Safety and Immunogenicity Study of 2019-nCoV Vaccine (mRNA-1273) for Prophylaxis of SARS-CoV-2 Infection (COVID-19)
Phase I, Open-Label, Dose-Ranging Study of the Safety and Immunogenicity of 2019-nCoV Vaccine (mRNA-1273) in Healthy Adults
2 other identifiers
interventional
120
1 country
3
Brief Summary
This is a phase I, open-label, dose-ranging clinical trial in males and non-pregnant females, starting at 18 years of age, inclusive, who are in good health and meet all eligibility criteria. This clinical trial is designed to assess the safety, reactogenicity and immunogenicity of mRNA-1273 manufactured by ModernaTX, Inc. mRNA-1273 is a novel lipid nanoparticle (LNP)-encapsulated mRNA-based vaccine that encodes for a full-length, prefusion stabilized spike (S) protein of SARS-CoV-2. Enrollment will occur at up to 3 domestic clinical research sites. Up to one hundred and fifty-five subjects will be enrolled into one of thirteen cohorts (10 micrograms \[mcg\], 25 mcg, 50 mcg, 100 mcg, and 250 mcg). Subjects will receive an intramuscular (IM) injection (0.5 milliliters \[mL\]) of mRNA-1273 on Days 1 and 29 in the deltoid muscle and will be followed through 12 months post second vaccination (Day 394). Follow-up visits will occur 1, 2, and 4 weeks post each vaccination (Days 8, 15, 29, 36, 43, and 57), as well as 3, 6, and 12 months post second vaccination (Days 119, 209, and 394). The primary objective is to evaluate the safety and reactogenicity of a 2-dose vaccination schedule of mRNA-1273, given 28 days apart, across 5 dosages in healthy adults. Optional Substudy: This is an optional third mRNA-1273 vaccination substudy, in subjects 18 years of age and older, who received both the first and second mRNA-1273 vaccinations in the main study and meet all other substudy eligibility criteria. This optional third mRNA-1273 vaccination substudy is designed to assess safety, reactogenicity, and immunogenicity through 12 months post third vaccination (Day 731). Subjects who receive the third mRNA-1273 vaccination will exit the Schedule of Activities for the main study and will enter the Schedule of Activities for the optional substudy. Up to one hundred and twenty subject will be enrolled into two cohorts (consisting of participating subjects who received 2 doses of 25 or 50 mcg and participating subjects who received 2 doses of 100 and 250 mcg). Subjects will receive an IM injection (0.5 mL) at a dosage of 100 mcg/0.5 mL. The primary objective is to evaluate the safety and reactogenicity of a third mRNA-1273 vaccination, at a dosage of 100 mcg.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1 covid19
Started Mar 2020
Longer than P75 for phase_1 covid19
3 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
February 21, 2020
CompletedFirst Posted
Study publicly available on registry
February 25, 2020
CompletedStudy Start
First participant enrolled
March 16, 2020
CompletedPrimary Completion
Last participant's last visit for primary outcome
April 26, 2022
CompletedStudy Completion
Last participant's last visit for all outcomes
April 26, 2022
CompletedResults Posted
Study results publicly available
May 9, 2023
CompletedMarch 18, 2024
August 26, 2021
2.1 years
February 21, 2020
April 13, 2023
March 14, 2024
Conditions
Keywords
Outcome Measures
Primary Outcomes (7)
Frequency of Any Medically-attended Adverse Events (MAAEs)
Number of participants that experienced any MAAEs from Day 1 to Day 394.
Day 1 to Day 394
Frequency of Any New-onset Chronic Medical Conditions (NOCMCs)
Number of participants that experienced any NOCMCs from Day 1 to Day 394.
Day 1 to Day 394
Frequency of Any Serious Adverse Events (SAEs)
The number of participants that experience any SAEs from Day 1 to Day 394. An AE or suspected adverse reaction is considered serious if, in the view of either the participating site PI or appropriate sub-investigator or the sponsor, it results in: death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, or a congenital anomaly/birth defect.
Day 1 to Day 394
Frequency of Solicited Reactogenicity Adverse Events (AEs)
The number of participants that experienced at least one solicited (local and systemic) AE through 7 days post vaccination. Systemic events include: fatigue, headache, myalgia, arthralgia, nausea, chills and fever. Local events include: pain at injection site, erythema, and induration.
Through 7 days post-vaccination
Frequency of Any Unsolicited Adverse Events (AEs) by Relationship to Study Product and Severity
Number of events of any unsolicited AE through 28 days post vaccination by relationship to study product and severity, experienced by participants in the Safety Analysis population . Unsolicited AEs were events that were spontaneously reported by the subject, or revealed by observation, physical examination or other diagnostic procedures.
Through 28 days post-vaccination
Grade of Any Unsolicited Adverse Events (AEs)
Number of any unsolicited AEs through 28 days post vaccination by severity
Through 28 days post-vaccination
Grade of Solicited Reactogenicity Adverse Events (AEs)
Number of participants who experienced any solicited (local and systemic) AEs through 7 days post vaccination by grade. Systemic events include: fatigue, headache, myalgia, arthralgia, nausea, chills and fever. Local events include: pain at injection site, erythema, and induration.
Through 7 days post vaccination
Secondary Outcomes (6)
Geometric Mean Fold Rise (GMFR) in IgG Titer From Baseline Against RBD
Day 1 to Day 394
Geometric Mean Fold Rise (GMFR) in IgG Titer From Baseline Against S-2
Day 1 to Day 394
Geometric Mean Titer (GMT) of Antibody Against RBD
Day 1 to Day 394
Geometric Mean Titer (GMT) of Antibody Against S-2P
Day 1 to Day 394
Percentage of Participants Who Seroconverted Against RBD
Day 1 to Day 394
- +1 more secondary outcomes
Study Arms (15)
Arm 1
EXPERIMENTAL25 mcg of mRNA-1273 administered through 0.5 mL intramuscular injection in the deltoid muscle on Days 1 and 29 in participants from 18-55 years of age. N=15 (4 sentinel, 11 non-sentinel)
Arm 10
EXPERIMENTAL50 mcg of mRNA-1273 administered through 0.5 mL intramuscular injection in the deltoid muscle on Days 1 and 29 in participants from 18-55 years of age. N=15.
Arm 11
EXPERIMENTAL50 mcg of mRNA-1273 administered through 0.5 mL intramuscular injection in the deltoid muscle on Days 1 and 29 in participants from 56-70 years of age. N=10.
Arm 12
EXPERIMENTAL50 mcg of mRNA-1273 administered through 0.5 mL intramuscular injection in the deltoid muscle on Days 1 and 29 in participants 71 years of age or older. N=10.
Arm 13
EXPERIMENTAL10 mcg of mRNA-1273 administered through 0.5 mL intramuscular injection in the deltoid muscle on Days 1 and 29 in participants from 18-55 years of age. N=15.
Arm 14
EXPERIMENTALOptional third mRNA-1273 vaccination sub-study. 100 mcg of mRNA-1273 administered through 0.5 mL intramuscular injection in the deltoid muscle after Day 209 in participants from Arm 1,4,7,10, 11, and 12 from 18 years of age or older. N=70.
Arm 15
EXPERIMENTALOptional third mRNA-1273 vaccination sub-study. 100 mcg of mRNA-1273 administered through 0.5 mL intramuscular injection in the deltoid muscle no later than Day 394 in participants from Arm 2,3,5 and 8 from 18 years of age or older. N=50.
Arm 2
EXPERIMENTAL100 mcg of mRNA-1273 administered through 0.5 mL intramuscular injection in the deltoid muscle on Days 1 and 29 in participants from 18-55 years of age. N=15 (4 sentinel, 11 non-sentinel).
Arm 3
EXPERIMENTAL250 mcg of mRNA-1273 administered through 0.5 mL intramuscular injection in the deltoid muscle on Days 1 and 29 in participants from 18-55 years of age. N=15 (4 sentinel, 11 non-sentinel).
Arm 4
EXPERIMENTAL25 mcg of mRNA-1273 administered through 0.5 mL intramuscular injection in the deltoid muscle on Days 1 and 29 in participants from 56-70 years of age. N=10.
Arm 5
EXPERIMENTAL100 mcg of mRNA-1273 administered through 0.5 mL intramuscular injection in the deltoid muscle on Days 1 and 29 in participants from 56-70 years of age. N=10.
Arm 6
EXPERIMENTAL250 mcg of mRNA-1273 administered through 0.5 mL intramuscular injection in the deltoid muscle on Days 1 and 29 in participants from 56-70 years of age. N=10.
Arm 7
EXPERIMENTAL25 mcg of mRNA-1273 administered through 0.5 mL intramuscular injection in the deltoid muscle on Days 1 and 29 in participants 71 years of age or older. N=10.
Arm 8
EXPERIMENTAL100 mcg of mRNA-1273 administered through 0.5 mL intramuscular injection in the deltoid muscle on Days 1 and 29 in participants 71 years of age or older. N=10.
Arm 9
EXPERIMENTAL250 mcg of mRNA-1273 administered through 0.5 mL intramuscular injection in the deltoid muscle on Days 1 and 29 in participants 71 years of age or older. N=10.
Interventions
Lipid nanoparticle (LNP) dispersion containing an mRNA that encodes for the prefusion stabilized spike protein 2019-nCoV. mRNA-1273 consists of an mRNA Drug Substance that is manufactured into LNPs composed of the proprietary ionizable lipid, SM-102, and 3 commercially available lipids, cholesterol, DSPC, and PEG2000 DMG.
Eligibility Criteria
You may qualify if:
- A subject must meet all of the following criteria to be eligible to participate in this study:
- Provides written informed consent prior to initiation of any study procedures.
- Be able to understand and agrees to comply with planned study procedures and be available for all study visits.
- Agrees to the collection of venous blood per protocol.
- Male or non-pregnant female, \>/= to 18 years of age at time of enrollment.
- Body Mass Index (BMI) 18.0-35.0 kg/m\^2, inclusive (\< 56 years of age), at screening; BMI 18.0-30.0 kg/m\^2, inclusive (\>/= 56 years of age), at screening.
- Women of childbearing potential\* must agree to use or have practiced true abstinence\*\* or use at least one acceptable primary form of contraception.\*\*\*, \*\*\*\* Note: These criteria are applicable to females in a heterosexual relationship and child-bearing potential (i.e., the criteria do not apply to subjects in a same sex relationship).
- Not of childbearing potential - post-menopausal females (defined as having a history of amenorrhea for at least one year) or a documented status as being surgically sterile (hysterectomy, bilateral oophorectomy, tubal ligation/salpingectomy, or Essure(R) placement).
- True abstinence is 100% of time no sexual intercourse (male's penis enters the female's vagina). (Periodic abstinence \[e.g., calendar, ovulation, symptothermal, post-ovulation methods\] and withdrawal are not acceptable methods of contraception).
- Acceptable forms of primary contraception include monogamous relationship with a vasectomized partner who has been vasectomized for 180 days or more prior to the subject's first vaccination, intrauterine devices, birth control pills, and injectable/implantable/insertable hormonal birth control products.
- Must use at least one acceptable primary form of contraception for at least 30 days prior to the first vaccination and at least one acceptable primary form of contraception for 60 days after the last vaccination.
- Women of childbearing potential must have a negative urine or serum pregnancy test within 24 hours prior to each vaccination.
- Male subjects of childbearing potential\*: use of condoms to ensure effective contraception with a female partner of childbearing potential from first vaccination until 60 days after the last vaccination.
- \*Biological males who are post-pubertal and considered fertile until permanently sterile by bilateral orchiectomy or vasectomy.
- Male subjects agree to refrain from sperm donation from the time of first vaccination until 60 days after the last vaccination.
- +25 more criteria
You may not qualify if:
- A subject who meets any of the following criteria will be excluded from participation in this study:
- Positive pregnancy test either at screening or just prior to each vaccine administration.
- Female subject who is breastfeeding or plans to breastfeed from the time of the first vaccination through 60 days after the last vaccination.
- Has any medical disease or condition that, in the opinion of the participating site principal investigator (PI) or appropriate sub-investigator, precludes study participation.\*
- \*Including acute, subacute, intermittent or chronic medical disease or condition that would place the subject at an unacceptable risk of injury, render the subject unable to meet the requirements of the protocol, or may interfere with the evaluation of responses or the subject's successful completion of this trial.
- Presence of self-reported or medically documented significant medical or psychiatric condition(s).\*
- \*Significant medical or psychiatric conditions include but are not limited to: Respiratory disease (e.g., chronic obstructive pulmonary disease \[COPD\], asthma) requiring daily medications currently or any treatment of respiratory disease exacerbations (e.g., asthma exacerbation) in the last 5 years. Asthma medications: inhaled, oral, or intravenous (IV) corticosteroids, leukotriene modifiers, long and short acting beta agonists, theophylline, ipratropium, biologics.
- Significant cardiovascular disease (e.g., congestive heart failure, cardiomyopathy, ischemic heart disease), history of myocarditis or pericarditis as an adult, myocardial infarction (MI) within past 6 months, coronary artery bypass surgery or stent placement, or uncontrolled cardiac arrhythmia.
- Neurological or neurodevelopmental conditions (e.g., history of migraines in the past 5 years, epilepsy, stroke, seizures in the last 3 years, encephalopathy, focal neurologic deficits, Guillain-Barré syndrome, encephalomyelitis, transverse myelitis, stroke or transient ischemic attack, multiple sclerosis, Parkinson's disease, amyotrophic lateral sclerosis, Creutzfeldt-Jakob disease, or Alzheimer's disease).
- Ongoing malignancy or recent diagnosis of malignancy in the last five years excluding basal cell and squamous cell carcinoma of the skin, which are allowed.
- An autoimmune disease, including hypothyroidism without a defined non-autoimmune cause, localized or history of psoriasis.
- An immunodeficiency of any cause. Chronic kidney disease, estimated glomerular filtration rate (eGFR) \<60 mL/min/1.73m\^2.
- Has an acute illness\*, as determined by the participating site PI or appropriate sub-investigator, with or without fever \[oral temperature \>/= 38.0 degrees Celsius (100.4 degrees Fahrenheit)\] within 72 hours prior to each vaccination.
- \*An acute illness which is nearly resolved with only minor residual symptoms remaining is allowable if, in the opinion of the participating site PI or appropriate sub-investigator, the residual symptoms will not interfere with the ability to assess safety parameters as required by the protocol.
- Has a positive test result for hepatitis B surface antigen, hepatitis C virus antibody, or human immunodeficiency virus (HIV) types 1 or 2 antibodies at screening.
- +42 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (3)
The Hope Clinic of Emory University
Decatur, Georgia, 30030-1705, United States
National Institutes of Health - Clinical Center - Vaccine Research Center Clinical Trials Program
Bethesda, Maryland, 20892, United States
Kaiser Permanente Washington Health Research Institute
Seattle, Washington, 98101-1466, United States
Related Publications (8)
Bangaru S, Jackson AM, Copps J, Fernandez-Quintero ML, Torres JL, Richey ST, Nogal B, Sewall LM, Torrents de la Pena A, Rehman A, Guebre-Xabier M, Girard B, Das R, Corbett-Helaire KS, Seder RA, Graham BS, Edwards DK, Patel N, Smith G, Ward AB. Structural serology of polyclonal antibody responses to mRNA-1273 and NVX-CoV2373 COVID-19 vaccines. Cell Rep. 2025 Jul 22;44(7):115986. doi: 10.1016/j.celrep.2025.115986. Epub 2025 Jul 8.
PMID: 40632654DERIVEDAnderson E, Jackson L, Rouphael N, Widge A, Montefiori D, Doria-Rose N, Suthar M, Cohen K, O'Connell S, Makowski M, Makhene M, Buchanan W, Spearman P, Creech CB, O'Dell S, Schmidt S, Leav B, Bennett H, Pajon R, Posavad C, Hural J, Beigel J, Albert J, Abebe K, Eaton A, Rostad C, Rebolledo P, Kamidani S, Graciaa D, Coler R, McDermott A, Ledgerwood J, Mascola J, DeRosa S, Neuzil K, McElrath MJ, Roberts P. Safety and Immunogenicity of a Third Dose of SARS-CoV-2 mRNA Vaccine - An Interim Analysis. Res Sq [Preprint]. 2022 May 3:rs.3.rs-1222037. doi: 10.21203/rs.3.rs-1222037/v1.
PMID: 35547849DERIVEDJochum S, Kirste I, Hortsch S, Grunert VP, Legault H, Eichenlaub U, Kashlan B, Pajon R. Clinical Utility of Elecsys Anti-SARS-CoV-2 S Assay in COVID-19 Vaccination: An Exploratory Analysis of the mRNA-1273 Phase 1 Trial. Front Immunol. 2022 Jan 19;12:798117. doi: 10.3389/fimmu.2021.798117. eCollection 2021.
PMID: 35126362DERIVEDGarrett ME, Galloway JG, Wolf C, Logue JK, Franko N, Chu HY, Matsen FA 4th, Overbaugh JM. Comprehensive characterization of the antibody responses to SARS-CoV-2 Spike protein finds additional vaccine-induced epitopes beyond those for mild infection. Elife. 2022 Jan 24;11:e73490. doi: 10.7554/eLife.73490.
PMID: 35072628DERIVEDJochum S, Kirste I, Hortsch S, Grunert VP, Legault H, Eichenlaub U, Kashlan B, Pajon R. Clinical utility of Elecsys Anti-SARS-CoV-2 S assay in COVID-19 vaccination: An exploratory analysis of the mRNA-1273 phase 1 trial. medRxiv [Preprint]. 2021 Oct 19:2021.10.04.21264521. doi: 10.1101/2021.10.04.21264521.
PMID: 34642699DERIVEDMendes BB, Sousa DP, Conniot J, Conde J. Nanomedicine-based strategies to target and modulate the tumor microenvironment. Trends Cancer. 2021 Sep;7(9):847-862. doi: 10.1016/j.trecan.2021.05.001. Epub 2021 Jun 3.
PMID: 34090865DERIVEDAnderson EJ, Rouphael NG, Widge AT, Jackson LA, Roberts PC, Makhene M, Chappell JD, Denison MR, Stevens LJ, Pruijssers AJ, McDermott AB, Flach B, Lin BC, Doria-Rose NA, O'Dell S, Schmidt SD, Corbett KS, Swanson PA 2nd, Padilla M, Neuzil KM, Bennett H, Leav B, Makowski M, Albert J, Cross K, Edara VV, Floyd K, Suthar MS, Martinez DR, Baric R, Buchanan W, Luke CJ, Phadke VK, Rostad CA, Ledgerwood JE, Graham BS, Beigel JH; mRNA-1273 Study Group. Safety and Immunogenicity of SARS-CoV-2 mRNA-1273 Vaccine in Older Adults. N Engl J Med. 2020 Dec 17;383(25):2427-2438. doi: 10.1056/NEJMoa2028436. Epub 2020 Sep 29.
PMID: 32991794DERIVEDJackson LA, Anderson EJ, Rouphael NG, Roberts PC, Makhene M, Coler RN, McCullough MP, Chappell JD, Denison MR, Stevens LJ, Pruijssers AJ, McDermott A, Flach B, Doria-Rose NA, Corbett KS, Morabito KM, O'Dell S, Schmidt SD, Swanson PA 2nd, Padilla M, Mascola JR, Neuzil KM, Bennett H, Sun W, Peters E, Makowski M, Albert J, Cross K, Buchanan W, Pikaart-Tautges R, Ledgerwood JE, Graham BS, Beigel JH; mRNA-1273 Study Group. An mRNA Vaccine against SARS-CoV-2 - Preliminary Report. N Engl J Med. 2020 Nov 12;383(20):1920-1931. doi: 10.1056/NEJMoa2022483. Epub 2020 Jul 14.
PMID: 32663912DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Lisa Jackson, MD, MPH
- Organization
- Kaiser Permanente Washington
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- LTE60
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- PREVENTION
- Intervention Model
- SEQUENTIAL
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
February 21, 2020
First Posted
February 25, 2020
Study Start
March 16, 2020
Primary Completion
April 26, 2022
Study Completion
April 26, 2022
Last Updated
March 18, 2024
Results First Posted
May 9, 2023
Record last verified: 2021-08-26