Either you have JavaScript disabled or your browser does not support Javascript . To work properly, this page requires JavaScript to be enabled.
How to enable JavaScript in your browser?

Phase I, Open-Label, Dose-Ranging Study of the Safety and Immunogenicity of 2019-nCoV Vaccine (mRNA-1273) in Healthy Adults

Trial Profile

Phase I, Open-Label, Dose-Ranging Study of the Safety and Immunogenicity of 2019-nCoV Vaccine (mRNA-1273) in Healthy Adults

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

Latest Information Update: 26 Aug 2020

At a glance

  • Drugs MRNA 1273 (Primary)
  • Indications COVID 2019 infections
  • Focus Adverse reactions; First in man
  • Most Recent Events

    • 26 Aug 2020 According to a Moderna Therapeutics media release, the company is presenting new interim safety and immunogenicity data from the cohorts of older adults from this NIH-led Phase 1 study, at the Centers for Disease Control and Preventions Advisory Committee on Immunization Practices (ACIP) August Meeting today.
    • 12 Aug 2020 According to an Emmes media release, the company has provided the data and statistical analysis support for this trial and three Emmes employees were co-authors on the Preliminary Report published in the New England Journal of Medicine on July 14.
    • 05 Aug 2020 According to an Moderna Therapeutics media release, Leveraging its mRNA platform and manufacturing facility with the AWS-powered research engine, Moderna delivered the first clinical batch of its vaccine candidate (mRNA-1273) against COVID-19 to the NIH for the Phase 1 trial 42 days after the initial sequencing of the virus.

Trial Overview

Purpose

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. 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.

Primary Endpoints

Frequency of solicited local reactogenicity adverse events (AEs)

[ Time Frame: Through 7 days post-vaccination]

Frequency of any medically-attended adverse events (MAAEs)

[ Time Frame: Day 1 to Day 394]

Frequency of any new-onset chronic medical conditions (NOCMCs)

[ Time Frame: Day 1 to Day 394]

Frequency of any serious adverse events (SAEs)

[ Time Frame: Day 1 to Day 394]

Frequency of any unsolicited adverse events (AEs)

[ Time Frame: Through 28 days post-vaccination]

Frequency of solicited systemic reactogenicity adverse events (AEs)

[ Time Frame: Through 7 days post-vaccination]

Grade of any unsolicited adverse events (AEs)

[ Time Frame: Through 28 days post-vaccination]

Grade of solicited local reactogenicity adverse events (AEs)

[ Time Frame: Through 7 days post-vaccination]

Grade of solicited systemic reactogenicity adverse events (AEs)

[ Time Frame: Through 7 days post-vaccination]

Other Endpoints

Geometric mean fold rise (GMFR) in IgG titer from baseline

time_frame: Day 1 to Day 57

Geometric mean titer (GMT) of antibody

time_frame: Day 57

Percentage of subjects who seroconverted

description: Seroconversion is defined as a 4-fold change in antibody titer from baseline
time_frame: Day 1 to Day 57 [1]

Diseases Treated

Indication Qualifiers Patient Segments
COVID 2019 infections prevention -

Subjects

  • Subject Type patients
  • Number

    Planned: 155

    Actual: 120

  • Sex male & female
  • Age Group 18-99 years; adult; elderly

Patient Inclusion Criteria

A subject must meet all of the following criteria to be eligible to participate in this study: 1. Provides written informed consent prior to initiation of any study procedures. 2. Be able to understand and agrees to comply with planned study procedures and be available for all study visits. 3. Agrees to the collection of venous blood per protocol. 4. Male or non-pregnant female, >/= to 18 years of age at time of enrollment. 5. 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. 6. 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. 7. Women of childbearing potential must have a negative urine or serum pregnancy test within 24 hours prior to each vaccination. 8. 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. 9. Male subjects agree to refrain from sperm donation from the time of first vaccination until 60 days after the last vaccination. 10. In good health.* *As determined by medical history and physical examination to evaluate acute or ongoing chronic medical diagnoses/conditions that have been present for at least 90 days, which would affect the assessment of safety of subjects. Chronic medical diagnoses/conditions should be stable for the last 60 days (no hospitalizations, emergency room (ER), or urgent care for condition or need for supplemental oxygen). This includes no change in chronic prescription medication, dose, or frequency as a result of deterioration of the chronic medical diagnosis/condition in the 60 days before enrollment. Any prescription change that is due to change of health care provider, insurance company, etc., or done for financial reasons, and in the same class of medication, will not be considered a deviation of this inclusion criterion. Any change in prescription medication due to improvement of a disease outcome, as determined by the participating site principal investigator (PI) or appropriate sub-investigator, will not be considered a deviation of this inclusion criterion. Subjects may be on chronic or as needed (prn) medications if, in the opinion of the participating site PI or appropriate sub-investigator, they pose no additional risk to subject safety or assessment of reactogenicity and immunogenicity, and do not indicate a worsening of medical diagnosis/condition. Similarly, medication changes subsequent to enrollment and study vaccination are acceptable provided the change was not precipitated by deterioration in the chronic medical condition, and there is no anticipated additional risk to the subject or interference with the evaluation of responses to study vaccination. 11. Oral temperature is less than 100.0 degrees Fahrenheit (37.8 degrees Celsius). 12. Pulse no greater than 100 beats per minute. 13. Systolic blood pressure (BP) is 85 to 150 mm Hg, inclusive. 14. Clinical screening laboratory evaluations (white blood cell (WBC), hemoglobin (Hgb), platelets (PLTs), alanine transaminase (ALT), aspartate transaminase (AST), creatinine (Cr), alkaline phosphatase (ALP), total bilirubin (T. Bili), Lipase, prothrombin time (PT), and partial thromboplastin time (PTT)) are within acceptable normal reference ranges at the clinical laboratory being used. 15. Must agree to have samples stored for secondary research. 16. Agrees to adhere to Lifestyle Considerations throughout study duration. 17. Must agree to refrain from donating blood or plasma during the study (outside of this study). Leukapheresis A subject must meet all of the following criteria to be eligible for leukapheresis: 1. Written informed consent for leukapheresis is provided. 2. Weight >/= 110 pounds. 3. Screening laboratory evaluations are within acceptable ranges at the site where the leukapheresis procedure will be performed. 4. Negative urine or serum pregnancy test within 48 hours of the leukapheresis procedure for women of childbearing potential. 5. Adequate bilateral antecubital venous access. 6. No use of blood thinners, aspirin or nonsteroidal anti-inflammatory drugs (NSAIDs) at least 5 days before the leukapheresis procedure. 7. Enrolled in cohorts 2, 3, 5, 10, or 11, and possibly cohort 6, if enrolled, and completed the two-dose vaccination series.

Patient Exclusion Criteria

A subject who meets any of the following criteria will be excluded from participation in this study: 1. Positive pregnancy test either at screening or just prior to each vaccine administration. 2. Female subject who is breastfeeding or plans to breastfeed from the time of the first vaccination through 60 days after the last vaccination. 3. 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. 4. 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. 5. 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. 6. 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. 7. Has participated in another investigational study involving any investigational product* within 60 days, or 5 half-lives, whichever is longer, before the first vaccine administration. *study drug, biologic or device 8. Currently enrolled in or plans to participate in another clinical trial with an investigational agent* that will be received during the study-reporting period.** *Including licensed or unlicensed vaccine, drug, biologic, device, blood product, or medication. **13 months after the first vaccination. 9. Has previously participated in an investigational study involving lipid nanoparticles (LNPs) (a component of the investigational vaccine assessed in this trial). 10. Has a history of hypersensitivity or severe allergic reaction (e.g., anaphylaxis, generalized urticaria, angioedema, other significant reaction) to any previous licensed or unlicensed vaccines. 11. Chronic use (more than 14 continuous days) of any medications that may be associated with impaired immune responsiveness.* *Including, but not limited to, systemic corticosteroids exceeding 10 mg/day of prednisone equivalent, allergy injections, immunoglobulin, interferon, immunomodulators, cytotoxic drugs, or other similar or toxic drugs during the preceding 6-month period prior to vaccine administration (Day 1). The use of low dose topical, ophthalmic, inhaled and intranasal steroid preparations will be permitted. 12. Anticipating the need for immunosuppressive treatment within the next 6 months. 13. Received immunoglobulins and/or any blood or blood products within the 4 months before the first vaccine administration or at any time during the study. 14. Has any blood dyscrasias or significant disorder of coagulation. 15. Has any chronic liver disease, including fatty liver. 16. Has a history of alcohol abuse or other recreational drug (excluding cannabis) use within 6 months before the first vaccine administration. 17. Has a positive test result for drugs of abuse at screening or before the first vaccine administration. If cannabis is the only detected drug, inclusion is permitted. 18. Has any abnormality or permanent body art (e.g., tattoo) that would interfere with the ability to observe local reactions at the injection site (deltoid region). 19. Received or plans to receive a licensed, live vaccine within 4 weeks before or after each vaccination. 20. Received or plans to receive a licensed, inactivated vaccine within 2 weeks before or after each vaccination. 21. Receipt of any other SARS-CoV-2 or other experimental coronavirus vaccine at any time prior to or during the study. 22. Close contact of anyone known to have SARS-CoV-2 infection within 30 days prior to vaccine administration. 23. History of COVID-19 diagnosis. 24. On current treatment with investigational agents for prophylaxis of COVID-19. 25. Current use of any prescription or over-the-counter medications within 7 days prior to vaccination, unless approved by the investigator or necessary to manage a chronic condition. 26. Plan to travel outside the United States (US) (continental US, Hawaii, and Alaska) from enrollment through 28 days after the second vaccination. 27. Reside in a nursing home or other skilled nursing facility or have a requirement for skilled nursing care. 28. Non-ambulatory. 29. For subjects >/= 56 years of age, history of chronic smoking within the prior year. 30. For subjects >/= 56 years of age, current smoking or vaping. 31. For subjects >/= 56 years of age, individuals currently working with high risk of exposure to SARS-CoV-2 (e.g., active health care workers with direct patient contact, emergency response personnel).

Trial Details

Identifiers

Identifier Owner
NCT04283461 ClinicalTrials.gov: US National Institutes of Health
20-0003 -
1UM1AI148373-01 -

Organisations

  • Affiliations Moderna Therapeutics

Trial Dates

  • Initiation Dates

    Planned : 19 Mar 2020

    Actual : 16 Mar 2020

  • Primary Completion Dates

    Planned : 22 Nov 2021

  • End Dates

    Planned : 22 Nov 2021

Other Details

  • Design multicentre; open; prospective; sequential
  • Phase of Trial Phase I
  • Location USA
  • Focus Adverse reactions; First in man

Interventions

Drugs Route Formulation
MRNA 1273Primary Drug Intramuscular Injection, Nanoparticles

Arm 1

25 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) Biological: mRNA-1273 (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.)

Arm 10

50 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. Biological: mRNA-1273 (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.)

Arm 11

50 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. Biological: mRNA-1273 (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.)

Arm 12

50 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. Biological: mRNA-1273 (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.)

Arm 13

10 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. Biological: mRNA-1273 (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.)

Arm 2

100 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). Biological: mRNA-1273 (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.)

Arm 3

250 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). Biological: mRNA-1273 (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.)

Arm 4

25 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. Biological: mRNA-1273 (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.)

Arm 5

100 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. Biological: mRNA-1273 (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.)

Arm 6

250 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. Biological: mRNA-1273 (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.)

Arm 7

25 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. Biological: mRNA-1273 (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.)

Arm 8

100 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. Biological: mRNA-1273 (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.)

Arm 9

250 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. Biological: mRNA-1273 (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.)

Results

Adverse events

Updated interim results from a phase I trial in healthy volunteers showed that treatment with mRNA 1273 was generally safe and well-tolerated, with no serious adverse events reported through day 57. Adverse events (AEs) were generally transient and mild to moderate in severity. The most notable adverse events were seen at the 250µg dose level, with three of those 14 participants (21%) reported one or more severe events. Solicited systemic adverse events were more common after the second vaccination and occurred in seven of 13 (54%) participants in the 25µg group, all 15 participants in the 100µg group and all 14 participants in the 250µg group. The most commonly reported systemic adverse events following second vaccination at the 100 µg dose were fatigue (80%), chills (80%), headache (60%) and myalgia (53%), all of which were transient and mild or moderate in severity. The most common solicited local adverse event at the 100µg dose was pain at the injection site (100%), which was transient and mild or moderate in severity. Earlier, results from a phase I trial established a generally safe and well tolerated profile for mRNA 1273, which was consistent with the company's earlier infectious disease vaccine clinical studies. A solitary grade 3 adverse event of erythema at the injection site was seen in one volunteer, in the 100 µg dose cohort. The 250 µg dose level reflected the most notable adverse events in three volunteers with grade 3 systemic symptoms, only after the second dose. The adverse events were predominantly transient and self-resolving. Grade 4 adverse events or serious adverse events were not reported [2] [3] .

Immunogenicity

Interim results from a phase I trial showcased dose-dependent increases in binding titers across 25 µg, 100 µg and 250 µg dosage levels, and between prime and boost within the 25 µg and 100 µg dose levels. All volunteers aged 18-55 (n=15 per cohort) across all three dose levels seroconverted by day 15, after administration of a single dose. mRNA 1273 induced binding antibodies to the full-length SARS-CoV-2 Spike protein in all participants after the first vaccination, with all participants seroconverting by day 15. After two vaccinations, at day 57, geometric mean titers exceeded those seen in convalescent sera obtained from 38 individuals with confirmed COVID-19 diagnosis. Of the 38 individuals in the convalescent sera group, 15% were classified as having severe symptoms (hospitalization requiring intensive care and/or ventilation), 22% had moderate symptoms and 63% had mild symptoms. After the second vaccination, PsVNA neutralising antibody titers were detected in all participants in all dose cohorts. The day 57 geometric mean titers at the 100 µg dose were 2.1-fold higher than those seen in convalescent sera (n=38). Strong correlations were observed between the binding and neutralisation assays, and between the live virus and pseudovirus neutralization assays. A clear dose response was seen in geometric mean titers between the 25µg and 100µg dose levels, with minimal additional increases at the 250µg dose. Moreover, following second vaccination, mRNA 1273 elicited Th1-biased CD4 T-cell responses without significant elevation of Th2-biased CD4 T-cell responses. Earlier, results from the trial at day 43, two weeks after the second dose, at the 25 µg dose level (n=15), the binding antibody levels matched the levels observed in convalescent sera (blood samples from people who have recovered from COVID-19), tested in the same assay. At day 43, at the 100 µg dose level (n=10), binding antibody levels significantly surpassed the levels in convalescent sera. Samples were unavailable for remaining volunteers. These results were reported for the 25 µg and 100 µg dose level (ages 18-55) after two doses (day 43) and at the 250 µg level (ages 18-55) after one dose (day 29). Neutralising antibody data from first four volunteers in each of the 25 µg and 100 µg dose level cohorts, also exhibited an evoking of neutralising antibodies in all eight volunteers, as determined by plaque reduction neutralization (PRNT) assays against live SARS-CoV-2, following administration of mRNA 1273. At day 43, neutralising antibody levels either matched or exceeded levels characteristically seen in the convalescent sera. Protective neutralising titres seen at the 25 µg and 100 µg dose levels in the trial displayed consistency with those seen in a preclinical mouse challenge model [2] [3] .

Publications

  1. Moderna Therapeutics. Moderna Announces Publication in The New England Journal of Medicine of Interim Results From Phase 1 Study of Its mRNA Vaccine Against COVID-19 (mRNA-1273). Media-Rel 2020;.

    Media Release
  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. Jackson LA, Anderson EJ, Rouphael NG, Roberts PC, Makhene M, Coler RN, et al. An mRNA Vaccine against SARS-CoV-2 - Preliminary Report. . N-Engl-J-Med 2020;.

    PubMed | CrossRef Fulltext

Authors

Author Total Publications First Author Last Author
Albert J 1 - -
Anderson EJ 1 - -
Beigel JH 1 - 1
Bennett H 1 - -
Buchanan W 1 - -
Chappell JD 1 - -
Coler RN 1 - -
Corbett KS 1 - -
Cross K 1 - -
Denison MR 1 - -
Doria-Rose NA 1 - -
Flach B 1 - -
Graham BS 1 - -
Jackson LA 1 1 -
Ledgerwood JE 1 - -
Makhene M 1 - -
Makowski M 1 - -
Mascola JR 1 - -
McCullough MP 1 - -
McDermott A 1 - -
Moderna Therapeutics 2 2 2
Morabito KM 1 - -
Neuzil KM 1 - -
O'Dell S 1 - -
Padilla M 1 - -
Peters E 1 - -
Pikaart-Tautges R 1 - -
Pruijssers AJ 1 - -
Roberts PC 1 - -
Rouphael NG 1 - -
Schmidt SD 1 - -
Stevens LJ 1 - -
Sun W 1 - -
Swanson PA 2nd 1 - -

Trial Centres

Investigators

Investigator Centre Name Trial Centre Country
20-0003 Central Contact
12062872061 KPWA.vaccine@kp.org
show details
-

Centres

Centre Name Location Trial Centre Country
-
-
-
Emory Vaccine Center - The Hope Clinic Decatur, Georgia USA
Kaiser Permanente Washington Health Research Institute - Vaccines and Infectious Diseases Seattle, Washington USA
National Institute of Allergy and Infectious Diseases (NIAID)
-
-
National Institutes of Health - Clinical Center - Vaccine Research Center Clinical Trials Program Bethesda, Maryland USA

Trial History

Event Date Event Type Comment
26 Aug 2020 Other trial event According to a Moderna Therapeutics media release, the company is presenting new interim safety and immunogenicity data from the cohorts of older adults from this NIH-led Phase 1 study, at the Centers for Disease Control and Preventions Advisory Committee on Immunization Practices (ACIP) August Meeting today. Updated 31 Aug 2020
12 Aug 2020 Other trial event According to an Emmes media release, the company has provided the data and statistical analysis support for this trial and three Emmes employees were co-authors on the Preliminary Report published in the New England Journal of Medicine on July 14. Updated 19 Aug 2020
05 Aug 2020 Other trial event According to an Moderna Therapeutics media release, Leveraging its mRNA platform and manufacturing facility with the AWS-powered research engine, Moderna delivered the first clinical batch of its vaccine candidate (mRNA-1273) against COVID-19 to the NIH for the Phase 1 trial 42 days after the initial sequencing of the virus. Updated 08 Aug 2020
20 Jul 2020 Other trial event Last checked against ClinicalTrials.gov record. Updated 20 Jul 2020
16 Jul 2020 Status change - active, no longer recruiting Status changed from recruiting to active, no longer recruiting. Updated 20 Jul 2020
14 Jul 2020 Interim results Interim results (n=45) for 25-mcg and 100-mcg dose groups, published in the New England Journal of Medicine. Updated 23 Jul 2020
14 Jul 2020 Other trial event According to an Moderna Therapeutics media release, the company has completed the enrollment of the additional seven cohorts from this study : a 50 µg cohort in adults 18-55 (n=15), three cohorts of older adults and three cohorts of elderly adults. Updated 17 Jul 2020
14 Jul 2020 Interim results Results (n=45, Day 57) of the two-dose vaccination schedule are presented in a Moderna Therapeutics media release. Updated 17 Jul 2020
14 Jul 2020 Interim results According to an Moderna Therapeutics media release, data from this study were published in the journal of The New England Journal of Medicine. Updated 17 Jul 2020
08 Jul 2020 Other trial event According to an Moderna Therapeutics media release, the cohorts of older adults (ages 56-70, n=30) and elderly adults (ages 71 and above, n=30) from this study has completed enrolment. Results from this study will be published once available. Updated 13 Jul 2020
11 Jun 2020 Other trial event According to an Moderna Therapeutics media release,enrollment in 9 of 12 cohorts complete. The NIH will be submitting the data to a peer-reviewed clinical publication. Updated 17 Jun 2020
28 May 2020 Protocol amendment Number of arms changed from 9 to 13, Experimental Arm 10, 11, 12 and 13 added. Planned number of patients increased. Updated 01 Jun 2020
28 May 2020 Other trial event Planned number of patients changed from 105 to 155. Updated 01 Jun 2020
28 May 2020 Completion date Planned End Date changed from 20 Sep 2021 to 22 Nov 2021. Updated 01 Jun 2020
28 May 2020 Other trial event Planned primary completion date changed from 20 Sep 2021 to 22 Nov 2021. Updated 01 Jun 2020
18 May 2020 Protocol amendment According to an Moderna Therapeutics media release, the trial is amended to include a 50 µg dose level cohort across each of the three age groups. Updated 22 May 2020
18 May 2020 Interim results Positive interim data presented in the Moderna Therapeutics Media Release. Updated 22 May 2020
12 May 2020 Other trial event According to an Moderna Therapeutics media release, the company is awaiting full set of clinical data from this study. Updated 15 May 2020
30 Apr 2020 Protocol amendment Number of arms changed from 3 to 9. Arm 4 - Arm 9 added. Number of patients changed from 45 to 105. Patient eligibility criteria amended. Updated 05 May 2020
30 Apr 2020 Completion date Planned End Date changed from 1 Jun 2021 to 20 Sep 2021. Updated 05 May 2020
30 Apr 2020 Other trial event Planned primary completion date changed from 1 Jun 2021 to 20 Sep 2021. Updated 05 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
27 Apr 2020 Other trial event According to a Moderna Therapeutics media release, Data from the original cohort of healthy adult volunteers ages 18 to 55 years will be reported once available. Updated 04 May 2020
17 Apr 2020 Other trial event Planned number of patients changed from 45 to 105, according to according to a Moderna Therapeutics media release. Updated 21 Apr 2020
17 Apr 2020 Other trial event According to a Moderna Therapeutics media release, enrollment of the first 45 participants in the trial is now complete. The investigators have expanded the trial and will enroll an additional 60 participants: 30 adults ages 56 to 70 years and 30 adults ages 71 years and older in the Atlanta, Bethesda or Seattle areas. Updated 21 Apr 2020
16 Apr 2020 Protocol amendment According to a Moderna Therapeutics media release, the NIH recently amended the Phase 1 protocol to include an additional six cohorts: three cohorts of older adults (ages 51-70) and three cohorts of elderly adults (age 71 and above). Enrollment for these cohorts is ongoing. Updated 20 Apr 2020
16 Apr 2020 Other trial event According to a Moderna Therapeutics media release, it has completed enrollment of 3 dose cohorts (25 µg, 100 µg and 250 µg); expanding to an additional 6 cohorts of older adults and elderly adults. Updated 20 Apr 2020
14 Apr 2020 Other trial event According to a Moderna Therapeutics media release, this trial continues on track with enrollment of participants at the highest dose Updated 15 Apr 2020
16 Mar 2020 Other trial event According to a Moderna Therapeutics media release, this trial is led by Lisa A. Jackson, M.D., (senior investigator at Kaiser Permanente Washington Health Research Institute (KPWHRI) in Seattle). Updated 20 Mar 2020
16 Mar 2020 Other trial event According to a Moderna Therapeutics media release, the company announced that the first participant has been dosed in this study. Updated 18 Mar 2020
05 Mar 2020 Status change - recruiting Status changed from not yet recruiting to recruiting. Updated 11 Mar 2020
02 Mar 2020 Other trial event New source identified and integrated (ClinicalTrials.gov: US National Institutes of Health: NCT04283461) Updated 02 Mar 2020
27 Feb 2020 Other trial event Planned initiation date changed from 6 Mar 2020 to 19 Mar 2020. Updated 03 Mar 2020
24 Feb 2020 Other trial event According to an Moderna Therapeutics media release, the company announced that it has shipped the first batch of mRNA-1273 to the National Institute of Allergy and Infectious Diseases (NIAID), a part of the National Institutes of Health (NIH) to be used in the planned Phase 1 study.Manufacture of this batch was funded by the Coalition for Epidemic Preparedness Innovations (CEPI). Updated 26 Feb 2020
21 Feb 2020 Status change - not yet recruiting Status changed from planning to not yet recruiting. Updated 02 Mar 2020
14 Feb 2020 New trial record New trial record Updated 14 Feb 2020
10 Feb 2020 Other trial event According to a Moderna Therapeutics media release, the company will conduct this study in collaboration with National Institutes of Health. Updated 14 Feb 2020
10 Feb 2020 Other trial event According to a Moderna Therapeutics media release, The first clinical batch, including fill and finishing of vials, was completed on February 7. This mRNA vaccine was designed and manufactured in 25 days and is undergoing analytical testing prior to release to the NIH. Updated 14 Feb 2020

References

  1. ClinicalTrials.gov: US National Institutes of Health. Trial-Reg 2016;.

    Available from: URL: http://clinicaltrials.gov
  2. Moderna Therapeutics. Moderna Announces Publication in The New England Journal of Medicine of Interim Results From Phase 1 Study of Its mRNA Vaccine Against COVID-19 (mRNA-1273). Media-Rel 2020;.

    Media Release
  3. Moderna Therapeutics. Moderna Announces Positive Interim Phase 1 Data for its mRNA Vaccine (mRNA-1273) Against Novel Coronavirus. Media-Rel 2020;.

    Media Release
  4. Moderna Therapeutics. AWS Powers Modernas Digital Biotechnology Platform to Develop New Class of Vaccines and Therapeutics. Media-Rel 2020;.

    Media Release
  5. 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
  6. Moderna Therapeutics. Moderna to Present New Interim Clinical Data About mRNA Vaccine Against COVID-19 (mRNA-1273) at Advisory Committee on Immunization Practices (ACIP) Meeting. Media-Rel 2020;.

    Media Release
  7. Emmes. Emmes Announces its Role in Phase 1 COVID-19 Vaccine Trial. Media-Rel 2020;.

    Media Release
  8. Jackson LA, Anderson EJ, Rouphael NG, Roberts PC, Makhene M, Coler RN, et al. An mRNA Vaccine against SARS-CoV-2 - Preliminary Report. . N-Engl-J-Med 2020;.

    PubMed | CrossRef Fulltext
  9. 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
  10. Moderna Therapeutics. Moderna Receives FDA Fast Track Designation for mRNA Vaccine (mRNA-1273) Against Novel Coronavirus. Media-Rel 2020;.

    Media Release
  11. National Institutes of Health. NIH clinical trial of investigational vaccine for COVID-19 begins. Media-Rel 2020;.

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

    Media Release
  13. Moderna Therapeutics. Moderna Highlights Opportunity of mRNA Vaccines at its First Vaccines Day. Media-Rel 2020;.

    Media Release
  14. Moderna Therapeutics. Moderna Announces Progress in Prophylactic Vaccines Modality with CMV Vaccine Phase 2 Study Data Now Expected in Third Quarter 2020 and Expands Investment in This Core Modality with Three New Development Candidates. Media-Rel 2020;.

    Media Release
  15. National Institute of Allergy and Infectious Diseases. NIH Clinical Trial of a Vaccine for COVID-19 Now Enrolling Older Adults. Media-Rel 2020;.

    Media Release
  16. 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
  17. Moderna Therapeutics. Moderna Advances Late-Stage Development of its Vaccine (mRNA-1273) Against COVID-19. Media-Rel 2020;.

    Media Release
  18. Moderna Therapeutics. Moderna Ships mRNA Vaccine Against Novel Coronavirus (mRNA-1273) for Phase 1 Study. Media-Rel 2020;.

    Media Release
Back to top