Clinical trial NCT05715944: Incidence of COVID-19 Following Vaccination in Botswana Against SARS CoV 2
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: COVID-19
Keywords: AZD 1222
ChAdOx1
Lead sponsor: Botswana Harvard AIDS Institute Partnership
Sponsor class: OTHER
Collaborators: name: AstraZeneca
name: Botswana Ministry of Health
First posted: 2023-02-08
Enrollment: 10888
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: AZD1222-00001 is a single-arm, Open-label, Phase 3b Study of the Incidence of Severe COVID 19 and Adverse Events Following AZD1222 COVID-19 Vaccination in Botswana Against SARS-CoV-2. Study participants are adults ≥ 18 years of age who have not already received a COVID-19 vaccine primary series and/or booster. Up to 50,000 participants are to be enrolled in the study. A total of 900 enrolled participants will also participate in a sub-study assessing the immunogenicity of AZD1222. These 900 participants in the sub-cohort will have additional assessments.

Safety is assessed for the duration of the study. AEs are recorded at 4 weeks post the first, second and booster vaccination dose and quarterly; participants are contacted via text, or telephone call as part of follow up.
Primary purpose: PREVENTION

Brief summary: 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.

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

Eligibility criteria: 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.

Primary outcomes:
measure: Occurrence of severe COVID-19 disease among individuals vaccinated with AZD1222,
timeFrame: From at least 15 days after the second or booster dose up to 12 months following the first vaccination dose
measure: Occurrence of Adverse Events among individuals vaccinated with at least one dose AZD1222
timeFrame: Up to 12 months following the first vaccination dose
Secondary outcomes:
measure: 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
timeFrame: 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,
measure: 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
timeFrame: 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 outcomes:
measure: Comparing the primary endpoint of incidence of severe COVID-19 cases to the incidence before vaccination using an observed versus expected method
timeFrame: 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
measure: Monitoring the genetic diversity of breakthrough SARS-CoV-2 infections in a sub-cohort of study participants
timeFrame: Follow up of up to one year
measure: Estimating the occurrence of SARS-CoV-2 infections in a sub-cohort of study participants
timeFrame: Follow up of up to one year
measure: Assessing the humoral immunogenicity of AZD1222 vaccinated participants over time in a sub-cohort of study participants
timeFrame: Follow up of up to one year
measure: Assessing cell mediated immune responses of AZD1222 vaccinated participants over time in a sub-cohort of study participants
timeFrame: Follow up of up to one year
measure: Assessing additional immune responses following AZD1222 vaccine as a primary COVID-19 vaccination series or as a booster
timeFrame: Follow up of up to one year
Locations:
city: Gaborone
country: Botswana
facility: Botswana Harvard Health Partnership
Study officials:
affiliation: Botswana Harvard AIDS Institute Partnership
name: Joseph M Makhema, FRCP
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Botswana, Botswana Harvard Health Partnership
name: Tendani Gaolathe, M.,Med
role: STUDY_DIRECTOR
References: