A Phase 3b, Open-Label, Safety and Immunogenicity Study of SARS-CoV-2 mRNA-1273 Vaccine in Adult Solid Organ Transplant Recipients and Healthy Controls
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 234
- 试验地点
- 15
- 主要终点
- Parts A and B: Number of SOT Participants With Unsolicited Adverse Events (AEs)
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •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.
排除标准
- •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
- •Participated in an interventional clinical study within 28 days prior to Day 0 or plans to donate blood products while participating in this study.
- •Healthy Participants
- •Key Inclusion Criteria for Part A:
- •In good general health without current or previous diagnosis of immunocompromising condition, immune-mediated disease, or other immunosuppressive condition, according to investigator assessment, at the time of consent, and has not been vaccinated with any COVID-19 vaccine at the time of consent.
- •Understands, agrees, and is able to comply with the study procedures and provides written informed consent.
- •For female participants of childbearing potential: negative pregnancy test, adequate contraception or has abstained from all activities that could result in pregnancy for at least 28 days prior to the first injection (Day 1), agreement to continue adequate contraception or abstinence through 3 months following the second injection (Day 29), and not currently breastfeeding.
- •Is medically stable, according to investigator's judgment, during the 3 months before signing consent.
- •Key Exclusion Criteria for Part A:
- •Has a known close contact with anyone with laboratory confirmed SARS-CoV-2 infection or COVID-19 within 2 weeks prior to vaccine administration or known history of SARS-CoV-2 infection or positive SARS-CoV-2 test.
- •Has prior or planned administration of a coronavirus vaccine (for example, SARS-CoV-2, SARS-CoV, or MERS-CoV vaccine).
- •Has current treatment with investigational agents for either prophylaxis against COVID-19 or treatment of COVID-19 (for example, anti-SARS-CoV-2 monoclonal antibodies).
- •Has a medical, psychiatric, or occupational condition that may pose additional risk as a result of participation or that could interfere with safety assessments or interpretation of results according to the investigator's judgment.
- •Has a history of a diagnosis or condition that, in the judgment of the investigator, may affect study endpoint assessment or compromise participant safety.
- •Received any non-study vaccine within 28 days before or after any dose of vaccine (except for seasonal influenza vaccine, which is not permitted within 14 days before or after any dose of vaccine)
- •Received intravenous blood products (red blood cells, platelets, immunoglobulins) within 3 months prior to Day
- •Received systemic immunosuppressants or immune-modifying drugs for >14 days in total within 6 months prior to Screening (for corticosteroids ≥20 mg/day of prednisone equivalent).
- •Participated in an interventional clinical study within 28 days prior to Day 0 or plans to donate blood products while participating in this study.
- •Inclusion Criteria for Part B:
- •Participants must have been previously enrolled in this study (mRNA-1273-P304), are actively participating in Part A, and at least 4 months from the last dose; or participant is either a kidney or a liver SOT recipient who is at least 90 days after transplantation at the time of consent and who completed primary vaccination series (3 doses for mRNA COVID-19 vaccine; 2 doses for non-mRNA COVID-19 vaccine or at least 1 dose of non-mRNA combined with 1 dose of mRNA COVID-19 vaccine) under the EUA who are at least 4 months from the last dose. All primary COVID-19 vaccination series must be completed after transplant.
- •Female participants of childbearing potential may be enrolled in the study if the participant has a negative pregnancy test on the day of the first injection (booster dose Day 1).
- •Exclusion Criteria for Part B:
- •Exclusion Criteria in Part A will apply except:
- •prior or planned administration of a coronavirus vaccine and current treatment with investigational agents for either prophylaxis against COVID-
- •known close contact with anyone with laboratory-confirmed SARS-CoV-2 infection or COVID-19 within 2 weeks prior to vaccine administration or any known history of SARS-CoV-2 infection or positive SARSCoV-2 test will apply only to new SOT participants who will be enrolled in Part B.
研究组 & 干预措施
mRNA-1273
Part A: All participants (healthy participants and SOT participants) who were unvaccinated prior to enrollment will receive 2 intramuscular (IM) injections of 100 microgram (µg) mRNA-1273 on Day 1 and Day 29.
All SOT participants who were unvaccinated prior to enrollment will be offered the opportunity to receive a third primary dose of mRNA-1273 at Day 85 as per the emergency use authorization (EUA) Fact Sheet available at the time of protocol finalization.
SOT participants who were previously vaccinated with 2 doses of Moderna COVID-19 vaccine under the EUA prior to enrollment will receive Dose 3 on Day 1.
Part B: All eligible participants from Part A will be offered to receive a 100 µg booster dose of mRNA-1273 who are at least 4 months from the last dose. SOT recipients who completed primary COVID-19 vaccination series under EUA (outside of the mRNA-1273-P304 study) will receive a 100 µg booster dose on booster dose Day 1.
干预措施: mRNA-1273 (Biological)
结局指标
主要结局
Parts A and B: Number of SOT Participants With Unsolicited Adverse Events (AEs)
时间窗: 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.
Parts A and B: Number of SOT Participants With Serious Adverse Events (SAEs)
时间窗: 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 Unsolicited AEs
时间窗: 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)
时间窗: 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 SAEs
时间窗: 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
时间窗: 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 MAAEs
时间窗: 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 Healthy Participants With AESIs, Including Myocarditis/Pericarditis
时间窗: 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)
时间窗: 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)
时间窗: 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
时间窗: 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
时间窗: 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 Healthy Participants With Solicited Local and Systemic ARs
时间窗: 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: GMC of SARS-CoV-2-Specific nAb 28 Days After Dose 3
时间窗: 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 Solicited Local and Systemic Adverse Reactions (ARs)
时间窗: 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 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
时间窗: 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.
Part A: Geometric Mean Concentration (GMC) of Serum SARS-CoV-2-Specific Neutralizing Antibody (nAb) After the Second Dose in Unvaccinated Participants
时间窗: 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.
次要结局
- Part A: GMC of SARS-CoV-2-Specific nAb for Unvaccinated Participants Receiving the 2-Dose Regimen(Days 1, 28 days after Dose 1, 28 days after Dose 2, 6 months after Dose 2, and 1 year after Dose 2)
- Part A: 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)
- 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)
- Part A: GMFR of nAb for Unvaccinated Participants Receiving the 2-Dose Regimen Relative to Day 1(28 days after Dose 1, 28 days after Dose 2, 6 months after Dose 2, and 1 year after Dose 2)
- Part A: GMFR of nAb for Unvaccinated and Previously Vaccinated Participants Receiving the 3-Dose Regimen Relative to Day 1(28 days after Dose 3, 6 months after Dose 3, 1 year after Dose 3)
- Part A: GMC of SARS-CoV-2-Specific nAb for Unvaccinated and Previously Vaccinated Participants Receiving the 3-Dose Regimen(28 days after Dose 3, 6 months after Dose 3, and 1 year after Dose 3)
- Part A: Number of Healthy Participants With the Occurrence of COVID-19(14 days after second and third injection)
- 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)
- Part A: Number of Healthy Participants With the Occurrence of Severe COVID-19(14 days after second and third injection)
- Parts A and B: Number of SOT Participants Who Changed Immunosuppressant Therapy(Throughout the study period (up to Day 450))
- 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)
- Part A: Number of SOT Participants With Asymptomatic SARS-CoV-2 Infection(14 days after second and third injection)
- Part A: Number of Healthy Participants With Asymptomatic SARS-CoV-2 Infection(14 days after second and third injection)
- Part A: Number of SOT Participants With the Occurrence of COVID-19(14 days after second and third injection)
- Part A: Number of SOT Participants With the Occurrence of Severe COVID-19(14 days after second and third injection)