Phase 3
N=14,001
Efficacy Study of COVID-19 mRNA Vaccine in Regions With SARS-CoV-2 Variants of Concern
SARS-CoV-2 Infection · HIV Infections · COVID-19
Bottom Line
View on ClinicalTrials.gov: NCT05168813 ↗Enrolled (actual)
14,001
Serious AEs
1.8%
Results posted
Nov 2025
Primary outcome: Primary: Part A: Number of Participants With a First Occurrence of CDC-defined COVID-19 Starting 1 Day After Month 0 Dose Until Month 6 Dose in FAS Cohort Between Analysis Group 1 (AG1) and Analysis Group 2-1 (AG2-1) — 76; 151 Participants — p=< .001
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- Moderna mRNA-1273 (Biological); Moderna mRNA-1273.222 (Biological); Vaccine 3 Dose (Biological); Vaccine 2 Dose (Biological)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- COVID-19 Prevention Network
- Primary completion
- Apr 2024
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Part A: Number of Participants With a First Occurrence of CDC-defined COVID-19 Starting 1 Day After Month 0 Dose Until Month 6 Dose in FAS Cohort Between Analysis Group 1 (AG1) and Analysis Group 2-1 (AG2-1) |
76; 151 | < .001 sig |
| PRIMARY Part A: Number of Participants With a First Occurrence of COVE-defined COVID-19 Starting 1 Day After Month 0 Dose Until Month 6 Dose in FAS Cohort Between Analysis Group 1 (AG1) and Analysis Group 2-1 (AG2-1 |
30; 40 | 0.003 sig |
| PRIMARY Part A: Number of Participants With a First Occurrence of COVE-based Severe COVID-19 Starting 1 Day After Month 0 Dose Until Month 6 Dose in FAS Between Analysis Group 1 (AG1) and Analysis Group 2-1 (AG2-1) |
5; 4 | 0.056 |
| PRIMARY Part B: Number of Participants With a First Occurrence of CDC-based COVID-19 Starting 14 Days After Month 6 Dose Until End of Follow up in RM6 Cohort Between Month 6 Monovalent and Bivalent Boost Groups |
151; 142 | 0.449 |
| PRIMARY Part B: Number of Participants With a First Occurrence of COVE-based COVID-19 Starting 14 Days After Month 6 Dose Until End of Follow up in RM6 Cohort Between Month 6 Monovalent and Bivalent Boost Group |
8; 7 | 0.23 |
| PRIMARY Part B: Number of Participants With a First Occurrence of COVE-based Severe COVID-19 Starting 14 Days After Month 6 Dose Until End of Follow up in RM6 Cohort Between Month 6 Monovalent and Bivalent Groups |
1; 0 | — |
| PRIMARY Part A: Number of Participants With Solicited Adverse Events in the Safety Subset |
320; 428; 68; 82; 158; 167 | — |
| PRIMARY Part B: Number of Participants With Solicited Adverse Events in the Safety Subset |
877; 71; 290; 9; 135; 6 | — |
| PRIMARY Part A: Number of Participants With Unsolicited Adverse Events in the Safety Subset |
506; 668; 91; 134; 16; 7 | — |
| PRIMARY Part B: Number of Participants With Unsolicited Adverse Events in the Safety Subset |
1290; 87; 9; 0; 17; 1 | — |
| PRIMARY Part A: Number of Participants With Serious Adverse Events (SAEs) |
84; 126; 5; 32 | — |
| PRIMARY Part B: Number of Participants With Serious Adverse Events (SAEs) |
212; 45 | — |
| PRIMARY Part A: Number of Participants With Adverse Events of Special Interest (AESIs) |
36; 59; 4; 19 | — |
| PRIMARY Part B: Number of Participants With Adverse Events of Special Interest (AESIs) |
111; 27 | — |
| SECONDARY Part A: Number of Participants With First CDC-based COVID-19 Occurrence From 1 Day After Month 0 Dose to Month 6 Dose in FAS Cohort, Comparing Baseline SARS-CoV-2 Negative vs Positive, Regardless of HIV Status |
86; 179 | < .001 sig |
| SECONDARY Part A: Number of Participants With First COVE-based COVID-19 Occurrence From 1 Day After Month 0 Dose to Month 6 Dose in FAS Cohort, Comparing Baseline SARS-CoV-2 Negative vs Positive, Regardless of HIV Statu |
34; 45 | < .001 sig |
| SECONDARY Part A: Number of Participants With First COVE-based Severe COVID-19 Occurrence From 1 Day After Month 0 Dose to Month 6 Dose in FAS Cohort, Comparing Baseline SARS-CoV-2 Negative vs Positive, Regardless of HI |
7; 6 | 0.02 sig |
| SECONDARY Part B: Number of Participants With a First Occurrence of CDC-based COVID-19 Starting 14 Days After Month 6 Dose Until End of Follow up in RM6 Cohort Who Have Month 6 Hybrid Immunity Between Month 6 Monovalent and Bivalent Boost Groups |
140; 123 | 0.218 |
| SECONDARY Part B: Number of Participants With a First Occurrence of CDC-based COVID-19 Starting 14 Days After Month 6 Dose Until End of Follow up in RM6 Cohort Who Have Month 6 Vaccine Immunity Between Month 6 Monovalent and Bivalent Boost Group |
11; 19 | 0.135 |
| SECONDARY Part A: Geometric Mean Titers (GMTs) of SARS-CoV-2 Antibodies as Measured by Neutralizing Antibody (NAb) Assay |
348; 9; 324; 372; 9; 9 | — |
| SECONDARY Part A: Geometric Mean Titers (GMTs) of SARS-CoV-2 Antibodies as Measured by Meso Scale Discovery-electrochemiluminescence Assay (MSD-ECL) |
52023; 5978; 52088; 48473; 4822; 5977 | — |
| SECONDARY Part A: Geometric Mean Titers of T-Cell Responses as Measured by Intracellular Cytokine Staining (ICS) Assay at Month 0 |
0.0418; 0.0201; 0.0514; 0.035; 0.051; 0.0212 | — |
| SECONDARY Part A: Geometric Mean Titers of T-Cell Responses as Measured by Intracellular Cytokine Staining (ICS) Assay at Peak Timepoint |
0.0396; 0.0178; 0.0459; 0.0354; 0.0269; 0.0135 | — |
| SECONDARY Part B: Geometric Mean Titers (GMTs) of SARS-CoV-2 Antibodies as Measured by Neutralizing Antibody Assay |
750; 1121.4; 970.4; 390.3; 124.8; 169.2 | — |
| SECONDARY SARS-CoV-2 Viral Persistence and Evolution Among Participants Virologically Diagnosed With SARS-CoV-2 |
2.27; 3.3; 1.17; 0; 3.85; 0.76 | — |
Summary
The study will evaluate the clinical efficacy of different dosing regimens of the Moderna COVID-19 mRNA vaccine (100 mcg) in preventing COVID-19 disease in people who are living with HIV or have comorbidities associated with elevated risk of severe COVID-19, with the different vaccine regimens assessed determined by whether the participant had evidence of prior SARS-CoV-2 infection at enrollment.
Eligibility Criteria
Inclusion Criteria
General and Demographic Criteria
- Age ≥ 18 years if participant self-reports living with HIV or another comorbidity known to be associated with severe COVID-19, for example (CDC.gov for exhaustive list):
- Hypertension
- Type 2 diabetes mellitus
- Overweight, obese, or severely obese (ie, body mass index [BMI] ≥ 25 kg/m2)
- Heart conditions, such as heart failure, coronary artery disease, or cardiomyopathies
- Chronic kidney disease
- COPD (chronic obstructive pulmonary disease)
- Cancer
- Non-HIV immunocompromised state (weakened immune system) or solid organ transplant
- Pregnancy
- Sickle cell disease
- Smoking
- Willingness to be followed and remain in the catchment area for the planned duration of the study.
- Ability and willingness to provide informed consent.
- Willingness to discuss HIV infection status, undergo related testing/monitoring labs, and receive counseling and referrals to minimize HIV acquisition/improve HIV care as appropriate based on their infection status.
- Assessment of Understanding (AoU): Participant demonstrates understanding of this study; completes a questionnaire prior to first vaccination with demonstration of understanding of all questionnaire items answered incorrectly.
- Agrees not to enroll in another interventional study of an investigational research agent until after the study is completed and all the data has been obtained. Enrollment in studies of investigational research agents for the treatment of COVID-19 is allowed for participants who develop COVID-19 disease.
Exclusion Criteria
General
- Acutely ill 72 hours prior to or at screening. Participants meeting this criterion may be rescheduled within the relevant window periods. Participants with minor illnesses can be enrolled at the discretion of the investigator.
- History of angioedema or anaphylaxis.
Vaccines and other injections
- Prior receipt of a SARS-CoV-2 vaccine.
- History of severe allergic reaction to any ingredient of this vaccine (lipids (SM-102, polyethylene glycol [PEG] 2000 dimyristoyl glycerol [DMG], cholesterol, and 1,2-distearoyl-sn-glycero-3-phosphocholine [DSPC]), tromethamine, tromethamine hydrochloride, acetic acid, sodium acetate trihydrate, and sucrose).
- Live attenuated vaccines received within 30 days before first vaccination (eg, measles, mumps, and rubella [MMR]; oral polio vaccine [OPV]; varicella; yellow fever; live attenuated influenza vaccine, live attenuated zoster vaccine).
- Any vaccines that are not live attenuated vaccines and were received within 14 days prior to first vaccination (eg, tetanus, human papilloma virus (HPV), pneumococcal, Hepatitis A or B).
- Blood products, systemic immunoglobulins, or monoclonal antibodies (including against SARS-CoV-2) received within 90 days before first vaccination.
Data sourced from ClinicalTrials.gov (NCT05168813). 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.