Safety and Immunogenicity Study of a SARS-CoV-2 (COVID-19) Variant Vaccine (mRNA-1273.351) in Naïve and Previously Vaccinated Adults
Phase 1, Open-Label, Randomized Study of the Safety and Immunogenicity of a SARS-CoV-2 Variant Vaccine (mRNA-1273.351) in Naïve and Previously Vaccinated Adults
2 other identifiers
interventional
135
1 country
4
Brief Summary
This is a phase 1, open-label, randomized clinical trial in males and non-pregnant females, 18 years of age and older, who are in good health, have no known history of COVID-19 or SARS-CoV-2 infection, and meet all other eligibility criteria. This clinical trial is designed to assess the safety, reactogenicity and immunogenicity of mRNA-1273.351 manufactured by ModernaTX, Inc, given in vaccination schedules alone, sequentially, or coadministered with mRNA-1273. mRNA-1273.351 is a novel lipid nanoparticle (LNP)-encapsulated mRNA-based vaccine that encodes for a full-length, prefusion stabilized S protein of the SARS-CoV-2 B.1.351 variant. Enrollment will occur at approximately five domestic clinical research sites. This study includes two cohorts. Cohort 1 will provide rapid information about the immunogenicity of mRNA-1273.351 in a previously vaccinated group. This cohort can inform near term public health decisions if the variant virus becomes more widespread. Cohort 2 will evaluate different strategies for generation of cross protective immune responses in a naïve population. This cohort will take longer to provide information on the immunogenicity of mRNA-1273.351, but is important to inform future public health strategies. Cohort 1 will include approximately 60 subjects 18 years of age and older who received two vaccinations of mRNA-1273 at dosages of 50 mcg, 100 mcg, or 250 mcg in the Phase 1 clinical trial (DMID 20-0003). Subjects in Cohort 1 will receive a single intramuscular (IM) injection of the designated vaccine and will be followed through 12 months after vaccination. Follow-up visits will occur on Days 8, 15, and 29, as well as 3, 6, and 12 months after the vaccination. Cohort 2 will include approximately 150 participants 18 through 55 years of age who have not received a COVID-19 vaccine, have no known history of COVID-19 or SARS-CoV-2 infection, and do not have underlying conditions that are associated with an increased risk of severe illness from SARS-CoV-2 infection. Enrollment may close before the full 150 participants based on estimates on the timing of immunogenicity results and the need to inform public health decisions. They will be randomly assigned to one of 8 treatment arms and will receive 2 or 3 IM injections of the vaccine and followed through 12 months after the last vaccination. Follow-up visits will occur 7, 14, and 28 days after each vaccination, as well as 3, 6 and 12 months post the last vaccination. The primary objective is to evaluate the safety and reactogenicity of mRNA-1273 and mRNA-1273.351 vaccines, in naïve and previously vaccinated individuals.
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 2021
Typical duration for phase_1 covid19
4 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
March 4, 2021
CompletedFirst Posted
Study publicly available on registry
March 5, 2021
CompletedStudy Start
First participant enrolled
March 31, 2021
CompletedPrimary Completion
Last participant's last visit for primary outcome
July 5, 2022
CompletedStudy Completion
Last participant's last visit for all outcomes
July 5, 2022
CompletedResults Posted
Study results publicly available
September 13, 2023
CompletedMarch 18, 2024
April 6, 2021
1.3 years
March 4, 2021
June 22, 2023
March 14, 2024
Conditions
Keywords
Outcome Measures
Primary Outcomes (8)
Number of Participants With Any Medically-attended Adverse Events (MAAEs)
Number of participants that experienced MAAEs during the course of the study.
Day 1 to study completion, up to 1 year post last dose
Frequency of Any New-onset Chronic Medical Conditions (NOCMCs)
Number of participants that experienced any NOCMCs during the course of the study.
Day 1 to study completion, up to 1 year post last dose
Frequency of Any Protocol Specified Adverse Events of Special Interest (AESIs)
Number of participants that experienced any AESIs during the course of the study. An adverse event of special interest (serious or non-serious) is one of scientific and medical concern specific to the sponsor's product or program, for which ongoing monitoring and rapid communication by the investigator to the sponsor is required. AESIs include anosmia, ageusia, subacute thyroiditis, acute pancreatitis, appendicitis, rhabdomyolysis, acute respiratory distress syndrome, coagulation disorders, acute cardiovascular injury, acute kidney injury, acute liver injury, dermatologic findings, multisystem inflammatory disorders, thrombocytopenia, acute aseptic arthritis, new onset of or worsening of neurologic disease, anaphylaxis, and other syndromes.
Day 1 to study completion, up to 1 year post last dose
Frequency of Any Serious Adverse Events (SAEs)
The number of participants that experience any SAEs from Day 1 to study completion. 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 study completion, up to 1 year post last dose
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.
Day 1 through Day 7 for Arms 1A-2H, Day 29 through Day 36 for Arms 2A-2H, Day 57-64 for Arms 2A-2B
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.
Day 1 through Day 7 for Arms 1A-2H, Day 29 through Day 36 for Arms 2A-2H, Day 57-64 for Arms 2A-2B
Frequency of Unsolicited Adverse Events (AEs) by Relationship to Study Product
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.
Day 1 through Day 29 for Arms 1A-2H, Day 29 through Day 57 for Arms 2A-2H, Day 57 through Day 85 from Arms 2A-2B
Grade of Any Unsolicited Adverse Events (AEs)
Number of any unsolicited AEs through 28 days post vaccination by severity.
Day 1 through Day 29 for Arms 1A-2H, Day 29 through Day 57 for Arms 2A-2H, Day 57 through Day 85 from Arms 2A-2B
Secondary Outcomes (24)
Geometric Mean Titer (GMT) of Antibody Against WA-1 S2-P for Arms 1A and 1B
Day 1 Pre-Booster Dose, Day 15, Day 29, Day 91, Day 181, Day 366
Geometric Mean Titer (GMT) of Antibody Against WA-1 S2-P for Arms 2A and 2B
Day 1 Pre-Dose, Day 15, Day 29, Day 43, Day 57, Day 71, Day 85, Day 147, Day 237, Day 422
Geometric Mean Titer (GMT) of Antibody Against WA-1 S2-P for Arms 2C-H
Day 1 Pre-Dose, Day 15, Day 29, Day 43, Day 57, Day 119, Day 209, Day 394
Geometric Mean Titer (GMT) of Antibody Against B.1.351 S2-P for Arms 1A and 1B
Day 1 Pre-Booster Dose, Day 15, Day 29, Day 91, Day 181, Day 366
Geometric Mean Titer (GMT) of Antibody Against B.1.351 S2-P for Arms 2A and 2B
Day 1 Pre-Dose, Day 15, Day 29, Day 43, Day 57, Day 71, Day 85, Day 147, Day 237, Day 422
- +19 more secondary outcomes
Study Arms (10)
Arm 1A
EXPERIMENTAL50 mcg of mRNA-1273.351 administered through 0.5 mL intramuscular injection in the deltoid muscle on Day 1 in participants who received two vaccinations of mRNA-1273 in DMID Protocol 20-0003 (NCT04283461). N=30.
Arm 1B
EXPERIMENTAL25 mcg of mRNA-1273 and 25 mcg of mRNA-1273.351 administered through 0.5 mL intramuscular injection in the deltoid muscle on Day 1 in participants who received two vaccinations of mRNA-1273 in DMID Protocol 20-0003 (NCT04283461). N=30.
Arm 2A
EXPERIMENTAL100 mcg mRNA-1273 administered through 0.5 mL intramuscular injection in the deltoid muscle on Days 1 and 29, and 50 mcg mRNA-1273.351 administered through 0.5 mL intramuscular injection in the deltoid on Day 57 in COVID-19 naïve participants. N=15
Arm 2B
EXPERIMENTAL50 mcg mRNA-1273 administered through 0.5 mL intramuscular injection in the deltoid muscle on Days 1 and 29, and 50 mcg mRNA-1273.351 administered through 0.5 mL intramuscular injection in the deltoid on Day 57 in COVID-19 naïve participants. N=15
Arm 2C
EXPERIMENTAL100 mcg mRNA-1273.351 administered through 0.5 mL intramuscular injection in the deltoid muscle on Days 1 and 29 in COVID-19 naïve participants. N=20
Arm 2D
EXPERIMENTAL50 mcg mRNA-1273.351 administered through 0.5 mL intramuscular injection in the deltoid muscle on Days 1 and 29 in COVID-19 naïve participants. N=20
Arm 2E
EXPERIMENTAL100 mcg mRNA-1273 administered through 0.5 mL intramuscular injection in the deltoid muscle on Day 1, and 100 mcg mRNA-1273.351 administered through 0.5 mL intramuscular injection in the deltoid on Day 29 in COVID-19 naïve participants. N=20
Arm 2F
EXPERIMENTAL50 mcg mRNA-1273 administered through 0.5 mL intramuscular injection in the deltoid muscle on Day 1, and 50 mcg mRNA-1273.351 administered through 0.5 mL intramuscular injection in the deltoid on Day 29 in COVID-19 naïve participants. N=20
Arm 2G
EXPERIMENTAL50 mcg of mRNA-1273 and 50 mcg of mRNA-1273.351 administered through 0.5 mL intramuscular injection in the deltoid muscle on Days 1 and 29 in COVID-19 naïve participants. N=20
Arm 2H
EXPERIMENTAL25 mcg of mRNA-1273 and 25 mcg of mRNA-1273.351 administered through 0.5 mL intramuscular injection in the deltoid muscle on Days 1 and 29 in COVID-19 naïve participants. N=20
Interventions
Lipid nanoparticle (LNP) dispersion containing an mRNA that encodes for the pre fusion stabilized spike protein of the Wuhan-Hu-1 strain of SARS-CoV-2. 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, 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC), and PEG2000 DMG.
Lipid nanoparticle (LNP) dispersion containing an mRNA that encodes for the pre fusion stabilized spike protein of the B.1.351 variant SARS-CoV-2 strain. mRNA-1273.351 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, 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC), and PEG2000 DMG.
Eligibility Criteria
You may qualify if:
- 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.
- Cohort 1: previously received 2 doses of mRNA-1273 intramuscular (IM) as part of DMID 20-0003.
- Cohort 1: Male or non-pregnant female, \>/= 18 years of age at time of enrollment. Cohort 2: Male or non-pregnant female, 18 through 55 years of age at time of enrollment.
- Women of childbearing potential\* must agree to practice 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).
- \*\* 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.
- In good health.\*
- Oral temperature is less than 100.0 degrees Fahrenheit (37.8 degrees Celsius).
- Must agree to have samples stored for secondary research.
- Agrees to adhere to Lifestyle Considerations throughout study duration.
- Must agree to refrain from donating blood or plasma during the study (outside of this study).
You may not qualify if:
- Positive pregnancy test prior to each vaccine administration.
- BMI \> 40.0 kg / m\^2.
- Female subject who is breastfeeding.
- Has any medical disease or condition that, in the opinion of the participating site 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.
- Type 2 diabetes mellitus, not including prediabetes.
- 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.
- +17 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (4)
The Hope Clinic of Emory University
Decatur, Georgia, 30030-1705, United States
Cincinnati Children's Hospital Medical Center Vaccine Research Center
Cincinnati, Ohio, 45229-3039, United States
Vanderbilt University - Pediatric - Vanderbilt Vaccine Research Center
Nashville, Tennessee, 37232-0004, United States
Kaiser Permanente Washington Health Research Institute
Seattle, Washington, 98101-1466, United States
Related Publications (1)
Anderson 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: 35547849DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Lisa Jackson
- 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
- RANDOMIZED
- Masking
- NONE
- Purpose
- PREVENTION
- Intervention Model
- PARALLEL
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
March 4, 2021
First Posted
March 5, 2021
Study Start
March 31, 2021
Primary Completion
July 5, 2022
Study Completion
July 5, 2022
Last Updated
March 18, 2024
Results First Posted
September 13, 2023
Record last verified: 2021-04-06