromized patients: 0 Mean age: 39.2 Age range: NR | |
| Description of participants Healthy SARS-CoV-2 serology/DNA negative adults in two centres in China | |
| Primary outcome | |
| In the register Adverse reactions/events rate [ Time Frame: 7 days after vaccination ]; Adverse reactions/events rate [ Time Frame: 28 days after vaccination ]; Seroconversion rate of Neutralizing antibodies against SARS-CoV-2 Phase IIa (Day 0, 14 schedule) [ Time Frame: 14 days after the second vaccination ]; Seroconversion rate of Neutralizing antibodies against SARS-CoV-2 Phase IIa (Day 0, 28 schedule) [ Time Frame: 28 days after the second vaccination ]; Seroconversion rate of IgG antibodies against SARS-CoV-2 Phase IIa (Day 0, 14 schedule) [ Time Frame: 14 days after the second vaccination ]; Seroconversion rate of IgG antibodies against SARS-CoV-2 Phase IIa (Day 0, 28 schedule) [ Time Frame: 28 days after the second vaccination ] | |
| In the report Seroconversion rates of the anti-SARS-CoV-2 neutralizing antibody and ELISA IgG antibody at days 14 (0, 14 procedure) and 28 (0, 28 procedure), respectively, after the boost immunization | |
| Variants description | |
| Variants | |
| Description | |
| Documents avalaible |
Protocol NR Statistical plan * Data-sharing stated:
NR |
| 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 paper, the study registry was used in data extraction and risk of bias assessment. Neither study protocol not statistical analysis plan was available at the time of data extraction. The reported results are from Phase II of a Phase I/II trial (NCT04412538). Based on data from Phase I, Phase II assessed medium and high doses of the vaccine, but not low doses. The study achieved its pre-stated sample size. There were few differences between the published article and the trial registry in population, procedures, interventions and outcomes. Cellular immune response was specified as an outcome in the trial registry but was not reported in the paper. |