SARS-CoV-2
Conditions
Keywords
mRNA-1273, mRNA-1273 vaccine, SARS-CoV-2, SARS-CoV-2 Vaccine, Coronavirus, Virus Diseases, Messenger RNA, COVID-19, COVID-19 Vaccine, Moderna
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.
Interventions
BIOLOGICALmRNA-1273
Sterile liquid for injection
Sponsors
ModernaTX, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
PREVENTION
Masking
NONE
Intervention model description
This is an open-label, single intervention study; there is no randomization
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 | 28 days after BD injection (BD-Day 29) | 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. |
| Parts A and B: Number of Healthy Participants With Unsolicited AEs | Up to 28 days post-vaccination | 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. |
| Parts A and B: Number of SOT Participants With Medically-Attended Adverse Events (MAAEs) | Throughout the study period (up to Day 450) | 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. |
| Parts A and B: Number of Healthy Participants With MAAEs | Throughout the study period (up to Day 394) | 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. |
| Parts A and B: Number of SOT Participants With Serious Adverse Events (SAEs) | Throughout the study period (up to Day 450) | 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. |
| Parts A and B: Number of Healthy Participants With SAEs | Throughout the study period (up to Day 394) | 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. |
| Parts A and B: Number of SOT Participants With Adverse Event of Special Interests (AESIs), Including Myocarditis/Pericarditis | Throughout the study period (up to Day 450) | 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. |
| Parts A and B: Number of Healthy Participants With AESIs, Including Myocarditis/Pericarditis | Throughout the study period (up to Day 394) | 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. |
| Parts A and B: Number of SOT Participants With AEs Leading to Discontinuation From Dosing and/or Study Participation (Withdrawal) | Throughout the study period (up to Day 450) | 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. |
| Parts A and B: Number of Healthy Participants With AEs Leading to Discontinuation From Dosing and/or Study Participation (Withdrawal) | Throughout the study period (up to Day 394) | 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. |
| Parts A and B: Number of SOT Participants With Adjudicated Biopsy-Proven Organ Rejection | Throughout the study period (up to Day 450) | A summary of SAEs and all nonserious AEs (Other), regardless of causality, is located in the Reported Adverse Events section. |
| Parts A and B: Number of Healthy Participants With Biopsy-Proven Organ Rejection | Throughout the study period (up to Day 394) | A summary of SAEs and all nonserious AEs (Other), regardless of causality, is located in the Reported Adverse Events section. |
| Parts A and B: Number of SOT Participants With Solicited Local and Systemic Adverse Reactions (ARs) | 7 days post-vaccination | 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. |
| Parts A and B: Number of Healthy Participants With Solicited Local and Systemic ARs | 7 days post-vaccination | 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. |
| Part A: Geometric Mean Concentration (GMC) of Serum SARS-CoV-2-Specific Neutralizing Antibody (nAb) After the Second Dose in Unvaccinated Participants | Day 57 (for 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. |
| Part A: GMC of SARS-CoV-2-Specific nAb 28 Days After Dose 3 | 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. |
| Parts A and B: Number of SOT Participants With Unsolicited Adverse Events (AEs) | Up to 28 days post-vaccination | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | 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. |
| 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 | 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. |
| 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 | 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. |
| 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 | 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. |
| Part A: GM Value of Anti-SARS-CoV-2 S-specific bAb 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 | 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. |
| Part A: Geometric Mean Fold-Rise (GMFR) of bAb 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 | 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. |
| Part A: GMFR of bAb 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 | 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. |
| Part A: Number of SOT Participants With Asymptomatic SARS-CoV-2 Infection | 14 days after second and third injection | 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. |
| Part A: Number of Healthy Participants With Asymptomatic SARS-CoV-2 Infection | 14 days after second and third injection | 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. |
| Part A: Number of SOT Participants With the Occurrence of COVID-19 | 14 days after second and third injection | 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. |
| Part A: Number of Healthy Participants With the Occurrence of COVID-19 | 14 days after second and third injection | 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. |
| Part A: Number of SOT Participants With the Occurrence of Severe COVID-19 | 14 days after second and third injection | 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. |
| Part A: Number of Healthy Participants With the Occurrence of Severe COVID-19 | 14 days after second and third injection | 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. |
| Parts A and B: Number of SOT Participants Who Changed Immunosuppressant Therapy | Throughout the study period (up to Day 450) | 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. |
| 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 | 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. |
Countries
United States
Participant flow
Recruitment details
A total of 214 solid organ transplant (SOT) participants (137 SOT kidney and 77 SOT liver participants) and 20 healthy participants were enrolled for the study.
Pre-assignment details
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. Data reported for each arm in the Outcome Measures as specified in the Outcome Measure title.
Participants by arm
| Arm | Count |
|---|---|
| SOT Kidney Participants Unvaccinated or previously vaccinated SOT kidney participants received up to 3 100-μg doses of mRNA-1273 vaccine in Part A and a single 100-μg BD of mRNA-1273 vaccine in Part B. | 137 |
| SOT Liver Participants Unvaccinated or previously vaccinated SOT liver participants received up to 3 100-μg doses of mRNA-1273 vaccine in Part A and a single 100-μg BD of mRNA-1273 vaccine in Part B. | 77 |
| Healthy Participants Healthy participants received 2 doses of mRNA-1273 vaccine in Part A and a single 100-μg BD of mRNA-1273 vaccine in Part B. | 20 |
| Total | 234 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 |
|---|---|---|---|---|---|---|---|---|---|
| Part A (Primary Series) | Lost to Follow-up | 1 | 0 | 0 | 2 | 0 | 0 | 0 | 0 |
| Part A (Primary Series) | Withdrawal by Subject | 0 | 1 | 0 | 1 | 0 | 0 | 0 | 0 |
| Part B (Booster Dose) | Death | 0 | 0 | 0 | 0 | 1 | 2 | 1 | 0 |
| Part B (Booster Dose) | Lost to Follow-up | 0 | 0 | 0 | 0 | 3 | 5 | 1 | 2 |
| Part B (Booster Dose) | Other Than Specified | 0 | 0 | 0 | 0 | 0 | 1 | 1 | 0 |
| Part B (Booster Dose) | Protocol Deviation | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
| Part B (Booster Dose) | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 2 | 0 | 1 |
Baseline characteristics
| Characteristic | SOT Kidney Participants | SOT Liver Participants | Healthy Participants | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 29 Participants | 19 Participants | 2 Participants | 50 Participants |
| Age, Categorical Between 18 and 65 years | 108 Participants | 58 Participants | 18 Participants | 184 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 15 Participants | 5 Participants | 2 Participants | 22 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 121 Participants | 71 Participants | 18 Participants | 210 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 0 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Asian | 8 Participants | 3 Participants | 2 Participants | 13 Participants |
| Race (NIH/OMB) Black or African American | 23 Participants | 13 Participants | 3 Participants | 39 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 2 Participants | 0 Participants | 3 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 10 Participants | 4 Participants | 3 Participants | 17 Participants |
| Race (NIH/OMB) White | 94 Participants | 55 Participants | 11 Participants | 160 Participants |
| Sex: Female, Male Female | 62 Participants | 38 Participants | 10 Participants | 110 Participants |
| Sex: Female, Male Male | 75 Participants | 39 Participants | 10 Participants | 124 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 | 4 / 137 | 0 / 77 | 4 / 214 | 0 / 20 |
| other Total, other adverse events | 49 / 137 | 38 / 77 | 87 / 214 | 13 / 20 |
| serious Total, serious adverse events | 28 / 137 | 17 / 77 | 45 / 214 | 1 / 20 |
Outcome results
Primary
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)
Population: The per protocol (PP) immunogenicity set (Part A) included all participants who received at least 1 dose of study drug, had no immunologic/virologic evidence of prior COVID-19 at baseline/pre-vaccination, had post-injection results available for at least 1 assay component corresponding to the immunogenicity analysis objective, and had no major protocol deviations that impacted immune response. 'Overall number of participants analyzed' = participants analyzed for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| SOT Kidney Participants | Part A: Geometric Mean Concentration (GMC) of Serum SARS-CoV-2-Specific Neutralizing Antibody (nAb) After the Second Dose in Unvaccinated Participants | 54.2 AU/mL |
| SOT Liver Participants | Part A: Geometric Mean Concentration (GMC) of Serum SARS-CoV-2-Specific Neutralizing Antibody (nAb) After the Second Dose in Unvaccinated Participants | 187.9 AU/mL |
| SOT Total | Part A: Geometric Mean Concentration (GMC) of Serum SARS-CoV-2-Specific Neutralizing Antibody (nAb) After the Second Dose in Unvaccinated Participants | 1658.4 AU/mL |
Primary
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
Population: The PP immunogenicity set (Part A) included all participants who received at least 1 dose of study drug, had no immunologic/virologic evidence of prior COVID-19 at baseline/pre-vaccination, had post-injection results available for at least 1 assay component corresponding to the immunogenicity analysis objective, and had no major protocol deviations that impacted immune response. 'Overall number of participants analyzed' = participants analyzed for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| SOT Kidney Participants | Part A: GMC of SARS-CoV-2-Specific nAb 28 Days After Dose 3 | 353.5 AU/mL |
| SOT Liver Participants | Part A: GMC of SARS-CoV-2-Specific nAb 28 Days After Dose 3 | 1340.2 AU/mL |
| SOT Total | Part A: GMC of SARS-CoV-2-Specific nAb 28 Days After Dose 3 | 538.4 AU/mL |
Primary
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.
Time frame: 28 days after BD injection (BD-Day 29)
Population: The PP set (Part B) included all participants who received BD of study drug, had no immunologic or virologic evidence of prior COVID-19 at pre-booster before the BD, had post-booster results available for at least 1 assay component corresponding to the immunogenicity analysis objective, and had no major protocol deviations that impacted immune response during the period corresponding to the immunogenicity analysis objective.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| SOT Kidney Participants | 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 | 430.7 AU/mL |
| SOT Liver Participants | 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 | 3946.0 AU/mL |
Primary
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.
Time frame: Throughout the study period (up to Day 394)
Population: Safety set included all participants who received at least 1 dose of study drug in this study.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| SOT Kidney Participants | Parts A and B: Number of Healthy Participants With AESIs, Including Myocarditis/Pericarditis | 1 Participants |
Primary
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.
Time frame: Throughout the study period (up to Day 394)
Population: Safety set included all participants who received at least 1 dose of study drug in this study.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| SOT Kidney Participants | Parts A and B: Number of Healthy Participants With AEs Leading to Discontinuation From Dosing and/or Study Participation (Withdrawal) | 0 Participants |
Primary
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)
Population: Safety set included all participants who received at least 1 dose of study drug in this study.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| SOT Kidney Participants | Parts A and B: Number of Healthy Participants With Biopsy-Proven Organ Rejection | 0 Participants |
Primary
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.
Time frame: Throughout the study period (up to Day 394)
Population: Safety set included all participants who received at least 1 dose of study drug in this study.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| SOT Kidney Participants | Parts A and B: Number of Healthy Participants With MAAEs | 14 Participants |
Primary
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.
Time frame: Throughout the study period (up to Day 394)
Population: Safety set included all participants who received at least 1 dose of study drug in this study.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| SOT Kidney Participants | Parts A and B: Number of Healthy Participants With SAEs | 1 Participants |
Primary
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.
Time frame: 7 days post-vaccination
Population: Any study injection solicited safety set included all participants who received any (first, second, third, or booster) study injection and contributed any solicited AR data following that injection.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| SOT Kidney Participants | Parts A and B: Number of Healthy Participants With Solicited Local and Systemic ARs | Solicited Local ARs | 16 Participants |
| SOT Kidney Participants | Parts A and B: Number of Healthy Participants With Solicited Local and Systemic ARs | Solicited Systemic ARs | 19 Participants |
Primary
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
Population: Safety set included all participants who received at least 1 dose of study drug in this study.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| SOT Kidney Participants | Parts A and B: Number of Healthy Participants With Unsolicited AEs | 12 Participants |
Primary
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)
Population: Safety set included all participants who received at least 1 dose of study drug in this study.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| SOT Kidney Participants | Parts A and B: Number of SOT Participants With Adjudicated Biopsy-Proven Organ Rejection | 1 Participants |
| SOT Liver Participants | Parts A and B: Number of SOT Participants With Adjudicated Biopsy-Proven Organ Rejection | 2 Participants |
| SOT Total | Parts A and B: Number of SOT Participants With Adjudicated Biopsy-Proven Organ Rejection | 3 Participants |
Primary
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)
Population: Safety set included all participants who received at least 1 dose of study drug in this study.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| SOT Kidney Participants | Parts A and B: Number of SOT Participants With Adverse Event of Special Interests (AESIs), Including Myocarditis/Pericarditis | 15 Participants |
| SOT Liver Participants | Parts A and B: Number of SOT Participants With Adverse Event of Special Interests (AESIs), Including Myocarditis/Pericarditis | 13 Participants |
| SOT Total | Parts A and B: Number of SOT Participants With Adverse Event of Special Interests (AESIs), Including Myocarditis/Pericarditis | 28 Participants |
Primary
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)
Population: Safety set included all participants who received at least 1 dose of study drug in this study.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| SOT Kidney Participants | Parts A and B: Number of SOT Participants With AEs Leading to Discontinuation From Dosing and/or Study Participation (Withdrawal) | 4 Participants |
| SOT Liver Participants | Parts A and B: Number of SOT Participants With AEs Leading to Discontinuation From Dosing and/or Study Participation (Withdrawal) | 0 Participants |
| SOT Total | Parts A and B: Number of SOT Participants With AEs Leading to Discontinuation From Dosing and/or Study Participation (Withdrawal) | 4 Participants |
Primary
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)
Population: Safety set included all participants who received at least 1 dose of study drug in this study.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| SOT Kidney Participants | Parts A and B: Number of SOT Participants With Medically-Attended Adverse Events (MAAEs) | 86 Participants |
| SOT Liver Participants | Parts A and B: Number of SOT Participants With Medically-Attended Adverse Events (MAAEs) | 56 Participants |
| SOT Total | Parts A and B: Number of SOT Participants With Medically-Attended Adverse Events (MAAEs) | 142 Participants |
Primary
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)
Population: Safety set included all participants who received at least 1 dose of study drug in this study.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| SOT Kidney Participants | Parts A and B: Number of SOT Participants With Serious Adverse Events (SAEs) | 29 Participants |
| SOT Liver Participants | Parts A and B: Number of SOT Participants With Serious Adverse Events (SAEs) | 19 Participants |
| SOT Total | Parts A and B: Number of SOT Participants With Serious Adverse Events (SAEs) | 48 Participants |
Primary
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
Population: Any study injection solicited safety set included all participants who received any (first, second, third, or booster) study injection and contributed any solicited AR data following that injection. Here, 'Number analyzed' signifies participants evaluable for the specified category.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| SOT Kidney Participants | Parts A and B: Number of SOT Participants With Solicited Local and Systemic Adverse Reactions (ARs) | Solicited Local ARs | 116 Participants |
| SOT Kidney Participants | Parts A and B: Number of SOT Participants With Solicited Local and Systemic Adverse Reactions (ARs) | Solicited Systemic ARs | 102 Participants |
| SOT Liver Participants | Parts A and B: Number of SOT Participants With Solicited Local and Systemic Adverse Reactions (ARs) | Solicited Local ARs | 65 Participants |
| SOT Liver Participants | Parts A and B: Number of SOT Participants With Solicited Local and Systemic Adverse Reactions (ARs) | Solicited Systemic ARs | 70 Participants |
| SOT Total | Parts A and B: Number of SOT Participants With Solicited Local and Systemic Adverse Reactions (ARs) | Solicited Local ARs | 181 Participants |
| SOT Total | Parts A and B: Number of SOT Participants With Solicited Local and Systemic Adverse Reactions (ARs) | Solicited Systemic ARs | 172 Participants |
Primary
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
Population: Safety set included all participants who received at least 1 dose of study drug in this study.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| SOT Kidney Participants | Parts A and B: Number of SOT Participants With Unsolicited Adverse Events (AEs) | 48 Participants |
| SOT Liver Participants | Parts A and B: Number of SOT Participants With Unsolicited Adverse Events (AEs) | 41 Participants |
| SOT Total | Parts A and B: Number of SOT Participants With Unsolicited Adverse Events (AEs) | 89 Participants |
Secondary
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
Population: PP immunogenicity set (Part A): all participants who received at least 1 dose of study drug, had no immunologic/virologic evidence of prior COVID-19 at baseline, had post-injection results available for at least 1 assay component corresponding to immunogenicity analysis, and had no major protocol deviations that impacted immune response. 'Overall number of participants analyzed' = participants analyzed for this outcome measure. 'Number analyzed' = participants evaluable at specified timepoint.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| SOT Kidney Participants | Part A: Geometric Mean Fold-Rise (GMFR) of bAb for Unvaccinated Participants Receiving the 2-Dose Regimen Relative to Day 1 | 28 days after Dose 1 | 4.9 ratio |
| SOT Kidney Participants | Part A: Geometric Mean Fold-Rise (GMFR) of bAb for Unvaccinated Participants Receiving the 2-Dose Regimen Relative to Day 1 | 28 days after Dose 2 | 45.4 ratio |
| SOT Kidney Participants | Part A: Geometric Mean Fold-Rise (GMFR) of bAb for Unvaccinated Participants Receiving the 2-Dose Regimen Relative to Day 1 | 6 months after Dose 2 | 2448.1 ratio |
| SOT Kidney Participants | Part A: Geometric Mean Fold-Rise (GMFR) of bAb for Unvaccinated Participants Receiving the 2-Dose Regimen Relative to Day 1 | 1 year after Dose 2 | 1299.4 ratio |
| SOT Liver Participants | Part A: Geometric Mean Fold-Rise (GMFR) of bAb for Unvaccinated Participants Receiving the 2-Dose Regimen Relative to Day 1 | 1 year after Dose 2 | 4865.6 ratio |
| SOT Liver Participants | Part A: Geometric Mean Fold-Rise (GMFR) of bAb for Unvaccinated Participants Receiving the 2-Dose Regimen Relative to Day 1 | 28 days after Dose 1 | 20.5 ratio |
| SOT Liver Participants | Part A: Geometric Mean Fold-Rise (GMFR) of bAb for Unvaccinated Participants Receiving the 2-Dose Regimen Relative to Day 1 | 6 months after Dose 2 | 5884.0 ratio |
| SOT Liver Participants | Part A: Geometric Mean Fold-Rise (GMFR) of bAb for Unvaccinated Participants Receiving the 2-Dose Regimen Relative to Day 1 | 28 days after Dose 2 | 399.0 ratio |
| SOT Total | Part A: Geometric Mean Fold-Rise (GMFR) of bAb for Unvaccinated Participants Receiving the 2-Dose Regimen Relative to Day 1 | 1 year after Dose 2 | 2567.2 ratio |
| SOT Total | Part A: Geometric Mean Fold-Rise (GMFR) of bAb for Unvaccinated Participants Receiving the 2-Dose Regimen Relative to Day 1 | 28 days after Dose 2 | 5092.9 ratio |
| SOT Total | Part A: Geometric Mean Fold-Rise (GMFR) of bAb for Unvaccinated Participants Receiving the 2-Dose Regimen Relative to Day 1 | 6 months after Dose 2 | 1710.0 ratio |
| SOT Total | Part A: Geometric Mean Fold-Rise (GMFR) of bAb for Unvaccinated Participants Receiving the 2-Dose Regimen Relative to Day 1 | 28 days after Dose 1 | 441.9 ratio |
Secondary
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
Population: PP immunogenicity set (Part A): all participants who received at least 1 dose of study drug, had no immunologic/virologic evidence of prior COVID-19 at baseline, had post-injection results available for at least 1 assay component corresponding to immunogenicity analysis, and had no major protocol deviations that impacted immune response. 'Overall number of participants analyzed' = participants analyzed for this outcome measure. 'Number analyzed' = participants evaluable at specified timepoint.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| SOT Kidney Participants | Part A: Geometric Mean (GM) Value of Anti-SARS-CoV-2 S-specific Binding Antibody (bAb) for Unvaccinated Participants Receiving the 2-Dose Regimen | 6 months after Dose 2 | 84460.0 AU/mL |
| SOT Kidney Participants | Part A: Geometric Mean (GM) Value of Anti-SARS-CoV-2 S-specific Binding Antibody (bAb) for Unvaccinated Participants Receiving the 2-Dose Regimen | 28 days after Dose 2 | 3190.1 AU/mL |
| SOT Kidney Participants | Part A: Geometric Mean (GM) Value of Anti-SARS-CoV-2 S-specific Binding Antibody (bAb) for Unvaccinated Participants Receiving the 2-Dose Regimen | Day 1 | 68.3 AU/mL |
| SOT Kidney Participants | Part A: Geometric Mean (GM) Value of Anti-SARS-CoV-2 S-specific Binding Antibody (bAb) for Unvaccinated Participants Receiving the 2-Dose Regimen | 28 days after Dose 1 | 346.4 AU/mL |
| SOT Kidney Participants | Part A: Geometric Mean (GM) Value of Anti-SARS-CoV-2 S-specific Binding Antibody (bAb) for Unvaccinated Participants Receiving the 2-Dose Regimen | 1 year after Dose 2 | 44828.0 AU/mL |
| SOT Liver Participants | Part A: Geometric Mean (GM) Value of Anti-SARS-CoV-2 S-specific Binding Antibody (bAb) for Unvaccinated Participants Receiving the 2-Dose Regimen | 28 days after Dose 2 | 20734.0 AU/mL |
| SOT Liver Participants | Part A: Geometric Mean (GM) Value of Anti-SARS-CoV-2 S-specific Binding Antibody (bAb) for Unvaccinated Participants Receiving the 2-Dose Regimen | Day 1 | 59.1 AU/mL |
| SOT Liver Participants | Part A: Geometric Mean (GM) Value of Anti-SARS-CoV-2 S-specific Binding Antibody (bAb) for Unvaccinated Participants Receiving the 2-Dose Regimen | 28 days after Dose 1 | 1213.9 AU/mL |
| SOT Liver Participants | Part A: Geometric Mean (GM) Value of Anti-SARS-CoV-2 S-specific Binding Antibody (bAb) for Unvaccinated Participants Receiving the 2-Dose Regimen | 6 months after Dose 2 | 202997.0 AU/mL |
| SOT Liver Participants | Part A: Geometric Mean (GM) Value of Anti-SARS-CoV-2 S-specific Binding Antibody (bAb) for Unvaccinated Participants Receiving the 2-Dose Regimen | 1 year after Dose 2 | 167863.0 AU/mL |
| SOT Total | Part A: Geometric Mean (GM) Value of Anti-SARS-CoV-2 S-specific Binding Antibody (bAb) for Unvaccinated Participants Receiving the 2-Dose Regimen | 1 year after Dose 2 | 161241.8 AU/mL |
| SOT Total | Part A: Geometric Mean (GM) Value of Anti-SARS-CoV-2 S-specific Binding Antibody (bAb) for Unvaccinated Participants Receiving the 2-Dose Regimen | 6 months after Dose 2 | 97534.9 AU/mL |
| SOT Total | Part A: Geometric Mean (GM) Value of Anti-SARS-CoV-2 S-specific Binding Antibody (bAb) for Unvaccinated Participants Receiving the 2-Dose Regimen | Day 1 | 53.6 AU/mL |
| SOT Total | Part A: Geometric Mean (GM) Value of Anti-SARS-CoV-2 S-specific Binding Antibody (bAb) for Unvaccinated Participants Receiving the 2-Dose Regimen | 28 days after Dose 2 | 272797.7 AU/mL |
| SOT Total | Part A: Geometric Mean (GM) Value of Anti-SARS-CoV-2 S-specific Binding Antibody (bAb) for Unvaccinated Participants Receiving the 2-Dose Regimen | 28 days after Dose 1 | 23668.2 AU/mL |
Secondary
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.
Time frame: 28 days after Dose 3, 6 months after Dose 3, and 1 year after Dose 3
Population: PP immunogenicity set (Part A): all participants who received at least 1 dose of study drug, had no immunologic/virologic evidence of prior COVID-19 at baseline, had post-injection results available for at least 1 assay component corresponding to immunogenicity analysis, and had no major protocol deviations that impacted immune response. 'Overall number of participants analyzed' = participants analyzed for this outcome measure. 'Number analyzed' = participants evaluable at specified timepoint.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| SOT Kidney Participants | Part A: GMC of SARS-CoV-2-Specific nAb for Unvaccinated and Previously Vaccinated Participants Receiving the 3-Dose Regimen | 6 months after Dose 3 | 222.5 AU/mL |
| SOT Kidney Participants | 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 | 353.5 AU/mL |
| SOT Kidney Participants | Part A: GMC of SARS-CoV-2-Specific nAb for Unvaccinated and Previously Vaccinated Participants Receiving the 3-Dose Regimen | 1 year after Dose 3 | 990.7 AU/mL |
| SOT Liver Participants | Part A: GMC of SARS-CoV-2-Specific nAb for Unvaccinated and Previously Vaccinated Participants Receiving the 3-Dose Regimen | 6 months after Dose 3 | 867.2 AU/mL |
| SOT Liver Participants | 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 | 1340.2 AU/mL |
| SOT Liver Participants | Part A: GMC of SARS-CoV-2-Specific nAb for Unvaccinated and Previously Vaccinated Participants Receiving the 3-Dose Regimen | 1 year after Dose 3 | 480.8 AU/mL |
| SOT Total | 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 | 538.4 AU/mL |
| SOT Total | Part A: GMC of SARS-CoV-2-Specific nAb for Unvaccinated and Previously Vaccinated Participants Receiving the 3-Dose Regimen | 1 year after Dose 3 | 899.7 AU/mL |
| SOT Total | Part A: GMC of SARS-CoV-2-Specific nAb for Unvaccinated and Previously Vaccinated Participants Receiving the 3-Dose Regimen | 6 months after Dose 3 | 292.1 AU/mL |
Secondary
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
Population: PP immunogenicity set (Part A): all participants who received at least 1 dose of study drug, had no immunologic/virologic evidence of prior COVID-19 at baseline, had post-injection results available for at least 1 assay component corresponding to immunogenicity analysis, and had no major protocol deviations that impacted immune response. 'Overall number of participants analyzed' = participants analyzed for this outcome measure. 'Number analyzed' = participants evaluable at specified timepoint.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| SOT Kidney Participants | Part A: GMC of SARS-CoV-2-Specific nAb for Unvaccinated Participants Receiving the 2-Dose Regimen | 6 months after Dose 2 | 859.0 AU/mL |
| SOT Kidney Participants | Part A: GMC of SARS-CoV-2-Specific nAb for Unvaccinated Participants Receiving the 2-Dose Regimen | 28 days after Dose 2 | 54.2 AU/mL |
| SOT Kidney Participants | Part A: GMC of SARS-CoV-2-Specific nAb for Unvaccinated Participants Receiving the 2-Dose Regimen | Day 1 | 13.9 AU/mL |
| SOT Kidney Participants | Part A: GMC of SARS-CoV-2-Specific nAb for Unvaccinated Participants Receiving the 2-Dose Regimen | 28 days after Dose 1 | 18.6 AU/mL |
| SOT Kidney Participants | Part A: GMC of SARS-CoV-2-Specific nAb for Unvaccinated Participants Receiving the 2-Dose Regimen | 1 year after Dose 2 | 412.0 AU/mL |
| SOT Liver Participants | Part A: GMC of SARS-CoV-2-Specific nAb for Unvaccinated Participants Receiving the 2-Dose Regimen | 28 days after Dose 2 | 187.9 AU/mL |
| SOT Liver Participants | Part A: GMC of SARS-CoV-2-Specific nAb for Unvaccinated Participants Receiving the 2-Dose Regimen | Day 1 | 13.6 AU/mL |
| SOT Liver Participants | Part A: GMC of SARS-CoV-2-Specific nAb for Unvaccinated Participants Receiving the 2-Dose Regimen | 28 days after Dose 1 | 28.4 AU/mL |
| SOT Liver Participants | Part A: GMC of SARS-CoV-2-Specific nAb for Unvaccinated Participants Receiving the 2-Dose Regimen | 6 months after Dose 2 | 4134.0 AU/mL |
| SOT Liver Participants | Part A: GMC of SARS-CoV-2-Specific nAb for Unvaccinated Participants Receiving the 2-Dose Regimen | 1 year after Dose 2 | 7285.0 AU/mL |
| SOT Total | Part A: GMC of SARS-CoV-2-Specific nAb for Unvaccinated Participants Receiving the 2-Dose Regimen | 1 year after Dose 2 | 1439.3 AU/mL |
| SOT Total | Part A: GMC of SARS-CoV-2-Specific nAb for Unvaccinated Participants Receiving the 2-Dose Regimen | 6 months after Dose 2 | 948.5 AU/mL |
| SOT Total | Part A: GMC of SARS-CoV-2-Specific nAb for Unvaccinated Participants Receiving the 2-Dose Regimen | Day 1 | 11.2 AU/mL |
| SOT Total | Part A: GMC of SARS-CoV-2-Specific nAb for Unvaccinated Participants Receiving the 2-Dose Regimen | 28 days after Dose 2 | 1658.4 AU/mL |
| SOT Total | Part A: GMC of SARS-CoV-2-Specific nAb for Unvaccinated Participants Receiving the 2-Dose Regimen | 28 days after Dose 1 | 58.2 AU/mL |
Secondary
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.
Time frame: 28 days after Dose 3, 6 months after Dose 3, 1 year after Dose 3
Population: PP immunogenicity set (Part A): all participants who received at least 1 dose of study drug, had no immunologic/virologic evidence of prior COVID-19 at baseline, had post-injection results available for at least 1 assay component corresponding to immunogenicity analysis, and had no major protocol deviations that impacted immune response. 'Overall number of participants analyzed' = participants analyzed for this outcome measure. 'Number analyzed' = participants evaluable at specified timepoint.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| SOT Kidney Participants | Part A: GMFR of bAb for Unvaccinated and Previously Vaccinated Participants Receiving the 3-Dose Regimen Relative to Day 1 | 6 months after Dose 3 | 554.9 ratio |
| SOT Kidney Participants | Part A: GMFR of bAb for Unvaccinated and Previously Vaccinated Participants Receiving the 3-Dose Regimen Relative to Day 1 | 28 days after Dose 3 | 275.5 ratio |
| SOT Kidney Participants | Part A: GMFR of bAb for Unvaccinated and Previously Vaccinated Participants Receiving the 3-Dose Regimen Relative to Day 1 | 1 year after Dose 3 | 690.8 ratio |
| SOT Liver Participants | Part A: GMFR of bAb for Unvaccinated and Previously Vaccinated Participants Receiving the 3-Dose Regimen Relative to Day 1 | 6 months after Dose 3 | 824.1 ratio |
| SOT Liver Participants | Part A: GMFR of bAb for Unvaccinated and Previously Vaccinated Participants Receiving the 3-Dose Regimen Relative to Day 1 | 28 days after Dose 3 | 1556.2 ratio |
| SOT Liver Participants | Part A: GMFR of bAb for Unvaccinated and Previously Vaccinated Participants Receiving the 3-Dose Regimen Relative to Day 1 | 1 year after Dose 3 | 746.2 ratio |
| SOT Total | Part A: GMFR of bAb for Unvaccinated and Previously Vaccinated Participants Receiving the 3-Dose Regimen Relative to Day 1 | 28 days after Dose 3 | 490.7 ratio |
| SOT Total | Part A: GMFR of bAb for Unvaccinated and Previously Vaccinated Participants Receiving the 3-Dose Regimen Relative to Day 1 | 1 year after Dose 3 | 701.5 ratio |
| SOT Total | Part A: GMFR of bAb for Unvaccinated and Previously Vaccinated Participants Receiving the 3-Dose Regimen Relative to Day 1 | 6 months after Dose 3 | 633.1 ratio |
Secondary
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.
Time frame: 28 days after Dose 3, 6 months after Dose 3, 1 year after Dose 3
Population: PP immunogenicity set (Part A): all participants who received at least 1 dose of study drug, had no immunologic/virologic evidence of prior COVID-19 at baseline, had post-injection results available for at least 1 assay component corresponding to immunogenicity analysis, and had no major protocol deviations that impacted immune response. 'Overall number of participants analyzed' = participants analyzed for this outcome measure. 'Number analyzed' = participants evaluable at specified timepoint.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| SOT Kidney Participants | Part A: GMFR of nAb for Unvaccinated and Previously Vaccinated Participants Receiving the 3-Dose Regimen Relative to Day 1 | 6 months after Dose 3 | 16.2 ratio |
| SOT Kidney Participants | 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 | 16.6 ratio |
| SOT Kidney Participants | Part A: GMFR of nAb for Unvaccinated and Previously Vaccinated Participants Receiving the 3-Dose Regimen Relative to Day 1 | 1 year after Dose 3 | 990.7 ratio |
| SOT Liver Participants | Part A: GMFR of nAb for Unvaccinated and Previously Vaccinated Participants Receiving the 3-Dose Regimen Relative to Day 1 | 6 months after Dose 3 | 65.8 ratio |
| SOT Liver Participants | 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 | 56.8 ratio |
| SOT Liver Participants | Part A: GMFR of nAb for Unvaccinated and Previously Vaccinated Participants Receiving the 3-Dose Regimen Relative to Day 1 | 1 year after Dose 3 | 480.8 ratio |
| SOT Total | 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 | 25.0 ratio |
| SOT Total | Part A: GMFR of nAb for Unvaccinated and Previously Vaccinated Participants Receiving the 3-Dose Regimen Relative to Day 1 | 1 year after Dose 3 | 899.7 ratio |
| SOT Total | Part A: GMFR of nAb for Unvaccinated and Previously Vaccinated Participants Receiving the 3-Dose Regimen Relative to Day 1 | 6 months after Dose 3 | 25.8 ratio |
Secondary
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
Population: PP immunogenicity set (Part A): all participants who received at least 1 dose of study drug, had no immunologic/virologic evidence of prior COVID-19 at baseline, had post-injection results available for at least 1 assay component corresponding to immunogenicity analysis, and had no major protocol deviations that impacted immune response. 'Overall number of participants analyzed' = participants analyzed for this outcome measure. 'Number analyzed' = participants evaluable at specified timepoint.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| SOT Kidney Participants | Part A: GMFR of nAb for Unvaccinated Participants Receiving the 2-Dose Regimen Relative to Day 1 | 28 days after Dose 1 | 1.3 ratio |
| SOT Kidney Participants | Part A: GMFR of nAb for Unvaccinated Participants Receiving the 2-Dose Regimen Relative to Day 1 | 28 days after Dose 2 | 3.7 ratio |
| SOT Kidney Participants | Part A: GMFR of nAb for Unvaccinated Participants Receiving the 2-Dose Regimen Relative to Day 1 | 6 months after Dose 2 | 171.8 ratio |
| SOT Kidney Participants | Part A: GMFR of nAb for Unvaccinated Participants Receiving the 2-Dose Regimen Relative to Day 1 | 1 year after Dose 2 | 82.4 ratio |
| SOT Liver Participants | Part A: GMFR of nAb for Unvaccinated Participants Receiving the 2-Dose Regimen Relative to Day 1 | 1 year after Dose 2 | 1457.0 ratio |
| SOT Liver Participants | Part A: GMFR of nAb for Unvaccinated Participants Receiving the 2-Dose Regimen Relative to Day 1 | 28 days after Dose 1 | 2.1 ratio |
| SOT Liver Participants | Part A: GMFR of nAb for Unvaccinated Participants Receiving the 2-Dose Regimen Relative to Day 1 | 6 months after Dose 2 | 826.8 ratio |
| SOT Liver Participants | Part A: GMFR of nAb for Unvaccinated Participants Receiving the 2-Dose Regimen Relative to Day 1 | 28 days after Dose 2 | 13.8 ratio |
| SOT Total | Part A: GMFR of nAb for Unvaccinated Participants Receiving the 2-Dose Regimen Relative to Day 1 | 1 year after Dose 2 | 145.1 ratio |
| SOT Total | Part A: GMFR of nAb for Unvaccinated Participants Receiving the 2-Dose Regimen Relative to Day 1 | 28 days after Dose 2 | 148.4 ratio |
| SOT Total | Part A: GMFR of nAb for Unvaccinated Participants Receiving the 2-Dose Regimen Relative to Day 1 | 6 months after Dose 2 | 96.4 ratio |
| SOT Total | Part A: GMFR of nAb for Unvaccinated Participants Receiving the 2-Dose Regimen Relative to Day 1 | 28 days after Dose 1 | 5.2 ratio |
Secondary
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
Population: PP immunogenicity set (Part A): all participants who received at least 1 dose of study drug, had no immunologic/virologic evidence of prior COVID-19 at baseline, had post-injection results available for at least 1 assay component corresponding to immunogenicity analysis, and had no major protocol deviations that impacted immune response. 'Overall number of participants analyzed' = participants analyzed for this outcome measure. 'Number analyzed' = participants evaluable at specified timepoint.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| SOT Kidney Participants | Part A: GM Value of Anti-SARS-CoV-2 S-specific bAb for Unvaccinated and Previously Vaccinated Participants Receiving the 3-Dose Regimen | 6 months after Dose 3 | 19289.6 AU/mL |
| SOT Kidney Participants | Part A: GM Value of Anti-SARS-CoV-2 S-specific bAb for Unvaccinated and Previously Vaccinated Participants Receiving the 3-Dose Regimen | 28 days after Dose 3 | 26674.0 AU/mL |
| SOT Kidney Participants | Part A: GM Value of Anti-SARS-CoV-2 S-specific bAb for Unvaccinated and Previously Vaccinated Participants Receiving the 3-Dose Regimen | 1 year after Dose 3 | 66847.7 AU/mL |
| SOT Liver Participants | Part A: GM Value of Anti-SARS-CoV-2 S-specific bAb for Unvaccinated and Previously Vaccinated Participants Receiving the 3-Dose Regimen | 6 months after Dose 3 | 69076.5 AU/mL |
| SOT Liver Participants | Part A: GM Value of Anti-SARS-CoV-2 S-specific bAb for Unvaccinated and Previously Vaccinated Participants Receiving the 3-Dose Regimen | 28 days after Dose 3 | 167141.1 AU/mL |
| SOT Liver Participants | Part A: GM Value of Anti-SARS-CoV-2 S-specific bAb for Unvaccinated and Previously Vaccinated Participants Receiving the 3-Dose Regimen | 1 year after Dose 3 | 42266.8 AU/mL |
| SOT Total | Part A: GM Value of Anti-SARS-CoV-2 S-specific bAb for Unvaccinated and Previously Vaccinated Participants Receiving the 3-Dose Regimen | 28 days after Dose 3 | 47260.9 AU/mL |
| SOT Total | Part A: GM Value of Anti-SARS-CoV-2 S-specific bAb for Unvaccinated and Previously Vaccinated Participants Receiving the 3-Dose Regimen | 1 year after Dose 3 | 62884.2 AU/mL |
| SOT Total | Part A: GM Value of Anti-SARS-CoV-2 S-specific bAb for Unvaccinated and Previously Vaccinated Participants Receiving the 3-Dose Regimen | 6 months after Dose 3 | 24895.7 AU/mL |
Secondary
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.
Time frame: 14 days after second and third injection
Population: The mITT set (Part A) included all participants who received at least 1 dose of study drug, had no immunologic or virologic evidence of prior COVID-19 at baseline/pre-vaccination before the first dose of study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| SOT Kidney Participants | Part A: Number of Healthy Participants With Asymptomatic SARS-CoV-2 Infection | 4 Participants |
Secondary
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.
Time frame: 14 days after second and third injection
Population: The mITT set (Part A) included all participants who received at least 1 dose of study drug, had no immunologic or virologic evidence of prior COVID-19 at baseline/pre-vaccination before the first dose of study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| SOT Kidney Participants | Part A: Number of Healthy Participants With the Occurrence of COVID-19 | 2 Participants |
Secondary
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.
Time frame: 14 days after second and third injection
Population: The mITT set (Part A) included all participants who received at least 1 dose of study drug, had no immunologic or virologic evidence of prior COVID-19 at baseline/pre-vaccination before the first dose of study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| SOT Kidney Participants | Part A: Number of Healthy Participants With the Occurrence of Severe COVID-19 | 0 Participants |
Secondary
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.
Time frame: 14 days after second and third injection
Population: The modified intent-to-treat (mITT) set (Part A) included all participants who received at least 1 dose of study drug, had no immunologic or virologic evidence of prior COVID-19 at baseline/pre-vaccination before the first dose of study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| SOT Kidney Participants | Part A: Number of SOT Participants With Asymptomatic SARS-CoV-2 Infection | 0 Participants |
| SOT Liver Participants | Part A: Number of SOT Participants With Asymptomatic SARS-CoV-2 Infection | 1 Participants |
| SOT Total | Part A: Number of SOT Participants With Asymptomatic SARS-CoV-2 Infection | 8 Participants |
| Part A (Primary Series): Cohort A2 and A3 (SOT Liver Participants) | Part A: Number of SOT Participants With Asymptomatic SARS-CoV-2 Infection | 4 Participants |
Secondary
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.
Time frame: 14 days after second and third injection
Population: The mITT set (Part A) included all participants who received at least 1 dose of study drug, had no immunologic or virologic evidence of prior COVID-19 at baseline/pre-vaccination before the first dose of study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| SOT Kidney Participants | Part A: Number of SOT Participants With the Occurrence of COVID-19 | 0 Participants |
| SOT Liver Participants | Part A: Number of SOT Participants With the Occurrence of COVID-19 | 0 Participants |
| SOT Total | Part A: Number of SOT Participants With the Occurrence of COVID-19 | 12 Participants |
| Part A (Primary Series): Cohort A2 and A3 (SOT Liver Participants) | Part A: Number of SOT Participants With the Occurrence of COVID-19 | 7 Participants |
Secondary
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.
Time frame: 14 days after second and third injection
Population: The mITT set (Part A) included all participants who received at least 1 dose of study drug, had no immunologic or virologic evidence of prior COVID-19 at baseline/pre-vaccination before the first dose of study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| SOT Kidney Participants | Part A: Number of SOT Participants With the Occurrence of Severe COVID-19 | 0 Participants |
| SOT Liver Participants | Part A: Number of SOT Participants With the Occurrence of Severe COVID-19 | 0 Participants |
| SOT Total | Part A: Number of SOT Participants With the Occurrence of Severe COVID-19 | 1 Participants |
| Part A (Primary Series): Cohort A2 and A3 (SOT Liver Participants) | Part A: Number of SOT Participants With the Occurrence of Severe COVID-19 | 2 Participants |
Secondary
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.
Time frame: Throughout the study period (up to Day 450)
Population: Safety set included all participants who received at least 1 dose of study drug in this study.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| SOT Kidney Participants | Parts A and B: Number of SOT Participants Who Changed Immunosuppressant Therapy | 52 Participants |
| SOT Liver Participants | Parts A and B: Number of SOT Participants Who Changed Immunosuppressant Therapy | 37 Participants |
| SOT Total | Parts A and B: Number of SOT Participants Who Changed Immunosuppressant Therapy | 89 Participants |