Sisonke (Together): OPEN LABEL TRIAL COVID-19 (Sisonke)

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)

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

Study Overview

• Status: Completed
• Conditions: SARS (Severe Acute Respiratory Syndrome)
• Intervention / Treatment: Biological: To monitor the effectiveness of the single dose Ad26.COV2.S COVID-19 vaccine

Detailed 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

• Study Type: Interventional
• Enrollment (Actual): 477102
• Phase: Phase 3

Contacts and Locations

Study Locations

• South Africa
  • Cape Town, South Africa, 7975
    • Desmond Tutu Health Foundation - Masiphumelele Research Office
  • Rustenburg, South Africa, 0299
    • The Aurum Institute: Rustenburg Clinical Research Centre, Dr Lawrence
  • Eastern Cape
    • Mthatha, Eastern Cape, South Africa, 5100
      • Nelson Mandela Academic Clinical Research Unit (NeMACRU)
    • Port Elizabeth, Eastern Cape, South Africa, 6001
      • Phoenix Pharma Pty Ltd
  • Free State
    • Bloemfontein, Free State, South Africa, 9300
      • Josha Research
  • Gauteng
    • Germiston, Gauteng, South Africa, 1401
      • CRISMO Research Centre, Dr Bhekithemba
    • Johannesburg, Gauteng, South Africa, 1862
      • Perinatal HIV Research Unit (PHRU), SOWETO
    • Johannesburg, Gauteng, South Africa, 2001
      • Wits RHI: Shandukani Research Centre
    • Johannesburg, Gauteng, South Africa
      • Themba Lethu HIV Research Unit (CHRU), Dr
    • Pretoria, Gauteng, South Africa, 0122
      • Synexus SA - Stanza Clinical Research Centre
    • Pretoria, Gauteng, South Africa, 0152
      • Setshaba Research Centre,
    • Pretoria, Gauteng, South Africa, 0184
      • Synexus Watermeyer Clinical Research Centre,
    • Pretoria, Gauteng, South Africa
      • Ndlovu Research Centre
  • Gauteng - South
    • Johannesburg, Gauteng - South, South Africa, 1632
      • The Aurum Institute: Tembisa Clinical Research Centre
    • Johannesburg, Gauteng - South, South Africa, 1809
      • Perinatal HIV Research Unit Kliptown
  • KWA ZULU Natal
    • Bothas Hill, KWA ZULU Natal, South Africa, 3660
      • Botha's Hill Clinical Research Site
    • Durban, KWA ZULU Natal, South Africa, 4001
      • CAPRISA eThekwini Clinical Research Site, Dr
    • Durban, KWA ZULU Natal, South Africa
      • CAPRISA Vulindlela Clinical Research Site, Dr
    • Ladysmith, KWA ZULU Natal, South Africa, 3370
      • Qhakaza Mbokodo Research Clinic
  • Kwa Zulu Natal
    • Durban, Kwa Zulu Natal, South Africa, 4030
      • Chatsworth Clinical Research Site
    • Tongaat, Kwa Zulu Natal, South Africa, 4400
      • Tongaat Clinical Research Site, Dr
  • Mpumalanga
    • Middleburg, Mpumalanga, South Africa, 1050
      • Mzansi Ethical Research Centre
  • North WEST Province
    • Klerksdorp, North WEST Province, South Africa, 2571
      • The Aurum Institute Klerksdorp Clinical Research Centre
  • Western CAPE
    • Cape Town, Western CAPE, South Africa, 7781
      • Emavundleni Research Centre
    • Cape Town, Western CAPE, South Africa, 7784
      • Khayelitsha CRS, Dr Amy Ward / Dr Graeme Meintjes
    • Somerset West, Western CAPE, South Africa, 7130
      • Synexus Helderberg Clinical Research Centre, Dr Vera
  • Western Cape
    • Cape Town, Western Cape, South Africa, 7505
      • FAMCRU (Family Clinical Research Unit),
    • Cape Town, Western Cape, South Africa, 7530
      • TASK Central
    • Cape Town, Western Cape, South Africa, 7530
      • TASK Clinical Research Centre
    • Cape Town, Western Cape, South Africa, 7925
      • Desmond Tutu Health Foundation CTU J52 Old Main Building Groote SchuurHospital
    • Worcester, Western Cape, South Africa, 6850
      • South African Vaccine Initiative (SATVI), Dr Angelique Kany Kany

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 101 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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
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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Collaborators and Investigators

• Sponsor: Wits Health Consortium (Pty) Ltd
• Collaborators: Fred Hutchinson Cancer Center; Janssen Vaccines & Prevention B.V.; National Institute for Communicable Diseases, South Africa; Right to Care; National Department of Health of South Africa; KwaZulu-Natal Research Innovation and Sequencing Platform - KRISP; Hutchinson Center Research Institute of South Africa (HCRISA); Bio Analytical Research Corporation; Dis-Chem Pharmacy; BioVac; Biocair; Clinical Laboratory Services
• Investigators: Principal Investigator: Glenda E Gray, MBChB, Non-Executive Director

Publications and helpful links

General Publications

• Takuva S, Takalani A, Seocharan I, Yende-Zuma N, Reddy T, Engelbrecht I, Faesen M, Khuto K, Whyte C, Bailey V, Trivella V, Peter J, Opie J, Louw V, Rowji P, Jacobson B, Groenewald P, Dorrington RE, Laubscher R, Bradshaw D, Moultrie H, Fairall L, Sanne I, Gail-Bekker L, Gray G, Goga A, Garrett N; Sisonke study team. Safety evaluation of the single-dose Ad26.COV2.S vaccine among healthcare workers in the Sisonke study in South Africa: A phase 3b implementation trial. PLoS Med. 2022 Jun 21;19(6):e1004024. doi: 10.1371/journal.pmed.1004024. eCollection 2022 Jun.
• Bekker LG, Garrett N, Goga A, Fairall L, Reddy T, Yende-Zuma N, Kassanjee R, Collie S, Sanne I, Boulle A, Seocharan I, Engelbrecht I, Davies MA, Champion J, Chen T, Bennett S, Mametja S, Semenya M, Moultrie H, de Oliveira T, Lessells RJ, Cohen C, Jassat W, Groome M, Von Gottberg A, Le Roux E, Khuto K, Barouch D, Mahomed H, Wolmarans M, Rousseau P, Bradshaw D, Mulder M, Opie J, Louw V, Jacobson B, Rowji P, Peter JG, Takalani A, Odhiambo J, Mayat F, Takuva S, Corey L, Gray GE; Sisonke Protocol Team; Sisonke Study Team. Effectiveness of the Ad26.COV2.S vaccine in health-care workers in South Africa (the Sisonke study): results from a single-arm, open-label, phase 3B, implementation study. Lancet. 2022 Mar 19;399(10330):1141-1153. doi: 10.1016/S0140-6736(22)00007-1.

Study record dates

Study Major Dates

• Study Start (Actual): February 17, 2021
• Primary Completion (Actual): March 31, 2022
• Study Completion (Actual): March 31, 2022

Study Registration Dates

• First Submitted: February 17, 2021
• First Submitted That Met QC Criteria: April 6, 2021
• First Posted (Actual): April 9, 2021

Study Record Updates

• Last Update Posted (Actual): August 1, 2022
• Last Update Submitted That Met QC Criteria: July 29, 2022
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Severe Acute Respiratory Syndrome
• Other Study ID Numbers: Sisonke (Together): OPEN LABEL

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No