Dose-Confirmation Study to Evaluate the Safety, Reactogenicity, and Immunogenicity of mRNA-1273 COVID-19 Vaccine in Adults Aged 18 Years and Older
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
2 other identifiers
interventional
660
1 country
8
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2
Started May 2020
Shorter than P25 for phase_2
8 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
May 13, 2020
CompletedFirst Posted
Study publicly available on registry
May 28, 2020
CompletedStudy Start
First participant enrolled
May 29, 2020
CompletedPrimary Completion
Last participant's last visit for primary outcome
October 28, 2021
CompletedStudy Completion
Last participant's last visit for all outcomes
October 28, 2021
CompletedResults Posted
Study results publicly available
December 30, 2022
CompletedDecember 30, 2022
December 1, 2022
1.4 years
May 13, 2020
October 21, 2022
December 6, 2022
Conditions
Keywords
Outcome Measures
Primary Outcomes (7)
Number of Participants With Solicited Local and Systemic Adverse Reactions (ARs)
Solicited ARs, including local and systemic ARs were collected in the eDiary. Local ARs included: pain at injection site, erythema (redness) at injection site, swelling/induration (hardness) at injection site, and localized axillary swelling or tenderness ipsilateral to the injection arm. Systemic ARs included: headache, fatigue, myalgia (muscle aches all over the body), arthralgia (aching in several joints), nausea/vomiting, rash, body temperature (potentially fever), and chills. All solicited ARs (local and systemic) considered causally related to injection. ARs were graded 0-4 as reviewed and confirmed by Investigator; lower score indicates lower severity and a higher score indicates greater severity. Note, not all solicited ARs were considered adverse events (AEs). The Investigator reviewed whether the solicited AR was also to be recorded as an AE. A summary of SAEs and all nonserious AEs ("Other"), regardless of causality, is located in the Reported "Adverse Events" section.
7 days post-vaccination
Number of Participants With Unsolicited AEs
An AE was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. A treatment-emergent AE (TEAE) was defined as any event not present before exposure to vaccine or any event already present that worsens in intensity or frequency after exposure. Any abnormal laboratory test result (hematology, clinical chemistry, or prothrombin time \[PT\]/partial thromboplastin time \[PTT\]) or other safety assessment (for example, electrocardiogram, radiological scan, vital sign measurement), including one that worsens from baseline and is considered clinically significant in the medical and scientific judgment of the Investigator. A summary of SAEs and all nonserious AEs ("Other") reported up to the end of the study (up to Month 15), regardless of causality, is located in the Reported "Adverse Events" section.
Up to 28 days post-vaccination
Number of Participants With Medically-Attended Adverse Events (MAAEs)
An MAAE is an AE that leads to an unscheduled visit to a healthcare practitioner (HCP). A summary of SAEs and all nonserious AEs ("Other"), regardless of causality, is located in the Reported "Adverse Events" section.
Up to Month 15
Number of Participants With SAEs
An SAE was defined as any AE that resulted in death, is life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in disability/permanent damage, was a congenital anomaly/birth defect, or was an important medical event. A summary of SAEs and all nonserious AEs ("Other"), regardless of causality, is located in the Reported "Adverse Events" section.
Up to Month 15
Part A: Level of Severe Acute Respiratory Syndrome Coronavirus (SARS-COV-2)-Specific Binding Antibody (bAb) as Measured by Enzyme-Linked Immunosorbent Assay (ELISA)
The geometric mean (GM) level of VAC58 spike immunoglobulin G (IgG) antibodies, as measured by ELISA specific to the SARS-CoV-2 spike protein is reported. Antibody values reported as below the lower limit of quantification (LLOQ) were replaced by 0.5\*LLOQ. Values that were greater than the upper limit of quantification (ULOQ) were converted to the ULOQ if actual values were not available. LLOQ was 1 and ULOQ was 2052. The 95% confidence intervals (CIs) were calculated based on the t-distribution of the log-transformed values or the difference in the log-transformed values for GM value, respectively, then back transformed to the original scale for presentation.
Days 1 (Baseline), 29, 43, 57, and 209
Part B: Level of SARS-CoV-2-Specific bAb as Measured by ELISA
The GM level of VAC65 spike IgG antibodies, as measured by ELISA specific to the SARS-CoV-2 spike protein is reported. Antibody values reported as below the LLOQ were replaced by 0.5\*LLOQ. Values that were greater than the ULOQ are converted to the ULOQ. LLOQ was 1 and ULOQ was 2052. The 95% CIs were calculated based on the t-distribution of the log-transformed values or the difference in the log-transformed values for GM value, respectively, then back transformed to the original scale for presentation. The PP Set included participants with a study injection, required baseline data, had postinjection results at timepoint of primary interest for immunogenicity analysis, no major protocol deviations impacting immune response, and didn't have SARS-CoV-2.
Days 1 (Baseline) and 29
Part C: Level of SARS-CoV-2-Specific bAb as Measured by MSD
The GM level of SARS-CoV-2 protein antibody against B.1.351, as measured by MSD MULTIPLEX is reported. Antibody values reported as below the LLOQ were replaced by 0.5\*LLOQ. Values that were greater than the ULOQ are converted to the ULOQ. LLOQ was 18 and ULOQ was 4200000. The 95% CIs were calculated based on the t-distribution of the log-transformed values or the difference in the log-transformed values for GM value, respectively, then back transformed to the original scale for presentation.
Days 1 (Baseline), 8, 15, and 29
Secondary Outcomes (6)
Part A: Titer of SARS-CoV-2-Specific Neutralizing Antibody (nAb)
Days 1 (Baseline), 29, 43, 57, and 209
Part B: Titer of SARS-CoV-2-Specific nAb
Days 1 (Baseline), 29, and 181
Part C: Titer of SARS-CoV-2-Specific nAb
Days 1 (Baseline), 8, 15, 29, and 181
Part A: Percentage of Participants With Seroconversion From Baseline
Days 29, 43, and 57
Part B: Percentage of Participants With Seroconversion From Baseline
Days 29 and 181
- +1 more secondary outcomes
Study Arms (9)
mRNA-1273: Dose 50 microgram (ug) - Participants Aged 18-54 years
EXPERIMENTALPart 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.
mRNA-1273: Dose 50 ug - Participants Aged 55+ years
EXPERIMENTALPart 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.
mRNA-1273: Dose 100 ug - Participants Aged 18-54 years
EXPERIMENTALPart 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.
mRNA-1273: Dose 100 ug - Participants Aged 55+ years
EXPERIMENTALPart 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.
Placebo (Part A) and mRNA-1273 100 ug (Part B) - Participants Aged 18-54 years
PLACEBO COMPARATORPart 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.
Placebo (Part A) and mRNA-1273 100 ug (Part B) - Participants Aged 55+ years
PLACEBO COMPARATORPart 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.
mRNA 1273.351 20 ug (Part C)
EXPERIMENTALPart C: Participants will receive 1 IM booster dose of 20 ug of mRNA 1273.351 on Day 1.
mRNA 1273.351 50 ug (Part C)
EXPERIMENTALPart C: Participants will receive 1 IM booster dose of 50 ug of mRNA 1273.351 on Day 1.
mRNA-1273/mRNA-1273.351 mixture (Part C)
EXPERIMENTALPart C: Participants will receive 1 IM booster dose of 50 ug of mRNA-1273/mRNA-1273.351 mixture on Day 1.
Interventions
Sterile liquid for injection
0.9% sodium chloride (normal saline) injection
Sterile liquid for injection
Eligibility Criteria
You may qualify if:
- 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:
- 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.
- Understands and agrees to comply with the study procedures and provides written informed consent.
- According to the assessment of the investigator, is in good general health and can comply with study procedures.
- 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.
- 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.
- +7 more criteria
You may not qualify if:
- 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:
- Pregnant or breastfeeding.
- 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.
- Current treatment with investigational agents for prophylaxis against COVID-19.
- 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.
- Is a healthcare worker or a member of an emergency response team.
- Current use of any inhaled substance (for example, tobacco or cannabis smoke, nicotine vapors).
- History of chronic smoking (≥1 cigarette a day) within 1 year of the Screening Visit (Day 0).
- 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).
- Known history of hypotension or systolic blood pressure \<85 mmHg at the Screening Visit (Day 0).
- Diabetes mellitus
- Diagnosis of chronic pulmonary disease (for example, chronic obstructive pulmonary disease, asthma)
- Chronic cardiovascular disease
- Resides in a nursing home
- Grade 1 or higher toxicity on clinical safety laboratory testing at the Screening Visit (Day 0)
- +14 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (8)
Meridian Clinical Research
Savannah, Georgia, 31406, United States
Alliance for Multispecialty Research
Newton, Kansas, 67114, United States
Alliance for Multispecialty Research
Kansas City, Missouri, 64114, United States
Meridian Clinical Research
Norfolk, Nebraska, 68701, United States
Trial Management Associates
Wilmington, North Carolina, 28403, United States
Meridian Clinical Research
Dakota Dunes, South Dakota, 57049, United States
Benchmark Research
Austin, Texas, 78705, United States
Benchmark Research
San Angelo, Texas, 76904, United States
Related Publications (5)
Kirste I, Hortsch S, Grunert VP, Legault H, Maglinao M, Eichenlaub U, Kashlan B, Pajon R, Jochum S. Quantifying the Vaccine-Induced Humoral Immune Response to Spike-Receptor Binding Domain as a Surrogate for Neutralization Testing Following mRNA-1273 (Spikevax) Vaccination Against COVID-19. Infect Dis Ther. 2023 Jan;12(1):177-191. doi: 10.1007/s40121-022-00711-y. Epub 2022 Nov 15.
PMID: 36376733DERIVEDChalkias S, Eder F, Essink B, Khetan S, Nestorova B, Feng J, Chen X, Chang Y, Zhou H, Montefiori D, Edwards DK, Girard B, Pajon R, Dutko FJ, Leav B, Walsh SR, Baden LR, Miller JM, Das R. Safety, immunogenicity and antibody persistence of a bivalent Beta-containing booster vaccine against COVID-19: a phase 2/3 trial. Nat Med. 2022 Nov;28(11):2388-2397. doi: 10.1038/s41591-022-02031-7. Epub 2022 Oct 6.
PMID: 36202997DERIVEDChu L, Vrbicky K, Montefiori D, Huang W, Nestorova B, Chang Y, Carfi A, Edwards DK, Oestreicher J, Legault H, Dutko FJ, Girard B, Pajon R, Miller JM, Das R, Leav B, McPhee R. Immune response to SARS-CoV-2 after a booster of mRNA-1273: an open-label phase 2 trial. Nat Med. 2022 May;28(5):1042-1049. doi: 10.1038/s41591-022-01739-w. Epub 2022 Mar 3.
PMID: 35241844DERIVEDChoi A, Koch M, Wu K, Chu L, Ma L, Hill A, Nunna N, Huang W, Oestreicher J, Colpitts T, Bennett H, Legault H, Paila Y, Nestorova B, Ding B, Montefiori D, Pajon R, Miller JM, Leav B, Carfi A, McPhee R, Edwards DK. Safety and immunogenicity of SARS-CoV-2 variant mRNA vaccine boosters in healthy adults: an interim analysis. Nat Med. 2021 Nov;27(11):2025-2031. doi: 10.1038/s41591-021-01527-y. Epub 2021 Sep 15.
PMID: 34526698DERIVEDChu 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.
PMID: 33707061DERIVED
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Results Point of Contact
- Title
- Moderna Clinical Trials Support Center
- Organization
- ModernaTX, Inc.
Publication Agreements
- PI is Sponsor Employee
- No
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- DOUBLE
- Who Masked
- PARTICIPANT, INVESTIGATOR
- Masking Details
- 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.
- Purpose
- PREVENTION
- Intervention Model
- SEQUENTIAL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
May 13, 2020
First Posted
May 28, 2020
Study Start
May 29, 2020
Primary Completion
October 28, 2021
Study Completion
October 28, 2021
Last Updated
December 30, 2022
Results First Posted
December 30, 2022
Record last verified: 2022-12
Data Sharing
- IPD Sharing
- Will not share