Trial ChiCTR2100051391
Publication Xia N, Research Square, 2023
Dates: 2021-12-16 to 2022-05-31
Funding: Mixed (National Science and Technology Major731
Project, National Natural Science Foundation of
China , Fujian Provincial Science and Technology Plan Project,Provincial Natural Science Foundation of Fujian, Xiamen Science and Technology Plan Special Projects, Ministry of Education, Xiamen University,Bill & Melinda Gates
Foundation and by Beijing Wantai Biological Pharmacy Enterprise)
Conflict of interest: no COI
| Methods | |
| RCT | |
| Location :
Multicenter / Multinational Follow-up duration (months): 6 | |
| CA4-dNS1-nCoV-RBD (n = 8600) Placebo (n = 8610) | |
| Inclusion criteria | Aged ≥18 years old at the time of enrollment; Be able to comply with the requirements of clinical study protocol and complete all trial procedures, and sign informed consent form; Those who have received at least one dose of other COVID-19 vaccines (marketed or investigational) with an interval of ≥ 6 months between the last dose and the date when the subjects sign the informed consent for this study; Those who are negative for HIV screening (depending on the relevant policy of the country where the trial is conduct, if qualification for HIV testing is required in the country, this information will be obtained mainly by inquiry while protecting the subject’s privacy); Fertile males and females of childbearing potential who are willing to take appropriate contraceptive measures from signing ICF to 3 months after the last dose, including abstinence or effective contraceptive measures (e.g., intrauterine or implantable contraceptive devices, oral contraception, combination of contraceptive diaphragm or condom with contraceptive gel); women of childbearing potential should be negative for pregnancy test on the day of vaccination (if applicable). Healthy people or people with a mild underlying disease that has remained stable without exacerbation (not requiring hospitalization or without major modification of the treatment regimen) within at least 3 months prior to inclusion in the |
| Exclusion criteria | Prior history of COVID-19, or SARS-CoV-2 RT-PCR-positive at screening;Pregnant or lactating women; Fever on the day of vaccination or within 3 days prior to vaccination (oral temperature ≥37.5℃/ear temperature ≥ 37.5℃ / axillary temperature ≥37.3℃); Those who had any acute disease in the past 5 days that requires systemic antibiotic or antiviral treatment (including but not limited to the use of anti-influenza virus drugs such as Tamiflu, Relenza, Symmetrel or Flumadine); Those who had low immune function caused by immunodeficiency diseases, diseases of important organs, cancer, and immune diseases (e.g., Guillain Barre syndrome, systemic lupus erythematosus, rheumatoid arthritis, alienia or splenectomy caused by any condition, and other immune disease that may affect immune response at the investigator’s discretion); Long-term use (defined as ≥14 days) of immunosuppressants or other immunomodulators (for glucocorticoids, e.g., ≥10 mg/day prednisone or equivalent dose; inhaled and topical steroids are allowed) within 6 months prior to the first vaccination; History of hemorrhagic diseases (e.g., factor deficiency, thrombocytopenia or other coagulation disorders), or hemorrhagic tendency, or continuous requirement of anticoagulants; Having been injected with immunoglobulins and/or blood products within 3 months before receiving the investigational vaccine; Received subunit or inactivated vaccine within 14 days before vaccination, or received live attenuated vaccine within 28 days before vaccination; Participation in a clinical trial of another product within 1 month prior to vaccination, or planning to participate in a clinical trial of another product during the study; Having a history of severe allergic reactions or severe adverse reactions from previous immunizations, or allergy to any component of the investigational vaccine; Patients deemed by the investigator as unsuitable for using nasal spray (those with severe rhinitis or nasal deformities, etc.); Planning to relocate permanently from the current area prior to the completion of the study or to leave the current area for a long period (preventing compliance with the prescribed visit schedule) during the study visits; Other conditions that the investigators consider unsuitable for this clinical study. |
| Interventions | |
| Intervention
2 IN doses of 0.2×10^7 cell culture infective dose 50% (CCID50) dNS1-RBD, 14 days apart, at least 6 months (median 201 days) after any COVID-19 prime vaccine. |
|
| Control
2 IN doses of placebo, 14 days apart, at least 6 months (median 201 days) after any COVID-19 prime vaccine. | |
| Participants | |
| Randomized 17210 participants | |
| Characteristics of participants Type of participants: Adults N=17210 7795 males Children: 0 Pregnant women: 0 Immunocompromized patients: 0 Mean age: Age range: 18-89 | |
| Description of participants Adultsincluding healthy and mild stable co-morbidities without prior COVID-19 history in 33 centres in Philippines, South Africa, Colombia and Vietnam | |
| Primary outcome | |
| In the register 1) Virologically confirmed (RT-PCR-positive) symptomatic COVID-19 cases of any severity that occurs for the first time at least 14 days (= 15 days) after the second vaccination; 2) All serious adverse events (SAEs), other medically attended AEs (MAAEs), and adverse events of special interest (AESIs) from the first dose to 12 months after the second dose in all subjects; 3) All solicited adverse events within 7 days following the first and second vaccinations in all subjects; 4) All unsolicited adverse events that occur during the interval between doses and within 30 days after the second vaccination in all subjects. | |
| In the report Serious adverse events (SAE), medically attended adverse events (MAAE) and adverse events of special interest (AESI) from day 0 (after the first dose) through 12 months after the final dose; solicited adverse events (AE) for 7 days after each dose; and unsolicited adverse events for 30 days after each dose; Symptomatic COVID-19 confirmed by reverse-transcriptase-polymerase-chain-reaction (RT-PCR) test occurring at least 14 days after the second dose in the per-protocol population (participants who were followed-up for at least two weeks after the second dose and had no major protocol deviatiations) | |
| Variants description | |
| Variants | |
| Description From report: "Here, we report safety and efficacy data from a multi-centre randomized, double-blind, placebo- controlled phase 3 clinical trial of Pneucolin® (two doses, 14 days apart) in adults (18 years and older) during the Omicron circulation. | |
| Documents avalaible |
Protocol NR Statistical plan * Data-sharing stated:
Yes |
| 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 | n addition to the pre-print article, the study registry was used in data extraction and risk of bias assessment. Preliminary analysis as of the cutoff date July 31, 2022. Extracted here only the stratum of participants with COVID-19 vaccination history.Included participants might have been previously vaccinated with 1, 2 3 or 4 doses of COVID-19 vaccine before receiving the intervention.The target sample size specified in the registry for both strata combined (N=31,038) was achieved. There is no change from the trial registration in the intervention and control treatments. |