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

ModernaTX, Inc.234 enrolled

Overview

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 Type

INTERVENTIONAL

Allocation

Purpose

PREVENTION

Masking

NONE

Enrollment

234

Conditions

SARS-CoV-2

Interventions

mRNA-1273BIOLOGICAL

Sterile liquid for injection

Eligibility

Sex: ALLMin age: 18 YearsHealthy volunteers:

Medical Language ↔ Plain English

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.

Locations (15)

Aventiv Research Inc

Mesa, Arizona, United States

California Institute of Renal Research

San Diego, California, United States

Outcomes

Primary Outcomes

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.

Time frame: 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.

Time frame: 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.

Time frame: Throughout the study period (up to Day 450)

Parts A and B: Number of Healthy Participants With MAAEs

Data from ClinicalTrials.gov

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Yale University School of Medicine

New Haven, Connecticut, United States

Tampa General Medical Group

Tampa, Florida, United States

Piedmont Transplant Institute

Atlanta, Georgia, United States

Brigham and Women's Hospital

Boston, Massachusetts, United States

University of Massachusetts Medical School

Worcester, Massachusetts, United States

University of Nebraska Medical Center

Omaha, Nebraska, United States

Northwell Health

Manhasset, New York, United States

Colombia University Medical Center

New York, New York, United States

...and 5 more locations

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.

Time frame: 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.

Time frame: Throughout the study period (up to Day 450)

Parts A and B: Number of Healthy Participants With SAEs

Time frame: 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.

Time frame: Throughout the study period (up to Day 450)

Parts A and B: Number of Healthy Participants With AESIs, Including Myocarditis/Pericarditis

Time frame: 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.

Time frame: 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)

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 7 days post-vaccination

Parts A and B: Number of Healthy Participants With Solicited Local and Systemic ARs

Time frame: 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.

Time frame: 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.

Time frame: 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

Time frame: 28 days after BD injection (BD-Day 29)

Secondary Outcomes

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.

Time frame: 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

Time frame: 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.

Time frame: 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

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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

Time frame: 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.