Trial NCT04796896
Publication Creech CB, N Engl J Med, 2022
Dates: 2021-03-15 to 2021-08-30
Funding: Public/non profit (The Office of the Assistant Secretary for Preparedness and Response, Biomedical Advanced Research and Development Authority; the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health.)
Conflict of interest: Yes
| Methods | |
| RCT | |
| Location :
Multicenter / Canada, USA Follow-up duration (months): 8 | |
| 50 mcg mRNA-1273 (n = 3012) placebo (n = 1004) |
|
| Inclusion criteria | Male or female; 6-<12 years of age at the time of consent/assent (screening visit); in good general health, in the opinion of the investigator, based on review of medical history and screening physical examination; If the participant had a chronic disease (eg, asthma, diabetes mellitus, cystic fibrosis, human immunodeficiency virus [HIV] infection), the disease should be stable, per investigator assessment, so that the participant can be considered eligible for inclusion. Stable diseases were those which had no change in status or in the medications required to control them in the 6 months prior to screening visit. Note: a change in medication for dose optimization (eg, insulin dose changes), change within class of medication, or reduction in dose were not considered signs of instability; the parent(s)/ Legally Acceptable Representative (LARs) understood and were willing and physically able to comply with protocol-mandated follow-up, including all procedures, and provided written informed consent and participants were willing to provide assent; Participants 2 years or older and had a body mass index at or above the third percentile according to WHO Child Growth Standards at the screening visit; Female participants of nonchildbearing potential were enrolled in the study. Nonchildbearing potential was defined as premenarche. Special inclusion criteria for female participants who had reached menarche: Female participants of childbearing potential were enrolled in the study if the participant fulfilled all the following criteria: had a negative pregnancy test at screening. Pregnancy test will be performed if deemed appropriate by the investigator, Had practiced adequate contraception or abstained from all activities that could result in pregnancy for at least 28 days prior to the first injection (day 1), Had agreed to continue adequate contraception or abstinence through 3 months, Was not currently breastfeeding. Adequate female contraception was defined as abstinence or consistent and correct use of a US Food and Drug Administration-approved contraceptive method in accordance with the product label. |
| Exclusion criteria | Known history of SARS-CoV-2 infection within 2 weeks prior to administration of IP or known close contact with anyone with laboratory confirmed SARS-CoV-2 infection or COVID19 within 2 weeks prior to administration of IP; acutely ill or febrile 24 hours prior to or at the screening visit. Fever was defined as a body temperature ≥38.0°C/≥100.4°F. Participants who met this criterion could have visits rescheduled within the relevant study visit windows. Afebrile participants with minor illnesses were enrolled at the discretion of the investigator; Had previously been administered an investigational or approved CoV (eg, SARS-CoV-2, SARS-CoV, Middle East respiratory syndrome-CoV) vaccine; Had undergone treatment with investigational or approved agents for prophylaxis against Covid-19 (eg, receipt of SARS-CoV-2 monoclonal antibodies) within 6 months of enrollment; Had a known hypersensitivity to a component of the vaccine or its excipients. Hypersensitivity included, but was not limited to, anaphylaxis or immediate allergic reaction of any severity to a previous dose of messenger RNA Covid-19 vaccine or any of its components (including polyethylene glycol [PEG] or immediate allergic reaction of any severity to polysorbate); Had a medical or psychiatric condition that, according to the investigator’s judgment, may pose additional risk because of participation, interfere with safety assessments, or interfere with interpretation of results; Had a history of a diagnosis or condition that, in the judgment of the investigator, may affect study endpoint assessment or compromise participant safety, specifically the following: Congenital or acquired immunodeficiency, excluding HIV infection, as described in Inclusion Criteria 2, Chronic hepatitis or suspected active hepatitis, A bleeding disorder that was considered a contraindication to IM injection or phlebotomy, Dermatologic conditions that could affect local solicited AR assessments, Any prior diagnosis of malignancy (excluding nonmelanoma skin cancer), Febrile seizures: In Part 2 of the study, a history of a single, simple febrile seizure was allowed for children 6 years and older; Had received the following: Any routine vaccination with inactivated or live vaccine(s) within 14 days of the first vaccination or plans to receive such a vaccine through 14 days following the last study vaccination, Influenza vaccine could be given, however, not within 14 days of or following Dose 1 or Dose 2. If a participant received an influenza vaccine, this was captured within the concomitant medication electronic case report form, Systemic immunosuppressants or immune-modifying drugs for >14 days in total within 6 months of the day of enrollment (for corticosteroids, ≥1 mg/kg/day or ≥10 mg/day prednisone equivalent, if participant weighed >10 kg). Participants could have visits rescheduled for enrollment if they no longer met this criterion within the screening visit window. Inhaled, nasal, and topical steroids were allowed, Intravenous or subcutaneous blood products (red cells, platelets, immunoglobulins) within 3 months of enrollment; Had participated in an interventional clinical study within 28 days prior to the screening visit or planned to do so while participating in this study; Was an immediate family member, or household contact, of an employee of the study site or Moderna or someone otherwise directly involved with the conduct of the study. As applicable, family members/household contacts of employees of the larger institution or affiliated private practice not part of the study site were enrolled. |
| Interventions | |
| Intervention
2 IM doses of 50 mcg mRNA-1273, 28 days apart |
|
| Control
2 IM doses of saline placebo, 28 days apart | |
| Participants | |
| Randomized 4016 participants | |
| Characteristics of participants Type of participants: Children N=4016 2035 males Children: 4016 Pregnant women: 0 Immunocompromized patients: 4 Mean age: Age range: 6-11 | |
| Description of participants Children aged 6-11 years, healthy or with stable chronic conditions and no known recent history of COVID-19 infection, at 87 centers in Canada and USA. | |
| Primary outcome | |
| In the register 1. Solicited Local and Systemic Adverse Reactions (ARs) (7 days after each injection); 2. Unsolicited Adverse Events (AEs) (28 days after each injection); 3. Medically-Attended AEs (MAAEs) (1 year after booster dose); 4. Serious Adverse Events (SAEs) [ Time Frame: Up to Day 514 (1 year after booster dose); 5. Adverse Events of Special Interest (AESIs), Including Multisystem Inflammatory Syndrome in Children (MIS-C), Myocarditis and/or Pericarditis (1 year after booster dose); 6. AEs Leading to Discontinuation From Study Post-Booster Dose Through the Last Day of Study Participation; 7. Serum Antibody Levels that Meet or Exceed the Threshold of Protection From COVID-19 (1 month after second injection); 8. Geometric Mean (GM) Value of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Specific Serum Antibody (1 month after second injection); 9. Seroresponse Rate of Vaccine Recipients (1 month after second injection) 10) GM Value of Post-Booster Dose SARS-CoV-2 Specific Serum Antibody (post third dose); 11) Seroresponse Rate of Post-Booster Dose of Vaccine Recipients (post third dose). | |
| In the report 1. Solicited local and systemic ARs through 7 days after each injection; 2. Unsolicited AEs through 28 days after each injection; 3. MAAEs through the entire study period; 4. SAEs through the entire study period; 5. AESIs, including MIS-C and myocarditis and/or pericarditis, through the entire study period; 6. The proportion of participants with a serum antibody level at day ≥57 antibody threshold of protection; 7. The GM value of serum antibody level and seroresponse rate from Study P204 vaccine recipients at day 57 compared with those from young adult (18≤25 years of age) vaccine recipients (day 57) in the clinical endpoint efficacy trial | |
| Variants description | |
Variants
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| Description * | |
| Documents avalaible |
Protocol Yes. In English Statistical plan Yes Data-sharing stated:
Yes, Once the KidCOVE trial is completed |
| 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 primary and secondary outcomes in the article reflect those in the registries. The trial (n = 4016) achieved its target sample size (n = 4000). |