Efficacy Study of COVID-19 mRNA Vaccine in Regions With SARS-CoV-2 Variants of Concern (CoVPN3008)

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

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.

Study Overview

• Status: Completed
• Conditions: HIV Infections; COVID-19; SARS-CoV-2 Infection
• Intervention / Treatment: Biological: Moderna mRNA-1273; Biological: Moderna mRNA-1273.222; Biological: Vaccine 3 Dose; Biological: Vaccine 2 Dose

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 14237
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Botswana
  • Gaborone, Botswana
    • Gaborone CRS
• Eswatini
  • Hhohho Region
    • Mbabane, Hhohho Region, Eswatini
      • Eswatini Prevention Center CRS
• Kenya
  • Eldoret, Kenya
    • Moi University Clinical Research Centre
  • Kisumu, Kenya, 40100
    • Kisumu - Kombewa CRS
  • Kisumu, Kenya
    • Kisumu Crs
• Malawi
  • Blantyre, Malawi
    • Blantyre CRS
  • Lilongwe, Malawi
    • Malawi CRS
• South Africa
  • Elandsdoorn, South Africa
    • Ndlovu Research Centre CoVPN CRS
  • Johannesburg, South Africa
    • Kliptown Soweto CRS
  • Klerksdorp, South Africa
    • PHRU Matlosana CRS
  • Welkom, South Africa
    • MERC Welkom
  • Eastern Cape
    • East London, Eastern Cape, South Africa
      • Synergy Biomed Research Institute
    • Mthatha, Eastern Cape, South Africa
      • Nelson Mandela Academic Research Unit CRS
    • Port Elizabeth, Eastern Cape, South Africa
      • PHOENIX Pharma (Pty) Ltd
  • Free State
    • Bloemfontein, Free State, South Africa
      • Josha Resarch CRS
  • Gauteng
    • Ga-Rankuwa, Gauteng, South Africa
      • MeCRU CRS
    • Johannesburg, Gauteng, South Africa
      • Clinical HIV Research Unit (CHRU)/ Helen Joseph CRS
    • Johannesburg, Gauteng, South Africa
      • Newtown Clinical Research
    • Johannesburg, Gauteng, South Africa
      • Soweto - Bara CRS
    • Johannesburg, Gauteng, South Africa
      • Wits RHI Ward 21 CRS
    • Pretoria, Gauteng, South Africa
      • MERC Kempton Park
    • Pretoria, Gauteng, South Africa
      • Synexus Stanza Clinical Research Centre (CRS)
    • Tembisa, Gauteng, South Africa
      • Tembisa Clinic 4 CoVPN CRS
  • KwaZulu-Natal
    • Durban, KwaZulu-Natal, South Africa
      • CAPRISA eThekwini CRS
    • Durban, KwaZulu-Natal, South Africa
      • Tongaat CRS
    • Durban, KwaZulu-Natal, South Africa
      • Vulindlela CRS
    • Isipingo, KwaZulu-Natal, South Africa
      • Isipingo CRS
    • Ladysmith, KwaZulu-Natal, South Africa
      • Qhakaza Mbokodo Research Clinic CRS
  • Mpumalanga
    • Middelburg, Mpumalanga, South Africa
      • MERC Middelburg
  • North West
    • Klerksdorp, North West, South Africa
      • Aurum Institute Klerksdorp CRS
    • Rustenburg, North West, South Africa
      • Rustenburg CRS
  • Western Cape
    • Cape Town, Western Cape, South Africa
      • Emavundleni CRS
    • Cape Town, Western Cape, South Africa
      • FAM-CRU (Family Clinical Research Unit)
    • Cape Town, Western Cape, South Africa
      • Groote Schuur HIV CRS
    • Cape Town, Western Cape, South Africa
      • Masiphumelele Clinical Research Site (MASI) CRS
    • Cape Town, Western Cape, South Africa
      • TASK Central
    • Cape Town, Western Cape, South Africa
      • Univeristy of Cape Town Lung CRS Institute
    • George, Western Cape, South Africa
      • TASK Eden
    • Stellenbosch, Western Cape, South Africa
      • Synexus Helderberg
• Uganda
  • Entebbe, Uganda
    • UVRI-IAVI HIV Vaccine Program LTD. CRS
  • Kampala, Uganda
    • Joint Clinical Research Centre
  • Kampala, Uganda
    • MU-JHU Research Collaboration CRS
  • Kampala, Uganda
    • Baylor-Uganda CRS
• Zambia
  • Lusaka, Zambia
    • Matero Reference Clinic CRS
  • Lusaka, Zambia
    • Cfhrz Crs
  • Lusaka, Zambia
    • UNC Global Projects / Kamwala District Health Centre
  • Ndola, Zambia
    • Zambia Emory HIV Research Project - Ndola CoVPN CRS

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

General and Demographic Criteria

1. 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
2. Willingness to be followed and remain in the catchment area for the planned duration of the study.
3. Ability and willingness to provide informed consent.
4. 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.
5. 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.
6. 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

1. 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.

2. History of angioedema or anaphylaxis.

   Vaccines and other injections

3. Prior receipt of a SARS-CoV-2 vaccine.
4. 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).
5. 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).
6. 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).
7. Blood products, systemic immunoglobulins, or monoclonal antibodies (including against SARS-CoV-2) received within 90 days before first vaccination.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Study Group 1; 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; 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).; Biological: Moderna mRNA-1273.222; 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).; Biological: Vaccine 3 Dose; COVID-19 mRNA vaccine in 100 mcg dose given as IM injection into the deltoid muscle on Months 0, 1, and 6.
Experimental: Study Group 2; 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; 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).; Biological: Moderna mRNA-1273.222; 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).; Biological: Vaccine 2 Dose; COVID-19 mRNA vaccine is to be administered as IM injection into the deltoid muscle on Months 0 and 6.
Experimental: Study Group 3; 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; 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).; Biological: Moderna mRNA-1273.222; 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).; Biological: Vaccine 3 Dose; COVID-19 mRNA vaccine in 100 mcg dose given as IM injection into the deltoid muscle on Months 0, 1, and 6.
Experimental: Study Group 4; 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; 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).; Biological: Moderna mRNA-1273.222; 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).; Biological: Vaccine 2 Dose; COVID-19 mRNA vaccine is to be administered as IM injection into the deltoid muscle on Months 0 and 6.
Experimental: Monovalent; 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; 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).
Experimental: Bivalent; 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-1273.222) 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).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	Day of Month 6 vaccination up to Month 18

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	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.	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.	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.	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.	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.	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.	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.	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		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.	Participants testing positive for SARS-CoV-2 had additional nasab swabs taken fortnightly until testing negative, up to a maximum of 18 months

Collaborators and Investigators

• Sponsor: COVID-19 Prevention Network
• Collaborators: National Institute of Allergy and Infectious Diseases (NIAID); Medical Research Council, South Africa
• Investigators: Study Chair: Nigel Garrett, Centre for the AIDS Programme of Research in South Africa (CAPRISA); Study Chair: Philip Kotze, Qhakaza Mbokodo Research Clinic; Study Chair: Sufia Dadabhai, Blantyre CRS / Johns Hopkins Research Project; Study Chair: Nyaradzo Mgodi, University of Zimbabwe Clinical Trials Research Centre

Publications and helpful links

General Publications

• Garrett N, Tapley A, Hudson A, Dadabhai S, Zhang B, Mgodi NM, Andriesen J, Takalani A, Fisher LH, Kee JJ, Magaret CA, Villaran M, Hural J, Andersen-Nissen E, Ferarri G, Miner MD, Le Roux B, Wilkinson E, Lessells R, de Oliveira T, Odhiambo J, Shah P, Polakowski L, Yacovone M, Samandari T, Chirenje Z, Elyanu PJ, Makhema J, Kamuti E, Nuwagaba-Biribonwoha H, Badal-Faesen S, Brumskine W, Coetzer S, Dawson R, Delany-Moretlwe S, Diacon AH, Fry S, Gill KM, Ebrahim Hoosain ZA, Hosseinipour MC, Inambao M, Innes C, Innes S, Kalonji D, Kasaro M, Kassim P, Kayange N, Kilembe W, Laher F, Malahleha M, Maluleke VL, Mboya G, McHarry K, Mitha E, Mngadi K, Mda P, Moloantoa T, Mutuluuza CK, Naicker N, Naicker V, Nana A, Nanvubya A, Nchabeleng M, Otieno W, Potgieter EL, Potloane D, Punt Z, Said J, Singh Y, Tayob MS, Vahed Y, Wabwire DO, McElrath MJ, Kublin JG, Bekker LG, Gilbert PB, Corey L, Gray GE, Huang Y, Kotze P; CoVPN 3008 Ubuntu Study Team. Hybrid versus vaccine immunity of mRNA-1273 among people living with HIV in East and Southern Africa: a prospective cohort analysis from the multicentre CoVPN 3008 (Ubuntu) study. EClinicalMedicine. 2025 Jan 20;80:103054. doi: 10.1016/j.eclinm.2024.103054. eCollection 2025 Feb.

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2021
• Primary Completion (Actual): April 19, 2024
• Study Completion (Actual): April 19, 2024

Study Registration Dates

• First Submitted: December 21, 2021
• First Submitted That Met QC Criteria: December 21, 2021
• First Posted (Actual): December 23, 2021

Study Record Updates

• Last Update Posted (Actual): April 21, 2026
• Last Update Submitted That Met QC Criteria: April 9, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: SARS-CoV-2; HIV; COVID-19
• Additional Relevant MeSH Terms: Blood-Borne Infections; Urogenital Diseases; Genital Diseases; Immune System Diseases; Respiratory Tract Infections; Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases; Lung Diseases; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Pneumonia, Viral; Pneumonia; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; COVID-19; HIV Infections; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Biological Products; Complex Mixtures; Viral Vaccines; mRNA Vaccines; Nucleic Acid-Based Vaccines; Vaccines, Synthetic; Recombinant Proteins; COVID-19 Vaccines; Antigens; Vaccines; 2019-nCoV Vaccine mRNA-1273
• Other Study ID Numbers: CoVPN 3008; UM1AI068614 (U.S. NIH Grant/Contract)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes