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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

Trial Profile

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

Status: Active, no longer recruiting
Phase of Trial: Phase II

Latest Information Update: 12 May 2021

At a glance

  • Drugs MRNA 1273 (Primary) ; MRNA 1273 351 (Primary)
  • Indications COVID 2019 infections
  • Focus Adverse reactions; Pharmacodynamics
  • Sponsors Moderna Therapeutics
  • Most Recent Events

    • 12 May 2021 According to a Moderna media release, A manuscript describing these preliminary results was submitted as a preprint to medRxiv and will be submitted for peer-reviewed publication upon completion of the multivalent mRNA-1273.211 booster arm.
    • 03 May 2021 Planned End Date changed from 6 Oct 2021 to 1 Nov 2021.
    • 03 May 2021 Planned primary completion date changed from 31 Mar 2021 to 1 Nov 2021.

Trial Overview

Purpose

This dose-confirmation, phase II clinical study is designed to assess the safety, reactogenicity, and immunogenicity of 2 dose levels of mRNA-1273 SARS-COV-2 vaccine in adults 18 years of age or older.

Primary Endpoints

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

Other Endpoints

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

description: 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.
time_frame: Day 1 through 6 months after last vaccination

Level of SARS CoV-2-Specific Serum Binding Antibody

time_frame: Day 1 through 6 months after last vaccination [1]

Diseases Treated

Indication Qualifiers Patient Segments
COVID 2019 infections prevention -

Subjects

  • Subject Type volunteers
  • Number

    Planned: 660

  • Sex male & female
  • Age Group ≥ 18 years; adult

Patient Inclusion Criteria

Key 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

Patient 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.

Trial Details

Identifiers

Identifier Owner
NCT04405076 ClinicalTrials.gov: US National Institutes of Health
mRNA1273P201 -
75A50120C00034 -

Organisations

  • Sponsors Moderna Therapeutics
  • Affiliations Moderna Therapeutics

Trial Dates

  • Initiation Dates

    Actual : 29 May 2020

  • Primary Completion Dates

    Planned : 01 Nov 2021

  • End Dates

    Planned : 01 Nov 2021

Other Details

  • Design double-blind; multicentre; open; prospective; randomised; sequential
  • Phase of Trial Phase II
  • Location USA
  • Focus Adverse reactions; Pharmacodynamics

Interventions

Drugs Route Formulation
MRNA 1273Primary Drug Intramuscular Injection
MRNA 1273 351Primary Drug Intramuscular Injection

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. Biological: Biological: mRNA-1273 (Sterile liquid for injection) Biological: Placebo (0.9% sodium chloride (normal saline) injection)

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. Biological: Biological: mRNA-1273 (Sterile liquid for injection) Biological: Placebo (0.9% sodium chloride (normal saline) injection)

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. Biological: Biological: mRNA-1273 (Sterile liquid for injection) Biological: mRNA-1273.351 (Sterile liquid for injection)

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. Biological: Biological: mRNA-1273 (Sterile liquid for injection)

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. Biological: Biological: mRNA-1273 (Sterile liquid for injection)

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. Biological: Biological: mRNA-1273 (Sterile liquid for injection)

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. Biological: Biological: mRNA-1273 (Sterile liquid for injection)

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. Biological: mRNA-1273.351 (Sterile liquid for injection)

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. Biological: mRNA-1273.351 (Sterile liquid for injection)

Results

Publications

  1. Chu L, McPhee R, Huang W, Bennett H, Pajon R, Nestorova B, et al. A preliminary report of a randomized controlled phase 2 trial of the safety and immunogenicity of mRNA-1273 SARS-CoV-2 vaccine. . Vaccine 2021;.

    PubMed | CrossRef Fulltext

Authors

Author Total Publications First Author Last Author
Bennett H 1 - -
Chu L 1 1 -
Huang W 1 - -
Leav B 1 - 1
McPhee R 1 - -
Nestorova B 1 - -
Pajon R 1 - -

Trial Centres

Investigators

Investigator Centre Name Trial Centre Country
-
Advanced Clinical Research/Velocity, Benchmark Research, Heartland Research Associates, Meridian Clinical Research, Trial Management Associates USA
Moderna Clinical Trials
855-663-6762
clinicaltrials@modernatx.com
show details
-

Centres

Centre Name Location Trial Centre Country
-
-
-
Advanced Clinical Research/Velocity West Jordan, Utah USA
Benchmark Research Austin, Texas USA
Benchmark Research San Angelo, Texas USA
Biomedical Advanced Research and Development Authority
-
-
Heartland Research Associates Kansas City, Missouri USA
Heartland Research Associates Newton, Kansas USA
Meridian Clinical Research Dakota Dunes, South Dakota USA
Meridian Clinical Research Norfolk, Nebraska USA
Meridian Clinical Research Omaha, Nebraska USA
Meridian Clinical Research Savannah, Georgia USA
ModernaTX, Inc.
-
-
Trial Management Associates Wilmington, North Carolina USA

Trial History

Event Date Event Type Comment
12 May 2021 Other trial event According to a Moderna media release, A manuscript describing these preliminary results was submitted as a preprint to medRxiv and will be submitted for peer-reviewed publication upon completion of the multivalent mRNA-1273.211 booster arm. Updated 25 May 2021
07 May 2021 Other trial event Last checked against the ClinicalTrials.gov record. Updated 07 May 2021
03 May 2021 Completion date Planned End Date changed from 6 Oct 2021 to 1 Nov 2021. Updated 07 May 2021
03 May 2021 Other trial event Planned primary completion date changed from 31 Mar 2021 to 1 Nov 2021. Updated 07 May 2021
22 Mar 2021 Protocol amendment Protocol amended to include Part C (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. Anticipated enrolment of patients increased from 600 to 660. Number of study treatment arms increased from 6 to 9. Updated 25 Mar 2021
22 Mar 2021 Other trial event Planned number of patients changed from 600 to 660. Updated 25 Mar 2021
09 Feb 2021 Interim results A preliminary results published in the Vaccine Updated 17 Mar 2021
08 Feb 2021 Protocol amendment Time frame for primary and secondary outcome measures amended. Updated 12 Feb 2021
08 Feb 2021 Completion date Planned End Date changed from 31 Aug 2021 to 6 Oct 2021. Updated 12 Feb 2021
15 Jan 2021 Completion date Planned End Date changed from 1 Aug 2021 to 31 Aug 2021. Updated 22 Jan 2021
15 Jan 2021 Other trial event Planned primary completion date changed from 1 Mar 2021 to 31 Mar 2021. Updated 22 Jan 2021
27 Jul 2020 Other trial event According to a Moderna Therapeutics media release, PPD supported the Phase 2 study for this vaccine program. Updated 30 Jul 2020
08 Jul 2020 Other trial event According to a Moderna Therapeutics media release, the cohort of an older adults (n=300) has now been fully enrolled in this study. Updated 13 Jul 2020
08 Jul 2020 Other trial event According to a Moderna Therapeutics media release, on 25 June 2020, after reviewing the safety data from the sentinel cohort of older adults, the Data and Safety Monitoring Committee recommended to proceed with enrollment of this study. Updated 13 Jul 2020
08 Jul 2020 Status change - active, no longer recruiting Status changed from recruiting to active, no longer recruiting, according to a Moderna Therapeutics media release. Updated 13 Jul 2020
11 Jun 2020 Other trial event According to a Moderna Therapeutics media release, the first cohort of healthy adults ages 18-54 years (n=300) in this study is fully enrolled. The sentinel participants in the cohort of older adults ages 55 years and above (n=50) is fully enrolled. Updated 17 Jun 2020
01 Jun 2020 Other trial event New source identified and integrate (ClinicalTrials.gov: US National Institutes of Health: NCT04405076). Updated 01 Jun 2020
01 Jun 2020 Status change - recruiting Status changed from planning to recruiting. Updated 01 Jun 2020
29 May 2020 Other trial event According to a Moderna Therapeutics media release, first participants in each age cohort have been dosed. Updated 05 Jun 2020
18 May 2020 Protocol amendment According to a Moderna Therapeutics media release, based on the interim results from phase I trial, the study will be amended to study two dose levels, 50 µg and 100 µg, with the aim of selecting a dose for pivotal studies. Updated 22 May 2020
07 May 2020 Other trial event According to a Moderna Therapeutics media release, the U.S. Food and Drug Administration (FDA) has completed the review of Investigational New Drug (IND) application allowing company to initiate this study. The company expected to initiate this study shortly. Updated 12 May 2020
27 Apr 2020 Other trial event According to a Moderna Therapeutics, the company has submitted an Investigational New Drug application to the U.S. Food and Drug Administration (FDA) for the company's mRNA vaccine candidate (mRNA-1273) against the novel coronavirus (SARS-CoV-2) to evaluate mRNA-1273 in Phase 2 and late-stage studies if supported by safety data from the Phase 1 study led by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health. Updated 04 May 2020
27 Apr 2020 Other trial event According to a Moderna Therapeutics, The company intends to enroll 600 healthy participants across two cohorts of adults ages 18-55 years (n=300) and older adults ages 55 years and above (n=300). Participants will be followed through 12 months after the second vaccination. Updated 04 May 2020
27 Apr 2020 Other trial event According to a Moderna Therapeutics, the company has received initial feedback from the FDA on the design of the planned Phase 2 study. Updated 04 May 2020
27 Apr 2020 Other trial event According to a Moderna Therapeutics, Funding from the Biomedical Advanced Research and Development Authority (BARDA), part of the Office of the Assistant Secretary for Preparedness and Response within the U.S. Department of Health and Human Services, supported the planning for these studies and also will support the late-stage clinical development programs, as well as the scale-up of mRNA-1273 manufacturing. Updated 04 May 2020
16 Apr 2020 Other trial event According to a Modern Therapeutics, Phase 2 study expected to begin in Q2 2020, following safety data from ongoing Phase 1 study Updated 20 Apr 2020
18 Mar 2020 New trial record New trial record Updated 18 Mar 2020
16 Mar 2020 Other trial event According to a Modern Therapeutics, the company is actively preparing for a potential Phase 2 study under its own IND which could begin in a few months. Updated 18 Mar 2020

References

  1. ClinicalTrials.gov: US National Institutes of Health. Trial-Reg 2021;.

    Available from: URL: http://clinicaltrials.gov
  2. Moderna Therapeutics. Moderna Announces Positive Interim Phase 1 Data for its mRNA Vaccine (mRNA-1273) Against Novel Coronavirus. Media-Rel 2020;.

    Media Release
  3. Moderna Therapeutics. Moderna Announces First Participant Dosed in NIH-led Phase 1 Study of mRNA Vaccine (mRNA-1273) Against Novel Coronavirus. Media-Rel 2020;.

    Media Release
  4. Moderna Therapeutics. Moderna Announces First Participants in Each Age Cohort Dosed in Phase 2 Study of mRNA Vaccine (mRNA-1273) Against Novel Coronavirus. Media-Rel 2020;.

    Media Release
  5. Moderna Therapeutics. Moderna Reports First Quarter 2020 Financial Results and Provides Business Updates. Media-Rel 2020;.

    Media Release
  6. Moderna Therapeutics. Moderna Announces IND Submitted to U.S. FDA for Phase 2 Study of mRNA Vaccine (mRNA-1273) Against Novel Coronavirus. Media-Rel 2020;.

    Media Release
  7. Moderna Therapeutics. Moderna Completes Enrollment of Phase 2 Study of its mRNA Vaccine Against COVID-19 (mRNA-1273). Media-Rel 2020;.

    Media Release
  8. Chu L, McPhee R, Huang W, Bennett H, Pajon R, Nestorova B, et al. A preliminary report of a randomized controlled phase 2 trial of the safety and immunogenicity of mRNA-1273 SARS-CoV-2 vaccine. . Vaccine 2021;.

    PubMed | CrossRef Fulltext
  9. Moderna Therapeutics. Moderna Announces New Supply Agreement with Australia for 25 Million Doses of its COVID-19 Vaccine. Media-Rel 2021;.

    Media Release
  10. Moderna Therapeutics. Moderna Announces Phase 3 COVE Study of mRNA Vaccine Against COVID-19 (mRNA-1273) Begins. Media-Rel 2020;.

    Media Release
  11. Moderna Therapeutics. Moderna Announces Award from U.S. Government Agency BARDA for up to $483 Million to Accelerate Development of mRNA Vaccine (mRNA-1273) Against Novel Coronavirus. Media-Rel 2020;.

    Media Release
  12. Moderna Therapeutics. Moderna Advances Late-Stage Development of its Vaccine (mRNA-1273) Against COVID-19. Media-Rel 2020;.

    Media Release
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