Incidence of COVID-19 Following Vaccination in Botswana Against SARS CoV 2

Open-Label, Single-Arm, Phase 3b Study of the Incidence of Severe COVID-19 and Adverse Events Following AZD1222 COVID-19 Vaccination in Botswana Against SARS-CoV-2, AZD1222 - ESR-21-21311

The AstraZeneca Study is a single-arm, open-label, interventional, Phase 3b study to determine the incidence of laboratory-confirmed COVID-19 hospitalizations, disease severity, and deaths and attributable adverse events (AEs) in participants in Botswana given 1 to 2 injections of AZD1222 eight to twelve weeks apart as primary series and/or 1 injection as booster dose. Length of follow-up will be 6 to 12 months, depending upon at which dose a participant is enrolled.

Study Overview

• Status: Completed
• Conditions: COVID-19
• Intervention / Treatment: Drug: AZD 1222

Detailed Description

The AstraZeneca Study is an Open-Label, Single-Arm, Phase 3b Study of the incidence of severe COVID-19 and adverse events following AZD1222 COVID-19 vaccination in Botswana against SARS-CoV-2. The study enrolled adult participants >18 years (previously >40 years) in Botswana and vaccinate them with 1 to 2 doses of AZD 1222, as primary series and/or 1 dose as booster.

Primary Objectives:

1. To assess the occurrence of severe COVID-19 disease among individuals vaccinated with AZD1222 by number of vaccine doses.
2. To assess AEs among individuals vaccinated with at least one dose of AZD1222.

Secondary Objectives:

1. To assess the occurrence of COVID-19 disease among individuals vaccinated with AZD1222 by number of vaccine doses by age group, co-morbidity group, the severity of disease and the time since the last dose.
2. To estimate the incidence of symptomatic SARS-CoV-2 infections in a sub-cohort of study participants among individuals vaccinated with at least one dose of AZD1222 by number of vaccine doses

• Study Type: Interventional
• Enrollment (Actual): 10888
• Phase: Phase 3

Contacts and Locations

Study Locations

• Botswana
  • Gaborone, Botswana
    • Botswana Harvard Health Partnership

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Participants are eligible to be included in the study only if all of the following criteria apply:

Type of Participant

• Participants who have willingness and ability to comply with study requirements/procedures (if applicable, with assistance by legally authorised representative) based on the assessment of the investigator.
• Participants who have not yet received 3 doses of COVID-19 vaccine (2 as primary series and a booster dose). Persons who have received no prior vaccination are eligible to enroll at Day 0 to start a primary series. Persons who have received a single dose of COVID-19 vaccine at least 8 week prior (note that this includes persons who have received a single dose of Johnson & Johnson vaccine) are eligible to enroll at Day 70 to complete their primary series and receive a booster dose 3 months thereafter. Persons who have received a primary series of COVID-19 vaccine at least 3 months prior are eligible to enroll at Day 170 to receive a booster.
• Informed Consent
• Capable of giving signed informed consent, as described in Appendix A, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.
• Note: A separate informed consent will be used for optional sample collection.
• Provision of signed and dated written ICF prior to any mandatory study specific procedures, sampling, and analyses.
• Age
• Participant must be ≥ 18years of age at the time of signing the informed consent and residing in the catchment area of select hospitals in Botswana.

Exclusion Criteria:

Participants are excluded from the study if any of the following criteria apply:

Prior/Concomitant Therapy

• Receipt of, or planned receipt of a COVID-19 vaccine booster dose, or any medications or investigational products indicated for the prevention of SARS-CoV-2 infection or treatment of COVID-19.
• Note: For study participants who become hospitalised with COVID-19, receipt of licensed treatment options and/or participation in investigational treatment studies is permitted.
• Receipt of any vaccine (licensed or investigational) other than licensed influenza vaccines within 30 days prior to and after administration of study intervention (i.e. the first, second and booster doses). Outside these periods, other routine vaccinations are permitted as clinically indicated.
• Medical Conditions
• Hypersensitivity to the active substance or to any of the excipients listed in Section 6.1.
• The participant reports being pregnant or nursing or has a positive pregnancy test at the time of enrolment or is planning on becoming pregnant within 6 months (for those enrolled at primary series dose 1) or 3 months (for those enrolled at primary series dose 2) of the first vaccination in the study.
• Additional details are described in Section 5.2.1.
• Individuals with risk factors for or reported history of thrombosis and/or thrombocytopenia.
• Clinically significant bleeding (eg, factor deficiency, coagulopathy, or platelet disorder) or prior history of significant bleeding or bruising following intramuscular injections or venepuncture.
• History of Guillain-Barré syndrome.
• Any confirmed or suspected immunosuppressive or immunodeficient state, including Asplenia.
• Severe and/or uncontrolled cardiovascular disease, respiratory disease, gastrointestinal disease, liver disease, renal disease, endocrine disorder, and neurological illness, as judged by the investigator (mild/moderate well-controlled comorbidities are allowed).
• Any other significant disease, disorder, or finding that may significantly increase the risk to the participant because of participation in the study, affect the ability of the participant to participate in the study, or impair interpretation of the study data.
• Note: The AESIs as outlined in the CSP should be considered when evaluating a participant for this Exclusion Criteria as the presence of these AESIs, especially if untreated or uncontrolled, may be a safety risk to the participant, affect the ability of the participant to participate in the study, or impair interpretation of the study data.
• Other Criteria
• Current participation in any other research studies that would interfere with the objectives of this study. The determination of whether participation in another study would be exclusionary for a given participant will be made by the investigator/designee.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: AZD 1222; AZD1222 vaccine Dose Formulation: 10 mM histidine, 7.5% (w/v) sucrose, 35 mM sodium chloride, 1 mM magnesium chloride, 0.1% (w/v) polysorbate 80, 0.1 mM edetate disodium, 0.5% (w/v) ethanol, at pH 6.6 Current/Former names/alias(es):ChAdOx1 nCoV-19	Drug: AZD 1222; Vaccine; Other Names: ChAdOx1 nCoV-19

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Occurrence of severe COVID-19 disease among individuals vaccinated with AZD1222,	Occurrence of hospitalizations and deaths due to laboratory-confirmed SARS CoV 2 infection	From at least 15 days after the second or booster dose up to 12 months following the first vaccination dose
Occurrence of Adverse Events among individuals vaccinated with at least one dose AZD1222	Occurrence of Serious Adverse Events and Adverse Events of Special Interest up to 12 months following the first vaccination dose	Up to 12 months following the first vaccination dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Occurrence of COVID-19 disease among individuals vaccinated with AZD1222 by number of vaccine doses and vaccine exposure, by age group, comorbidity group, severity of disease, and the time since the last dose	Occurrence of hospitalizations and deaths due to laboratory-confirmed SARS-CoV-2 infection from at least 22 days after the first dose / at least 15 days after the second or booster dose, up to 12 months following the first vaccination dose, by age group, comorbidity group, severity of disease, number of vaccine doses, and the time since the last dose; Occurrence of laboratory-confirmed symptomatic infection from at least 22 days after the first dose / at least 15 days after the second or booster dose, up to 12 months following the first vaccination dose, by age group, comorbidity group, severity of disease, number of vaccine doses, and the time since the first or second dose	From at least 22 days after the first dose / at least 15 days after the second or booster dose, up to 12 months following the first vaccination dose,
Incidence of symptomatic SARS-CoV-2 infections in a sub-cohort of study participants among individuals vaccinated with at least one dose of AZD1222, by number of vaccine doses, and by vaccine exposure	• Occurrence of laboratory-confirmed symptomatic infection from at least 22 days after the first dose / at least 15 days after the second or booster dose, up to 12 months following the first vaccination dose	From at least 22 days after the first dose / at least 15 days after the second or booster dose, up to 12 months following the first vaccination dose

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Comparing the primary endpoint of incidence of severe COVID-19 cases to the incidence before vaccination using an observed versus expected method	• Occurrence of hospitalizations and deaths in subjects vaccinated with AZD1222 vaccine as a primary COVID-19 vaccination series or booster dose due to laboratory-confirmed SARSCoV2 infection from at least 15 days after the last dose up to 6-12 months following the first vaccination dose received as part of the study, and the occurrence in 3-month and 6-month periods before the introduction of the AZD1222 vaccine	From at least 15 days after the last dose up to 6-12 months following the first vaccination dose received as part of the study
Monitoring the genetic diversity of breakthrough SARS-CoV-2 infections in a sub-cohort of study participants	• Genotypic analysis of SARS-CoV-2 from swabs collected for severe COVID-19 cases and on Day 1 illness visit in infected study participants in the sub-cohort	Follow up of up to one year
Estimating the occurrence of SARS-CoV-2 infections in a sub-cohort of study participants	• The incidence of SARS-CoV-2 infection defined by the presence of nucleocapsid antibodies occurring post-dose of study intervention	Follow up of up to one year
Assessing the humoral immunogenicity of AZD1222 vaccinated participants over time in a sub-cohort of study participants	Magnitude of SARS-CoV-2 specific antibody binding and neutralization titres (geometric mean titre); Seroresponse rate of SARS-CoV-2 specific antibody binding and neutralization titres	Follow up of up to one year
Assessing cell mediated immune responses of AZD1222 vaccinated participants over time in a sub-cohort of study participants	• Quantification of (IFN-γ) ELISpot responses to SARS-CoV-2 S protein	Follow up of up to one year
Assessing additional immune responses following AZD1222 vaccine as a primary COVID-19 vaccination series or as a booster	• Other exploratory assays for humoral and cellular immune responses may be performed based upon emerging safety, efficacy, and immunogenicity data	Follow up of up to one year

Collaborators and Investigators

• Sponsor: Botswana Harvard AIDS Institute Partnership
• Collaborators: AstraZeneca; Botswana Ministry of Health
• Investigators: Principal Investigator: Joseph M Makhema, FRCP, Botswana Harvard AIDS Institute Partnership; Study Director: Tendani Gaolathe, M.,Med, University of Botswana, Botswana Harvard Health Partnership

Study record dates

Study Major Dates

• Study Start (ACTUAL): September 15, 2021
• Primary Completion (ACTUAL): December 30, 2022
• Study Completion (ACTUAL): December 30, 2022

Study Registration Dates

• First Submitted: November 9, 2022
• First Submitted That Met QC Criteria: February 6, 2023
• First Posted (ACTUAL): February 8, 2023

Study Record Updates

• Last Update Posted (ACTUAL): February 8, 2023
• Last Update Submitted That Met QC Criteria: February 6, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Keywords: ChAdOx1; AZD 1222
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19
• Other Study ID Numbers: BHP150

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No