Dose-Confirmation Study to Evaluate the Safety, Reactogenicity, and Immunogenicity of mRNA-1273 COVID-19 Vaccine in Adults Aged 18 Years and Older
Condition: SARS-CoV-2
Intervention: Biological: mRNA-1273; Placebo; mRNA-1273.351
Intervention description: Sterile liquid for injection; 0.9% sodium chloride (normal saline) injection; Sterile liquid for injection
Phase: Phase 2
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Sequential Assignment
Masking: Double (Participant, Investigator)
Masking description: Part A is observer-blind. During Part B participants may request to be unblinded by scheduling a Participant Decision clinic visit. Part C is open-label.
Enrollment: 660.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: mRNA-1273; mRNA-1273 vaccine; mRNA-1273.351; SARS-CoV-2; SARS-CoV-2 Vaccine; Coronavirus; Virus Diseases; Messenger RNA; COVID 19; COVID 19 Vaccine; Moderna

Summary:

      This clinical study will assess the safety, reactogenicity, and immunogenicity of 2 dose
      levels of mRNA-1273 Severe Acute Respiratory Syndrome coronavirus (SARS-COV-2) vaccine in
      adults 18 years of age or older.
    

Eligibility criteria:

        Key Inclusion Criteria:

        Each participant must meet all of the following criteria during the screening period and at
        Day 1, unless noted otherwise, to be enrolled in this study:

          1. Male or female, 18 years of age or older at the time of consent (Screening Visit, Day
             0). For Part B, participants must have been previously enrolled in the mRNA-1273 P201
             study.

          2. Understands and agrees to comply with the study procedures and provides written
             informed consent.

          3. According to the assessment of the investigator, is in good general health and can
             comply with study procedures.

          4. Female participants of nonchildbearing potential may be enrolled in the study.
             Nonchildbearing potential is defined as surgically sterile (history of bilateral tubal
             ligation, bilateral oophorectomy, hysterectomy) or postmenopausal (defined as
             amenorrhea for ≥12 consecutive months prior to Screening (Day 0) without an
             alternative medical cause). A follicle-stimulating hormone (FSH) level may be measured
             at the discretion of the investigator to confirm postmenopausal status.

          5. Female participants of childbearing potential may be enrolled in the study if the
             participant fulfills all the following criteria:

               -  Has a negative pregnancy test at Screening (Day 0) and on the day of the first
                  injection (Day 1).

               -  Has practiced 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).

               -  Has agreed to continue adequate contraception through 3 months following the
                  second injection (Day 29).

               -  Is not currently breastfeeding.

             Adequate female contraception is defined as consistent and correct use of a Food and
             Drug Administration (FDA) approved contraceptive method in accordance with the product
             label. For example:

               -  Barrier method (such as condoms, diaphragm, or cervical cap) used in conjunction
                  with spermicide

               -  Intrauterine device

               -  Prescription hormonal contraceptive taken or administered via oral (pill),
                  transdermal (patch), subdermal, or IM route

               -  Sterilization of a female participant's monogamous male partner prior to entry
                  into the study Note: periodic abstinence (for example, calendar, ovulation,
                  symptothermal, post-ovulation methods) and withdrawal are not acceptable methods
                  of contraception.

          6. Male participants engaging in activity that could result in pregnancy of sexual
             partners must agree to practice adequate contraception from the time of the first
             injection and through 3 months after the last injection.

        Adequate contraception for male participants is defined as:

          -  Monogamous relationship with a female partner using an intrauterine device or hormonal
             contraception (described above)

          -  Use of barrier methods and spermicide

          -  History of surgical sterilization

          -  Male participants with partners who have become pregnant prior to Screening are
             eligible to participate in the study.

        Additional Key Inclusion Criteria for Part C

        1. Participants must have been previously enrolled in the mRNA-1273-P301 study and must
        have received 2 doses of mRNA-1273 in Part A, has been unblinded and aware of their actual
        treatment in Study mRNA-1273-P301, must have been compliant in Study mRNA-1273-P301 (was
        not withdrawn or discontinued early), and has been at least 6 months since their second
        dose in Study mRNA-1273-P301 prior to enrollment in this part.

        Key Exclusion Criteria:

        Participants meeting any of the following criteria at the Screening Visit (Day 0) or at Day
        1, unless noted otherwise, will be excluded from the study:

          1. Pregnant or breastfeeding.

          2. Is acutely ill or febrile 24 hours prior to or at the Screening Visit (Day 0). Fever
             is defined as a body temperature ≥38.0°Celsius/100.4°Fahrenheit. Participants meeting
             this criterion may be rescheduled within the relevant window periods. Afebrile
             participants with minor illnesses can be enrolled at the discretion of the
             investigator.

          3. Current treatment with investigational agents for prophylaxis against COVID-19.

          4. 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.

          5. Is a healthcare worker or a member of an emergency response team.

          6. Current use of any inhaled substance (for example, tobacco or cannabis smoke, nicotine
             vapors).

          7. History of chronic smoking (≥1 cigarette a day) within 1 year of the Screening Visit
             (Day 0).

          8. History of illegal substance use or alcohol abuse within the past 2 years. This
             exclusion does not apply to historical cannabis use that was formerly illegal in the
             participant's state but is legal at the time of Screening.

          9. Known history of hypertension, or systolic blood pressure >150 millimeter of mercury
             (mmHg) in participants in Cohort 1 (≥18 to <55 years old) or systolic blood pressure
             >160 mmHg in participants in Cohort 2 (≥55 years old) at the Screening Visit (Day 0).

         10. Known history of hypotension or systolic blood pressure <85 mmHg at the Screening
             Visit (Day 0).

         11. Diabetes mellitus

         12. Diagnosis of chronic pulmonary disease (for example, chronic obstructive pulmonary
             disease, asthma)

         13. Chronic cardiovascular disease

         14. Resides in a nursing home

         15. Grade 1 or higher toxicity on clinical safety laboratory testing at the Screening
             Visit (Day 0)

         16. Current or previous diagnosis of immunocompromising condition, immune-mediated
             disease, or other immunosuppressive condition.

         17. Received systemic immunosuppressants or immune-modifying drugs for >14 days in total
             within 6 months prior to the Screening Visit (Day 0) (for corticosteroids ≥20
             milligrams (mg)/day of prednisone equivalent). Topical tacrolimus is allowed if not
             used within 14 days prior to the Screening Visit (Day 0).

         18. Anticipating the need for immunosuppressive treatment at any time during participation
             in the study.

         19. Positive serology for hepatitis B virus surface antigen, hepatitis C virus antibody,
             or human immunodeficiency virus (HIV) type 1 or 2 antibodies identified at the
             Screening Visit (Day 0).

         20. History of anaphylaxis, urticaria, or other significant AR requiring medical
             intervention after receipt of a vaccine.

         21. Bleeding disorder considered a contraindication to IM injection or phlebotomy.

         22. Diagnosis of malignancy within previous 10 years (excluding non-melanoma skin cancer).

         23. Has received or plans to receive a licensed vaccine ≤28 days prior to the first
             injection (Day 1) or plans to receive a licensed vaccine within 28 days before or
             after any study injection. Licensed influenza vaccines may be received more than 14
             days before or after any study injection.

         24. Receipt of systemic immunoglobulins or blood products within 3 months prior to the
             Screening Visit (Day 0) or plans for receipt during the study.

         25. Has donated ≥450 mL of blood products within 28 days prior to the Screening Visit (Day
             0) or plans to donate blood products during the study.

         26. Participated in an interventional clinical study (other than mRNA-1273 P301) within 28
             days prior to the Screening Visit (Day 0) or plans to do so while participating in
             this study.

         27. Is an immediate family member or household member of study personnel

        Additional Key Exclusion Criteria for Part C

          1. Is SARS-CoV-2 positive by Reverse transcription polymerase chain reaction (RT-PCR)
             (central or local testing) at baseline or at any time during the mRNA-1273-P301 study
             regardless of the presence or absence of symptoms consistent with COVID-19.

          2. Had any SAE in the mRNA-1273-P301 study.