Efficacy Study of COVID-19 mRNA Vaccine in Regions With SARS-CoV-2 Variants of Concern

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Multi-Center, Randomized, Efficacy Study of COVID-19 mRNA Vaccine in Regions With SARS-CoV-2 Variants of Concern

Conditions
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SARS-CoV-2 Infection, HIV Infections, COVID-19

Intervention / Treatment
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* Biological: Moderna mRNA-1273
* Biological: Vaccine 3 Dose
* Biological: Vaccine 2 Dose


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1<br>This arm will assess the relative vaccine efficacy (RVE) of a 3- vs. 2-dose COVID-19 mRNA vaccine regimen to prevent virologically confirmed, symptomatic COVID-19 in adult people living with HIV who are SARS-CoV-2 negative at baseline. | Biological: Moderna mRNA-1273<br>* 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).<br>Biological: Vaccine 3 Dose<br>* COVID-19 mRNA vaccine in 100 mcg dose given as IM injection into the deltoid muscle on Day 1, Day 29, and Day 169.<br>|
| Experimental: Group 2<br>This arm will assess the relative vaccine efficacy (RVE) of a 2- vs. 1-dose COVID-19 mRNA vaccine regimen to prevent virologically confirmed symptomatic COVID-19 in adult people living with HIV who are SARS-CoV-2 positive at baseline. | Biological: Moderna mRNA-1273<br>* 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).<br>Biological: Vaccine 2 Dose<br>* COVID-19 mRNA vaccine is to be administered as IM injection into the deltoid muscle on Day 1 and Day 169.<br>|
| Experimental: Group 3<br>This arm will assess the relative vaccine efficacy (RVE) of a 3- vs. 2-dose COVID-19 mRNA vaccine regimen to prevent virologically confirmed, symptomatic COVID-19 in HIV negative adults who are SARS-CoV-2 negative at baseline. | Biological: Moderna mRNA-1273<br>* 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).<br>Biological: Vaccine 3 Dose<br>* COVID-19 mRNA vaccine in 100 mcg dose given as IM injection into the deltoid muscle on Day 1, Day 29, and Day 169.<br>|
| Experimental: Group 4<br>This arm will assess the relative vaccine efficacy (RVE) of a 2- vs. 1-dose COVID-19 mRNA vaccine regimen to prevent virologically confirmed symptomatic COVID-19 in HIV negative adults who are SARSCoV-2 positive at baseline. | Biological: Moderna mRNA-1273<br>* 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).<br>Biological: Vaccine 2 Dose<br>* COVID-19 mRNA vaccine is to be administered as IM injection into the deltoid muscle on Day 1 and Day 169.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Positive result of acute SARS-CoV-2 infection | Assessed by nucleic acid amplification testing (NAAT) of a nasal swab, plus clinical signs indicative of severe systemic illness or respiratory failure; or Acute Respiratory Distress Syndrome (ARDS); or significant acute renal, hepatic or neurologic dysfunction; or admission to an intensive care unit or death | Measured 1 day after Month 0 dose until Month 6 dose | 
| Positive result of Severe COVID-19 | Assessed by nucleic acid amplification testing (NAAT) of a nasal swab, plus clinical signs indicative of severe systemic illness or respiratory failure; or Acute Respiratory Distress Syndrome (ARDS); or significant acute renal, hepatic or neurologic dysfunction; or admission to an intensive care unit or death | Measured 1 day after Month 0 dose until Month 6 dose | 
| Positive result of acute SARS-CoV-2 infection | Assessed by nucleic acid amplification testing (NAAT) of a nasal swab, plus clinical signs indicative of severe systemic illness or respiratory failure; or Acute Respiratory Distress Syndrome (ARDS); or significant acute renal, hepatic or neurologic dysfunction; or admission to an intensive care unit or death | Measured least 14 days after the Month 6 dose, through study completion, an average of 1 year | 
| Positive result of Severe COVID-19 | Assessed by nucleic acid amplification testing (NAAT) of a nasal swab, plus clinical signs indicative of severe systemic illness or respiratory failure; or Acute Respiratory Distress Syndrome (ARDS); or significant acute renal, hepatic or neurologic dysfunction; or admission to an intensive care unit or death | Measured least 14 days after the Month 6 dose, through study completion, an average of 1 year | 
| Number of Adverse events | Positive result of acute SARS-CoV-2 infection assessed by nucleic acid amplification testing (NAAT) of a nasal swab, plus clinical signs indicative of severe systemic illness or respiratory failure; or Acute Respiratory Distress Syndrome (ARDS); or significant acute renal, hepatic or neurologic dysfunction; or admission to an intensive care unit or death | Measured both pre-Month 6 and post-Month 6 stages | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Positive result of acute and severe SARS-CoV-2 infection | Assessed by nucleic acid amplification testing (NAAT) of a nasal swab, plus clinical signs indicative of severe systemic illness or respiratory failure; or Acute Respiratory Distress Syndrome (ARDS); or significant acute renal, hepatic or neurologic dysfunction; or admission to an intensive care unit or death | Measured at least 14 days after the last pre-Month 6 dose until the Month 6 dose | 
| Positive result of acute and severe SARS-CoV-2 infection | Assessed by nucleic acid amplification testing (NAAT) of a nasal swab, plus clinical signs indicative of severe systemic illness or respiratory failure; or Acute Respiratory Distress Syndrome (ARDS); or significant acute renal, hepatic or neurologic dysfunction; or admission to an intensive care unit or death | Measured starting 1 day after dose 1 through 14 days after the last pre-Month 6 dose until the Month 6 dose. | 
| Positive result of acute and severe SARS-CoV-2 infection | Assessed by nucleic acid amplification testing (NAAT) of a nasal swab, plus clinical signs indicative of severe systemic illness or respiratory failure; or Acute Respiratory Distress Syndrome (ARDS); or significant acute renal, hepatic or neurologic dysfunction; or admission to an intensive care unit or death | Measured at least 14 days after Month 6 injection | 
| Positive result of acute and severe SARS-CoV-2 infection | Assessed by nucleic acid amplification testing (NAAT) of a nasal swab, plus clinical signs indicative of severe systemic illness or respiratory failure; or Acute Respiratory Distress Syndrome (ARDS); or significant acute renal, hepatic or neurologic dysfunction; or admission to an intensive care unit or death | Measured at least 14 days after the Month 6 dose, through study completion, an average of 1 year | 
| Positive result of acute and severe SARS-CoV-2 infection | Positive result of acute SARS-CoV-2 infection assessed by nucleic acid amplification testing (NAAT) of a nasal swab, plus clinical signs indicative of severe systemic illness or respiratory failure; or Acute Respiratory Distress Syndrome (ARDS); or significant acute renal, hepatic or neurologic dysfunction; or admission to an intensive care unit or death | Measured least 14 days after the Month 6 dose, through study completion, an average of 1 year | 
| Number of SARS-CoV-2 infection | Measured by neutralization phenotypes and viral genotypic characteristics of SARS-CoV-2 at diagnosis. | Measured at 1 day after dose 1, 14 days after the last pre-Month6 dose , or 14 days after Month 6 dose, through study completion, an average of 1 year | 
| Number of SARS-CoV-2 infection | SARS-CoV-2 infection diagnosed by seroconversion throughout the study | Measured at starting 1 day after dose 1, 14 days after the last pre-Month 6 dose , or 14 days after Month 6 dose, through study completion, an average of 1 year | 
| Positive result of acute and severe SARS-CoV-2 infection | SARS-CoV-2 infection diagnosed by seroconversion in the absence of symptoms | Measured at starting 1 day after dose 1, 14 days after the last dose before Month 6 dose, or 14 days after Month 6 dose through study completion, an average of 1 year | 
| Number of SARS-CoV-2 infection | Positive result of acute SARS-CoV-2 infection assessed by nucleic acid amplification testing (NAAT) of a nasal swab, plus clinical signs indicative of severe systemic illness or respiratory failure; or Acute Respiratory Distress Syndrome (ARDS); or significant acute renal, hepatic or neurologic dysfunction; or admission to an intensive care unit or death. | Measured at starting 1 day after dose 1 or 14 days after the last dose before Month 6 dose through study completion, an average of 1 year | 
| Number of SARS-CoV-2 infection | SARS-CoV-2 viral load (as inferred from RT-PCR cycle threshold values) | Through study completion after Dose 1 vaccination, an average of 1 year | 
| Number of SARS-CoV-2 infection | Viral whole genome sequences | Through study completion after Dose 1 vaccination, an average of 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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SARS-CoV-2, HIV, COVID-19