Sisonke (Together): OPEN LABEL TRIAL COVID-19

SARS (Severe Acute Respiratory Syndrome) Clinical Trial

— Sisonke  

Official title:

Open-label, Single-arm Phase 3B Implementation Study to Monitor the Effectiveness of the Single-dose Ad26.COV2.S COVID-19 Vaccine Among Health Care Workers in South Africa (VAC31518COV3012)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04838795
• Other study ID #: Sisonke (Together): OPEN LABEL
• Status: Completed
• Phase: Phase 3
• Start date: February 17, 2021
• Est. completion date: March 31, 2022

Study information

• Verified date: October 2021
• Source: Wits Health Consortium (Pty) Ltd
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

To monitor the effectiveness of the single-dose Ad26.COV2.S COVID-19 vaccine among health care workers (HCW) in South Africa

Description:

Purpose To monitor the effectiveness of the single dose Ad26.COV2.S COVID-19 vaccine among health care workers (HCW) as compared to the general unvaccinated population 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, but currently no vaccine has been rolled out. The recent promising results of the 'ENSEMBLE' trial conducted by Janssen in South Africa, and the availability of a limited amount of vaccine doses, provide the rationale for a cohort study of vaccinated HCWs to inform the larger vaccine rollout. Study participants Health Care workers age 18 and above working in the South African public and private health care sector (N=500 000) 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 single dose of vaccine at enrolment; to monitor outcomes the DATCOV surveillance system and NICD line list will be reviewed for up to 2 years post-vaccination. A sub-cohort (approx. 850-1000 people) consisting of special sub-populations will be followed up at approx. 1, 3, 6 weeks and 6 months post vaccination. This group will also have outcomes monitored for up to a further 18 months, bringing their total follow-up duration to 2 years post-vaccination Study products Ad26.COV2.S by Janssen administered as a single injection Primary objectives • To assess the effectiveness of Ad26.COV2.S vaccine on severe COVID, hospitalizations and deaths in HCWs as compared with the general unvaccinated population in South Africa. Secondary objectives • To estimate the incidence of symptomatic SARS CoV-2 infections in HCW - To estimate vaccine uptake among HCWs in South Africa - To monitor the genetic diversity of breakthrough SARS CoV-2 infections To monitor immunological responses (neutralising, non-neutralising antibodies and T cell responses) in HCWs with breakthrough infections - To measure baseline SARS CoV-2 antibody testing to evaluate pre-existing immunity in up to 100 000 HCWs. - In a subgroup of participants (approx. 850-1000 people) including representative sub-populations of interest, e.g. elderly, immune compromised: - To compare serum neutralization and immune responses before and after vaccination at 0, 6 weeks and up to 6 months. - To explore clotting parameters post vaccination at weeks 0, 1, 3. - To monitor for asymptomatic infection Exploratory objectives To set up a comprehensive safety desk and establish a link between the national pharmacovigilance system to assist with monitoring safety and any unexpected adverse effects

Recruitment information / eligibility

• Status: Completed
• Enrollment: 477102
• Est. completion date: March 31, 2022
• Est. primary completion date: March 31, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 105 Years

Eligibility

Inclusion criteria

• Age 18 and older
• Health care worker in the private or public service
• The President and Deputy President of South Africa* (The President and Deputy President of South Africa have been included in the protocol to address the issue of vaccine hesitancy. )
• Willingness and ability to comply 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. Inclusion criteria for the sub-cohort
• Age 18 and older
• Health care worker in the private or public service
• Willingness and ability to comply with all scheduled visits, vaccination plan, laboratory tests, and other study procedures, with follow-up at an ENSEMBLE site.
• 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
• 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
• Participant reports being pregnant at time of enrolment, planning conception within 3 months.
• Participants who report breastfeeding at the time of enrolment will be excluded.
• 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.
• History of severe adverse reaction associated with a vaccine and/or severe allergic reaction (e.g., anaphylaxis) to any component of the vaccine.
• Participants who have experienced major venous and arterial thrombosis occurring with thrombocytopenia following vaccination with any COVID-19 vaccine should not enrol in Sisonke.
• Participants with a history of heparin-induced thrombocytopenia.

Note:

• Vaccination within 14-90 days with other COVID19 or non-specific vaccines are not exclusionary but should be discussed with study PI or designee. Conditions of interest: We note that international reports of VITT have not identified a risk factor, nor does there appear to be any prothrombotic state that indicates a risk factor for this immune response. Nevertheless, the Sisonke study will enrol participants with chronic history of severe clotting disorders only after consultation and approval of the study Protocol Safety Review Team (PSRT).

We have identified certain specific conditions of special interest such as:

• cerebral venous sinus thrombosis,
• antiphospholipid syndrome
• Individuals on therapeutic anticoagulants for current or previous arterial or venous thrombosis or embolism

Related Conditions & MeSH terms

• SARS (Severe Acute Respiratory Syndrome)
• Severe Acute Respiratory Syndrome

Intervention

Biological:
• To monitor the effectiveness of the single dose Ad26.COV2.S COVID-19 vaccine
To monitor the effectiveness of the single dose Ad26.COV2.S COVID-19 vaccine among health care workers (HCW) as compared to the general unvaccinated population in South Africa

Locations

Country	Name	City	State
South Africa	Josha Research	Bloemfontein	Free State
South Africa	Botha's Hill Clinical Research Site	Bothas Hill	KWA ZULU Natal
South Africa	Desmond Tutu Health Foundation - Masiphumelele Research Office	Cape Town
South Africa	Desmond Tutu Health Foundation CTU J52 Old Main Building Groote SchuurHospital	Cape Town	Western Cape
South Africa	Emavundleni Research Centre	Cape Town	Western CAPE
South Africa	FAMCRU (Family Clinical Research Unit),	Cape Town	Western Cape
South Africa	Khayelitsha CRS, Dr Amy Ward / Dr Graeme Meintjes	Cape Town	Western CAPE
South Africa	TASK Central	Cape Town	Western Cape
South Africa	TASK Clinical Research Centre	Cape Town	Western Cape
South Africa	CAPRISA eThekwini Clinical Research Site, Dr	Durban	KWA ZULU Natal
South Africa	CAPRISA Vulindlela Clinical Research Site, Dr	Durban	KWA ZULU Natal
South Africa	Chatsworth Clinical Research Site	Durban	Kwa Zulu Natal
South Africa	CRISMO Research Centre, Dr Bhekithemba	Germiston	Gauteng
South Africa	Perinatal HIV Research Unit (PHRU), SOWETO	Johannesburg	Gauteng
South Africa	Perinatal HIV Research Unit Kliptown	Johannesburg	Gauteng - South
South Africa	The Aurum Institute: Tembisa Clinical Research Centre	Johannesburg	Gauteng - South
South Africa	Themba Lethu HIV Research Unit (CHRU), Dr	Johannesburg	Gauteng
South Africa	Wits RHI: Shandukani Research Centre	Johannesburg	Gauteng
South Africa	The Aurum Institute Klerksdorp Clinical Research Centre	Klerksdorp	North WEST Province
South Africa	Qhakaza Mbokodo Research Clinic	Ladysmith	KWA ZULU Natal
South Africa	Mzansi Ethical Research Centre	Middleburg	Mpumalanga
South Africa	Nelson Mandela Academic Clinical Research Unit (NeMACRU)	Mthatha	Eastern Cape
South Africa	PHOENIX Pharma Pty Ltd	Port Elizabeth	Eastern Cape
South Africa	Ndlovu Research Centre	Pretoria	Gauteng
South Africa	Setshaba Research Centre,	Pretoria	Gauteng
South Africa	Synexus SA - Stanza Clinical Research Centre	Pretoria	Gauteng
South Africa	Synexus Watermeyer Clinical Research Centre,	Pretoria	Gauteng
South Africa	The Aurum Institute: Rustenburg Clinical Research Centre, Dr Lawrence	Rustenburg
South Africa	Synexus Helderberg Clinical Research Centre, Dr Vera	Somerset West	Western CAPE
South Africa	Tongaat Clinical Research Site, Dr	Tongaat	Kwa Zulu Natal
South Africa	South African Vaccine Initiative (SATVI), Dr Angelique Kany Kany	Worcester	Western Cape

Sponsors (13)

Lead Sponsor

Collaborator

Wits Health Consortium (Pty) Ltd

Bio Analytical Research Corporation, Biocair, BioVac, Clinical Laboratory Services, Dis-Chem Pharmacy, Fred Hutchinson Cancer Center, Hutchinson Center Research Institute of South Africa (HCRISA), Janssen Vaccines & Prevention B.V., KwaZulu-Natal Research Innovation and Sequencing Platform - KRISP, National Department of Health of South Africa, National Institute for Communicable Diseases, South Africa, Right to Care

Country where clinical trial is conducted

South Africa, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	To monitor for safety and any unexpected adverse effects of the vaccine administration	To conduct pharmacovigilance to monitor for safety and any unexpected adverse effects of the vaccine administration	24 Months
Primary	Number of severe COVID, hospitalizations and deaths in HCWs as compared with the general unvaccinated population in South Africa	Rates of hospitalizations and deaths among vaccinated HCWs versus general unvaccinated population	24 Months
Secondary	The number of symptomatic SARSCoV-2 infections among vaccinated HCWs	Incidence rate of SARS CoV-2 infection as indicated by self-report and validation in national laboratory records.; Rates of severe disease in HCW who are found to be RT-PCR positive at anytime up to 2 years post vaccination	24 Months
Secondary	The measure of genetic diversity of breakthrough SARSCoV-2 infections	Genetic diversity of breakthrough infection virus as determined by whole genome sequencing. This will be recovered from national laboratories.	24 months
Secondary	Monitoring for asymptomatic infection in a sub-set (10 000) of HCWs	Rates of asymptomatic infection at baseline and follow up using SARS CoV-2 virus and antibody testing.	24 Months
Secondary	Monitor for safety and any unexpected adverse effects of the vaccine administration -pharmacovigilance	Conduct Pharmacovigilance to monitor for safety and adverse events Numbers of safety events and/or unexpected adverse effects reported to the study team Monitor pregnancies and pregnancy outcomes reported to safety desk.	24 Months
Secondary	The vaccine uptake among HCWs in South Africa	Proportion of HCWs approached for study participation taking part in the study and receiving the vaccine	12 Months