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

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ClinicalTrials.gov Identifier: NCT04405076
Recruitment Status : Active, not recruiting
First Posted : May 28, 2020
Last Update Posted : May 5, 2021
Sponsor:
Collaborator:
Biomedical Advanced Research and Development Authority
Information provided by (Responsible Party):
ModernaTX, Inc.

Tracking Information
First Submitted Date  ICMJE May 13, 2020
First Posted Date  ICMJE May 28, 2020
Last Update Posted Date May 5, 2021
Actual Study Start Date  ICMJE May 29, 2020
Estimated Primary Completion Date November 1, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 8, 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: Up to Month 15 ]
  • Number of Participants with Serious Adverse Events (SAEs) [ Time Frame: Up to Month 15 ]
  • Change from Baseline in the Measure of Clinical Safety Laboratory Values in Cohort 2 [ Time Frame: Part A: Baseline, 1 month after last vaccination ]
  • Number of Participants with Abnormalities in Blood Pressure, Temperature, HR, or Respiratory Rate [ Time Frame: Up to Month 15 ]
  • Number of Participants with Abnormalities in Physical Examinations [ Time Frame: Up to Month 15 ]
  • Level of SARS-CoV-2-Specific Binding Antibody (bAb) as Measured by Enzyme-Linked Immunosorbent Assay (ELISA) [ Time Frame: Day 1 through 6 months after last vaccination ]
Original Primary Outcome Measures  ICMJE
 (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 ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 22, 2021)
  • Titer of SARS-CoV-2-Specific Neutralizing Antibody (nAb) [ Time Frame: Day 1 through 6 months after last vaccination ]
  • Seroconversion as Measured by an Increase of SARS-CoV-2-Specific Neutralizing Antibody (nAb) Titer [ Time Frame: Day 1 through 6 months after last vaccination ]
    Seroconversion as measured by an increase of SARS-CoV-2-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.
  • Level of SARS CoV-2-Specific Serum Binding Antibody [ Time Frame: Day 1 through 6 months after last vaccination ]
Original Secondary Outcome Measures  ICMJE
 (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.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE 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  ICMJE 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

This is a 3-part Phase 2a study, with Part A (Blinded Phase), Part B (Open-label Interventional Phase), and Part C (Rollover Proof of Concept).

Participants in Part A are blinded to their treatment assignment, with participants receiving either 2 active mRNA-1273 vaccine doses or placebo. Part B of the study is designed to offer participants to be unblinded so that participants who received placebo in Part A can request 2 doses of open-label mRNA-1273 vaccine. Additionally, participants who originally received 1 or 2 doses of mRNA-1273 (50 microgram [μg] or 100 μg vaccine) during Part A, will have the opportunity to request to receive a single booster dose of mRNA-1273.

Part C will be a proof-of-concept rollover study to evaluate a vaccine to treat mutations of SARS-CoV2, such as the S-protein of the B.1.351 variant. Part C will include approximately 60 participants, who are currently enrolled in Moderna's Phase 3 mRNA-1273-P301 study (NCT04470427), have already been unblinded, and have previously received 2 doses of mRNA-1273 at least 6 months earlier. At enrollment into Part C of this study, their participation in mRNA-1273-P301 study will be terminated. Part C will evaluate the safety and immunogenicity of 2 dose levels (20 µg and 50 µg) of mRNA-1273.351 and mRNA-1273/mRNA-1273.351 mixture (50 µg total), given as a single booster dose.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE 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.
Primary Purpose: Prevention
Condition  ICMJE SARS-CoV-2
Intervention  ICMJE
  • Biological: Biological: mRNA-1273
    Sterile liquid for injection
  • Biological: Placebo
    0.9% sodium chloride (normal saline) injection
  • Biological: mRNA-1273.351
    Sterile liquid for injection
Study Arms  ICMJE
  • Experimental: mRNA-1273: Dose 50 microgram (ug) - Participants Aged 18-54 years

    Part A: Participants aged 18-54 years will receive 1 intramuscular (IM) injection of 50 ug mRNA-1273 on Day 1 and on Day 29.

    Part B: Participants aged 18-54 years who choose to be unblinded and received 50 ug mRNA-1273 during Part A, will receive 1 IM injection of mRNA-1273 (booster dose) on Day 1.

    Intervention: Biological: Biological: mRNA-1273
  • Experimental: mRNA-1273: Dose 50 ug - Participants Aged 55+ years

    Part A: Participants aged 55+ years will receive 1 IM injection of 50 ug mRNA-1273 on Day 1 and on Day 29.

    Part B: Participants aged 55+ years who choose to be unblinded and received 50 ug mRNA-1273 during Part A, will receive 1 IM injection of mRNA-1273 (booster dose) on Day 1.

    Intervention: Biological: Biological: mRNA-1273
  • Experimental: mRNA-1273: Dose 100 ug - Participants Aged 18-54 years

    Part A: Participants aged 18-54 years will receive 1 IM injection of 100 ug mRNA-1273 on Day 1 and on Day 29.

    Part B: Participants aged 18-54 years who choose to be unblinded and received 100 ug mRNA-1273 during Part A, will receive 1 IM injection of mRNA-1273 (booster dose) on Day 1.

    Intervention: Biological: Biological: mRNA-1273
  • Experimental: mRNA-1273: Dose 100 ug - Participants Aged 55+ years

    Part A: Participants aged 55+ years will receive 1 IM injection of 100 ug mRNA-1273 on Day 1 and on Day 29.

    Part B: Participants aged 55+ years who choose to be unblinded and received 100 ug mRNA-1273 during Part A, will receive 1 IM injection of mRNA-1273 (booster dose) on Day 1.

    Intervention: Biological: Biological: mRNA-1273
  • Placebo Comparator: Placebo (Part A) and mRNA-1273 100 ug (Part B) - Participants Aged 18-54 years

    Part A: Participants aged 18-54 years will receive 1 IM injection of mRNA-1273-matching placebo on Day 1 and on Day 29.

    Part B: Participants aged 18-54 who choose to be unblinded and received mRNA-1273-matching placebo during Part A, will receive 1 IM injection of 100 ug mRNA-1273 on Day 1 and Day 29.

    Interventions:
    • Biological: Biological: mRNA-1273
    • Biological: Placebo
  • Placebo Comparator: Placebo (Part A) and mRNA-1273 100 ug (Part B) - Participants Aged 55+ years

    Part A: Participants aged 55+ years will receive 1 IM injection of mRNA-1273-matching placebo on Day 1 and on Day 29.

    Part B: Participants aged 55+ years who choose to be unblinded and received mRNA-1273-matching placebo during Part A, will receive 1 IM injection of 100 ug mRNA-1273 on Day 1 and Day 29.

    Interventions:
    • Biological: Biological: mRNA-1273
    • Biological: Placebo
  • Experimental: mRNA 1273.351 20 ug (Part C)
    Part C: Participants will receive 1 IM booster dose of 20 ug of mRNA 1273.351 on Day 1.
    Intervention: Biological: mRNA-1273.351
  • Experimental: mRNA 1273.351 50 ug (Part C)
    Part C: Participants will receive 1 IM booster dose of 50 ug of mRNA 1273.351 on Day 1.
    Intervention: Biological: mRNA-1273.351
  • Experimental: mRNA-1273/mRNA-1273.351 mixture (Part C)
    Part C: Participants will receive 1 IM booster dose of 50 ug of mRNA-1273/mRNA-1273.351 mixture on Day 1.
    Interventions:
    • Biological: Biological: mRNA-1273
    • Biological: mRNA-1273.351
Publications * Chu L, McPhee R, Huang W, Bennett H, Pajon R, Nestorova B, Leav B; mRNA-1273 Study Group. A preliminary report of a randomized controlled phase 2 trial of the safety and immunogenicity of mRNA-1273 SARS-CoV-2 vaccine. Vaccine. 2021 May 12;39(20):2791-2799. doi: 10.1016/j.vaccine.2021.02.007. Epub 2021 Feb 9.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Estimated Enrollment  ICMJE
 (submitted: March 22, 2021)
660
Original Estimated Enrollment  ICMJE
 (submitted: May 26, 2020)
600
Estimated Study Completion Date  ICMJE November 1, 2021
Estimated Primary Completion Date November 1, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04405076
Other Study ID Numbers  ICMJE 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  ICMJE
Plan to Share IPD: No
Responsible Party ModernaTX, Inc.
Study Sponsor  ICMJE ModernaTX, Inc.
Collaborators  ICMJE Biomedical Advanced Research and Development Authority
Investigators  ICMJE Not Provided
PRS Account ModernaTX, Inc.
Verification Date May 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP