Clinical trial NCT05168813: Efficacy Study of COVID-19 mRNA Vaccine in Regions With SARS-CoV-2 Variants of Concern
Official title: Multi-Center, Randomized, Efficacy Study of COVID-19 mRNA Vaccine in Regions With SARS-CoV-2 Variants of Concern
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: SARS-CoV-2 Infection
HIV Infections
COVID-19
Keywords: SARS-CoV-2
HIV
COVID-19
Lead sponsor: COVID-19 Prevention Network
Sponsor class: NETWORK
Collaborators: name: National Institute of Allergy and Infectious Diseases (NIAID)
name: Medical Research Council, South Africa
First posted: 2021-12-23
Enrollment: 14232
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Positive result of acute SARS-CoV-2 infection
timeFrame: Measured 1 day after Month 0 dose until Month 6 dose
measure: Positive result of Severe COVID-19
timeFrame: Measured 1 day after Month 0 dose until Month 6 dose
measure: Positive result of acute SARS-CoV-2 infection
timeFrame: Measured least 14 days after the Month 6 dose, through study completion, an average of 1 year
measure: Positive result of Severe COVID-19
timeFrame: Measured least 14 days after the Month 6 dose, through study completion, an average of 1 year
measure: Number of Adverse events
timeFrame: Measured both pre-Month 6 and post-Month 6 stages
Secondary outcomes:
measure: Positive result of acute and severe SARS-CoV-2 infection
timeFrame: Measured at least 14 days after the last pre-Month 6 dose until the Month 6 dose
measure: Positive result of acute and severe SARS-CoV-2 infection
timeFrame: Measured starting 1 day after dose 1 through 14 days after the last pre-Month 6 dose until the Month 6 dose.
measure: Positive result of acute and severe SARS-CoV-2 infection
timeFrame: Measured at least 14 days after Month 6 injection
measure: Positive result of acute and severe SARS-CoV-2 infection
timeFrame: Measured at least 14 days after the Month 6 dose, through study completion, an average of 1 year
measure: Positive result of acute and severe SARS-CoV-2 infection
timeFrame: Measured least 14 days after the Month 6 dose, through study completion, an average of 1 year
measure: Number of SARS-CoV-2 infection
timeFrame: 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
measure: Number of SARS-CoV-2 infection
timeFrame: 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
measure: Positive result of acute and severe SARS-CoV-2 infection
timeFrame: 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
measure: Number of SARS-CoV-2 infection
timeFrame: 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
measure: Number of SARS-CoV-2 infection
timeFrame: Through study completion after Dose 1 vaccination, an average of 1 year
measure: Number of SARS-CoV-2 infection
timeFrame: Through study completion after Dose 1 vaccination, an average of 1 year
Other outcomes:
Locations:
city: Gaborone
country: Botswana
facility: Gaborone CRS
city: Eldoret
country: Kenya
facility: Moi University Clinical Research Centre
city: Kisumu
country: Kenya
facility: Kisumu - Kombewa CRS
city: Kisumu
country: Kenya
facility: Kisumu Crs
city: Blantyre
country: Malawi
facility: Blantyre CRS
city: Lilongwe
country: Malawi
facility: Malawi CRS
city: East London
country: South Africa
facility: Synergy Biomed Research Institute
state: Eastern Cape
city: Mthatha
country: South Africa
facility: Nelson Mandela Academic Research Unit CRS
state: Eastern Cape
city: Port Elizabeth
country: South Africa
facility: PHOENIX Pharma (Pty) Ltd
state: Eastern Cape
city: Bloemfontein
country: South Africa
facility: Josha Resarch CRS
state: Free State
city: Ga-Rankuwa
country: South Africa
facility: MeCRU CRS
state: Gauteng
city: Johannesburg
country: South Africa
facility: Clinical HIV Research Unit (CHRU)/ Helen Joseph CRS
state: Gauteng
city: Johannesburg
country: South Africa
facility: Newtown Clinical Research
state: Gauteng
city: Johannesburg
country: South Africa
facility: Soweto - Bara CRS
state: Gauteng
city: Johannesburg
country: South Africa
facility: Wits RHI Ward 21 CRS
state: Gauteng
city: Pretoria
country: South Africa
facility: MERC Kempton Park
state: Gauteng
city: Pretoria
country: South Africa
facility: Synexus Stanza Clinical Research Centre (CRS)
state: Gauteng
city: Tembisa
country: South Africa
facility: Tembisa Clinic 4 CoVPN CRS
state: Gauteng
city: Durban
country: South Africa
facility: CAPRISA eThekwini CRS
state: KwaZulu-Natal
city: Durban
country: South Africa
facility: Tongaat CRS
state: KwaZulu-Natal
city: Durban
country: South Africa
facility: Vulindlela CRS
state: KwaZulu-Natal
city: Isipingo
country: South Africa
facility: Isipingo CRS
state: KwaZulu-Natal
city: Ladysmith
country: South Africa
facility: Qhakaza Mbokodo Research Clinic CRS
state: KwaZulu-Natal
city: Middelburg
country: South Africa
facility: MERC Middelburg
state: Mpumalanga
city: Klerksdorp
country: South Africa
facility: Aurum Institute Klerksdorp CRS
state: North West
city: Rustenburg
country: South Africa
facility: Rustenburg CRS
state: North West
city: Cape Town
country: South Africa
facility: Emavundleni CRS
state: Western Cape
city: Cape Town
country: South Africa
facility: FAM-CRU (Family Clinical Research Unit)
state: Western Cape
city: Cape Town
country: South Africa
facility: Groote Schuur HIV CRS
state: Western Cape
city: Cape Town
country: South Africa
facility: Masiphumelele Clinical Research Site (MASI) CRS
state: Western Cape
city: Cape Town
country: South Africa
facility: TASK Central
state: Western Cape
city: Cape Town
country: South Africa
facility: Univeristy of Cape Town Lung CRS Institute
state: Western Cape
city: George
country: South Africa
facility: TASK Eden
state: Western Cape
city: Stellenbosch
country: South Africa
facility: Synexus Helderberg
state: Western Cape
city: Elandsdoorn
country: South Africa
facility: Ndlovu Research Centre CoVPN CRS
city: Johannesburg
country: South Africa
facility: Kliptown Soweto CRS
city: Klerksdorp
country: South Africa
facility: PHRU Matlosana CRS
city: Welkom
country: South Africa
facility: MERC Welkom
city: Mbabane
country: Swaziland
facility: Eswatini Prevention Center CRS
state: Hhohho
city: Entebbe
country: Uganda
facility: UVRI-IAVI HIV Vaccine Program LTD. CRS
city: Kampala
country: Uganda
facility: Baylor-Uganda CRS
city: Kampala
country: Uganda
facility: Joint Clinical Research Centre
city: Kampala
country: Uganda
facility: MU-JHU Research Collaboration CRS
city: Lusaka
country: Zambia
facility: Cfhrz Crs
city: Lusaka
country: Zambia
facility: Matero Reference Clinic CRS
city: Lusaka
country: Zambia
facility: UNC Global Projects / Kamwala District Health Centre
city: Ndola
country: Zambia
facility: Zambia Emory HIV Research Project - Ndola CoVPN CRS
Study officials:
affiliation: Centre for the AIDS Programme of Research in South Africa (CAPRISA)
name: Nigel Garrett
role: STUDY_CHAIR
affiliation: Qhakaza Mbokodo Research Clinic
name: Philip Kotze
role: STUDY_CHAIR
affiliation: Blantyre CRS / Johns Hopkins Research Project
name: Sufia Dadabhai
role: STUDY_CHAIR
affiliation: University of Zimbabwe Clinical Trials Research Centre
name: Nyaradzo Mgodi
role: STUDY_CHAIR
References: