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

HIV Infections Clinical Trial

— CoVPN3008  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05168813
• Other study ID #: CoVPN 3008
• Secondary ID: UM1AI068614
• Status: Completed
• Phase: Phase 2/Phase 3
• Start date: December 1, 2021
• Est. completion date: April 19, 2024

Study information

• Verified date: May 2024
• Source: COVID-19 Prevention Network
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The study will evaluate the clinical efficacy of different dosing regimens of the Moderna COVID-19 mRNA vaccine (100 mcg) in preventing COVID-19 disease in people who are living with HIV or have comorbidities associated with elevated risk of severe COVID-19, with the different vaccine regimens assessed determined by whether the participant had evidence of prior SARS-CoV-2 infection at enrollment.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 14232
• Est. completion date: April 19, 2024
• Est. primary completion date: April 19, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Communicable Diseases
• COVID-19
• HIV Infections
• Infections
• SARS-CoV-2 Infection

Intervention

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).
• Vaccine 3 Dose
COVID-19 mRNA vaccine in 100 mcg dose given as IM injection into the deltoid muscle on Day 1, Day 29, and Day 169.
• Vaccine 2 Dose
COVID-19 mRNA vaccine is to be administered as IM injection into the deltoid muscle on Day 1 and Day 169.

Locations

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

Sponsors (3)

Lead Sponsor	Collaborator
COVID-19 Prevention Network	Medical Research Council, South Africa, National Institute of Allergy and Infectious Diseases (NIAID)

Countries where clinical trial is conducted

Botswana,  Kenya,  Malawi,  South Africa,  Swaziland,  Uganda,  Zambia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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	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
Secondary	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.
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Number of SARS-CoV-2 infection	Viral whole genome sequences	Through study completion after Dose 1 vaccination, an average of 1 year