Clinical trial NCT04860297: A Study to Evaluate Safety and Immunogenicity of mRNA-1273 Vaccine to Prevent COVID-19 in Adult Organ Transplant Recipients and in Healthy Adult Participants
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: SARS-CoV-2
Keywords: mRNA-1273
mRNA-1273 vaccine
SARS-CoV-2
SARS-CoV-2 Vaccine
Coronavirus
Virus Diseases
Messenger RNA
COVID-19
COVID-19 Vaccine
Moderna
Lead sponsor: ModernaTX, Inc.
Sponsor class: INDUSTRY
First posted: 2021-04-26
Enrollment: 234
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: This is an open-label, single intervention study; there is no randomization
Primary purpose: PREVENTION

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.


Eligibility 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 Exclusion Criteria for Part A:

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

Inclusion Criteria for Part B:

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

Exclusion Criteria for Part B:

* Exclusion Criteria in Part A will apply except:

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

Primary outcomes:
measure: Parts A and B: Number of SOT Participants With Unsolicited Adverse Events (AEs)
timeFrame: Up to 28 days post-vaccination
measure: Parts A and B: Number of Healthy Participants With Unsolicited AEs
timeFrame: Up to 28 days post-vaccination
measure: Parts A and B: Number of SOT Participants With Medically-Attended Adverse Events (MAAEs)
timeFrame: Throughout the study period (up to Day 450)
measure: Parts A and B: Number of Healthy Participants With MAAEs
timeFrame: Throughout the study period (up to Day 394)
measure: Parts A and B: Number of SOT Participants With Serious Adverse Events (SAEs)
timeFrame: Throughout the study period (up to Day 450)
measure: Parts A and B: Number of Healthy Participants With SAEs
timeFrame: Throughout the study period (up to Day 394)
measure: Parts A and B: Number of SOT Participants With Adverse Event of Special Interests (AESIs), Including Myocarditis/Pericarditis
timeFrame: Throughout the study period (up to Day 450)
measure: Parts A and B: Number of Healthy Participants With AESIs, Including Myocarditis/Pericarditis
timeFrame: Throughout the study period (up to Day 394)
measure: Parts A and B: Number of SOT Participants With AEs Leading to Discontinuation From Dosing and/or Study Participation (Withdrawal)
timeFrame: Throughout the study period (up to Day 450)
measure: Parts A and B: Number of Healthy Participants With AEs Leading to Discontinuation From Dosing and/or Study Participation (Withdrawal)
timeFrame: Throughout the study period (up to Day 394)
measure: Parts A and B: Number of SOT Participants With Adjudicated Biopsy-Proven Organ Rejection
timeFrame: Throughout the study period (up to Day 450)
measure: Parts A and B: Number of Healthy Participants With Biopsy-Proven Organ Rejection
timeFrame: Throughout the study period (up to Day 394)
measure: Parts A and B: Number of SOT Participants With Solicited Local and Systemic Adverse Reactions (ARs)
timeFrame: 7 days post-vaccination
measure: Parts A and B: Number of Healthy Participants With Solicited Local and Systemic ARs
timeFrame: 7 days post-vaccination
measure: Part A: Geometric Mean Concentration (GMC) of Serum SARS-CoV-2-Specific Neutralizing Antibody (nAb) After the Second Dose in Unvaccinated Participants
timeFrame: Day 57 (for unvaccinated participants)
measure: Part A: GMC of SARS-CoV-2-Specific nAb 28 Days After Dose 3
timeFrame: 28 days after Dose 3
measure: 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
timeFrame: 28 days after BD injection (BD-Day 29)
Secondary outcomes:
measure: Part A: GMC of SARS-CoV-2-Specific nAb for Unvaccinated Participants Receiving the 2-Dose Regimen
timeFrame: Days 1, 28 days after Dose 1, 28 days after Dose 2, 6 months after Dose 2, and 1 year after Dose 2
measure: Part A: GMC of SARS-CoV-2-Specific nAb for Unvaccinated and Previously Vaccinated Participants Receiving the 3-Dose Regimen
timeFrame: 28 days after Dose 3, 6 months after Dose 3, and 1 year after Dose 3
measure: Part A: GMFR of nAb for Unvaccinated Participants Receiving the 2-Dose Regimen Relative to Day 1
timeFrame: 28 days after Dose 1, 28 days after Dose 2, 6 months after Dose 2, and 1 year after Dose 2
measure: Part A: GMFR of nAb for Unvaccinated and Previously Vaccinated Participants Receiving the 3-Dose Regimen Relative to Day 1
timeFrame: 28 days after Dose 3, 6 months after Dose 3, 1 year after Dose 3
measure: Part A: Geometric Mean (GM) Value of Anti-SARS-CoV-2 S-specific Binding Antibody (bAb) for Unvaccinated Participants Receiving the 2-Dose Regimen
timeFrame: Days 1, 28 days after Dose 1, 28 days after Dose 2, 6 months after Dose 2, and 1 year after Dose 2
measure: Part A: GM Value of Anti-SARS-CoV-2 S-specific bAb for Unvaccinated and Previously Vaccinated Participants Receiving the 3-Dose Regimen
timeFrame: 28 days after Dose 3, 6 months after Dose 3, and 1 year after Dose 3
measure: Part A: Geometric Mean Fold-Rise (GMFR) of bAb for Unvaccinated Participants Receiving the 2-Dose Regimen Relative to Day 1
timeFrame: 28 days after Dose 1, 28 days after Dose 2, 6 months after Dose 2, and 1 year after Dose 2
measure: Part A: GMFR of bAb for Unvaccinated and Previously Vaccinated Participants Receiving the 3-Dose Regimen Relative to Day 1
timeFrame: 28 days after Dose 3, 6 months after Dose 3, 1 year after Dose 3
measure: Part A: Number of SOT Participants With Asymptomatic SARS-CoV-2 Infection
timeFrame: 14 days after second and third injection
measure: Part A: Number of Healthy Participants With Asymptomatic SARS-CoV-2 Infection
timeFrame: 14 days after second and third injection
measure: Part A: Number of SOT Participants With the Occurrence of COVID-19
timeFrame: 14 days after second and third injection
measure: Part A: Number of Healthy Participants With the Occurrence of COVID-19
timeFrame: 14 days after second and third injection
measure: Part A: Number of SOT Participants With the Occurrence of Severe COVID-19
timeFrame: 14 days after second and third injection
measure: Part A: Number of Healthy Participants With the Occurrence of Severe COVID-19
timeFrame: 14 days after second and third injection
measure: Parts A and B: Number of SOT Participants Who Changed Immunosuppressant Therapy
timeFrame: Throughout the study period (up to Day 450)
Other outcomes:
Locations:
city: Mesa
country: United States
facility: Aventiv Research Inc
state: Arizona
city: San Diego
country: United States
facility: California Institute of Renal Research
state: California
city: New Haven
country: United States
facility: Yale University School of Medicine
state: Connecticut
city: Tampa
country: United States
facility: Tampa General Medical Group
state: Florida
city: Atlanta
country: United States
facility: Piedmont Transplant Institute
state: Georgia
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: Worcester
country: United States
facility: University of Massachusetts Medical School
state: Massachusetts
city: Omaha
country: United States
facility: University of Nebraska Medical Center
state: Nebraska
city: Manhasset
country: United States
facility: Northwell Health
state: New York
city: New York
country: United States
facility: Colombia University Medical Center
state: New York
city: Cincinnati
country: United States
facility: University of Cincinnati
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic Hospital
state: Ohio
city: Philadelphia
country: United States
facility: Hospital of The University of Pennsylvania
state: Pennsylvania
city: Providence
country: United States
facility: Rhode Island Hospital
state: Rhode Island
city: Seattle
country: United States
facility: University of Washington Medical Center
state: Washington
Study officials:
References: