Trial NCT04495933
Publication Chappell K, Lancet, 2021
Dates: 2020-06-23 to 2020-08-17
Funding: Public/non profit (Coalition for Epidemic Preparedness Innovations; National Health and Medical Research Council, Queensland Government, and philanthropic sources.)
Conflict of interest: Yes
| Methods | |
| RCT | |
| Location :
Single center / Australia Follow-up duration (months): 1.84 | |
| •Placebo, 2 doses (n=24) •5-mcg SARS-CoV-2 Sclamp, 2 doses (n=24) •15-mcg SARS-CoV-2 Sclamp, 2 doses (n=24) •45-mcg SARS-CoV-2 Sclamp, 2 doses (n=24) •45-mcg SARS-CoV-2 Sclamp, 1 dose followed by placebo (n=24) |
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| Inclusion criteria | Healthy male or non-pregnant female; ≥18 and ≤55 years of age ; BMI >18 and <34.0 kg/m2 and body weight ≥50.0 kg for males and ≥45.0 kg for females ; absence of clinically significant history of neurological, endocrine, cardiovascular, respiratory, haematological, immunological, psychiatric, gastrointestinal, renal, hepatic, and metabolic disease ; Non-smokers or social smokers (defined as the equivalent of fewer than 10 cigarettes per week) ; able and willing to use at least 2 highly effective methods of contraception commencing at enrolment, during the study and for 3 months after last treatment administration ; WOCBP must have a negative urine pregnancy test prior to receiving each dose ; able to attend all visits for the duration of the study and to comply with all study procedures according to the study schedule ; informed consent. |
| Exclusion criteria | Any clinically significant abnormality or vital sign abnormality at physical examination, clinically significant abnormal laboratory test results or positive test for HIV, hepatitis B, or hepatitis C found during medical screening ; any acute or chronic ongoing illness which, in the judgement of the investigator, may preclude the subject's participation ; an active COVID-19 infection (positive COVID-19 test: nasal/oropharyngeal swab and/or positive serum antibody response) at screening, or Day 1, or has been in close contact with someone who has an active COVID-19 infection, or has recovered from a previous COVID-19, SARS-CoV-1, or MERS infection ; Positive pregnancy, urine drug screen, or alcohol breath test at screening ; Known history of allergic reactions or hypersensitivity to vaccines, or to any excipient in the formulation (including the adjuvant, MF59C.1) ; Presence of a known, or suspected, impairment of the immune system including, but not limited to, HIV, autoimmune disorders, immunosuppressant therapy, and diabetes mellitus ; History of a known, or suspected, respiratory system disorder including, but not limited to, cystic fibrosis, reactive airway disease, emphysema, chronic bronchitis, chronic obstructive pulmonary disease (COPD), or asthma, excluding childhood asthma ; History of significant alcohol abuse within 12 months prior to screening ; Positive test for drugs of abuse or a history of drug abuse within 12 months prior to screening ; Participation in a clinical research study involving the administration of an investigational, or marketed, drug or device within 30 days prior to receiving the first treatment ; Use of medications: Prescription medication within 14 days prior to the first dosing ; Any medication, or treatments, that may affect the immune system ; Any registered vaccine administered within 30 days prior to enrolment in the study, or who plan to receive any non-study vaccines within 28 days of the second dose of the study vaccine ; Any other investigational coronavirus vaccine i.e. SARS-CoV-1, SARS-CoV-2, MERS etc. at any time prior to, or during, the study ; Over-the-counter products within 7 days prior to the first dosing ; Donation of plasma within 7 days prior to dosing. Donation or loss of blood (excluding volume drawn at screening) of 50 mL to 499 mL of blood within 30 days, or more than 499 mL within 56 days prior to the first dosing ; Receipt of blood products within 2 months prior to the first study treatment administration (Day 1), or planned receipt of blood products during the study period ; Breast-feeding subject, or subject who plans to breastfeed from the time of first dose through 60 days after last study treatment administration ; Presence of tattoos, scarring, skin discoloration, or any other skin disturbances at the injection site which, in the opinion of the Investigator, may inhibit the ability to effectively perform an injection site assessment ; Employee or immediate relative of an employee of the clinical site, any of its affiliates or partners, or Syneos Health ; Any reason which, in the opinion of the Investigator, would interfere with the primary study objectives or prevent the subject from participating in the study. |
| Interventions | |
| Intervention
2 IM doses of 5-mcg SARS-CoV-2 Sclamp 28 days apart. 2 IM doses of 15-mcg SARS-CoV-2 Sclamp 28 days apart. 2 IM doses of 45-mcg SARS-CoV-2 Sclamp 28 days apart. 1 IM dose 45-mcg SARS-CoV-2 Sclamp Day 0, 1 IM dose saline Day 28 |
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| Control
2 IM doses of saline 28 days apart. | |
| Participants | |
| Randomized 120 participants | |
| Characteristics of participants Type of participants: Healthy volunteers N=120 65 males Children: 0 Pregnant women: 0 Immunocompromized patients: 0 Mean age: 32.5 Age range: 18-55 | |
| Description of participants Healthy SARS-CoV-2 infection-free adults aged 18-55 at one center in Australia. | |
| Primary outcome | |
| In the register Frequency of Solicited local reactogenicity adverse events (AEs) [ Time Frame: 7 days following each vaccination (at Days 1 and 29) ]; Frequency of Solicited systemic reactogenicity adverse events (AEs) [ Time Frame: 7 days following each vaccination (at Days 1 and 29) ]; Grading of Solicited local reactogenicity adverse events (AEs) [ Time Frame: 7 days following each vaccination (at Days 1 and 29) ]; Grading of Solicited systemic reactogenicity adverse events (AEs) [ Time Frame: 7 days following each vaccination (at Days 1 and 29) ]; Unsolicited adverse events (AEs) [ Time Frame: 28 days following each vaccination (at Days 1 and 29) ]; Serious adverse events (SAEs), Medically attended adverse events (MAAEs) and any Adverse events (AEs) leading to study withdrawal at any time during the study [ Time Frame: through study completion (394 days) ]; Geometric Mean Titer (GMT) of the serum antibody response [ Time Frame: 28 days following each vaccination (Days 29 and 57) ]; Geometric Mean Titer (GMT) of the serum neutralizing antibody (NAb) response to SARS-CoV-2 virus [ Time Frame: 28 days following each vaccination (Days 29 and 57) ] | |
| In the report The primary safety endpoints included the frequency, duration, and intensity of solicited local and systemic adverse events (AEs) for 7 days after each dose, the frequency, duration, intensity, and relatedness of unsolicited AEs through Day 57, and the frequency of serious AEs and AEs leading to study discontinuation throughout the study. The primary immunogenicity endpoints included the geometric mean of the serum antibody response to SARS-CoV-2 Sclamp compared with placebo by antigen-specific enzyme-linked immunosorbent assay (ELISA) at Day 29 and Day 57, and the geometric mean of the serum neutralising antibody titres to SARS-CoV-2 virus compared with placebo at Day 29 and Day 57. | |
| Variants description | |
| Variants | |
| Description | |
| Documents avalaible |
Protocol NR Statistical plan * Data-sharing stated:
Yes, Immediately after publication with no end date. |
| 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 retrospective trial registry and supplementary appendices were used in data extraction and assessment of risk of bias. Neither protocol nor statistical analysis plan was available. The 45mcg followed by placebo arm was not included in the trial registry. Other than that there were no substantive difference between the registry and the pre-print article in population, procedures, interventions or outcomes. This is an early interim analysis of a Phase 1 study in which follow up is ongoing. The study achieved its pre-stated sample size. This trial was updated on May 20th, 2021 after publication of study report. |