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

Sponsor

ModernaTX, Inc. (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04860297

Collaborator

(none)

240

Enrollment

Locations

Arm

33.5

Anticipated Duration (Months)

120

Patients Per Site

3.6

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
SARS-CoV-2	Biological: mRNA-1273	Phase 3

Study Design

Study Type:

Interventional

Anticipated Enrollment :

240 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Intervention Model Description:

This is an open-label, single intervention study; there is no randomizationThis is an open-label, single intervention study; there is no randomization

Masking:

None (Open Label)

Primary Purpose:

Prevention

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

Actual Study Start Date :

Apr 16, 2021

Anticipated Primary Completion Date :

May 31, 2023

Anticipated Study Completion Date :

Jan 31, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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 with a non-Moderna COVID-19 under EUA (outside of the mRNA-1273-P304 study) will receive a 100 µg booster dose on booster dose Day 1.	Biological: mRNA-1273 Sterile liquid for injection

Arm

Intervention/Treatment

Experimental: 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 with a non-Moderna COVID-19 under EUA (outside of the mRNA-1273-P304 study) will receive a 100 µg booster dose on booster dose Day 1.

Biological: mRNA-1273

Sterile liquid for injection

Outcome Measures

Primary Outcome Measures

Number of Participants with Solicited Local and Systemic Adverse Reactions (ARs) in Part A [Up to Day 92]
Number of Participants with Solicited Local and Systemic ARs in Part B [Day 8]
Number of Participants with Unsolicited Adverse Events (AEs) in Part A [Up to Day 113]
Number of Participants with Unsolicited AEs in Part B [Day 29]
Number of Participants with Medically-Attended AEs (MAAEs) [up to approximately 1 year]
Number of Participants with Serious AEs (SAEs) [up to approximately 1 year]
Number of Participants with AEs of Special Interest (AESIs) [up to approximately 1 year]
Number of Participants with AEs Leading to Withdrawal [up to approximately 1 year]
Number of Participants with Biopsy-Proven Organ Rejection [up to approximately 1 year]
Geometric Mean Titer (GMT) of SARS-CoV-2 Specific Neutralizing Antibody (nAb) for Participants in Part A [28 days after last dose (Day 57 for unvaccinated participants who received 2 doses, Day 113 for unvaccinated SOT participants who received 3 doses, and Day 29 for previously vaccinated SOT participants)]
GMT of SARS-CoV-2 Specific nAB for Participants in Part B [28 days after booster dose (booster dose Day 29)]

Secondary Outcome Measures

Geometric Mean (GM) of SARS-CoV-2 Binding Antibody (bAb) for Unvaccinated Participants Receiving 2-Dose Regimen [Day 1, 29, 57, 209, and 394]
GM of SARS-CoV-2 bAb for Unvaccinated SOT Participants Receiving 3-Dose Regimen [Day 1, 29, 57, 85, 113, 265, and 450]
GM of SARS-CoV-2 bAb for Previously Vaccinated SOT Participants [Day 1, 29, 180, and 365]
Geometric Mean Fold Rise (GMFR) of bAb Relative to Day 1 for Unvaccinated Participants Receiving 2-Dose Regimen [Day 29, 57, 209, and 394]
GMFR of bAb Relative to Day 1 for Unvaccinated SOT Participants Receiving 3-Dose Regimen [Day 29, 57, 85, 113, 265, and 450]
GMFR of bAb Relative to Day 1 for Previously Vaccinated SOT Participants [Day 29, 180, and 365]
The GMT Values of SARS-CoV-2-Specific nAb for Unvaccinated Participants Receiving 2-Dose Regimen [Day 1, 29, 209, and 394]
The GMT Values of SARS-CoV-2-Specific nAb for Unvaccinated SOT Participants Receiving 3-Dose Regimen [Day 1, 29, 85, 113, 265, and 450]
The GMT Values of SARS-CoV-2-Specific nAb for Previously Vaccinated SOT Participants [Day 1, 29, 180, and 365]
GMFR of nAb Relative to Day 1 For Unvaccinated Participants Receiving 2-Dose Regimen [Day 29, 57, 209, and 394]
GMFR of nAb Relative to Day 1 for Unvaccinated SOT Participants Receiving 3-Dose Regimen [Day 29, 57, 85, 113, 265, and 450]
GMFR of nAb Relative to Day 1 for Previously Vaccinated SOT Participants [Day 29, 180, and 365]
Number of Transplant Recipients and Number of Healthy Participants (Who had a Negative SARS-CoV-2 at Baseline) with Asymptomatic SARS-CoV-2 Infection [Day 43 up to Day 394 for unvaccinated participants who received 2 doses, Day 99 up to Day 450 for unvaccinated SOT participants who received 3 doses, and Day 15 up to Day 365 for previously vaccinated SOT recipients]
Clinical signs indicative of asymptomatic SARS-CoV-2 infection as predefined for the study.
Number of Transplant Recipients and Number of Healthy Participants with a First Occurrence of Symptomatic COVID-19 Starting 14 Days after the Second Dose of Vaccine and after the Third Dose of Vaccine [Day 43 up to Day 394 for unvaccinated participants who received 2 doses, Day 99 up to Day 450 for unvaccinated SOT participants who received 3 doses, and Day 15 up to Day 365 for previously vaccinated SOT recipients]
Clinical signs indicative of symptomatic COVID-19 as predefined for the study.
Number of Transplant Recipients and Number of Healthy Participants with a First Occurrence of Severe COVID-19 Starting 14 Days after Second Dose of Vaccine and after the Third Dose of Vaccine [Day 43 up to Day 394 for unvaccinated participants who received 2 doses, Day 99 up to Day 450 for unvaccinated SOT participants who received 3 doses, and Day 15 up to Day 365 for previously vaccinated SOT recipients]
Clinical signs indicative of severe COVID-19 as predefined for the study.
Number of Participants with a Change in Immunosuppressant Medications to Treat Organ Transplant Rejection or to Improve Immune Tolerance [Up to Day 394 for unvaccinated participants who received 2 doses, Up to Day 450 for unvaccinated SOT participants who received 3 doses, Up to Day 365 for previously vaccinated SOT recipients]
Change in immunosuppressant medication is defined as any of the following: -any adjustments (temporarily or permanently) in immunosuppressants; -addition of new immunosuppressants; -or switching from one maintenance rejection prophylaxis regimen to another

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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

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 prior or planned administration of a coronavirus vaccine and current treatment with investigational agents for either prophylaxis against COVID-19.