Phase 1
N=120
Safety and Immunogenicity Study of 2019-nCoV Vaccine (mRNA-1273) for Prophylaxis of SARS-CoV-2 Infection (COVID-19)
COVID-19 · COVID-19 Immunisation
Bottom Line
View on ClinicalTrials.gov: NCT04283461 ↗Enrolled (actual)
120
Serious AEs
0.8%
Results posted
May 2023
Primary outcome: Primary: Frequency of Any Medically-attended Adverse Events (MAAEs) — 7; 6; 5; 7 Participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 1
- Interventions
- mRNA-1273 (Biological)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)
- Primary completion
- Apr 2022
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Frequency of Any Medically-attended Adverse Events (MAAEs) |
7; 6; 5; 7; 2; 6 | — |
| PRIMARY Frequency of Any New-onset Chronic Medical Conditions (NOCMCs) |
0; 0; 2; 2; 1; 3 | — |
| PRIMARY Frequency of Any Serious Adverse Events (SAEs) |
0; 0; 0; 0; 0; 0 | — |
| PRIMARY Frequency of Solicited Reactogenicity Adverse Events (AEs) |
11; 14; 15; 15; 8; 9 | — |
| PRIMARY Frequency of Any Unsolicited Adverse Events (AEs) by Relationship to Study Product and Severity |
28; 22; 15; 16; 9; 6 | — |
| PRIMARY Grade of Any Unsolicited Adverse Events (AEs) |
32; 27; 25; 27; 11; 6 | — |
| PRIMARY Grade of Solicited Reactogenicity Adverse Events (AEs) |
5; 0; 1; 0; 3; 4 | — |
| SECONDARY Geometric Mean Fold Rise (GMFR) in IgG Titer From Baseline Against RBD |
118.232; 46.423; 205.148; 151.985; 14.358; 24.082 | — |
| SECONDARY Geometric Mean Fold Rise (GMFR) in IgG Titer From Baseline Against S-2 |
278.826; 190.575; 656.649; 915.658; 55.693; 78.037 | — |
| SECONDARY Geometric Mean Titer (GMT) of Antibody Against RBD |
55.539; 588.031; 166.061; 575.528; 203.610; 348.980 | — |
| SECONDARY Geometric Mean Titer (GMT) of Antibody Against S-2P |
115.700; 353.726; 131.442; 178.484; 188.712; 563.378 | — |
| SECONDARY Percentage of Participants Who Seroconverted Against RBD |
100; 100; 100; 100; 60; 100 | — |
| SECONDARY Percentage of Participants Who Seroconverted Against S-2P |
100; 100; 100; 100; 90; 100 | — |
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.
Eligibility Criteria
Inclusion Criteria
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.
- 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.
- 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
Data sourced from ClinicalTrials.gov (NCT04283461). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.