COVID-19
Conditions
Keywords
mRNA-1283.222, mRNA-1273.222, mRNA-1283.815, mRNA-1273.815, SARS-CoV-2, SARS-CoV-2 Vaccine, Coronavirus, Virus Diseases, Messenger RNA, COVID-19, COVID-19 Vaccine, Moderna
Brief summary
The purpose of this study (Part 1 and Part 2) is to evaluate the relative vaccine efficacy (rVE), safety, reactogenicity, and immunogenicity of mRNA-1283.222 versus mRNA-1273.222 (Part 1) and mRNA-1283.815 versus mRNA-1273.815 (Part 2).
Interventions
BIOLOGICALmRNA-1283.222
Sterile liquid for injection
BIOLOGICALmRNA-1273.222
Sterile liquid for injection
BIOLOGICALmRNA-1283.815
Sterile liquid for injection
BIOLOGICALmRNA-1273.815
Sterile liquid for injection
Sponsors
ModernaTX, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
12 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
Key Inclusion Criteria: * Investigator's assessment that the participant understands and is willing and physically able to comply with protocol-mandated follow-up, including all procedures. * For female participants of childbearing potential: negative pregnancy test, adequate contraception or has abstained from all activities that could result in pregnancy for at least 28 days prior to the first injection, and agreement to continue adequate contraception or abstinence through 90 days following the vaccine administration. * Part 1: Has previously received a primary series of an authorized/approved COVID-19 vaccine. For participants ≥18 years of age, at least 1 booster dose must have also been received. Proof of prior vaccination is required. A heterologous vaccine regimen is acceptable. Part 2: No prior vaccination is required. For participants who have been previously vaccinated, proof of vaccination is required. Key
Exclusion criteria
* Has had close contact, as defined by the Centers for Disease Control and Prevention (CDC), with someone who had a SARS-CoV-2 infection in the past 14 days, or COVID-19 in the past 10 days. * Participant is acutely ill or febrile (temperature ≥38.0 degrees Celsius \[°C\]/100.4 degrees Fahrenheit \[°F\]) 72 hours prior to or at the Screening Visit or Day 1. * 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. * 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 equivalent) or is anticipating the need for immunosuppressive treatment at any time during participation in the study. * Has received or plans to receive any licensed vaccine ≤60 days prior to the study injection (Day 1) or plans to receive a licensed vaccine within 60 days after the study injection. * Has received systemic immunoglobulins or blood products within 90 days prior to the Screening Visit or plans to receive during the study. * 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. * 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. Note: Other inclusion and
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part 1: Geometric Mean (GM) of Omicron BA.4/5 at Day 29 | Day 29 | Antibody values reported as below the lower limit of quantification (LLOQ) were replaced by 0.5\*LLOQ. Values greater than the upper limit of quantification (ULOQ) were replaced by the ULOQ if actual values were not available. LLOQ was 103 arbitrary units (AU)/milliliter (mL) and ULOQ was 28571 AU/mL. |
| Part 1: Seroresponse Rate (SRR) Omicron BA.4/5 at Day 29 | Day 29 | Seroresponse was defined as an antibody value change from baseline below the LLOQ to ≥4\*LLOQ, or at least a 4-fold rise if baseline was ≥LLOQ and \<4\*LLOQ, or at least a 2-fold rise if baseline was ≥4\*LLOQ, where baseline referred to pre-booster. LLOQ was 103 AU/mL and ULOQ was 28571 AU/mL. |
| Part 1: GM of the Ancestral Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) D614G at Day 29 | Day 29 | Antibody values reported as below the LLOQ were replaced by 0.5\*LLOQ. Values greater than the ULOQ were replaced by the ULOQ if actual values were not available. LLOQ was 10 AU/mL and ULOQ was 111433 AU/mL. |
| Part 1: SRR of Ancestral SARS-CoV-2 D641G at Day 29 | Day 29 | Seroresponse was defined as an antibody value change from baseline below the LLOQ to ≥4\*LLOQ, or at least a 4-fold rise if baseline was ≥LLOQ and \<4\*LLOQ, or at least a 2-fold rise if baseline was ≥4\*LLOQ, where baseline referred to pre-booster. LLOQ was 10 AU/mL and ULOQ was 111433AU/mL. |
| Part 1: Number of Participants With First Event of Centers for Disease Control and Prevention (CDC)-Defined COVID-19 | From 14 days after injection up to Day 365 | CDC COVID-19 definition: the presence of at least 1 CDC listed symptom and positive reverse transcriptase polymerase chain reaction (RT-PCR) test on a respiratory sample. |
| Part 1: Number of Participants With Solicited Local and Systemic Adverse Reactions (ARs) | Up to Day 7 (7-day follow-up after vaccination) | Solicited ARs were recorded daily using electronic diaries (eDiaries). Local ARs: injection site pain, erythema (redness), swelling/induration (hardness); and axillary (underarm) swelling or tenderness ipsilateral to the side of injection. Systemic ARs: fever, headache, fatigue, myalgia, arthralgia, nausea/vomiting, and chills. Note, not all solicited ARs were considered adverse events (AEs). Investigator reviewed whether the solicited AR was also to be recorded as an AE. A Summary of serious AEs (SAEs) and nonserious AEs ("Other"), regardless of causality, is located in the "Reported Adverse Events" section. |
| Part 3: Number of Participants With Solicited Local and Systemic ARs | Up to Day 7 (7-day follow-up after vaccination) | Solicited ARs were recorded daily using eDiaries. Local ARs: injection site pain, erythema (redness), swelling/induration (hardness); and axillary (underarm) swelling or tenderness ipsilateral to the side of injection. Systemic ARs: fever, headache, fatigue, myalgia, arthralgia, nausea/vomiting, and chills. Note, not all solicited ARs were considered AEs. Investigator reviewed whether the solicited AR was also to be recorded as an AE. A Summary of SAEs and nonserious AEs ("Other"), regardless of causality, is located in the "Reported Adverse Events" section. |
| Part 1: Number of Participants With Unsolicited Adverse Events (AEs) | Up to Day 28 (28-day follow-up after vaccination) | An unsolicited AE was defined as any AE reported by the participant that was not specified as a solicited AR in the protocol. An AE was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. A summary of all Serious Adverse Events and Other Adverse Events (nonserious) regardless of causality is located in the 'Reported Adverse Events' Section. |
| Part 3: Number of Participants With Unsolicited AEs | Up to Day 28 (28-day follow-up after vaccination) | An unsolicited AE was defined as any AE reported by the participant that was not specified as a solicited AR in the protocol. An AE was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. A summary of all Serious Adverse Events and Other Adverse Events (nonserious) regardless of causality is located in the 'Reported Adverse Events' Section. |
| Part 1: Number of Participants With Any Serious AEs (SAEs), Medically Attended AEs (MAAEs), AEs Leading to Withdrawal From Study, and AEs of Special Interest (AESIs) | Day 1 up to Day 365 | SAEs were AEs that resulted in death, were life threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, a congenital anomaly or birth defect, or was a medically important event. MAAEs were AEs that lead to an unscheduled visit to a healthcare provider. AESIs were AEs (serious or nonserious) of scientific and medical concern specific to the Sponsor's product or program for which ongoing monitoring and immediate notification by the investigator to the Sponsor was required. AEs leading to the withdrawal from study reported for this endpoint also include the AEs that led to death. A summary of all Serious Adverse Events and Other Adverse Events (nonserious) regardless of causality is located in the 'Reported Adverse Events' Section. |
| Part 3: Number of Participants With Any SAEs, MAAEs, AEs Leading to Withdrawal From Study, and AESIs | Day 1 up to Day 181 | SAEs were AEs that resulted in death, were life threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, a congenital anomaly or birth defect, or was a medically important event. MAAEs were AEs that lead to an unscheduled visit to a healthcare provider. AESIs were AEs (serious or nonserious) of scientific and medical concern specific to the Sponsor's product or program for which ongoing monitoring and immediate notification by the investigator to the Sponsor was required. AEs leading to the withdrawal from study reported for this endpoint also include the AEs that led to death. A summary of all Serious Adverse Events and Other Adverse Events (nonserious) regardless of causality is located in the 'Reported Adverse Events' Section. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part 1: GMs of Omicron BA.4/5 and Ancestral SARS-CoV-2 D614G | Days 91, 181, and 365 | Antibody values reported as below the LLOQ were replaced by 0.5\*LLOQ. Values greater than the ULOQ were replaced by the ULOQ if actual values were not available. LLOQ was 103 AU/mL and ULOQ was 28571 AU/mL for Omicron BA.4/5. LLOQ was 10 AU/mL and ULOQ was 111433 AU/mL for ancestral SARS-CoV-2 D614G. |
| Part 1: SRR Against Omicron BA.4/5 and Ancestral SARS-CoV-2 D614G at Days 91, 181, and 365 | Days 91, 181, and 365 | Seroresponse was defined as an antibody value change from baseline below the LLOQ to ≥4\*LLOQ, or at least a 4-fold rise if baseline was ≥LLOQ and \<4\*LLOQ, or at least a 2-fold rise if baseline was ≥4\*LLOQ, where baseline referred to pre-booster. LLOQ was 103 AU/mL and ULOQ was 28571 AU/mL for Omicron BA.4/5. LLOQ was 10 AU/mL and ULOQ was 111433 AU/mL for ancestral SARS-CoV-2 D614G. |
| Part 1: Number of Participants With a SARS-CoV-2 Infection (Symptomatic or Asymptomatic) | From 14 days after injection up to Day 365 | SARS-CoV-2 infection (symptomatic or asymptomatic) was defined as (1) negative binding antibody (bAb) level against SARS-CoV-2 nucleocapsid protein and negative RT-PCR at baseline that became positive bAb level against SARS-CoV-2 nucleocapsid protein post-baseline, or (2) positive RT-PCR post-baseline. Asymptomatic SARS-CoV-2 infection was characterized by the absence of COVID-19 symptoms. |
| Part 3: GM of Omicron XBB.1.5 in Unvaccinated Participants | Day 29 | Antibody values reported as below the LLOQ were replaced by 0.5\*LLOQ. Values greater than the ULOQ were replaced by the ULOQ if actual values were not available. LLOQ was 38 AU/mL and ULOQ was 6960 AU/mL. |
| Part 3: GM of Omicron XBB.1.5 in All Study Participants | Day 29 | Antibody values reported as below the LLOQ were replaced by 0.5\*LLOQ. Values greater than the ULOQ were replaced by the ULOQ if actual values were not available. LLOQ was 38 AU/mL and ULOQ was 6960 AU/mL. |
| Part 3: SRR Against Omicron XBB.1.5 in Unvaccinated Participants | Day 29 | Seroresponse was defined as an antibody value change from baseline below the LLOQ to ≥4\*LLOQ, or at least a 4-fold rise if baseline was ≥LLOQ and \<4\*LLOQ, or at least a 2-fold rise if baseline was ≥4\*LLOQ, where baseline referred to last non-missing measurement on or before study vaccination day. LLOQ was 38 AU/mL and ULOQ was 6960 AU/mL. |
| Part 3: SRR Against Omicron XBB.1.5 in All Study Participants | Day 29 | Seroresponse was defined as an antibody value change from baseline below the LLOQ to ≥4\*LLOQ, or at least a 4-fold rise if baseline was ≥LLOQ and \<4\*LLOQ, or at least a 2-fold rise if baseline was ≥4\*LLOQ, where baseline referred to last non-missing measurement on or before study vaccination day. LLOQ was 38 AU/mL and ULOQ was 6960 AU/mL. |
Countries
Canada, Japan, United Kingdom, United States
Participant flow
Pre-assignment details
The study was planned to be conducted in 3 parts: Parts 1, 2, and 3. Given that the relative vaccine efficacy (rVE) objective was met (early success scenario), there was no Part 2 enrollment.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Categorical <=18 years | 495 Participants |
| Age, Categorical >=65 years | 3460 Participants |
| Age, Categorical Between 18 and 65 years | 3575 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 741 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 11315 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 106 Participants |
| Race/Ethnicity, Customized Race American Indian or Alaska Native | 59 Participants |
| Race/Ethnicity, Customized Race Asian | 447 Participants |
| Race/Ethnicity, Customized Race Black or African American | 260 Participants |
| Race/Ethnicity, Customized Race Multiple | 43 Participants |
| Race/Ethnicity, Customized Race Native Hawaiian or Other Pacific Islander | 6 Participants |
| Race/Ethnicity, Customized Race Not Reported | 3 Participants |
| Race/Ethnicity, Customized Race Other | 2 Participants |
| Race/Ethnicity, Customized Race Unknown | 0 Participants |
| Race/Ethnicity, Customized Race White | 4670 Participants |
| Sex: Female, Male Female | 7295 Participants |
| Sex: Female, Male Male | 6212 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 9 / 5,728 | 11 / 5,725 | 0 / 1,056 | 1 / 1,044 |
| other Total, other adverse events | 607 / 5,706 | 636 / 5,710 | 21 / 1,052 | 16 / 1,039 |
| serious Total, serious adverse events | 203 / 5,706 | 197 / 5,710 | 15 / 1,052 | 20 / 1,039 |
Outcome results
None listed