A Phase 2/3 interventional study of Moderna mRNA-1273 and Moderna mRNA-1273.222 in SARS-CoV-2 Infection, HIV Infections and COVID-19, sponsored by COVID-19 Prevention Network. Completed at 47 sites in 7 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-04-21.
Sponsored by COVID-19 Prevention Network · Phase 2/3, Interventional, and Prevention
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.
The study is constructed to help inform which vaccine regimen, likely in combination with enhanced HIV care, could serve as a public health model for an effective and cost-efficient approach to preventing SARS-CoV-2 disease, prolonged viral shedding, and the emergence of VOCs within this population. Moreover, we will evaluate whether immune responses postvaccination can be correlated to these clinically important outcomes.
The study will enroll 15,600 adults from many clinics in Eastern and Southern Africa. All participants in the study will get the study vaccine. There are 4 primary groups in this study. The groups differ in the number of doses of the study vaccine administered. The groups are organized by whether or not people are living with HIV and whether or not people have evidence of prior SARS-CoV-2 infection in their blood.
Group 1 includes people living with HIV and Group 3 includes people who are not living with HIV. All people in groups 1 and 3 will have no evidence of prior SARS-CoV-2 infection in their blood. Participants in Group 1 or Group 3 will get three doses of the study vaccine.
Group 2 includes people living with HIV and Group 4 includes people who are not living with HIV. All people in groups 2 and 4 will have evidence of prior SARS-CoV-2 infection in their blood. Participants in Group 2 or Group 4 will get two doses of the study vaccine.
There are 8 scheduled clinic visits over 18 months. Study visits may include physical examinations, medical history, vaccine injections, HIV testing, blood collection, nasal swabs, and questionnaires.
7,990 studies on the registry are indexed under COVID-19; 466 are open to participants now.
This study's enrollment of 14,237 is above the median of 102 across 4,364 interventional studies indexed under COVID-19.
Browse COVID-19 studies →COVID-19 Prevention Network is the lead sponsor of 4 studies on the registry; none are open to participants now.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
General and Demographic Criteria
Age ≥ 18 years if participant self-reports living with or another comorbidity known to be associated with severe COVID-19, for example (CDC.gov for exhaustive list):
Exclusion Criteria:
General
History of angioedema or anaphylaxis.
Vaccines and other injections
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Weight in kilograms divided by height in metres squared. Example: 70 kg and 1.75 m gives 70 ÷ (1.75 × 1.75) ≈ 22.9.
What counts as overweight or obesity differs between countries (some use lower cut-offs), so go by the range the study states.
Chronic obstructive pulmonary disease: long-term lung disease that makes it hard to breathe out, including emphysema and chronic bronchitis.
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Vaccines made with a weakened form of the germ, such as measles–mumps–rubella (MMR), chickenpox and yellow fever. They can be risky when the immune system is weakened. Flu injections are not live; the nasal flu spray is.
HIV
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
BMI (body mass index)
Weight in kilograms divided by height in metres squared. Example: 70 kg and 1.75 m gives 70 ÷ (1.75 × 1.75) ≈ 22.9.
What counts as overweight or obesity differs between countries (some use lower cut-offs), so go by the range the study states.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
COPD
Chronic obstructive pulmonary disease: long-term lung disease that makes it hard to breathe out, including emphysema and chronic bronchitis.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Immunosuppression
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Investigational drug or device
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Live vaccines
Vaccines made with a weakened form of the germ, such as measles–mumps–rubella (MMR), chickenpox and yellow fever. They can be risky when the immune system is weakened. Flu injections are not live; the nasal flu spray is.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
COVID-19 mRNA vaccine in 100 mcg dose to be administered as an IM injection into the deltoid muscle on Months 0, 1, and 6 among adults living with HIV who are SARS-CoV-2 negative at baseline.
Biological: Moderna mRNA-1273 · Biological: Moderna mRNA-1273.222 · Biological: Vaccine 3 Dose
COVID-19 mRNA vaccine in 100 mcg dose to be administered as an IM injection into the deltoid muscle on Months 0 and 6 among adults living with HIV who are SARS-CoV-2 positive at baseline.
Biological: Moderna mRNA-1273 · Biological: Moderna mRNA-1273.222 · Biological: Vaccine 2 Dose
COVID-19 mRNA vaccine in 100 mcg dose to be administered as an IM injection into the deltoid muscle on Months 0, 1, and 6 among HIV negative adults who are SARS-CoV-2 negative at baseline.
Biological: Moderna mRNA-1273 · Biological: Moderna mRNA-1273.222 · Biological: Vaccine 3 Dose
COVID-19 mRNA vaccine in 100 mcg dose to be administered as an IM injection into the deltoid muscle on Months 0 and 6 among HIV negative adults who are SARS-CoV-2 positive at baseline.
Biological: Moderna mRNA-1273 · Biological: Moderna mRNA-1273.222 · Biological: Vaccine 2 Dose
mRNA-1273 vaccine in 100 mcg dose to be administered as an IM injection into the deltoid muscle on Month 6.
Biological: Moderna mRNA-1273
mRNA-1273.222 vaccine in 100 mcg dose to be administered as an IM injection into the deltoid muscle on Month 6.
Biological: Moderna mRNA-1273.222
COVID-19 vaccine (mRNA-1273) developed by Moderna, Inc. is a lipid nanoparticle (LNP) dispersion of a messenger ribonucleic acid (mRNA) encoding the prefusion stabilized S protein of SARS-CoV-2 formulated in LNPs composed of 4 lipids (1 proprietary and 3 commercially available).
COVID-19 vaccine (mRNA-1273.222) developed by Moderna, Inc. is an updated bivalent version of Moderna's mRNA-1273 vaccine, composed of equal parts of mRNA-1273 and mRNA that encodes the S protein of the Omicron subvariants BA.4/.5 (which have the same S protein).
COVID-19 mRNA vaccine in 100 mcg dose given as IM injection into the deltoid muscle on Months 0, 1, and 6.
COVID-19 mRNA vaccine is to be administered as IM injection into the deltoid muscle on Months 0 and 6.
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)
The CDC-based COVID-19 endpoint is defined as the first occurrence of symptomatic NAAT-confirmed COVID-19 based on the following criteria: 1. At least ONE of the following systemic or respiratory symptoms: Fever (≥ 38C), chills, cough, shortness of breath and/or difficulty breathing, fatigue, muscle and/or body aches \[not related to exercise\], headache, new loss of taste/smell, sore throat, congestion, runny nose, nausea, vomiting, or diarrhea, AND 2. At least ONE (post-baseline) nasal swab (or respiratory sample, if hospitalized) positive for SARS-CoV-2 by NAAT. Because additional NAAT testing was performed at Month 1 for AG1 but not AG2-1, NAAT results at Month 1 were not considered. 3. The symptom date and NAAT positive date must be within 14 days of each other. The date of a COVID-19 endpoint according to the CDC-based definition is the earlier date of a symptom and the date of positive NAAT that satisfy the criteria stated above. The CDC criteria do not require adjudication.
Time frame: 1 day after Month 1 dose until Month 6 dose
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
The COVE-based COVID-19 endpoint is defined as the first occurrence of adjudicated symptomatic NAAT-confirmed COVID-19 based on the following criteria (same as in the Moderna mRNA-1273 COVE trial): 1. At least TWO of the following systemic symptoms: Fever ≥ 38◦C), chills, myalgia, headache, sore throat, new loss of taste or smell, OR 2. At least ONE of the following respiratory signs/symptoms: cough, shortness of breath or difficulty breathing, OR clinical or radiographical evidence of pneumonia, AND 3. At least ONE (post-baseline) nasal swab (or respiratory sample, if hospitalized) positive for SARS-CoV-2 by NAAT. The date of a COVID-19 endpoint is the later date of a symptom and the date of positive NAAT. The COVE criteria require adjudication.
Time frame: 1 day after Month 0 dose until Month 6 dose
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)
The COVE-based severe COVID-19 endpoint is defined as the first occurrence of a confirmed case of COVE-based COVID-19, plus any of the following: 1. Clinical signs indicative of severe systemic illness, Respiratory Rate ≥ 30 per minute, Heart Rate ≥ 125 beats per minute, SpO2 ≤ 93% on room air at sea level or PaO2/FIO2 less than 300 mm Hg, OR 2. Respiratory failure or Acute Respiratory Distress Syndrome (ARDS), (defined as needing high-flow oxygen, noninvasive or mechanical ventilation, or ECMO), evidence of shock (systolic blood pressure less than 90 mmHg, diastolic BP less than 60 mmHg or requiring vasopressors), OR 3. Significant acute renal, hepatic, or neurologic dysfunction, OR 4. Admission to an intensive care unit or death. The severe COVE criteria require adjudication.
Time frame: 1 day after Month 0 dose until Month 6 dose
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
The CDC-based COVID-19 endpoint is defined as the first occurrence of symptomatic NAAT-confirmed COVID-19 based on the following criteria: 1. At least ONE of the following systemic or respiratory symptoms: Fever (≥ 38C), chills, cough, shortness of breath and/or difficulty breathing, fatigue, muscle and/or body aches \[not related to exercise\], headache, new loss of taste/smell, sore throat, congestion, runny nose, nausea, vomiting, or diarrhea, AND 2. At least ONE (post-baseline) nasal swab (or respiratory sample, if hospitalized) positive for SARS-CoV-2 by NAAT. 3. The symptom date and NAAT positive date must be within 14 days of each other. The date of a COVID-19 endpoint according to the CDC-based definition is the earlier date of a symptom and the date of positive NAAT that satisfy the criteria stated above. The CDC criteria do not require adjudication.
Time frame: 14 days after Month 6 dose until end of follow up (up to 18 months)
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
The COVE-based COVID-19 endpoint is defined as the first occurrence of adjudicated symptomatic NAAT-confirmed COVID-19 based on the following criteria (same as in the Moderna mRNA-1273 COVE trial): 1. At least TWO of the following systemic symptoms: Fever ≥ 38◦C), chills, myalgia, headache, sore throat, new loss of taste or smell, OR 2. At least ONE of the following respiratory signs/symptoms: cough, shortness of breath or difficulty breathing, OR clinical or radiographical evidence of pneumonia, AND 3. At least ONE (post-baseline) nasal swab (or respiratory sample, if hospitalized) positive for SARS-CoV-2 by NAAT. The date of a COVID-19 endpoint is the later date of a symptom and the date of positive NAAT. The COVE criteria require adjudication.
Time frame: 14 days after Month 6 dose until end of follow up (up to 18 months)
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
Statistical analyses were not performed because there are fewer than 7 severe COVE-based severe COVID-19 starting 14 days after Month 6 dose until end of follow up in RM6 cohort.
Time frame: 14 days after Month 6 dose until end of follow up (up to 18 months)
Part A: Number of Participants With Solicited Adverse Events in the Safety Subset
All solicited adverse events/reactogenicity symptoms are followed until resolution and graded according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, dated July 2017. Local reacto symptoms collected are: erythema/redness, induration/swelling, lymphadenopathy, and pain/tenderness. Systemic reacto symptoms collected are: arthralgia, chills, fever, headache, malaise/fatigue, myalgia, and nausea.
Time frame: Up to 7 days following Month 0 vaccination (all Study Groups) and up to 7 days following Month 1 vaccination (Study Groups 1 and 3)
Part B: Number of Participants With Solicited Adverse Events in the Safety Subset
All solicited adverse events/reactogenicity symptoms are followed until resolution and graded according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, dated July 2017. Local reacto symptoms collected are: erythema/redness, induration/swelling, lymphadenopathy, and pain/tenderness. Systemic reacto symptoms collected are: arthralgia, chills, fever, headache, malaise/fatigue, myalgia, and nausea.
Time frame: Up to 7 days following Month 6 vaccination
Part A: Number of Participants With Unsolicited Adverse Events in the Safety Subset
All unsolicited AEs are graded according to the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, July 2017.
Time frame: Up to 28 days following Month 0 vaccination (all Study Groups) and up to 28 days following Month 1 vaccination (Study Groups 1 and 3)
Part B: Number of Participants With Unsolicited Adverse Events in the Safety Subset
All unsolicited AEs are graded according to the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, July 2017.
Time frame: Up to 28 days following Month 6 vaccination
Part A: Number of Participants With Serious Adverse Events (SAEs)
An SAE is any AE that results in any of the following outcomes: death, a life-threatening adverse event, a persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, congenital anomaly/birth defect, or is medically important.
Time frame: Up to Month 6
Part B: Number of Participants With Serious Adverse Events (SAEs)
An SAE is any AE that results in any of the following outcomes: death, a life-threatening adverse event, a persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, congenital anomaly/birth defect, or is medically important.
Time frame: Day of Month 6 vaccination up to Month 18
Part A: Number of Participants With Adverse Events of Special Interest (AESIs)
Adverse events of special interest (AESI) were described in Appendix L of the protocol. AESI for this protocol include but are not limited to potential immune-mediated diseases.
Time frame: Up to Month 6
Part B: Number of Participants With Adverse Events of Special Interest (AESIs)
Adverse events of special interest (AESI) were described in Appendix L of the protocol. AESI for this protocol include but are not limited to potential immune-mediated diseases.
Time frame: Day of Month 6 vaccination up to Month 18
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
The CDC-based COVID-19 endpoint is defined as the first occurrence of symptomatic NAAT-confirmed COVID-19 based on the following criteria: 1. At least ONE of the following systemic or respiratory symptoms: Fever (≥ 38C), chills, cough, shortness of breath and/or difficulty breathing, fatigue, muscle and/or body aches \[not related to exercise\], headache, new loss of taste/smell, sore throat, congestion, runny nose, nausea, vomiting, or diarrhea, AND 2. At least ONE (post-baseline) nasal swab (or respiratory sample, if hospitalized) positive for SARS-CoV-2 by NAAT. Because additional NAAT testing was performed at Month 1 for AG1 but not AG2-1, NAAT results at Month 1 were not considered. 3. The symptom date and NAAT positive date must be within 14 days of each other. The date of a COVID-19 endpoint according to the CDC-based definition is the earlier date of a symptom and the date of positive NAAT that satisfy the criteria stated above. The CDC criteria do not require adjudication.
Time frame: 1 day after Month 0 dose until Month 6 dose
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
The COVE-based COVID-19 endpoint is defined as the first occurrence of adjudicated symptomatic NAAT-confirmed COVID-19 based on the following criteria (same as in the Moderna mRNA-1273 COVE trial): 1. At least TWO of the following systemic symptoms: Fever ≥ 38◦C), chills, myalgia, headache, sore throat, new loss of taste or smell, OR 2. At least ONE of the following respiratory signs/symptoms: cough, shortness of breath or difficulty breathing, OR clinical or radiographical evidence of pneumonia, AND 3. At least ONE (post-baseline) nasal swab (or respiratory sample, if hospitalized) positive for SARS-CoV-2 by NAAT. The date of a COVID-19 endpoint is the later date of a symptom and the date of positive NAAT. The COVE criteria require adjudication.
Time frame: 1 day after Month 0 dose until Month 6 dose
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
The COVE-based severe COVID-19 endpoint is defined as the first occurrence of a confirmed case of COVE-based COVID-19, plus any of the following: 1. Clinical signs indicative of severe systemic illness, Respiratory Rate ≥ 30 per minute, Heart Rate ≥ 125 beats per minute, SpO2 ≤ 93% on room air at sea level or PaO2/FIO2 less than 300 mm Hg, OR 2. Respiratory failure or Acute Respiratory Distress Syndrome (ARDS), (defined as needing high-flow oxygen, noninvasive or mechanical ventilation, or ECMO), evidence of shock (systolic blood pressure less than 90 mmHg, diastolic BP less than 60 mmHg or requiring vasopressors), OR 3. Significant acute renal, hepatic, or neurologic dysfunction, OR 4. Admission to an intensive care unit or death. The severe COVE criteria require adjudication.
Time frame: 1 day after Month 0 dose until Month 6 dose
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
The CDC-based COVID-19 endpoint is defined as the first occurrence of symptomatic NAAT-confirmed COVID-19 based on these criteria: 1. At least ONE of the following systemic or respiratory symptoms: Fever (≥ 38C), chills, cough, shortness of breath and/or difficulty breathing, fatigue, muscle and/or body aches \[not related to exercise\], headache, new loss of taste/smell, sore throat, congestion, runny nose, nausea, vomiting, or diarrhea, AND 2. At least ONE (post-baseline) nasal swab (or respiratory sample, if hospitalized) positive for SARS-CoV-2 by NAAT. 3. The symptom date and NAAT positive date must be within 14 days of each other. The date of a COVID-19 endpoint according to the CDC-based definition is the earlier date of a symptom and date of positive NAAT that satisfy the criteria stated above. The CDC criteria do not require adjudication.
Time frame: 14 days after Month 6 dose until end of follow up (up to 18 months)
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
The CDC-based COVID-19 endpoint is defined as the first occurrence of symptomatic NAAT-confirmed COVID-19 based on these criteria: 1. At least ONE of the following systemic or respiratory symptoms: Fever (≥ 38C), chills, cough, shortness of breath and/or difficulty breathing, fatigue, muscle and/or body aches \[not related to exercise\], headache, new loss of taste/smell, sore throat, congestion, runny nose, nausea, vomiting, or diarrhea, AND 2. At least ONE (post-baseline) nasal swab (or respiratory sample, if hospitalized) positive for SARS-CoV-2 by NAAT. 3. The symptom date and NAAT positive date must be within 14 days of each other. The date of a COVID-19 endpoint according to the CDC-based definition is the earlier date of a symptom and date of positive NAAT that satisfy the criteria stated above. The CDC criteria do not require adjudication.
Time frame: 14 days after Month 6 dose until end of follow up (up to 18 months)
Part A: Geometric Mean Titers (GMTs) of SARS-CoV-2 Antibodies as Measured by Neutralizing Antibody (NAb) Assay
Linear regression is used to provide covariate-adjusted point and 95% confidence interval estimation of geometric mean titers. Covariates adjusted are HIV status at baseline, age, sex at birth, and BMI.
Time frame: Month 0, 4 weeks post final pre-Month 6 vaccination (peak timepoint)
Part A: Geometric Mean Titers (GMTs) of SARS-CoV-2 Antibodies as Measured by Meso Scale Discovery-electrochemiluminescence Assay (MSD-ECL)
Linear regression is used to provide covariate-adjusted point and 95% confidence interval estimation of geometric mean titers. Covariates adjusted are HIV status at baseline, age, sex at birth, and BMI.
Time frame: Month 0, 4 weeks post final pre-Month 6 vaccination (peak timepoint)
Part A: Geometric Mean Titers of T-Cell Responses as Measured by Intracellular Cytokine Staining (ICS) Assay at Month 0
Linear regression is used to provide covariate-adjusted point and 95% confidence interval estimation of geometric mean titers. Covariates adjusted are HIV status at baseline, age, sex at birth, and BMI.
Time frame: Month 0
Part A: Geometric Mean Titers of T-Cell Responses as Measured by Intracellular Cytokine Staining (ICS) Assay at Peak Timepoint
Linear regression is used to provide covariate-adjusted point and 95% confidence interval estimation of geometric mean titers. Covariates adjusted are HIV status at baseline, age, sex at birth, and BMI.
Time frame: 4 weeks post final pre-Month 6 vaccination (peak timepoint)
Part B: Geometric Mean Titers (GMTs) of SARS-CoV-2 Antibodies as Measured by Neutralizing Antibody Assay
Time frame: Months 6 and 7
SARS-CoV-2 Viral Persistence and Evolution Among Participants Virologically Diagnosed With SARS-CoV-2
Participants were considered to have persistent SARS-CoV-2 NAAT positivity if they had positive swabs lasting \>= 50 days during a single infection. A single infection was assumed unless the participant had a positive NAAT following either a single negative NAAT by \>= 90 days or two consecutive negative NAATs over any time interval, in which case it was considered a reinfection. In Part A, the first NAAT+ on or before the Month 6 dose for each ppt was considered. In Part B, the first NAAT+ after the Month 6 dose for each ppt was considered. Analysis of viral evolution was not done due to termination of resources for evaluation.
Time frame: Participants testing positive for SARS-CoV-2 had additional nasab swabs taken fortnightly until testing negative, up to a maximum of 18 months
The study was conducted in two parts: Part A (open-label) and Part B (blinded).
| Milestone | Part A (Open-label): Study Group 1 | Part A (Open Label): Study Group 2 | Part A (Open-label): Study Group 3 | Part A (Open-label): Study Group 4 | Part B (Blinded): mRNA-1273 at Month 6 | Part B (Blinded): mRNA-1273.222 at Month 6 |
|---|---|---|---|---|---|---|
| Started | 3740 | 7941 | 648 | 1672 | 0 | 0 |
| Full analysis set (fas) | 3740 | 7941 | 648 | 1672 | 0 | 0 |
| Safety set (ss) | 558 | 692 | 99 | 142 | 0 | 0 |
| Immunogenicity set (is) | 68 | 80 | 67 | 78 | 0 | 0 |
| Per-protocol set (pp) | 3604 | 7832 | 617 | 1607 | 0 | 0 |
| Completed | 3648 | 7819 | 624 | 1606 | 0 | 0 |
| Not completed | 92 | 122 | 24 | 66 | 0 | 0 |
| Withdrew: Lost to follow-up | 21 | 39 | 8 | 26 | 0 | 0 |
| Withdrew: Withdrawal by subject | 35 | 30 | 14 | 17 | 0 | 0 |
| Withdrew: Death | 23 | 28 | 1 | 9 | 0 | 0 |
| Withdrew: Physician decision | 0 | 1 | 0 | 2 | 0 | 0 |
| Withdrew: Participant unable to adhere to visit schedule | 10 | 18 | 0 | 7 | 0 | 0 |
| Withdrew: Protocol violation | 0 | 1 | 0 | 0 | 0 | 0 |
| Withdrew: Study terminated by sponsor | 3 | 4 | 1 | 5 | 0 | 0 |
| Withdrew: Other | 0 | 1 | 0 | 0 | 0 | 0 |
| Milestone | Part A (Open-label): Study Group 1 | Part A (Open Label): Study Group 2 | Part A (Open-label): Study Group 3 | Part A (Open-label): Study Group 4 | Part B (Blinded): mRNA-1273 at Month 6 | Part B (Blinded): mRNA-1273.222 at Month 6 |
|---|---|---|---|---|---|---|
| Started | 0 | 0 | 0 | 0 | 11243 | 2012 |
| Received month 6 vaccination set (fm6) | 0 | 0 | 0 | 0 | 11243 | 2012 |
| Randomized month 6 set (rm6) | 0 | 0 | 0 | 0 | 1976 | 2012 |
| Safety set (ss) | 0 | 0 | 0 | 0 | 1323 | 89 |
| Immunogenicity set (is) | 0 | 0 | 0 | 0 | 252 | 26 |
| Full per-protocol set (fpp) | 0 | 0 | 0 | 0 | 1960 | 2002 |
| Completed | 0 | 0 | 0 | 0 | 2086 | 1676 |
| Not completed | 0 | 0 | 0 | 0 | 9157 | 336 |
| Withdrew: Lost to follow-up | 0 | 0 | 0 | 0 | 219 | 88 |
| Withdrew: Withdrawal by subject | 0 | 0 | 0 | 0 | 91 | 55 |
| Withdrew: Death | 0 | 0 | 0 | 0 | 63 | 19 |
| Withdrew: Physician decision | 0 | 0 | 0 | 0 | 6 | 1 |
| Withdrew: Participant unable to adhere to visit schedule | 0 | 0 | 0 | 0 | 54 | 21 |
| Withdrew: Pregnancy | 0 | 0 | 0 | 0 | 1 | 0 |
| Withdrew: Study terminated by sponsor | 0 | 0 | 0 | 0 | 8682 | 125 |
| Withdrew: Other | 0 | 0 | 0 | 0 | 41 | 27 |
The CDC-based COVID-19 endpoint is defined as the first occurrence of symptomatic NAAT-confirmed COVID-19 based on the following criteria: 1. At least ONE of the following systemic or respiratory symptoms: Fever (≥ 38C), chills, cough, shortness of breath and/or difficulty breathing, fatigue, muscle and/or body aches \[not related to exercise\], headache, new loss of taste/smell, sore throat, congestion, runny nose, nausea, vomiting, or diarrhea, AND 2. At least ONE (post-baseline) nasal swab (or respiratory sample, if hospitalized) positive for SARS-CoV-2 by NAAT. Because additional NAAT testing was performed at Month 1 for AG1 but not AG2-1, NAAT results at Month 1 were not considered. 3. The symptom date and NAAT positive date must be within 14 days of each other. The date of a COVID-19 endpoint according to the CDC-based definition is the earlier date of a symptom and the date of positive NAAT that satisfy the criteria stated above. The CDC criteria do not require adjudication.
| Participants | Part A (Open-label): Study Group 1, Analysis Group 1 (AG1) | Part A (Open-label): Study Group 2, Analysis Group 2-1 (AG2-1) |
|---|---|---|
| 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 |
The COVE-based COVID-19 endpoint is defined as the first occurrence of adjudicated symptomatic NAAT-confirmed COVID-19 based on the following criteria (same as in the Moderna mRNA-1273 COVE trial): 1. At least TWO of the following systemic symptoms: Fever ≥ 38◦C), chills, myalgia, headache, sore throat, new loss of taste or smell, OR 2. At least ONE of the following respiratory signs/symptoms: cough, shortness of breath or difficulty breathing, OR clinical or radiographical evidence of pneumonia, AND 3. At least ONE (post-baseline) nasal swab (or respiratory sample, if hospitalized) positive for SARS-CoV-2 by NAAT. The date of a COVID-19 endpoint is the later date of a symptom and the date of positive NAAT. The COVE criteria require adjudication.
| Participants | Part A (Open-label): Study Group 1, Analysis Group 1 (AG1) | Part A (Open-label): Study Group 2, Analysis Group 2-1 (AG2-1) |
|---|---|---|
| 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 |
The COVE-based severe COVID-19 endpoint is defined as the first occurrence of a confirmed case of COVE-based COVID-19, plus any of the following: 1. Clinical signs indicative of severe systemic illness, Respiratory Rate ≥ 30 per minute, Heart Rate ≥ 125 beats per minute, SpO2 ≤ 93% on room air at sea level or PaO2/FIO2 less than 300 mm Hg, OR 2. Respiratory failure or Acute Respiratory Distress Syndrome (ARDS), (defined as needing high-flow oxygen, noninvasive or mechanical ventilation, or ECMO), evidence of shock (systolic blood pressure less than 90 mmHg, diastolic BP less than 60 mmHg or requiring vasopressors), OR 3. Significant acute renal, hepatic, or neurologic dysfunction, OR 4. Admission to an intensive care unit or death. The severe COVE criteria require adjudication.
| Participants | Part A (Open-label): Study Group 1, Analysis Group 1 (AG1) | Part A (Open-label): Study Group 2, Analysis Group 2-1 (AG2-1) |
|---|---|---|
| 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 |
The CDC-based COVID-19 endpoint is defined as the first occurrence of symptomatic NAAT-confirmed COVID-19 based on the following criteria: 1. At least ONE of the following systemic or respiratory symptoms: Fever (≥ 38C), chills, cough, shortness of breath and/or difficulty breathing, fatigue, muscle and/or body aches \[not related to exercise\], headache, new loss of taste/smell, sore throat, congestion, runny nose, nausea, vomiting, or diarrhea, AND 2. At least ONE (post-baseline) nasal swab (or respiratory sample, if hospitalized) positive for SARS-CoV-2 by NAAT. 3. The symptom date and NAAT positive date must be within 14 days of each other. The date of a COVID-19 endpoint according to the CDC-based definition is the earlier date of a symptom and the date of positive NAAT that satisfy the criteria stated above. The CDC criteria do not require adjudication.
| Participants | Part B (Blinded): mRNA-1273 at Month 6 | Part B (Blinded): mRNA-1273.222 at Month 6 |
|---|---|---|
| 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 |
The COVE-based COVID-19 endpoint is defined as the first occurrence of adjudicated symptomatic NAAT-confirmed COVID-19 based on the following criteria (same as in the Moderna mRNA-1273 COVE trial): 1. At least TWO of the following systemic symptoms: Fever ≥ 38◦C), chills, myalgia, headache, sore throat, new loss of taste or smell, OR 2. At least ONE of the following respiratory signs/symptoms: cough, shortness of breath or difficulty breathing, OR clinical or radiographical evidence of pneumonia, AND 3. At least ONE (post-baseline) nasal swab (or respiratory sample, if hospitalized) positive for SARS-CoV-2 by NAAT. The date of a COVID-19 endpoint is the later date of a symptom and the date of positive NAAT. The COVE criteria require adjudication.
| Participants | Part B (Blinded): mRNA-1273 at Month 6 | Part B (Blinded): mRNA-1273.222 at Month 6 |
|---|---|---|
| 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 |
Statistical analyses were not performed because there are fewer than 7 severe COVE-based severe COVID-19 starting 14 days after Month 6 dose until end of follow up in RM6 cohort.
| Participants | Part B (Blinded): mRNA-1273 at Month 6 | Part B (Blinded): mRNA-1273.222 at Month 6 |
|---|---|---|
| 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 |
All solicited adverse events/reactogenicity symptoms are followed until resolution and graded according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, dated July 2017. Local reacto symptoms collected are: erythema/redness, induration/swelling, lymphadenopathy, and pain/tenderness. Systemic reacto symptoms collected are: arthralgia, chills, fever, headache, malaise/fatigue, myalgia, and nausea.
| Participants | Part A (Open-label): Study Group 1 | Part A (Open Label): Study Group 2 | Part A (Open-label): Study Group 3 | Part A (Open-label): Study Group 4 |
|---|---|---|---|---|
| Any Reacto After Month 0 Vaccination — Grade 0 | 320 | 428 | 68 | 82 |
| Any Reacto After Month 0 Vaccination — Grade 1 | 158 | 167 | 19 | 37 |
| Any Reacto After Month 0 Vaccination — Grade 2 | 79 | 87 | 11 | 22 |
| Any Reacto After Month 0 Vaccination — Grade 3 | 1 | 9 | 1 | 1 |
| Any Reacto After Month 0 Vaccination — Grade 4 | 0 | 0 | 0 | 0 |
| Any Reacto After Month 0 Vaccination — Missing | 0 | 1 | 0 | 0 |
| Any Reacto After Month 1 Vaccination — Grade 0 | 352 | 0 | 65 | 0 |
| Any Reacto After Month 1 Vaccination — Grade 1 | 126 | 0 | 21 | 0 |
| Any Reacto After Month 1 Vaccination — Grade 2 | 59 | 0 | 9 | 0 |
| Any Reacto After Month 1 Vaccination — Grade 3 | 5 | 0 | 2 | 0 |
| Any Reacto After Month 1 Vaccination — Grade 4 | 0 | 0 | 0 | 0 |
| Any Reacto After Month 1 Vaccination — Missing | 1 | 0 | 1 | 0 |
| Erythema/Redness After Month 0 Vaccination — Grade 0 | 533 | 671 | 95 | 130 |
| Erythema/Redness After Month 0 Vaccination — Grade 1 | 18 | 14 | 3 | 9 |
| Erythema/Redness After Month 0 Vaccination — Grade 2 | 7 | 6 | 1 | 3 |
| Erythema/Redness After Month 0 Vaccination — Grade 3 | 0 | 0 | 0 | 0 |
| Erythema/Redness After Month 0 Vaccination — Grade 4 | 0 | 0 | 0 | 0 |
| Erythema/Redness After Month 0 Vaccination — Missing | 0 | 1 | 0 | 0 |
| Induration/Swelling After Month 0 Vaccination — Grade 0 | 508 | 636 | 96 | 125 |
| Induration/Swelling After Month 0 Vaccination — Grade 1 | 27 | 37 | 1 | 9 |
| Induration/Swelling After Month 0 Vaccination — Grade 2 | 23 | 18 | 2 | 8 |
| Induration/Swelling After Month 0 Vaccination — Grade 3 | 0 | 0 | 0 | 0 |
| Induration/Swelling After Month 0 Vaccination — Grade 4 | 0 | 0 | 0 | 0 |
| Induration/Swelling After Month 0 Vaccination — Missing | 0 | 1 | 0 | 0 |
| Lymphadenopathy After Month 0 Vaccination — Grade 0 | 517 | 657 | 93 | 132 |
| Lymphadenopathy After Month 0 Vaccination — Grade 1 | 33 | 23 | 4 | 6 |
| Lymphadenopathy After Month 0 Vaccination — Grade 2 | 7 | 11 | 1 | 4 |
| Lymphadenopathy After Month 0 Vaccination — Grade 3 | 1 | 0 | 1 | 0 |
| Lymphadenopathy After Month 0 Vaccination — Grade 4 | 0 | 0 | 0 | 0 |
| Lymphadenopathy After Month 0 Vaccination — Missing | 0 | 1 | 0 | 0 |
| Pain/Tenderness After Month 0 Vaccination — Grade 0 | 389 | 518 | 79 | 96 |
| Pain/Tenderness After Month 0 Vaccination — Grade 1 | 144 | 135 | 15 | 32 |
| Pain/Tenderness After Month 0 Vaccination — Grade 2 | 24 | 36 | 4 | 14 |
| Pain/Tenderness After Month 0 Vaccination — Grade 3 | 1 | 2 | 1 | 0 |
| Pain/Tenderness After Month 0 Vaccination — Grade 4 | 0 | 0 | 0 | 0 |
| Pain/Tenderness After Month 0 Vaccination — Missing | 0 | 1 | 0 | 0 |
| Erythema/Redness After Month 1 Vaccination — Grade 0 | 532 | 0 | 96 | 0 |
| Erythema/Redness After Month 1 Vaccination — Grade 1 | 3 | 0 | 1 | 0 |
| Erythema/Redness After Month 1 Vaccination — Grade 2 | 7 | 0 | 0 | 0 |
| Erythema/Redness After Month 1 Vaccination — Grade 3 | 0 | 0 | 0 | 0 |
| Erythema/Redness After Month 1 Vaccination — Grade 4 | 0 | 0 | 0 | 0 |
| Erythema/Redness After Month 1 Vaccination — Missing | 1 | 0 | 1 | 0 |
| Induration/Swelling After Month 1 Vaccination — Grade 0 | 509 | 0 | 94 | 0 |
| Induration/Swelling After Month 1 Vaccination — Grade 1 | 22 | 0 | 1 | 0 |
| Induration/Swelling After Month 1 Vaccination — Grade 2 | 11 | 0 | 2 | 0 |
| Induration/Swelling After Month 1 Vaccination — Grade 3 | 0 | 0 | 0 | 0 |
| Induration/Swelling After Month 1 Vaccination — Grade 4 | 0 | 0 | 0 | 0 |
| Induration/Swelling After Month 1 Vaccination — Missing | 1 | 0 | 1 | 0 |
| Lymphadenopathy After Month 1 Vaccination — Grade 0 | 513 | 0 | 90 | 0 |
| Lymphadenopathy After Month 1 Vaccination — Grade 1 | 24 | 0 | 5 | 0 |
| Lymphadenopathy After Month 1 Vaccination — Grade 2 | 5 | 0 | 2 | 0 |
| Lymphadenopathy After Month 1 Vaccination — Grade 3 | 0 | 0 | 0 | 0 |
| Lymphadenopathy After Month 1 Vaccination — Grade 4 | 0 | 0 | 0 | 0 |
| Lymphadenopathy After Month 1 Vaccination — Missing | 1 | 0 | 1 | 0 |
| Pain/Tenderness After Month 1 Vaccination — Grade 0 | 403 | 0 | 74 | 0 |
| Pain/Tenderness After Month 1 Vaccination — Grade 1 | 115 | 0 | 19 | 0 |
| Pain/Tenderness After Month 1 Vaccination — Grade 2 | 24 | 0 | 4 | 0 |
| Pain/Tenderness After Month 1 Vaccination — Grade 3 | 0 | 0 | 0 | 0 |
| Pain/Tenderness After Month 1 Vaccination — Grade 4 | 0 | 0 | 0 | 0 |
| Pain/Tenderness After Month 1 Vaccination — Missing | 1 | 0 | 1 | 0 |
| Arthralgia After Month 0 Vaccination — Grade 0 | 488 | 621 | 88 | 127 |
| Arthralgia After Month 0 Vaccination — Grade 1 | 48 | 45 | 7 | 8 |
| Arthralgia After Month 0 Vaccination — Grade 2 | 22 | 23 | 3 | 7 |
| Arthralgia After Month 0 Vaccination — Grade 3 | 0 | 2 | 1 | 0 |
| Arthralgia After Month 0 Vaccination — Grade 4 | 0 | 0 | 0 | 0 |
| Arthralgia After Month 0 Vaccination — Missing | 0 | 1 | 0 | 0 |
| Chills After Month 0 Vaccination — Grade 0 | 511 | 639 | 90 | 134 |
| Chills After Month 0 Vaccination — Grade 1 | 37 | 36 | 5 | 7 |
| Chills After Month 0 Vaccination — Grade 2 | 10 | 15 | 4 | 1 |
| Chills After Month 0 Vaccination — Grade 3 | 0 | 1 | 0 | 0 |
| Chills After Month 0 Vaccination — Grade 4 | 0 | 0 | 0 | 0 |
| Chills After Month 0 Vaccination — Missing | 0 | 1 | 0 | 0 |
| Fever After Month 0 Vaccination — Grade 0 | 540 | 660 | 97 | 140 |
| Fever After Month 0 Vaccination — Grade 1 | 11 | 19 | 1 | 2 |
| Fever After Month 0 Vaccination — Grade 2 | 7 | 10 | 1 | 0 |
| Fever After Month 0 Vaccination — Grade 3 | 0 | 2 | 0 | 0 |
| Fever After Month 0 Vaccination — Grade 4 | 0 | 0 | 0 | 0 |
| Fever After Month 0 Vaccination — Missing | 0 | 1 | 0 | 0 |
| Headache After Month 0 Vaccination — Grade 0 | 435 | 557 | 85 | 106 |
| Headache After Month 0 Vaccination — Grade 1 | 96 | 104 | 11 | 29 |
| Headache After Month 0 Vaccination — Grade 2 | 26 | 28 | 3 | 7 |
| Headache After Month 0 Vaccination — Grade 3 | 1 | 2 | 0 | 0 |
| Headache After Month 0 Vaccination — Grade 4 | 0 | 0 | 0 | 0 |
| Headache After Month 0 Vaccination — Missing | 0 | 1 | 0 | 0 |
| Malaise/Fatigue After Month 0 Vaccination — Grade 0 | 443 | 558 | 84 | 109 |
| Malaise/Fatigue After Month 0 Vaccination — Grade 1 | 86 | 91 | 9 | 27 |
| Malaise/Fatigue After Month 0 Vaccination — Grade 2 | 29 | 39 | 5 | 6 |
| Malaise/Fatigue After Month 0 Vaccination — Grade 3 | 0 | 3 | 1 | 0 |
| Malaise/Fatigue After Month 0 Vaccination — Grade 4 | 0 | 0 | 0 | 0 |
| Malaise/Fatigue After Month 0 Vaccination — Missing | 0 | 1 | 0 | 0 |
| Myalgia After Month 0 Vaccination — Grade 0 | 469 | 606 | 86 | 118 |
| Myalgia After Month 0 Vaccination — Grade 1 | 64 | 60 | 7 | 18 |
| Myalgia After Month 0 Vaccination — Grade 2 | 25 | 22 | 5 | 5 |
| Myalgia After Month 0 Vaccination — Grade 3 | 0 | 3 | 1 | 1 |
| Myalgia After Month 0 Vaccination — Grade 4 | 0 | 0 | 0 | 0 |
| Myalgia After Month 0 Vaccination — Missing | 0 | 1 | 0 | 0 |
| Nausea After Month 0 Vaccination — Grade 0 | 507 | 633 | 92 | 131 |
| Nausea After Month 0 Vaccination — Grade 1 | 36 | 38 | 6 | 9 |
| Nausea After Month 0 Vaccination — Grade 2 | 15 | 19 | 1 | 2 |
| Nausea After Month 0 Vaccination — Grade 3 | 0 | 1 | 0 | 0 |
| Nausea After Month 0 Vaccination — Grade 4 | 0 | 0 | 0 | 0 |
| Nausea After Month 0 Vaccination — Missing | 0 | 1 | 0 | 0 |
| Arthralgia After Month 1 Vaccination — Grade 0 | 482 | 0 | 85 | 0 |
| Arthralgia After Month 1 Vaccination — Grade 1 | 42 | 0 | 11 | 0 |
| Arthralgia After Month 1 Vaccination — Grade 2 | 17 | 0 | 1 | 0 |
| Arthralgia After Month 1 Vaccination — Grade 3 | 1 | 0 | 0 | 0 |
| Arthralgia After Month 1 Vaccination — Grade 4 | 0 | 0 | 0 | 0 |
| Arthralgia After Month 1 Vaccination — Missing | 1 | 0 | 1 | 0 |
| Chills After Month 1 Vaccination — Grade 0 | 494 | 0 | 89 | 0 |
| Chills After Month 1 Vaccination — Grade 1 | 35 | 0 | 6 | 0 |
| Chills After Month 1 Vaccination — Grade 2 | 11 | 0 | 2 | 0 |
| Chills After Month 1 Vaccination — Grade 3 | 2 | 0 | 0 | 0 |
| Chills After Month 1 Vaccination — Grade 4 | 0 | 0 | 0 | 0 |
| Chills After Month 1 Vaccination — Missing | 1 | 0 | 1 | 0 |
| Fever After Month 1 Vaccination — Grade 0 | 527 | 0 | 93 | 0 |
| Fever After Month 1 Vaccination — Grade 1 | 10 | 0 | 2 | 0 |
| Fever After Month 1 Vaccination — Grade 2 | 4 | 0 | 2 | 0 |
| Fever After Month 1 Vaccination — Grade 3 | 1 | 0 | 0 | 0 |
| Fever After Month 1 Vaccination — Grade 4 | 0 | 0 | 0 | 0 |
| Fever After Month 1 Vaccination — Missing | 1 | 0 | 1 | 0 |
| Headache After Month 1 Vaccination — Grade 0 | 433 | 0 | 79 | 0 |
| Headache After Month 1 Vaccination — Grade 1 | 85 | 0 | 15 | 0 |
| Headache After Month 1 Vaccination — Grade 2 | 21 | 0 | 2 | 0 |
| Headache After Month 1 Vaccination — Grade 3 | 3 | 0 | 1 | 0 |
| Headache After Month 1 Vaccination — Grade 4 | 0 | 0 | 0 | 0 |
| Headache After Month 1 Vaccination — Missing | 1 | 0 | 1 | 0 |
| Malaise/Fatigue After Month 1 Vaccination — Grade 0 | 428 | 0 | 75 | 0 |
| Malaise/Fatigue After Month 1 Vaccination — Grade 1 | 80 | 0 | 15 | 0 |
| Malaise/Fatigue After Month 1 Vaccination — Grade 2 | 30 | 0 | 5 | 0 |
| Malaise/Fatigue After Month 1 Vaccination — Grade 3 | 4 | 0 | 2 | 0 |
| Malaise/Fatigue After Month 1 Vaccination — Grade 4 | 0 | 0 | 0 | 0 |
| Malaise/Fatigue After Month 1 Vaccination — Missing | 1 | 0 | 1 | 0 |
| Myalgia After Month 1 Vaccination — Grade 0 | 464 | 0 | 84 | 0 |
| Myalgia After Month 1 Vaccination — Grade 1 | 62 | 0 | 11 | 0 |
| Myalgia After Month 1 Vaccination — Grade 2 | 14 | 0 | 1 | 0 |
| Myalgia After Month 1 Vaccination — Grade 3 | 2 | 0 | 1 | 0 |
| Myalgia After Month 1 Vaccination — Grade 4 | 0 | 0 | 0 | 0 |
| Myalgia After Month 1 Vaccination — Missing | 1 | 0 | 1 | 0 |
| Nausea After Month 1 Vaccination — Grade 0 | 501 | 0 | 87 | 0 |
| Nausea After Month 1 Vaccination — Grade 1 | 33 | 0 | 9 | 0 |
| Nausea After Month 1 Vaccination — Grade 2 | 7 | 0 | 1 | 0 |
| Nausea After Month 1 Vaccination — Grade 3 | 1 | 0 | 0 | 0 |
| Nausea After Month 1 Vaccination — Grade 4 | 0 | 0 | 0 | 0 |
| Nausea After Month 1 Vaccination — Missing | 1 | 0 | 1 | 0 |
All solicited adverse events/reactogenicity symptoms are followed until resolution and graded according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, dated July 2017. Local reacto symptoms collected are: erythema/redness, induration/swelling, lymphadenopathy, and pain/tenderness. Systemic reacto symptoms collected are: arthralgia, chills, fever, headache, malaise/fatigue, myalgia, and nausea.
| Participants | Part B (Blinded): mRNA-1273 at Month 6 | Part B (Blinded): mRNA-1273.222 at Month 6 |
|---|---|---|
| Any Reacto After Month 6 Vaccination — Grade 0 | 877 | 71 |
| Any Reacto After Month 6 Vaccination — Grade 1 | 290 | 9 |
| Any Reacto After Month 6 Vaccination — Grade 2 | 135 | 6 |
| Any Reacto After Month 6 Vaccination — Grade 3 | 17 | 0 |
| Any Reacto After Month 6 Vaccination — Grade 4 | 0 | 0 |
| Any Reacto After Month 6 Vaccination — Missing | 4 | 3 |
| Erythema/Redness After Month 6 Vaccination — Grade 0 | 1282 | 85 |
| Erythema/Redness After Month 6 Vaccination — Grade 1 | 28 | 1 |
| Erythema/Redness After Month 6 Vaccination — Grade 2 | 9 | 0 |
| Erythema/Redness After Month 6 Vaccination — Grade 3 | 0 | 0 |
| Erythema/Redness After Month 6 Vaccination — Grade 4 | 0 | 0 |
| Erythema/Redness After Month 6 Vaccination — Missing | 4 | 3 |
| Induration/Swelling After Month 6 Vaccination — Grade 0 | 1254 | 83 |
| Induration/Swelling After Month 6 Vaccination — Grade 1 | 50 | 2 |
| Induration/Swelling After Month 6 Vaccination — Grade 2 | 15 | 1 |
| Induration/Swelling After Month 6 Vaccination — Grade 3 | 0 | 0 |
| Induration/Swelling After Month 6 Vaccination — Grade 4 | 0 | 0 |
| Induration/Swelling After Month 6 Vaccination — Missing | 4 | 3 |
| Lymphadenopathy After Month 6 Vaccination — Grade 0 | 1235 | 84 |
| Lymphadenopathy After Month 6 Vaccination — Grade 1 | 59 | 2 |
| Lymphadenopathy After Month 6 Vaccination — Grade 2 | 23 | 0 |
| Lymphadenopathy After Month 6 Vaccination — Grade 3 | 2 | 0 |
| Lymphadenopathy After Month 6 Vaccination — Grade 4 | 0 | 0 |
| Lymphadenopathy After Month 6 Vaccination — Missing | 4 | 3 |
| Pain/Tenderness After Month 6 Vaccination — Grade 0 | 1010 | 76 |
| Pain/Tenderness After Month 6 Vaccination — Grade 1 | 244 | 7 |
| Pain/Tenderness After Month 6 Vaccination — Grade 2 | 56 | 3 |
| Pain/Tenderness After Month 6 Vaccination — Grade 3 | 9 | 0 |
| Pain/Tenderness After Month 6 Vaccination — Grade 4 | 0 | 0 |
| Pain/Tenderness After Month 6 Vaccination — Missing | 4 | 3 |
| Arthralgia After Month 6 Vaccination — Grade 0 | 1182 | 80 |
| Arthralgia After Month 6 Vaccination — Grade 1 | 90 | 2 |
| Arthralgia After Month 6 Vaccination — Grade 2 | 39 | 4 |
| Arthralgia After Month 6 Vaccination — Grade 3 | 8 | 0 |
| Arthralgia After Month 6 Vaccination — Grade 4 | 0 | 0 |
| Arthralgia After Month 6 Vaccination — Missing | 4 | 3 |
| Chills After Month 6 Vaccination — Grade 0 | 1208 | 82 |
| Chills After Month 6 Vaccination — Grade 1 | 74 | 2 |
| Chills After Month 6 Vaccination — Grade 2 | 29 | 2 |
| Chills After Month 6 Vaccination — Grade 3 | 8 | 0 |
| Chills After Month 6 Vaccination — Grade 4 | 0 | 0 |
| Chills After Month 6 Vaccination — Missing | 4 | 3 |
| Fever After Month 6 Vaccination — Grade 0 | 1282 | 86 |
| Fever After Month 6 Vaccination — Grade 1 | 26 | 0 |
| Fever After Month 6 Vaccination — Grade 2 | 8 | 0 |
| Fever After Month 6 Vaccination — Grade 3 | 3 | 0 |
| Fever After Month 6 Vaccination — Grade 4 | 0 | 0 |
| Fever After Month 6 Vaccination — Missing | 4 | 3 |
| Headache After Month 6 Vaccination — Grade 0 | 1043 | 74 |
| Headache After Month 6 Vaccination — Grade 1 | 213 | 9 |
| Headache After Month 6 Vaccination — Grade 2 | 57 | 3 |
| Headache After Month 6 Vaccination — Grade 3 | 6 | 0 |
| Headache After Month 6 Vaccination — Grade 4 | 0 | 0 |
| Headache After Month 6 Vaccination — Missing | 4 | 3 |
| Malaise/Fatigue After Month 6 Vaccination — Grade 0 | 1076 | 76 |
| Malaise/Fatigue After Month 6 Vaccination — Grade 1 | 164 | 7 |
| Malaise/Fatigue After Month 6 Vaccination — Grade 2 | 70 | 3 |
| Malaise/Fatigue After Month 6 Vaccination — Grade 3 | 9 | 0 |
| Malaise/Fatigue After Month 6 Vaccination — Grade 4 | 0 | 0 |
| Malaise/Fatigue After Month 6 Vaccination — Missing | 4 | 3 |
| Myalgia After Month 6 Vaccination — Grade 0 | 1136 | 79 |
| Myalgia After Month 6 Vaccination — Grade 1 | 124 | 5 |
| Myalgia After Month 6 Vaccination — Grade 2 | 52 | 2 |
| Myalgia After Month 6 Vaccination — Grade 3 | 7 | 0 |
| Myalgia After Month 6 Vaccination — Grade 4 | 0 | 0 |
| Myalgia After Month 6 Vaccination — Missing | 4 | 3 |
| Nausea After Month 6 Vaccination — Grade 0 | 1211 | 82 |
| Nausea After Month 6 Vaccination — Grade 1 | 77 | 2 |
| Nausea After Month 6 Vaccination — Grade 2 | 29 | 2 |
| Nausea After Month 6 Vaccination — Grade 3 | 2 | 0 |
| Nausea After Month 6 Vaccination — Grade 4 | 0 | 0 |
| Nausea After Month 6 Vaccination — Missing | 4 | 3 |
All unsolicited AEs are graded according to the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, July 2017.
| Participants | Part A (Open-label): Study Group 1 | Part A (Open Label): Study Group 2 | Part A (Open-label): Study Group 3 | Part A (Open-label): Study Group 4 |
|---|---|---|---|---|
| None | 506 | 668 | 91 | 134 |
| Mild | 16 | 7 | 1 | 2 |
| Moderate | 30 | 17 | 7 | 5 |
| Severe | 6 | 0 | 0 | 1 |
All unsolicited AEs are graded according to the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, July 2017.
| Participants | Part B (Blinded): mRNA-1273 at Month 6 | Part B (Blinded): mRNA-1273.222 at Month 6 |
|---|---|---|
| None | 1290 | 87 |
| Mild | 9 | 0 |
| Moderate | 17 | 1 |
| Severe | 5 | 1 |
| Death | 2 | 0 |
An SAE is any AE that results in any of the following outcomes: death, a life-threatening adverse event, a persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, congenital anomaly/birth defect, or is medically important.
| Participants | Part A (Open-label): Study Group 1 | Part A (Open Label): Study Group 2 | Part A (Open-label): Study Group 3 | Part A (Open-label): Study Group 4 |
|---|---|---|---|---|
| Part A: Number of Participants With Serious Adverse Events (SAEs) | 84 | 126 | 5 | 32 |
An SAE is any AE that results in any of the following outcomes: death, a life-threatening adverse event, a persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, congenital anomaly/birth defect, or is medically important.
| Participants | Part B (Blinded): mRNA-1273 at Month 6 | Part B (Blinded): mRNA-1273.222 at Month 6 |
|---|---|---|
| Part B: Number of Participants With Serious Adverse Events (SAEs) | 212 | 45 |
Adverse events of special interest (AESI) were described in Appendix L of the protocol. AESI for this protocol include but are not limited to potential immune-mediated diseases.
| Participants | Part A (Open-label): Study Group 1 | Part A (Open Label): Study Group 2 | Part A (Open-label): Study Group 3 | Part A (Open-label): Study Group 4 |
|---|---|---|---|---|
| Part A: Number of Participants With Adverse Events of Special Interest (AESIs) | 36 | 59 | 4 | 19 |
Adverse events of special interest (AESI) were described in Appendix L of the protocol. AESI for this protocol include but are not limited to potential immune-mediated diseases.
| Participants | Part B (Blinded): mRNA-1273 at Month 6 | Part B (Blinded): mRNA-1273.222 at Month 6 |
|---|---|---|
| Part B: Number of Participants With Adverse Events of Special Interest (AESIs) | 111 | 27 |
The CDC-based COVID-19 endpoint is defined as the first occurrence of symptomatic NAAT-confirmed COVID-19 based on the following criteria: 1. At least ONE of the following systemic or respiratory symptoms: Fever (≥ 38C), chills, cough, shortness of breath and/or difficulty breathing, fatigue, muscle and/or body aches \[not related to exercise\], headache, new loss of taste/smell, sore throat, congestion, runny nose, nausea, vomiting, or diarrhea, AND 2. At least ONE (post-baseline) nasal swab (or respiratory sample, if hospitalized) positive for SARS-CoV-2 by NAAT. Because additional NAAT testing was performed at Month 1 for AG1 but not AG2-1, NAAT results at Month 1 were not considered. 3. The symptom date and NAAT positive date must be within 14 days of each other. The date of a COVID-19 endpoint according to the CDC-based definition is the earlier date of a symptom and the date of positive NAAT that satisfy the criteria stated above. The CDC criteria do not require adjudication.
| Participants | Part A (Open-label): Analysis Group 1 (AG1) + Analysis Group 3 (AG3) | Part A (Open-label): Analysis Group 2-1 (AG2-1) + Analysis Group 4-1 (AG4-1) |
|---|---|---|
| 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 |
The COVE-based COVID-19 endpoint is defined as the first occurrence of adjudicated symptomatic NAAT-confirmed COVID-19 based on the following criteria (same as in the Moderna mRNA-1273 COVE trial): 1. At least TWO of the following systemic symptoms: Fever ≥ 38◦C), chills, myalgia, headache, sore throat, new loss of taste or smell, OR 2. At least ONE of the following respiratory signs/symptoms: cough, shortness of breath or difficulty breathing, OR clinical or radiographical evidence of pneumonia, AND 3. At least ONE (post-baseline) nasal swab (or respiratory sample, if hospitalized) positive for SARS-CoV-2 by NAAT. The date of a COVID-19 endpoint is the later date of a symptom and the date of positive NAAT. The COVE criteria require adjudication.
| Participants | Part A (Open-label): Analysis Group 1 (AG1) + Analysis Group 3 (AG3) | Part A (Open-label): Analysis Group 2-1 (AG2-1) + Analysis Group 4-1 (AG4-1) |
|---|---|---|
| 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 |
The COVE-based severe COVID-19 endpoint is defined as the first occurrence of a confirmed case of COVE-based COVID-19, plus any of the following: 1. Clinical signs indicative of severe systemic illness, Respiratory Rate ≥ 30 per minute, Heart Rate ≥ 125 beats per minute, SpO2 ≤ 93% on room air at sea level or PaO2/FIO2 less than 300 mm Hg, OR 2. Respiratory failure or Acute Respiratory Distress Syndrome (ARDS), (defined as needing high-flow oxygen, noninvasive or mechanical ventilation, or ECMO), evidence of shock (systolic blood pressure less than 90 mmHg, diastolic BP less than 60 mmHg or requiring vasopressors), OR 3. Significant acute renal, hepatic, or neurologic dysfunction, OR 4. Admission to an intensive care unit or death. The severe COVE criteria require adjudication.
| Participants | Part A (Open-label): Analysis Group 1 (AG1) + Analysis Group 3 (AG3) | Part A (Open-label): Analysis Group 2-1 (AG2-1) + Analysis Group 4-1 (AG4-1) |
|---|---|---|
| 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 |
The CDC-based COVID-19 endpoint is defined as the first occurrence of symptomatic NAAT-confirmed COVID-19 based on these criteria: 1. At least ONE of the following systemic or respiratory symptoms: Fever (≥ 38C), chills, cough, shortness of breath and/or difficulty breathing, fatigue, muscle and/or body aches \[not related to exercise\], headache, new loss of taste/smell, sore throat, congestion, runny nose, nausea, vomiting, or diarrhea, AND 2. At least ONE (post-baseline) nasal swab (or respiratory sample, if hospitalized) positive for SARS-CoV-2 by NAAT. 3. The symptom date and NAAT positive date must be within 14 days of each other. The date of a COVID-19 endpoint according to the CDC-based definition is the earlier date of a symptom and date of positive NAAT that satisfy the criteria stated above. The CDC criteria do not require adjudication.
| Participants | Part B (Blinded): Monovalent, Month 6 Hybrid Immunity | Part B (Blinded): Bivalent, Month 6 Hybrid Immunity |
|---|---|---|
| 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 |
The CDC-based COVID-19 endpoint is defined as the first occurrence of symptomatic NAAT-confirmed COVID-19 based on these criteria: 1. At least ONE of the following systemic or respiratory symptoms: Fever (≥ 38C), chills, cough, shortness of breath and/or difficulty breathing, fatigue, muscle and/or body aches \[not related to exercise\], headache, new loss of taste/smell, sore throat, congestion, runny nose, nausea, vomiting, or diarrhea, AND 2. At least ONE (post-baseline) nasal swab (or respiratory sample, if hospitalized) positive for SARS-CoV-2 by NAAT. 3. The symptom date and NAAT positive date must be within 14 days of each other. The date of a COVID-19 endpoint according to the CDC-based definition is the earlier date of a symptom and date of positive NAAT that satisfy the criteria stated above. The CDC criteria do not require adjudication.
| Participants | Part B (Blinded): Monovalent, Month 6 Vaccine Immunity | Part B (Blinded): Bivalent, Month 6 Vaccine Immunity |
|---|---|---|
| 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 |
Linear regression is used to provide covariate-adjusted point and 95% confidence interval estimation of geometric mean titers. Covariates adjusted are HIV status at baseline, age, sex at birth, and BMI.
| AU/ml | Part A (Open-label): Hybrid Immunity | Part A (Open-label): Vaccine Immunity | Part A (Open-label): Hybrid Immunity, PWH | Part A (Open-label): Hybrid Immunity, PWoH | Part A (Open-label): Vaccine Immunity, PWH | Part A (Open-label): Vaccine Immunity, PWoH |
|---|---|---|---|---|---|---|
| Month 0 nAb-ID50 BA.4/5 | 348 (265 to 459) | 9 (7 to 12) | 324 (219 to 477) | 372 (227 to 583) | 9 (7 to 14) | 9 (6 to 15) |
| Peak nAb-ID50 BA.4/5 | 4904 (3502 to 6846) | 705 (460 to 1065) | 5474 (3101 to 9417) | 4986 (2986 to 8350) | 996 (557 to 1726) | 326 (202 to 533) |
Linear regression is used to provide covariate-adjusted point and 95% confidence interval estimation of geometric mean titers. Covariates adjusted are HIV status at baseline, age, sex at birth, and BMI.
| AU/ml | Part A (Open-label): Hybrid Immunity | Part A (Open-label): Vaccine Immunity | Part A (Open-label): Hybrid Immunity, PWH | Part A (Open-label): Hybrid Immunity, PWoH | Part A (Open-label): Vaccine Immunity, PWH | Part A (Open-label): Vaccine Immunity, PWoH |
|---|---|---|---|---|---|---|
| Month 0 IgG N Index | 52023 (38843 to 68767) | 5978 (4191 to 8489) | 52088 (33740 to 79760) | 48473 (33007 to 71126) | 4822 (3226 to 7397) | 5977 (4926 to 7573) |
| Month 0 IgG Spike BA.5 | 17481 (13885 to 21634) | 480 (344 to 657) | 14893 (10481 to 21032) | 18066 (12261 to 25693) | 818 (546 to 1223) | 161 (129 to 196) |
| Peak IgG Spike BA.5 | 205247 (178321 to 236883) | 126285 (102488 to 156924) | 188439 (159506 to 224439) | 232660 (170309 to 314805) | 130327 (99833 to 167232) | 77390 (65364 to 93101) |
Linear regression is used to provide covariate-adjusted point and 95% confidence interval estimation of geometric mean titers. Covariates adjusted are HIV status at baseline, age, sex at birth, and BMI.
| % T-cells | Part A (Open-label): Hybrid Immunity | Part A (Open-label): Vaccine Immunity | Part A (Open-label): Hybrid Immunity, PWH | Part A (Open-label): Hybrid Immunity, PWoH |
|---|---|---|---|---|
| Month 0 CD4+ IFNg/IL2 in response to BA.4-5 N | 0.0418 (0.0352 to 0.0505) | 0.0201 (0.0159 to 0.0257) | 0.0514 (0.0359 to 0.0762) | 0.035 (0.0283 to 0.0434) |
| Month 0 CD4+ IFNg/IL2 in response to Spike BA.4/5 | 0.051 (0.0427 to 0.0601) | 0.0212 (0.0165 to 0.0272) | 0.0593 (0.0431 to 0.0804) | 0.0469 (0.0381 to 0.0573) |
| Month 0 CD4+ IFNg/IL2/CD154 in response to BA.4-5 N | 0.0568 (0.0475 to 0.068) | 0.0256 (0.0194 to 0.0342) | 0.0671 (0.0464 to 0.0998) | 0.0491 (0.0398 to 0.0609) |
| Month 0 CD4+ IFNg/IL2/CD154 in response to Spike BA.4/5 | 0.0757 (0.0638 to 0.0896) | 0.0298 (0.0226 to 0.039) | 0.0807 (0.0573 to 0.109) | 0.0737 (0.0595 to 0.0897) |
| Month 0 CD8+ IFNg/IL2 in response to BA.4-5 N | 0.025 (0.0205 to 0.0307) | 0.0149 (0.0126 to 0.0183) | 0.0229 (0.0162 to 0.0333) | 0.0264 (0.0206 to 0.0347) |
| Month 0 CD8+ IFNg/IL2 in response to Spike BA.4/5 | 0.0314 (0.0249 to 0.0401) | 0.0149 (0.0123 to 0.0183) | 0.0287 (0.0219 to 0.0384) | 0.0328 (0.0238 to 0.0459) |
Linear regression is used to provide covariate-adjusted point and 95% confidence interval estimation of geometric mean titers. Covariates adjusted are HIV status at baseline, age, sex at birth, and BMI.
| % T-cells | Part A (Open-label): Hybrid Immunity | Part A (Open-label): Vaccine Immunity | Part A (Open-label): Hybrid Immunity, PWH | Part A (Open-label): Hybrid Immunity, PWoH | Part A (Open-label): Vaccine Immunity, PWH | Part A (Open-label): Vaccine Immunity, PWoH |
|---|---|---|---|---|---|---|
| Peak CD4+ IFNg/IL2 in response to BA.4-5 N | 0.0396 (0.0339 to 0.0468) | 0.0178 (0.0145 to 0.0223) | 0.0459 (0.034 to 0.0638) | 0.0354 (0.0293 to 0.0431) | 0.0269 (0.0178 to 0.0418) | 0.0135 (0.012 to 0.0156) |
| Peak CD4+ IFNg/IL2 in response to Spike BA.4/5 | 0.2226 (0.1938 to 0.2531) | 0.2216 (0.1525 to 0.3053) | 0.2364 (0.1887 to 0.2925) | 0.214 (0.1766 to 0.2565) | 0.2463 (0.1331 to 0.4461) | 0.1704 (0.1539 to 0.1883) |
| Peak CD4+ IFNg/IL2/CD154 in response to BA.4-5 N | 0.0548 (0.0465 to 0.0639) | 0.0242 (0.0186 to 0.0314) | 0.0588 (0.0433 to 0.0801) | 0.0513 (0.0416 to 0.0631) | 0.0362 (0.023 to 0.0585) | 0.0156 (0.0137 to 0.018) |
| Peak CD4+ IFNg/IL2/CD154 in response to Spike BA.4/5 | 0.2786 (0.2454 to 0.3163) | 0.2883 (0.2077 to 0.3872) | 0.2943 (0.2404 to 0.3537) | 0.2681 (0.2217 to 0.3192) | 0.3138 (0.1734 to 0.5621) | 0.23 (0.2069 to 0.2551) |
| Peak CD8+ IFNg/IL2 in response to BA.4-5 N | 0.024 (0.0197 to 0.0296) | 0.0148 (0.0127 to 0.0181) | 0.0222 (0.0158 to 0.0322) | 0.0254 (0.0199 to 0.0321) | 0.0138 (0.0116 to 0.0171) | 0.0157 (0.0142 to 0.0179) |
| Peak CD8+ IFNg/IL2 in response to Spike BA.4/5 | 0.0481 (0.0381 to 0.061) | 0.0359 (0.0265 to 0.0478) | 0.0407 (0.0305 to 0.0552) | 0.0527 (0.0385 to 0.0733) | 0.0246 (0.0176 to 0.036) | 0.028 (0.021 to 0.0377) |
| AU/ml | Part B (Blinded): Monovalent, Month 6 Hybrid Immunity | Part B (Blinded): Monovalent, Month 6 Vaccine Immunity | Part B (Blinded): Bivalent, Month 6 Hybrid Immunity | Part B (Blinded): Bivalent, Month 6 Vaccine Immunity |
|---|---|---|---|---|
| Month 6 ID50 Titer to BA.4/5 | 750 (545.1 to 1031.9) | 1121.4 (603.5 to 2083.7) | 970.4 (709.8 to 1326.6) | 390.3 (189.6 to 803.5) |
| Month 6 ID50 Titer to XBB.1.5 | 124.8 (86 to 181.1) | 169.2 (99.5 to 287.8) | 194 (127.9 to 294.3) | 80.1 (38.9 to 164.9) |
| Month 6 ID80 Titer to BA.4/5 | 127 (97.3 to 165.7) | 174.5 (93.9 to 324.2) | 150.4 (110 to 205.6) | 72.8 (38.7 to 136.9) |
| Month 6 ID80 Titer to XBB.1.5 | 26.1 (19 to 35.9) | 34.4 (22.1 to 53.5) | 38.2 (26.5 to 55) | 21.9 (11.6 to 41.2) |
| Month 7 ID50 Titer to BA.4/5 | 2624.7 (2019.1 to 3411.9) | 2326.5 (1494.5 to 3621.6) | 4519.8 (3299.2 to 6191.9) | 1915.1 (849.9 to 4315.1) |
| Month 7 ID50 Titer to XBB.1.5 | 542.4 (375.7 to 783.1) | 607.9 (327.2 to 1129.5) | 1521.5 (1000 to 2315) | 577.6 (234.2 to 1424.4) |
| Month 7 ID80 Titer to BA.4/5 | 546.9 (420.7 to 710.9) | 511.5 (300.8 to 869.9) | 1033.6 (754.5 to 1416) | 369.3 (179.4 to 760.3) |
| Month 7 ID80 Titer to XBB.1.5 | 122.3 (84.7 to 176.6) | 126.8 (74.6 to 215.7) | 326.5 (214.6 to 496.8) | 115.5 (46.8 to 284.8) |
Participants were considered to have persistent SARS-CoV-2 NAAT positivity if they had positive swabs lasting \>= 50 days during a single infection. A single infection was assumed unless the participant had a positive NAAT following either a single negative NAAT by \>= 90 days or two consecutive negative NAATs over any time interval, in which case it was considered a reinfection. In Part A, the first NAAT+ on or before the Month 6 dose for each ppt was considered. In Part B, the first NAAT+ after the Month 6 dose for each ppt was considered. Analysis of viral evolution was not done due to termination of resources for evaluation.
| percentage of participants | Part A (Open-label): Study Group 1, Analysis Group 1 (AG1) | Part A (Open-label): Study Group 1, Analysis Group 2-2 (AG2-2) | Part A (Open-label): Study Group 2, Analysis Group 2-1 (AG2-1) | Part A (Open-label): Study Group 3, Analysis Group 3 (AG3) | Part A (Open-label): Study Group 3, Analysis Group 4-2 (AG4-2) | Part A (Open-label): Study Group 4, Analysis Group 4-1 (AG4-1) | Part B (Blinded): HIV+ Monovalent | Part B (Blinded): HIV+ Bivalent | Part B (Blinded): HIV- Monovalent | Part B (Blinded): HIV- Bivalent |
|---|---|---|---|---|---|---|---|---|---|---|
| SARS-CoV-2 Viral Persistence and Evolution Among Participants Virologically Diagnosed With SARS-CoV-2 | 2.27 (0.97 to 5.21) | 3.3 (1.85 to 5.82) | 1.17 (0.57 to 2.40) | 0 (0.00 to 12.46) | 3.85 (1.06 to 12.98) | 0.76 (0.13 to 4.17) | 1.31 (0.45 to 3.78) | 0 (0.00 to 1.88) | 0 (0.00 to 6.53) | 0 (0.00 to 7.71) |
Collected over Solicited AEs were collected for 7 days following each vaccination. Unsolicited AEs were collected for 28 days following each vaccination. Serious AEs were collected until end of follow up (up to 18 months).. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Part A (Open-label): Study Group 1 | 24/3,740 (0.6%) | 84/3,740 (2.2%) | 308/558 (55.2%) |
| Part A (Open Label): Study Group 2 | 31/7,941 (0.4%) | 126/7,941 (1.6%) | 270/692 (39%) |
| Part A (Open-label): Study Group 3 | 1/648 (0.2%) | 5/648 (0.8%) | 47/99 (47.5%) |
| Part A (Open-label): Study Group 4 | 9/1,672 (0.5%) | 32/1,672 (1.9%) | 62/142 (43.7%) |
| Part B (Blinded): mRNA-1273 at Month 6 | 63/11,243 (0.6%) | 212/11,243 (1.9%) | 450/1,323 (34%) |
| Part B (Blinded): mRNA-1273.222 at Month 6 | 19/2,012 (0.9%) | 45/2,012 (2.2%) | 15/89 (16.9%) |
| Event | Part A (Open-label): Study Group 1 | Part A (Open Label): Study Group 2 | Part A (Open-label): Study Group 3 | Part A (Open-label): Study Group 4 | Part B (Blinded): mRNA-1273 at Month 6 | Part B (Blinded): mRNA-1273.222 at Month 6 |
|---|---|---|---|---|---|---|
| PneumoniaInfections and infestations | 9/3740 | 6/7941 | 0/648 | 3/1672 | 13/11243 | 2/2012 |
| DeathGeneral disorders | 1/3740 | 2/7941 | 0/648 | 0/1672 | 13/11243 | 4/2012 |
| Diabetic ketoacidosisMetabolism and nutrition disorders | 0/3740 | 2/7941 | 0/648 | 3/1672 | 2/11243 | 0/2012 |
| Necrotising fasciitisInfections and infestations | 0/3740 | 0/7941 | 1/648 | 0/1672 | 0/11243 | 0/2012 |
| Ankle fractureInjury, poisoning and procedural complications | 1/3740 | 0/7941 | 1/648 | 0/1672 | 4/11243 | 1/2012 |
| Wrist fractureInjury, poisoning and procedural complications | 0/3740 | 0/7941 | 1/648 | 0/1672 | 1/11243 | 0/2012 |
| Systemic lupus erythematosusMusculoskeletal and connective tissue disorders | 0/3740 | 0/7941 | 1/648 | 0/1672 | 0/11243 | 1/2012 |
| Brain oedemaNervous system disorders | 0/3740 | 0/7941 | 1/648 | 0/1672 | 0/11243 | 0/2012 |
| Intentional self-injuryPsychiatric disorders | 0/3740 | 3/7941 | 1/648 | 0/1672 | 2/11243 | 0/2012 |
| Pulmonary tuberculosisInfections and infestations | 2/3740 | 12/7941 | 0/648 | 1/1672 | 8/11243 | 1/2012 |
| Event | Part A (Open-label): Study Group 1 | Part A (Open Label): Study Group 2 | Part A (Open-label): Study Group 3 | Part A (Open-label): Study Group 4 | Part B (Blinded): mRNA-1273 at Month 6 | Part B (Blinded): mRNA-1273.222 at Month 6 |
|---|---|---|---|---|---|---|
| Pain (Solicited)General disorders | 221/558 | 173/692 | 34/99 | 46/142 | 309/1323 | 10/89 |
| Headache (Solicited)Nervous system disorders | 182/558 | 134/692 | 25/99 | 36/142 | 276/1323 | 12/89 |
| Fatigue (Solicited)General disorders | 178/558 | 133/692 | 27/99 | 33/142 | 243/1323 | 10/89 |
| Myalgia (Solicited)Musculoskeletal and connective tissue disorders | 130/558 | 85/692 | 18/99 | 24/142 | 183/1323 | 7/89 |
| Arthralgia (Solicited)Musculoskeletal and connective tissue disorders | 112/558 | 70/692 | 17/99 | 15/142 | 137/1323 | 6/89 |
| Nausea (Solicited)Gastrointestinal disorders | 82/558 | 58/692 | 13/99 | 11/142 | 108/1323 | 4/89 |
| Chills (Solicited)General disorders | 82/558 | 52/692 | 12/99 | 8/142 | 111/1323 | 4/89 |
| Swelling (Solicited)General disorders | 72/558 | 55/692 | 4/99 | 17/142 | 65/1323 | 3/89 |
| Lymphadenopathy (Solicited)Blood and lymphatic system disorders | 64/558 | 34/692 | 9/99 | 10/142 | 84/1323 | 2/89 |
| Erythema (Solicited)Skin and subcutaneous tissue disorders | 33/558 | 20/692 | 5/99 | 12/142 | 37/1323 | 1/89 |
Overall SARS-CoV-2 neg indicates all anti-Spike (anti-S), anti-Nucleocapsid (anti-N), and virus detection (NAAT) neg. Overall SARS-CoV-2 pos indicates one of anti-S, anti-N, or NAAT pos. Only anti-S is used to determine study groups (SG) in the Participant Flow table. Anti-S, anti-N, and NAAT are used to determine analysis groups (AG) for analyses. SG1 (anti-S neg) includes AG1 (overall neg) and AG2-2 (overall pos). SG3 (anti-S neg) includes AG3 (overall neg) and AG4-2 (overall pos).
| Age, Continuous(years) | Part A (Open-label): Study Group 1, Analysis Group 1 (AG1) | Part A (Open-label): Study Group 1, Analysis Group 2-2 (AG2-2) | Part A (Open-label): Study Group 2, Analysis Group 2-1 (AG2-1) | Part A (Open-label): Study Group 3, Analysis Group 3 (AG3) | Part A (Open-label): Study Group 3, Analysis Group 4-2 (AG4-2) | Part A (Open-label): Study Group 4, Analysis Group 4-1 (AG4-1) | Total |
|---|---|---|---|---|---|---|---|
| Median | 39 (18 to 76) | 40 (18 to 73) | 39 (18 to 79) | 34 (19 to 84) | 39 (18 to 82) | 34 (18 to 86) | 39 (18 to 86) |
| Age, Customized(Participants) | Part A (Open-label): Study Group 1, Analysis Group 1 (AG1) | Part A (Open-label): Study Group 1, Analysis Group 2-2 (AG2-2) | Part A (Open-label): Study Group 2, Analysis Group 2-1 (AG2-1) | Part A (Open-label): Study Group 3, Analysis Group 3 (AG3) | Part A (Open-label): Study Group 3, Analysis Group 4-2 (AG4-2) | Part A (Open-label): Study Group 4, Analysis Group 4-1 (AG4-1) | Total |
|---|---|---|---|---|---|---|---|
| <=40 years | 1388 | 681 | 4484 | 260 | 136 | 1099 | 8048 |
| > years | 1088 | 583 | 3457 | 131 | 121 | 573 | 5953 |
| Sex: Female, Male(Participants) | Part A (Open-label): Study Group 1, Analysis Group 1 (AG1) | Part A (Open-label): Study Group 1, Analysis Group 2-2 (AG2-2) | Part A (Open-label): Study Group 2, Analysis Group 2-1 (AG2-1) | Part A (Open-label): Study Group 3, Analysis Group 3 (AG3) | Part A (Open-label): Study Group 3, Analysis Group 4-2 (AG4-2) | Part A (Open-label): Study Group 4, Analysis Group 4-1 (AG4-1) | Total |
|---|---|---|---|---|---|---|---|
| Female | 1676 | 911 | 6407 | 100 | 108 | 909 | 10111 |
| Male | 800 | 353 | 1534 | 291 | 149 | 763 | 3890 |
| Ethnicity (NIH/OMB)(Participants) | Part A (Open-label): Study Group 1, Analysis Group 1 (AG1) | Part A (Open-label): Study Group 1, Analysis Group 2-2 (AG2-2) | Part A (Open-label): Study Group 2, Analysis Group 2-1 (AG2-1) | Part A (Open-label): Study Group 3, Analysis Group 3 (AG3) | Part A (Open-label): Study Group 3, Analysis Group 4-2 (AG4-2) | Part A (Open-label): Study Group 4, Analysis Group 4-1 (AG4-1) | Total |
|---|---|---|---|---|---|---|---|
| Hispanic or Latino | 1 | 0 | 1 | 0 | 0 | 0 | 2 |
| Not Hispanic or Latino | 2475 | 1264 | 7940 | 391 | 257 | 1672 | 13999 |
| Unknown or Not Reported | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Race/Ethnicity, Customized(Participants) | Part A (Open-label): Study Group 1, Analysis Group 1 (AG1) | Part A (Open-label): Study Group 1, Analysis Group 2-2 (AG2-2) | Part A (Open-label): Study Group 2, Analysis Group 2-1 (AG2-1) | Part A (Open-label): Study Group 3, Analysis Group 3 (AG3) | Part A (Open-label): Study Group 3, Analysis Group 4-2 (AG4-2) | Part A (Open-label): Study Group 4, Analysis Group 4-1 (AG4-1) | Total |
|---|---|---|---|---|---|---|---|
| American Indian or Alaska Native | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Asian | 0 | 1 | 1 | 0 | 1 | 2 | 5 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Black or African American | 2433 | 1248 | 7848 | 358 | 233 | 1574 | 13694 |
| White | 0 | 0 | 1 | 4 | 0 | 0 | 5 |
| More than one race | 43 | 15 | 91 | 29 | 23 | 96 | 297 |
| Unknown or Not Reported | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Region of Enrollment(Participants) | Part A (Open-label): Study Group 1, Analysis Group 1 (AG1) | Part A (Open-label): Study Group 1, Analysis Group 2-2 (AG2-2) | Part A (Open-label): Study Group 2, Analysis Group 2-1 (AG2-1) | Part A (Open-label): Study Group 3, Analysis Group 3 (AG3) | Part A (Open-label): Study Group 3, Analysis Group 4-2 (AG4-2) | Part A (Open-label): Study Group 4, Analysis Group 4-1 (AG4-1) | Total |
|---|---|---|---|---|---|---|---|
| Eswatini | 53 | 19 | 130 | 1 | 0 | 6 | 209 |
| Malawi | 188 | 44 | 408 | 1 | 0 | 1 | 642 |
| Botswana | 22 | 20 | 30 | 13 | 7 | 27 | 119 |
| South Africa | 1530 | 808 | 5438 | 337 | 212 | 1463 | 9788 |
| Uganda | 191 | 93 | 796 | 17 | 16 | 71 | 1184 |
| Zambia | 257 | 179 | 584 | 7 | 14 | 74 | 1115 |
| Kenya | 235 | 101 | 555 | 15 | 8 | 30 | 944 |
PDFs hosted by the registry, ClinicalTrials.gov.
Ran from Dec 2021 to primary completion in Apr 2024, 28 months.
Results were first posted in Nov 2025, 1 year 7 months after primary completion.
Of 95 non-industry phase 2/3 interventional studies under COVID-19, half reached primary completion within 11 months of starting (the median), counting those still running; a quarter within 5 and three quarters within 22. This study's 28 months is above that.
Counting every sponsor, half of 168 studies reached it within 11 months; a quarter within 5 and three quarters within 19.
How these figures are worked out, and which studies are left out of them.
This study is completed, as verified in Apr 2026. You cannot join it, but the record below documents what was studied.
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