E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Virus Diseases [C02] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
- To demonstrate noninferiority of the immune response of mRNA-1273.529 compared to mRNA-1273 booster administered as a 4th dose against the B.1.1.529 strain at Day 29 or Month 3. - To evaluate the safety and reactogenicity of mRNA-1273.529 and mRNA-1273 administered as a booster dose. |
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E.2.2 | Secondary objectives of the trial |
- To demonstrate superiority of the immune response of mRNA-1273.529 compared to mRNA-1273 administered as a 4th dose against the B.1.1.529 strain at Day 29 or Month 3. - To demonstrate noninferiority of the immune response of mRNA-1273.529 compared to mRNA-1273 booster administered as a 4th dose against both the B.1.1.529 and the prototype strain at all evaluable time points. - To evaluate the seroresponse rate (SRR) of mRNA-1273.529 and mRNA-1273 boosters administered as a 4th dose. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Female participants of childbearing potential may be enrolled in the study if the participant has a negative pregnancy test at the Screening Visit and on the day of vaccination prior to vaccine dose being administered on Day 1; has practiced adequate contraception or has abstained from all activities that could result in pregnancy for at least 28 days prior to the first dose (Day 1); and has agreed to continue adequate contraception through 90 days following vaccine administration. - Participant has received 2 prior doses of one of the following approved/authorized COVID-19 vaccines: Moderna, Pfizer/BioNTech, Oxford/AstraZeneca, Janssen. A heterologous vaccine regimen is acceptable. - Participants who will receive the 4th dose as part of the study must have previously received a mRNA vaccine (Moderna or Pfizer/BioNTech) as the 3rd dose of a COVID-19 vaccine. Participants who will receive the 3rd dose as part of the study may have previously received 2 doses of an approved/authorized mRNA or a non-mRNA COVID-19 vaccine (a heterologous vaccine regimen is acceptable). |
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E.4 | Principal exclusion criteria |
- Participant had close contact (without personal protective equipment [PPE]) as defined by the Centers for Disease Control and Prevention (CDC) in the past 14 days to someone diagnosed with SARS-CoV-2 infection or COVID-19 within 10 days of the close contact. Participants may be rescreened after 14 days provided that they remain asymptomatic. - Participant is acutely ill or febrile (temperature ≥ 38.0°C/100.4°F) 72 hours prior to or at the Screening Visit or Day 1. - Participant has tested positive for SARS-CoV-2 by an authorized/approved lateral flow/rapid antigen or polymerase chain reaction (PCR) test within 90 days of Screening. - Participant has received a COVID-19 vaccine within 90 days of the Screening Visit. - Participant has received a total of 4 doses or more of COVID-19 vaccine. - Participant has received a COVID-19 vaccine at a dose different from the authorized/approved dose. - Any medical, psychiatric, or occupational condition, including reported history of substance abuse, that, in the opinion of the Investigator, might pose additional risk due to participation in the study or could interfere with the interpretation of study results. - Participant has received systemic immunosuppressants or immune-modifying drugs for >14 days in total within 181 days prior to screening (for corticosteroids ≥10 milligrams [mg]/day of prednisone or equivalent) or is anticipating the need for immunosuppressive treatment at any time during participation in the study. - Participant has received or plans to receive any licensed vaccine ≤28 days prior to the study injection (Day 1) or plans to receive a licensed vaccine within 28 days after the study injection (with the exception that approved seasonal influenza vaccine may be received by at least 7 days and preferably 14 days apart from the study injection). - Participant has received systemic immunoglobulins or blood products within 90 days prior to the Screening Visit or plans to receive during the study. - Participant has donated ≥450 milliliters (mL) of blood products within 28 days prior to the Screening Visit or plans to donate blood products during the study. - Participant has participated in an interventional clinical study within 28 days prior to the Screening Visit based on the medical history interview or plans to do so while participating in this study. |
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E.5 End points |
E.5.1 | Primary end point(s) |
1. Geometric Mean Titer (GMT) of mRNA-1273.529 and mRNA-1273 Against the B.1.1.529 Strain 2. Number of Participants with Solicited Local and Systemic Reactogenicity Adverse Reactions (ARs) 3. Number of Participants with Unsolicited Adverse Events (AEs) 4. Number of Participants with Serious AEs (SAEs) 5. Number of Participants with Medically Attended AEs (MAAEs) 6. Number of Participants with AEs Leading to Withdrawal 7. Number of Participants with AEs of Special Interest (AESIs) 8. GMT of mRNA-1273.214 and mRNA-1273 Against the B1.1.529 Strain 9. GMT of mRNA-1273.214 and mRNA-1273 Against the Prototype Strain |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Endpoint #1, #8, and #9: Up to Day 85 post-vaccination Endpoint #2: Up to Day 8 (7 days post-vaccination) Endpoint #3: Up to Day 29 (28 days post-vaccination) Endpoint #4 to #7: Day 1 to end of study (Day 359) |
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E.5.2 | Secondary end point(s) |
1. GMT of mRNA-1273.529 and mRNA-1273 Against the B.1.1.529 Strain 2. GMT of mRNA-1273.529 and mRNA-1273 Against the Prototype Strain 3. Seroresponse Rate of Vaccine Recipients 4. GMT of mRNA-1273.214 and mRNA-1273 Against Other Variant Strains 5. Number of Participants with Asymptomatic SARS-CoV-2 Infection Measured by Reverse Transcriptase Polymerase-chain Reaction (RT-PCR) 6. Number of Participants with Symptomatic SARS-CoV-2 Infection Measured by RT-PCR |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Endpoint #1 to #3: Days 1, 29, 85, 179, and 359 Endpoint #4: Days 29 and 85 Endpoint #5 and #6: Day 1 through the end of study (Day 359) |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | Yes |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
Phase A of this study will be observer-blinded. Phase B of the study will be open-label. |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 4 |
E.8.3 |
Will this trial be conducted at a single site globally?
| No |
E.8.4 | Will this trial be conducted at multiple sites globally? | Yes |
E.8.6 Trial involving sites outside the EEA |
E.8.6.2 | Trial being conducted completely outside of the EEA | Yes |
E.8.6.3 | Specify the countries outside of the EEA in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 4 |
E.8.9.2 | In all countries concerned by the trial days | 7 |