A Study to Evaluate Safety and Immunogenicity of mRNA-1273 Vaccine to Prevent COVID-19 in Adult Organ Transplant Recipients and in Healthy Adult Participants

A Phase 3b, Open-Label, Safety and Immunogenicity Study of SARS-CoV-2 mRNA-1273 Vaccine in Adult Solid Organ Transplant Recipients and Healthy Controls

This is an open-label study to evaluate the safety, reactogenicity, and immunogenicity of mRNA-1273 Severe Acute Respiratory Syndrome coronavirus (SARS-CoV-2) vaccine in adults with a kidney or liver solid organ transplant (SOT) and in healthy adult participants. The primary goal of the study is to evaluate the safety of mRNA-1273 and the serum antibody (Ab) responses obtained 28 days after the last dose of mRNA-1273.

Study Overview

• Status: Completed
• Conditions: SARS-CoV-2
• Intervention / Treatment: Biological: mRNA-1273

• Study Type: Interventional
• Enrollment (Actual): 234
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Mesa, Arizona, United States, 85206
      • Aventiv Research Inc
  • California
    • San Diego, California, United States, 92123
      • California Institute of Renal Research
  • Connecticut
    • New Haven, Connecticut, United States, 06519
      • Yale University School of Medicine
  • Florida
    • Tampa, Florida, United States, 33606
      • Tampa General Medical Group
  • Georgia
    • Atlanta, Georgia, United States, 30309
      • Piedmont Transplant Institute
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Brigham and Women's Hospital
    • Worcester, Massachusetts, United States, 01655
      • University of Massachusetts Medical School
  • Nebraska
    • Omaha, Nebraska, United States, 68198
      • University of Nebraska Medical Center
  • New York
    • Manhasset, New York, United States, 11030
      • Northwell Health
    • New York, New York, United States, 10032
      • Colombia University Medical Center
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • University of Cincinnati
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Hospital
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Hospital of the University of Pennsylvania
  • Rhode Island
    • Providence, Rhode Island, United States, 02903
      • Rhode Island Hospital
  • Washington
    • Seattle, Washington, United States, 98195
      • University of Washington Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Transplant Recipients

Key Inclusion Criteria for Part A:

• Is either a kidney or a liver transplant recipient who is at least 90 days after transplantation at the time of consent, and is either unvaccinated or previously vaccinated with 2 doses of Moderna COVID-19 vaccine who is at least 1 month after the second dose at the time of consent. Participants who received the 2 doses of Moderna COVID-19 vaccine before transplant are not eligible.
• Understands, agrees, and is able to comply with the study procedures and provides written informed consent.
• Received chronic immunosuppressive therapy for the prevention of allograft rejection for a minimum of 90 days before signing consent, including but not limited to: glucocorticoids (such as, prednisolone), immunophilin binding agents (such as, calcineurin inhibitors, mTOR inhibitors), or inhibitors of de novo nucleotide synthesis (such as, mycophenolic acid, mizoribine, leflunomide, azathioprine).
• 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, agreement to continue adequate contraception or abstinence through 3 months following the second dose (Day 29) for those receiving 2-dose regimen and, through 3 months following the third dose (Day 85) for those receiving 3-dose regimen, and through 3 months following the third dose (Day 1) for those previously vaccinated SOT participants, and not currently breastfeeding.
• Is medically stable, according to investigator's judgment, during the 3 months before signing consent.

Key Exclusion Criteria for Part A:

• Has prior or planned administration of a coronavirus vaccine (for example, SARS-CoV-2 [for unvaccinated participants only], SARS-CoV, or MERS [Middle East Respiratory Syndrome] -CoV vaccine).
• Has current treatment with investigational agents for either prophylaxis against COVID-19 (for unvaccinated participants only) or treatment of COVID-19 (such as, anti-SARS-CoV-2 monoclonal antibodies).
• A history of more than one solid organ transplanted (such as, kidney and pancreas). A history of previous kidney or liver transplant is acceptable.
• Has received therapies that have depleting properties on T cells, B cells, and plasma cells (examples of depletional therapies include, but are not limited to, antithymocyte globulin [ATG], monoclonal antibodies, and proteosome inhibitors) within the last 3 months prior to enrollment.
• A history of biopsy-proven T-cell- or Ab-mediated rejection within 3 months of informed consent, or suspected active or chronic rejection according to the investigator's judgment.
• Has a known close contact with anyone with laboratory confirmed SARS-CoV-2 infection within 2 weeks to vaccine administration or known history of SARS-CoV-2 infection or positive SARS-CoV-2 test.
• Has a medical, psychiatric, or occupational condition that may pose additional risk as a result of participation or that could interfere with safety assessments or interpretation of results according to the investigator's judgment.
• Has a history of clinically relevant donor-specific Ab.
• Has a history of complications of immunosuppression
• Suspected clinically relevant active hepatitis, including viral hepatitis, according to the investigator's judgment
• Known human immunodeficiency virus (HIV) infection
• Has a history of a diagnosis or condition that, in the judgment of the investigator, may affect study endpoint assessment or compromise participant safety.
• Received any non-study vaccine within 28 days before or after any dose of vaccine (except for seasonal influenza vaccine, which is not permitted within 14 days before or after any dose of vaccine)
• Received intravenous blood products (red blood cells, platelets, immunoglobulins) within 3 months prior to Day 1.
• Participated in an interventional clinical study within 28 days prior to Day 0 or plans to donate blood products while participating in this study.

Healthy Participants

Key Inclusion Criteria for Part A:

• In good general health without current or previous diagnosis of immunocompromising condition, immune-mediated disease, or other immunosuppressive condition, according to investigator assessment, at the time of consent, and has not been vaccinated with any COVID-19 vaccine at the time of consent.
• Understands, agrees, and is able to comply with the study procedures and provides written informed consent.
• 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 (Day 1), agreement to continue adequate contraception or abstinence through 3 months following the second injection (Day 29), and not currently breastfeeding.
• Is medically stable, according to investigator's judgment, during the 3 months before signing consent.

Key Exclusion Criteria for Part A:

• Has a known close contact with anyone with laboratory confirmed SARS-CoV-2 infection or COVID-19 within 2 weeks prior to vaccine administration or known history of SARS-CoV-2 infection or positive SARS-CoV-2 test.
• Has prior or planned administration of a coronavirus vaccine (for example, SARS-CoV-2, SARS-CoV, or MERS-CoV vaccine).
• Has current treatment with investigational agents for either prophylaxis against COVID-19 or treatment of COVID-19 (for example, anti-SARS-CoV-2 monoclonal antibodies).
• Has a medical, psychiatric, or occupational condition that may pose additional risk as a result of participation or that could interfere with safety assessments or interpretation of results according to the investigator's judgment.
• Has a history of a diagnosis or condition that, in the judgment of the investigator, may affect study endpoint assessment or compromise participant safety.
• Received any non-study vaccine within 28 days before or after any dose of vaccine (except for seasonal influenza vaccine, which is not permitted within 14 days before or after any dose of vaccine)
• Received intravenous blood products (red blood cells, platelets, immunoglobulins) within 3 months prior to Day 1.
• Received systemic immunosuppressants or immune-modifying drugs for >14 days in total within 6 months prior to Screening (for corticosteroids ≥20 mg/day of prednisone equivalent).
• Participated in an interventional clinical study within 28 days prior to Day 0 or plans to donate blood products while participating in this study.

Inclusion Criteria for Part B:

• Participants must have been previously enrolled in this study (mRNA-1273-P304), are actively participating in Part A, and at least 4 months from the last dose; or participant is either a kidney or a liver SOT recipient who is at least 90 days after transplantation at the time of consent and who completed primary vaccination series (3 doses for mRNA COVID-19 vaccine; 2 doses for non-mRNA COVID-19 vaccine or at least 1 dose of non-mRNA combined with 1 dose of mRNA COVID-19 vaccine) under the EUA who are at least 4 months from the last dose. All primary COVID-19 vaccination series must be completed after transplant.
• Female participants of childbearing potential may be enrolled in the study if the participant has a negative pregnancy test on the day of the first injection (booster dose Day 1).

Exclusion Criteria for Part B:

• Exclusion Criteria in Part A will apply except:

  1. prior or planned administration of a coronavirus vaccine and current treatment with investigational agents for either prophylaxis against COVID-19.
  2. known close contact with anyone with laboratory-confirmed SARS-CoV-2 infection or COVID-19 within 2 weeks prior to vaccine administration or any known history of SARS-CoV-2 infection or positive SARSCoV-2 test will apply only to new SOT participants who will be enrolled in Part B.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: mRNA-1273; Part A: All participants (healthy participants and SOT participants) who were unvaccinated prior to enrollment will receive 2 intramuscular (IM) injections of 100 microgram (µg) mRNA-1273 on Day 1 and Day 29. All SOT participants who were unvaccinated prior to enrollment will be offered the opportunity to receive a third primary dose of mRNA-1273 at Day 85 as per the emergency use authorization (EUA) Fact Sheet available at the time of protocol finalization. SOT participants who were previously vaccinated with 2 doses of Moderna COVID-19 vaccine under the EUA prior to enrollment will receive Dose 3 on Day 1. Part B: All eligible participants from Part A will be offered to receive a 100 µg booster dose of mRNA-1273 who are at least 4 months from the last dose. SOT recipients who completed primary COVID-19 vaccination series under EUA (outside of the mRNA-1273-P304 study) will receive a 100 µg booster dose on booster dose Day 1.

Biological: mRNA-1273; Sterile liquid for injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Parts A and B: Number of SOT Participants With Unsolicited Adverse Events (AEs)	An unsolicited AE was any AE reported by the participant that was not specified as a solicited adverse reaction (AR) or was specified as a solicited AR but started outside the protocol-defined period for reporting solicited ARs (that is, for the 7 days after each dose of vaccine). A summary of serious adverse events (SAEs) and all nonserious AEs ("Other") reported up to the end of the study (up to Day 419), regardless of causality, is located in the Reported "Adverse Events" section.	Up to 28 days post-vaccination
Parts A and B: Number of Healthy Participants With Unsolicited AEs	An unsolicited AE was any AE reported by the participant that was not specified as a solicited AR or was specified as a solicited AR but started outside the protocol-defined period for reporting solicited ARs (that is, for the 7 days after each dose of vaccine). A summary of SAEs and all nonserious AEs ("Other") reported up to the end of the study (up to Day 419), regardless of causality, is located in the Reported "Adverse Events" section.	Up to 28 days post-vaccination
Parts A and B: Number of SOT Participants With Medically-Attended Adverse Events (MAAEs)	An MAAE was an AE that led to an unscheduled visit to an healthcare practitioner (HCP). This included visits to a study site for unscheduled assessments (for example, abnormal laboratory test results follow-up, COVID-19) and visits to HCPs external to the study site (for example, urgent care, primary care physician). MAAEs were also required by protocol for routine surveillance of participants with symptoms for COVID-19 infection (fever, shortness of breath, cough, fatigue, muscle or body aches, headache, new loss of taste or smell, sore throat, congestion or runny nose, nausea or vomiting, and diarrhea). All confirmed symptomatic COVID-19 cases were recorded as MAAEs. A summary of SAEs and all nonserious AEs ("Other"), regardless of causality, is located in the Reported "Adverse Events" section.	Throughout the study period (up to Day 450)
Parts A and B: Number of Healthy Participants With MAAEs	An MAAE was an AE that led to an unscheduled visit to an HCP. This included visits to a study site for unscheduled assessments (for example, abnormal laboratory test results follow-up, COVID-19) and visits to HCPs external to the study site (for example, urgent care, primary care physician). MAAEs were also required by protocol for routine surveillance of participants with symptoms for COVID-19 infection (fever, shortness of breath, cough, fatigue, muscle or body aches, headache, new loss of taste or smell, sore throat, congestion or runny nose, nausea or vomiting, and diarrhea). All confirmed symptomatic COVID-19 cases were recorded as MAAEs. A summary of SAEs and all nonserious AEs ("Other"), regardless of causality, is located in the Reported "Adverse Events" section.	Throughout the study period (up to Day 394)
Parts A and B: Number of SOT Participants With Serious Adverse Events (SAEs)	An AE (including an AR) was considered an SAE if, in the view of either the investigator or Sponsor, it results in any of the following outcomes: death, was life-threatening, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, congenital anomaly or birth defect, or medically important event. A summary of SAEs and all nonserious AEs ("Other"), regardless of causality, is located in the Reported "Adverse Events" section.	Throughout the study period (up to Day 450)
Parts A and B: Number of Healthy Participants With SAEs	An AE (including an AR) was considered an SAE if, in the view of either the investigator or Sponsor, it results in any of the following outcomes: death, was life-threatening, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, congenital anomaly or birth defect, or medically important event. A summary of SAEs and all nonserious AEs ("Other"), regardless of causality, is located in the Reported "Adverse Events" section.	Throughout the study period (up to Day 394)
Parts A and B: Number of SOT Participants With Adverse Event of Special Interests (AESIs), Including Myocarditis/Pericarditis	An AESI was an AE (serious or non-serious) of scientific and medical concern specific to the Sponsor's product or program. AESIs included thrombocytopenia, new onset of or worsening of the protocol specified neurologic diseases, anaphylaxis, and myocarditis/pericarditis. A summary of SAEs and all nonserious AEs ("Other"), regardless of causality, is located in the Reported "Adverse Events" section.	Throughout the study period (up to Day 450)
Parts A and B: Number of Healthy Participants With AESIs, Including Myocarditis/Pericarditis	An AESI was an AE (serious or non-serious) of scientific and medical concern specific to the Sponsor's product or program. AESIs included thrombocytopenia, new onset of or worsening of the protocol specified neurologic diseases, anaphylaxis, and myocarditis/pericarditis. A summary of SAEs and all nonserious AEs ("Other"), regardless of causality, is located in the Reported "Adverse Events" section.	Throughout the study period (up to Day 394)
Parts A and B: Number of SOT Participants With AEs Leading to Discontinuation From Dosing and/or Study Participation (Withdrawal)	An AE was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not it is considered drug-related. A summary of SAEs and all nonserious AEs ("Other"), regardless of causality, is located in the Reported "Adverse Events" section.	Throughout the study period (up to Day 450)
Parts A and B: Number of Healthy Participants With AEs Leading to Discontinuation From Dosing and/or Study Participation (Withdrawal)	An AE was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not it is considered drug-related. A summary of SAEs and all nonserious AEs ("Other"), regardless of causality, is located in the Reported "Adverse Events" section.	Throughout the study period (up to Day 394)
Parts A and B: Number of SOT Participants With Adjudicated Biopsy-Proven Organ Rejection	A summary of SAEs and all nonserious AEs ("Other"), regardless of causality, is located in the Reported "Adverse Events" section.	Throughout the study period (up to Day 450)
Parts A and B: Number of Healthy Participants With Biopsy-Proven Organ Rejection	A summary of SAEs and all nonserious AEs ("Other"), regardless of causality, is located in the Reported "Adverse Events" section.	Throughout the study period (up to Day 394)
Parts A and B: Number of SOT Participants With Solicited Local and Systemic Adverse Reactions (ARs)	Solicited ARs, including local and systemic ARs were collected in the eDiary. Local ARs included: pain at injection site, erythema (redness) at injection site, swelling/induration (hardness) at injection site, and localized axillary swelling or tenderness ipsilateral to the injection arm. Systemic ARs included: headache, fatigue, myalgia (muscle aches all over the body), arthralgia (aching in several joints), nausea/vomiting, rash, body temperature (potentially fever), and chills. All solicited ARs (local and systemic) considered causally related to injection. ARs were graded 0-4 as reviewed and confirmed by Investigator; lower score indicates lower severity and a higher score indicates greater severity. Note, not all solicited ARs were considered AEs. The Investigator reviewed whether the solicited AR was also to be recorded as an AE. A summary of SAEs and all nonserious AEs ("Other"), regardless of causality, is located in the Reported "Adverse Events" section.	7 days post-vaccination
Parts A and B: Number of Healthy Participants With Solicited Local and Systemic ARs	Solicited ARs, including local and systemic ARs were collected in the eDiary. Local ARs included: pain at injection site, erythema (redness) at injection site, swelling/induration (hardness) at injection site, and localized axillary swelling or tenderness ipsilateral to the injection arm. Systemic ARs included: headache, fatigue, myalgia (muscle aches all over the body), arthralgia (aching in several joints), nausea/vomiting, rash, body temperature (potentially fever), and chills. All solicited ARs (local and systemic) considered causally related to injection. ARs were graded 0-4 as reviewed and confirmed by Investigator; lower score indicates lower severity and a higher score indicates greater severity. Note, not all solicited ARs were considered AEs. The Investigator reviewed whether the solicited AR was also to be recorded as an AE. A summary of SAEs and all nonserious AEs ("Other"), regardless of causality, is located in the Reported "Adverse Events" section.	7 days post-vaccination
Part A: Geometric Mean Concentration (GMC) of Serum SARS-CoV-2-Specific Neutralizing Antibody (nAb) After the Second Dose in Unvaccinated Participants	The GMC of VAC62 antibodies, as measured by pseudovirus neutralization assay (PsVNA) specific to the SARS-CoV-2 spike protein is reported. Antibody values reported as below the lower limit of quantification (LLOQ) were replaced by 0.5*LLOQ. Values that were greater than the upper limit of quantification (ULOQ) were converted to the ULOQ if actual values were not available. LLOQ was 10 and ULOQ was 111433 arbitrary units (AU)/milliliter (mL). The 95% confidence intervals (CIs) were calculated based on the t-distribution of the log-transformed values or the difference in the log-transformed values for GMC value, then back transformed to the original scale for presentation. Results in healthy participants were included as reference not for any comparisons.	Day 57 (for unvaccinated participants)
Part A: GMC of SARS-CoV-2-Specific nAb 28 Days After Dose 3	The GMC of VAC62 antibodies, as measured by PsVNA specific to the SARS-CoV-2 spike protein is reported. Antibody values reported as below the LLOQ were replaced by 0.5*LLOQ. Values that were greater than the ULOQ were converted to the ULOQ if actual values were not available. LLOQ was 10 and ULOQ was 111433 AU/mL. The 95% CIs were calculated based on the t-distribution of the log-transformed values or the difference in the log-transformed values for GMC value, then back transformed to the original scale for presentation.	28 days after Dose 3
Part B: GMC of SARS-CoV-2-Specific nAb 28 Days After the BD in SOT Participants Who Received the Moderna Primary Series and Non-Moderna Primary Series	The GMC of VAC62 antibodies, as measured by PsVNA specific to the SARS-CoV-2 spike protein is reported. Antibody values reported as below the LLOQ were replaced by 0.5*LLOQ. Values that were greater than the ULOQ were converted to the ULOQ if actual values were not available. LLOQ was 10 and ULOQ was 111433 AU/mL. The 95% CIs were calculated based on the t-distribution of the log-transformed values or the difference in the log-transformed values for GMC value, then back transformed to the original scale for presentation.	28 days after BD injection (BD-Day 29)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part A: GMC of SARS-CoV-2-Specific nAb for Unvaccinated Participants Receiving the 2-Dose Regimen	The GMC of VAC62 antibodies, as measured by pseudovirus neutralization assay PsVNA specific to the SARS-CoV-2 spike protein is reported. Antibody values reported as below the LLOQ were replaced by 0.5*LLOQ. Values that were greater than the ULOQ were replaced by the ULOQ if actual values were not available. LLOQ was 10 and ULOQ was 111433 AU/mL. The 95% CIs were calculated based on the t-distribution of the log-transformed values or the difference in the log-transformed values for GMC value, then back transformed to the original scale for presentation. Results in healthy participants were included as reference not for any comparisons. 95% CI cannot be calculated with an 'N' less than 2.	Days 1, 28 days after Dose 1, 28 days after Dose 2, 6 months after Dose 2, and 1 year after Dose 2
Part A: GMC of SARS-CoV-2-Specific nAb for Unvaccinated and Previously Vaccinated Participants Receiving the 3-Dose Regimen	The GMC of VAC62 antibodies, as measured by pseudovirus neutralization assay PsVNA specific to the SARS-CoV-2 spike protein is reported. Antibody values reported as below the LLOQ were replaced by 0.5*LLOQ. Values that were greater than the ULOQ were replaced by the ULOQ if actual values were not available. LLOQ was 10 and ULOQ was 111433 AU/mL. The 95% CIs were calculated based on the t-distribution of the log-transformed values or the difference in the log-transformed values for GMC value, then back transformed to the original scale for presentation. Results in healthy participants were included as reference not for any comparisons.	28 days after Dose 3, 6 months after Dose 3, and 1 year after Dose 3
Part A: GMFR of nAb for Unvaccinated Participants Receiving the 2-Dose Regimen Relative to Day 1	The GMFR measures the changes in immunogenicity titers or levels from Baseline within participants. The GMFR of VAC62 antibodies, as measured by PsVNA specific to the SARS-CoV-2 spike protein is reported. Antibody values reported as below the LLOQ were replaced by 0.5*LLOQ. Values that were greater than the ULOQ were replaced by the ULOQ if actual values were not available. LLOQ was 10 and ULOQ was 111433 AU/mL. The 95% CIs were calculated based on the t-distribution of the log-transformed values or the difference in the log-transformed values for GMC value, then back transformed to the original scale for presentation. Results in healthy participants were included as reference not for any comparisons. 95% CI cannot be calculated with an 'N' less than 2.	28 days after Dose 1, 28 days after Dose 2, 6 months after Dose 2, and 1 year after Dose 2
Part A: GMFR of nAb for Unvaccinated and Previously Vaccinated Participants Receiving the 3-Dose Regimen Relative to Day 1	The GMFR measures the changes in immunogenicity titers or levels from Baseline within participants. The GMFR of VAC62 antibodies, as measured by PsVNA specific to the SARS-CoV-2 spike protein is reported. Antibody values reported as below the LLOQ were replaced by 0.5*LLOQ. Values that were greater than the ULOQ were replaced by the ULOQ if actual values were not available. LLOQ was 10 and ULOQ was 111433 AU/mL. The 95% CIs were calculated based on the t-distribution of the log-transformed values or the difference in the log-transformed values for GMC value, then back transformed to the original scale for presentation. Results in healthy participants were included as reference not for any comparisons.	28 days after Dose 3, 6 months after Dose 3, 1 year after Dose 3
Part A: Geometric Mean (GM) Value of Anti-SARS-CoV-2 S-specific Binding Antibody (bAb) for Unvaccinated Participants Receiving the 2-Dose Regimen	The GM level of VAC123 spike antibodies, as measured by MesoScale Discovery (MSD) electrochemiluminescence (ECL) multiplex assay specific to the SARS-CoV-2 spike protein is reported. Antibody values reported as below the LLOQ were replaced by 0.5*LLOQ. Values that were greater than the ULOQ were replaced by the ULOQ if actual values were not available. LLOQ was 69 and ULOQ was 14400000 AU/mL. The 95% CIs were calculated based on the t-distribution of the log-transformed values or the difference in the log-transformed values for GM value, then back transformed to the original scale for presentation. Results in healthy participants were included as reference not for any comparisons. 95% CI cannot be calculated with an 'N' less than 2.	Days 1, 28 days after Dose 1, 28 days after Dose 2, 6 months after Dose 2, and 1 year after Dose 2
Part A: GM Value of Anti-SARS-CoV-2 S-specific bAb for Unvaccinated and Previously Vaccinated Participants Receiving the 3-Dose Regimen	The GM level of VAC123 spike antibodies, as measured by MSD ECL multiplex assay specific to the SARS-CoV-2 spike protein is reported. Antibody values reported as below the LLOQ were replaced by 0.5*LLOQ. Values that were greater than the ULOQ were replaced by the ULOQ if actual values were not available. LLOQ was 69 and ULOQ was 14400000 AU/mL. The 95% CIs were calculated based on the t-distribution of the log-transformed values or the difference in the log-transformed values for GM value, then back transformed to the original scale for presentation. Results in healthy participants were included as reference not for any comparisons.	28 days after Dose 3, 6 months after Dose 3, and 1 year after Dose 3
Part A: Geometric Mean Fold-Rise (GMFR) of bAb for Unvaccinated Participants Receiving the 2-Dose Regimen Relative to Day 1	The GMFR measures the changes in immunogenicity titers or levels from Baseline within participants. The GMFR of VAC123 spike antibodies, as measured by MSD ECL multiplex assay specific to the SARS-CoV-2 spike protein is reported. Antibody values reported as below the LLOQ were replaced by 0.5*LLOQ. Values that were greater than the ULOQ were replaced by the ULOQ if actual values were not available. LLOQ was 69 and ULOQ was 14400000 AU/mL. The 95% CIs were calculated based on the t-distribution of the log-transformed values or the difference in the log-transformed values for GMFR, then back transformed to the original scale for presentation. Results in healthy participants were included as reference not for any comparisons. 95% CI cannot be calculated with an 'N' less than 2.	28 days after Dose 1, 28 days after Dose 2, 6 months after Dose 2, and 1 year after Dose 2
Part A: GMFR of bAb for Unvaccinated and Previously Vaccinated Participants Receiving the 3-Dose Regimen Relative to Day 1	The GMFR measures the changes in immunogenicity titers or levels from Baseline within participants. The GMFR of VAC123 spike antibodies, as measured by MSD ECL multiplex assay specific to the SARS-CoV-2 spike protein is reported. Antibody values reported as below the LLOQ were replaced by 0.5*LLOQ. Values that were greater than the ULOQ were replaced by the ULOQ if actual values were not available. LLOQ was 69 and ULOQ was 14400000 AU/mL. The 95% CIs were calculated based on the t-distribution of the log-transformed values or the difference in the log-transformed values for GMFR, then back transformed to the original scale for presentation. Results in healthy participants were included as reference not for any comparisons.	28 days after Dose 3, 6 months after Dose 3, 1 year after Dose 3
Part A: Number of SOT Participants With Asymptomatic SARS-CoV-2 Infection	Asymptomatic SARS-CoV-2 infection was identified by absence of COVID-19 symptoms and infections as detected by reverse transcriptase polymerase chain reaction (RT-PCR) central or local test or serology test as binding antibody (bAb) level against SARS-CoV-2 nucleocapsid protein negative (as measured by Roche Elecsys) at Day 1 that became positive (as measured by Roche Elecsys) post-baseline or positive RT-PCR (CLIA-certified central or local) laboratory post-baseline at scheduled or unscheduled/illness visits. A summary of SAEs and all nonserious AEs ("Other") reported up to the end of the study (up to Day 419), regardless of causality, is located in the Reported "Adverse Events" section.	14 days after second and third injection
Part A: Number of Healthy Participants With Asymptomatic SARS-CoV-2 Infection	Asymptomatic SARS-CoV-2 infection was identified by absence of COVID-19 symptoms and infections as detected by reverse transcriptase polymerase chain reaction (RT-PCR1) central or local test or serology test as bAb level against SARS-CoV-2 nucleocapsid protein negative (as measured by Roche Elecsys) at Day 1 that became positive (as measured by Roche Elecsys) post-baseline or positive RT-PCR (CLIA-certified central or local) laboratory post-baseline at scheduled or unscheduled/illness visits. A summary of SAEs and all nonserious AEs ("Other") reported up to the end of the study (up to Day 419), regardless of causality, is located in the Reported "Adverse Events" section.	14 days after second and third injection
Part A: Number of SOT Participants With the Occurrence of COVID-19	COVID-19 case was identified as a positive post-baseline RT-PCR (CLIA-certified central or local) laboratory for SARS-CoV-2, together with at least 2 systemic symptoms: fever (≥ 38 degree celsius [°C]/≥ 100.4 degree fahrenheit [°F]), chills, myalgia, headache, sore throat, new olfactory and taste disorder(s), or at least 1 of the following respiratory signs/symptoms: cough, shortness of breath or difficulty breathing, or clinical or radiographical evidence of pneumonia. A summary of SAEs and all nonserious AEs ("Other") reported up to the end of the study (up to Day 419), regardless of causality, is located in the Reported "Adverse Events" section.	14 days after second and third injection
Part A: Number of Healthy Participants With the Occurrence of COVID-19	COVID-19 case was identified as a positive post-baseline RT-PCR (CLIA-certified central or local) laboratory for SARS-CoV-2, together with at least 2 systemic symptoms: fever (≥ 38°C/≥ 100.4°F), chills, myalgia, headache, sore throat, new olfactory and taste disorder(s), or at least 1 of the following respiratory signs/symptoms: cough, shortness of breath or difficulty breathing, or clinical or radiographical evidence of pneumonia. A summary of SAEs and all nonserious AEs ("Other") reported up to the end of the study (up to Day 419), regardless of causality, is located in the Reported "Adverse Events" section. A summary of SAEs and all nonserious AEs ("Other") reported up to the end of the study (up to Day 419), regardless of causality, is located in the Reported "Adverse Events" section.	14 days after second and third injection
Part A: Number of SOT Participants With the Occurrence of Severe COVID-19	Severe COVID-19 case was identified as a COVID-19 case (RT-PCR [CLIA-certified central or local] laboratory) for SARS-CoV-2, together with any of the following: respiratory rate ≥30 per minute, heart rate ≥125 beats per minute, oxygen saturation(SpO2) ≤93% on room air at sea level, or partial pressure of oxygen (PaO2)/fraction of inspired oxygen (FIO2) <300 millimeters of mercury (mmHg); or respiratory failure or acute respiratory distress syndrome (ARDS), defined as needing high-flow oxygen, noninvasive or mechanical ventilation, or extracorporeal membrane oxygenation) or evidence of shock (systolic blood pressure <90 mm Hg, diastolic BP <60 mm Hg, or requiring vasopressors); or significant acute renal, hepatic, or neurologic dysfunction; OR admission to an intensive care unit or death. A summary of SAEs and all nonserious AEs ("Other") reported up to the end of the study (up to Day 419), regardless of causality, is located in the Reported "Adverse Events" section.	14 days after second and third injection
Part A: Number of Healthy Participants With the Occurrence of Severe COVID-19	Severe COVID-19 case was identified as a COVID-19 case (RT-PCR [CLIA-certified central or local] laboratory) for SARS-CoV-2, together with any of the following: respiratory rate ≥30 per minute, heart rate ≥125 beats per minute, oxygen saturation(SpO2) ≤93% on room air at sea level, or partial pressure of oxygen (PaO2)/fraction of inspired oxygen (FIO2) <300 millimeters of mercury (mmHg); or respiratory failure or acute respiratory distress syndrome (ARDS), defined as needing high-flow oxygen, noninvasive or mechanical ventilation, or extracorporeal membrane oxygenation) or evidence of shock (systolic blood pressure <90 mm Hg, diastolic BP <60 mm Hg, or requiring vasopressors); or significant acute renal, hepatic, or neurologic dysfunction; OR admission to an intensive care unit or death. A summary of SAEs and all nonserious AEs ("Other") reported up to the end of the study (up to Day 419), regardless of causality, is located in the Reported "Adverse Events" section.	14 days after second and third injection
Parts A and B: Number of SOT Participants Who Changed Immunosuppressant Therapy	A summary of serious adverse events (SAEs) and all nonserious AEs ("Other") reported up to the end of the study (up to Day 419), regardless of causality, is located in the Reported "Adverse Events" section.	Throughout the study period (up to Day 450)

Collaborators and Investigators

• Sponsor: ModernaTX, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): April 16, 2021
• Primary Completion (Actual): May 22, 2023
• Study Completion (Actual): May 22, 2023

Study Registration Dates

• First Submitted: April 21, 2021
• First Submitted That Met QC Criteria: April 22, 2021
• First Posted (Actual): April 26, 2021

Study Record Updates

• Last Update Posted (Actual): June 18, 2024
• Last Update Submitted That Met QC Criteria: May 22, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Keywords: SARS-CoV-2; Coronavirus; COVID-19; SARS-CoV-2 Vaccine; Virus Diseases; Moderna; Messenger RNA; COVID-19 Vaccine; mRNA-1273 vaccine; mRNA-1273
• Other Study ID Numbers: mRNA-1273-P304

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No