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

NCT04860297 | Completed Phase 3 Results FDA Drug

• 1 other identifier: mRNA-1273-P304
• Study Type: interventional
• Target: 234
• Locations: 1 country
• Sites: 15

Brief Summary

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.

Conditions

SARS-CoV-2

Keywords

mRNA-1273; mRNA-1273 vaccine; SARS-CoV-2; SARS-CoV-2 Vaccine; Coronavirus; Virus Diseases; Messenger RNA; COVID-19; COVID-19 Vaccine; Moderna

Outcome Measures

Primary Outcomes (17)

• 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 Outcomes (15)

• Part A: GMC of SARS-CoV-2-Specific nAb for Unvaccinated Participants Receiving the 2-Dose Regimen

  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

  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

  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

  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

  Days 1, 28 days after Dose 1, 28 days after Dose 2, 6 months after Dose 2, and 1 year after Dose 2

Study Arms (1)

mRNA-1273

EXPERIMENTAL

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

Interventions

mRNA-1273 BIOLOGICAL

Sterile liquid for injection

mRNA-1273

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• ModernaTX, Inc.: lead

Study Sites (15)

Aventiv Research Inc

Mesa, Arizona, 85206, United States

Location

California Institute of Renal Research

San Diego, California, 92123, United States

Location

Yale University School of Medicine

New Haven, Connecticut, 06519, United States

Location

Tampa General Medical Group

Tampa, Florida, 33606, United States

Location

Piedmont Transplant Institute

Atlanta, Georgia, 30309, United States

Location

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

University of Massachusetts Medical School

Worcester, Massachusetts, 01655, United States

Location

University of Nebraska Medical Center

Omaha, Nebraska, 68198, United States

Location

Northwell Health

Manhasset, New York, 11030, United States

Location

Colombia University Medical Center

New York, New York, 10032, United States

Location

University of Cincinnati

Cincinnati, Ohio, 45219, United States

Location

Cleveland Clinic Hospital

Cleveland, Ohio, 44195, United States

Location

Hospital of The University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Rhode Island Hospital

Providence, Rhode Island, 02903, United States

Location

University of Washington Medical Center

Seattle, Washington, 98195, United States

Location

Related Publications (2)

• Girard B, Figueroa AL, De Rosa SC, McElrath MJ, Azzi JR, Stolman D, Siangphoe U, de Windt E, Miller JM, Das R, Priddy F. mRNA-1273 COVID-19 vaccine induces CD4+ T-cell responses among solid organ transplant recipients. Front Immunol. 2025 Apr 3;16:1505871. doi: 10.3389/fimmu.2025.1505871. eCollection 2025.

  PMID: 40248714 DERIVED

• Figueroa AL, Azzi JR, Eghtesad B, Priddy F, Stolman D, Siangphoe U, Leony Lasso I, de Windt E, Girard B, Zhou H, Miller JM, Das R. Safety and Immunogenicity of the mRNA-1273 Coronavirus Disease 2019 Vaccine in Solid Organ Transplant Recipients. J Infect Dis. 2024 Sep 23;230(3):e591-e600. doi: 10.1093/infdis/jiae140.

  PMID: 38513368 DERIVED

MeSH Terms

Conditions

Coronavirus Infections; Virus Diseases; COVID-19

Interventions

2019-nCoV Vaccine mRNA-1273

Condition Hierarchy (Ancestors)

Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Infections; Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

mRNA Vaccines; Nucleic Acid-Based Vaccines; Vaccines, Synthetic; Recombinant Proteins; Proteins; Amino Acids, Peptides, and Proteins; Vaccines; Biological Products; Complex Mixtures; COVID-19 Vaccines; Viral Vaccines; Antigens; Biological Factors

Limitations and Caveats

Healthy participants cohort was included as a control group in the evaluation of humoral and cell-mediated immune response only; no comparisons of safety data with the healthy participants were made.

Results Point of Contact

• Title: Moderna Clinical Trials Support Center
• Organization: ModernaTX, Inc.

clinicaltrials@modernatx.com

1-877-777-7187

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This is an open-label, single intervention study; there is no randomization

Study Record Dates

• First Submitted: April 21, 2021
• First Posted: April 26, 2021
• Study Start: April 16, 2021
• Primary Completion: May 22, 2023
• Study Completion: May 22, 2023
• Last Updated: June 18, 2024
• Results First Posted: June 18, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (15)