Sisonke 2 - A COVID-19 Vaccine Boost Open Label Study.

Study Overview
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Brief Summary
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To evaluate the effectiveness of the single dose Ad26.COV2.S COVID-19 vaccine plus a homologous boostwith Ad26.COV2.S COVID-19 vaccine among Sisonke participants as compared to unboosted Sisonkeparticipants; vaccinated; and unvaccinated populations in South Africa

Detailed Description
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Purpose To evaluate the effectiveness and safety of the single dose Ad26.COV2.S (Jansen) COVID-19 vaccine plus a homologous boost with Ad26.COV2.S (Janssen) COVID-19 vaccine among Sisonke participants as compared to unboosted Sisonke participants In addition the investigators will continue to evaluate VE of the Sisonke Boost compared to: i) Vaccinated populations pre boosts ii) Unvaccinated populations in South Africa. Study design Open-label, single-arm phase 3B vaccine implementation study Rationale South Africa is severely affected by the global COVID-19 epidemic, and following the initial prime vaccination among HCWs in the first 4 months of 2021. New data has demonstrated the safety and effectiveness of a booster dose given two months or more after the initial Ad26.COV2.S. This provides the rationale and feasibility for the evaluation of a homologous booster vaccine dose to the cohort of vaccinated Sisonke participants to inform the larger vaccine rollout. Study participants Sisonke participants age 18 and over working in the South African public and private health care sector (approx N=500 000) who were enrolled in Sisonke and have not subsequently had a further booster vaccine dose. Study sites Department of Health Vaccine Administration Sites across South Africa supported by the Sisonke (Together) (VAC31518COV3012) Trial Research Site Investigators and Study Staff Study duration Participants will receive a homologous Ad26.COV2.S (Janssen) booster dose of vaccine at least 6 months post the prime vaccination. The investigators will monitor outcomes utilising the DATCOV surveillance system and NHLS/NICD SARS COV-2 testing databases for up to 2 years post initial vaccination. Study products Ad26.COV2.S by Janssen administered as a single dose followed by a single booster injection. Primary objectives • To assess the effectiveness of Ad26.COV2.S vaccine as a homologous boost on severe COVID, hospitalizations and deaths in Sisonke participants as compared with the unboosted Sisonke populations. Secondary objectives To assess the effectiveness of Ad26.COV2.S vaccine as a homologous boost on severe COVID, hospitalizations and deaths in Sisonke participants as compared vaccinated and unvaccinated populations of essential workers in South Africa. To estimate the incidence of symptomatic SARS CoV-2 infections in Sisonke participants following a boost compared with the unboosted Sisonke populations and general vaccinated and unvaccinated population in South Africa To estimate booster dose uptake among Sisonke participants in South Africa To monitor the genetic diversity of breakthrough SARS CoV-2 infections. To monitor safety in the case of homologous boosts in Sisonke participants.

Official Title
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Open-label, Single-arm Phase 3B Implementation Study to Evaluate the Effectiveness of the Homologous Boostof Ad26.COV2.S COVID-19 Vaccine Following the Prime Dose Among Sisonke Participants in South Africa(VAC31518COV30XX)

Conditions
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SARS CoV 2 Infection

Intervention / Treatment
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* Biological: Booster vaccine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Age 18 and older All Sisonke participants Received a priming Ad26.SARS.COV.2.S vaccination as part of the Sisonke study at least 6 months prior Participants who are pregnant or report breastfeeding at the time of enrolment may be included. Willingness and ability to comply with vaccination plan and other study procedures. Capable of giving electronic or personal signed informed consent as described in Appendix 5, which includes compliance with the requirements in this protocol. Exclusion Criteria: Participants who have received boosting vaccination through other means. Any significant acute or chronic medical condition, situation or circumstance that in the opinion of the PI/designee makes the participant unsuitable for participation in the study, or jeopardises the safety or rights of the participant 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 PI/designee. Participants with a history of heparin-induced thrombocytopenia or TTS

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Interventional Model Description: Open-label, single-arm phase 3B vaccine implementation study
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Biological: Booster vaccine|To evaluate the effectiveness and safety of the single dose Ad26.COV2.S (Jansen) COVID-19 vaccine plus a homologous boost with Ad26.COV2.S (Janssen) COVID-19 vaccine among Sisonke participants as compared to unboosted Sisonke participants In addition we will continue to evaluate VE of the Sisonke Boost compared to: i) Vaccinated populations pre boosts ii) Unvaccinated populations in South Africa.|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To assess the effectiveness of Ad26.COV2.S (Janssen) boost vaccine on severe COVID, hospitalizations and deaths in Sisonke participants as compared to unboosted Sisonke participants (single Ad26 vaccine only) | Rates of hospitalizations and deaths among boosted Sisonke participants versus unboosted Sisonke participants and unvaccinated populations in South Africa | 24 Months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To assess the effectiveness of Ad26.COV2.S (Janssen) boost vaccine on severe COVID, hospitalizations and deaths in Sisonke participants as compared to the vaccinated and unvaccinated populations (no vaccination) in South Africa. | Rates of hospitalizations and deaths among boosted Sisonke participants versus unboosted vaccinated and unvaccinated populations in South Africa | 24 Months | 
| To estimate the incidence of symptomatic SARS CoV-2 infections among boosted Sisonke ppts. | Incidence rate of SARS CoV-2 infection as indicated by self-report and validation in national laboratory records. Rates of severe disease in Sisonke participants who are found to be RT-PCR positive at any time up to 2 years post prime vaccination | 24 months | 
| To monitor the genetic diversity of breakthrough SARS CoV-2 infections | Genetic diversity of breakthrough infection virus as determined by whole genome sequencing. This will be recovered from national laboratories. | 24 Months | 
| To estimate booster vaccine uptake among Sisonke participants in South Africa | Proportion of Sisonke participants approached for study participation taking part in the boost study and receiving the booster vaccine | 24 Months | 
| To monitor safety in homologous boosts | All SAEs and events of special interest will be collected and reported. | 24 Months |