Dose-Confirmation Study to Evaluate the Safety, Reactogenicity, and Immunogenicity of mRNA-1273 COVID-19 Vaccine in Adults Aged 18 Years and Older

• ClinicalTrials.gov Identifier: NCT04405076
• Recruitment Status: Active, not recruiting
• First Posted: May 28, 2020
• Last Update Posted: January 20, 2021
• Sponsor: ModernaTX, Inc.
• Collaborator: Biomedical Advanced Research and Development Authority
• Information provided by (Responsible Party): ModernaTX, Inc.

Tracking Information

• First Submitted Date: May 13, 2020
• First Posted Date: May 28, 2020
• Last Update Posted Date: January 20, 2021
• Actual Study Start Date: May 29, 2020
• Estimated Primary Completion Date: March 31, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 15, 2021)

• Number of Participants with Solicited Local and Systemic Adverse Reactions (ARs) [ Time Frame: 7 days post-vaccination ]
• Number of Participants with Unsolicited Adverse Events (AEs) [ Time Frame: 28 days post-vaccination ]
• Number of Participants with Medically-Attended Adverse Events (MAAEs) [ Time Frame: Month 0 through Month 13 ]
• Number of Participants with Serious Adverse Events (SAEs) [ Time Frame: Month 0 through Month 13 ]
• Change in the measure of clinical safety laboratory values in Cohort 2 from baseline [ Time Frame: Through 1 month after last vaccination ]
• The number and percentage of participants with abnormalities in blood pressure, temperature, HR or respiratory rate will be assessed. [ Time Frame: Through 1 year after last vaccination ]
• The number and percentage of participants with abnormalities in physical examinations will be assessed [ Time Frame: Through 1 year after last vaccination ]
• Evaluate immunogenicity of mRNA-1273 by titer of SARS-CoV-2-specific binding antibody (bAb) measured by enzyme-linked immunosorbent assay (ELISA) [ Time Frame: Through 1 year after the final dose ]

Original Primary Outcome Measures (submitted: May 26, 2020)

• Solicited local and systemic adverse reactions (ARs) [ Time Frame: 7 days post-vaccination ]
• Unsolicited adverse events (AEs) [ Time Frame: 28 days post-vaccination ]
• Medically-attended adverse events (MAAEs) [ Time Frame: Month 0 through Month 13 ]
• Serious adverse events (SAEs) [ Time Frame: Month 0 through Month 13 ]
• Change in the measure of clinical safety laboratory values in Cohort 2 from baseline [ Time Frame: Through 1 month after last vaccination ]
• The number and percentage of participants with abnormalities in blood pressure, temperature, HR or respiratory rate will be assessed. [ Time Frame: Through 1 year after last vaccination ]
• The number and percentage of participants with abnormalities in physical examinations will be assessed [ Time Frame: Through 1 year after last vaccination ]
• Evaluate immunogenicity of mRNA-1273 by titer of SARS-CoV-2-specific binding antibody (bAb) measured by enzyme-linked immunosorbent assay (ELISA) [ Time Frame: Through 1 year after the final dose ]

Current Secondary Outcome Measures (submitted: May 26, 2020)

• Titer of SARS-CoV-2-specific neutralizing antibody (nAb) [ Time Frame: Through 1 year post last vaccination ]
• Seroconversion as measured by an increase of SARS-CoV-2-specific neutralizing antibody (nAb) titer [ Time Frame: Through 1 year post last vaccination ]
  Seroconversion as measured by an increase of SARS-CoV-2-specific neutralizing antibody (nAb) titer either from below the limit of detection (LOD) or lower limit of quantification (LLOQ) to equal to or above LOD or LLOQ, or a 4-times higher titer in participants with pre-existing nAb titers.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Dose-Confirmation Study to Evaluate the Safety, Reactogenicity, and Immunogenicity of mRNA-1273 COVID-19 Vaccine in Adults Aged 18 Years and Older
• Official Title: A Phase 2a, Randomized, Observer-Blind, Placebo Controlled, Dose-Confirmation Study to Evaluate the Safety, Reactogenicity, and Immunogenicity of mRNA-1273 SARS-COV-2 Vaccine in Adults Aged 18 Years and Older
• Brief 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2

Study Design

Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Double (Participant, Investigator)
Masking Description:

Observer-blind

Primary Purpose: Prevention

• Condition: SARS-CoV-2

Intervention

• Biological: Biological: mRNA-1273
  Sterile liquid for injection
• Biological: Placebo
  Placebo: Saline
  Other Name: 0.9% sodium chloride (normal saline) injection

Study Arms

• Experimental: mRNA-1273: Dose 50 microgram (ug) - Adults Aged 18-54
  Adults aged 18-54 years will receive 1 intramuscular (IM) injection of 50 ug mRNA-1273 on Day 1 and on Day 29.
  Intervention: Biological: Biological: mRNA-1273
• Experimental: mRNA-1273: Dose 50 ug - Adults Aged 55+ years
  Adults aged 55+ years will receive 1 IM injection of 50 ug mRNA-1273 on Day 1 and on Day 29.
  Intervention: Biological: Biological: mRNA-1273
• Experimental: mRNA-1273: Dose 100 ug - Adults Aged 18-54
  Adults aged 18-54 years will receive 1 IM injection of 100 ug mRNA-1273 on Day 1 and on Day 29.
  Intervention: Biological: Biological: mRNA-1273
• Experimental: mRNA-1273: Dose 100 ug - Adults Aged 55+ years
  Adults aged 55+ years will receive 1 IM injection of 100 ug mRNA-1273 on Day 1 and on Day 29.
  Intervention: Biological: Biological: mRNA-1273
• Placebo Comparator: Placebo - Adults Aged 18-54
  Participants will receive 1 IM injection of mRNA-1273-matching placebo on Day 1 and on Day 29.
  Intervention: Biological: Placebo
• Placebo Comparator: Placebo - Adults Aged 55+ years
  Participants will receive 1 IM injection of mRNA-1273-matching placebo on Day 1 and on Day 29.
  Intervention: Biological: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: May 26, 2020): 600
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: August 31, 2021
• Estimated Primary Completion Date: March 31, 2021 (Final data collection date for primary outcome measure)

Eligibility Criteria

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).
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. Body mass index (BMI) of 18 kilograms/meter (kg/m)^2 to 30 kg/m^2 (inclusive) at the Screening Visit (Day 0).
5. 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.

6. 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 intramuscular (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.
7. 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.

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. Known history of SARS-CoV-2 infection or known exposure to someone with SARS CoV 2 infection or COVID-19.
2. Travel outside of the US in the 28 days prior to the Screening Visit (Day 0).
3. Pregnant or breastfeeding.
4. 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.
5. Prior administration of an investigational CoV (for example, SARS-CoV-2, SARS-CoV, MERS-CoV) vaccine.
6. Current treatment with investigational agents for prophylaxis against COVID-19.
7. 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.
8. Is a healthcare worker or a member of an emergency response team.
9. Current use of any inhaled substance (for example, tobacco or cannabis smoke, nicotine vapors).
10. History of chronic smoking (≥1 cigarette a day) within 1 year of the Screening Visit (Day 0).
11. 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.
12. 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).
13. Known history of hypotension or systolic blood pressure <85 mmHg at the Screening Visit (Day 0).
14. Diabetes mellitus
15. Diagnosis of chronic pulmonary disease (for example, chronic obstructive pulmonary disease, asthma)
16. Chronic cardiovascular disease
17. Resides in a nursing home
18. Grade 1 or higher toxicity on clinical safety laboratory testing at the Screening Visit (Day 0)
19. Current or previous diagnosis of immunocompromising condition, immune-mediated disease, or other immunosuppressive condition.
20. 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 mg/day of prednisone equivalent). Topical tacrolimus is allowed if not used within 14 days prior to the Screening Visit (Day 0).
21. Anticipating the need for immunosuppressive treatment at any time during participation in the study.
22. 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).
23. History of anaphylaxis, urticaria, or other significant AR requiring medical intervention after receipt of a vaccine.
24. Bleeding disorder considered a contraindication to IM injection or phlebotomy.
25. Diagnosis of malignancy within previous 10 years (excluding non-melanoma skin cancer).
26. 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.
27. Receipt of systemic immunoglobulins or blood products within 3 months prior to the Screening Visit (Day 0) or plans for receipt during the study.
28. 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.
29. Participated in an interventional clinical study within 28 days prior to the Screening Visit (Day 0) or plans to do so while participating in this study.
30. Is an immediate family member or household member of study personnel

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT04405076
• Other Study ID Numbers: mRNA-1273-P201; 75A50120C00034 ( Other Grant/Funding Number: BARDA )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Responsible Party: ModernaTX, Inc.
• Study Sponsor: ModernaTX, Inc.
• Collaborators: Biomedical Advanced Research and Development Authority
• Investigators: Not Provided
• PRS Account: ModernaTX, Inc.
• Verification Date: January 2021