Clinical trial NCT04838795: Sisonke (Together): OPEN LABEL TRIAL COVID-19
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: SARS (Severe Acute Respiratory Syndrome)
Lead sponsor: Wits Health Consortium (Pty) Ltd
Sponsor class: OTHER
Collaborators: name: National Department of Health of South Africa
name: National Institute for Communicable Diseases, South Africa
name: KwaZulu-Natal Research Innovation and Sequencing Platform - KRISP
name: Fred Hutchinson Cancer Center
name: Hutchinson Center Research Institute of South Africa (HCRISA)
name: Janssen Vaccines & Prevention B.V.
name: Bio Analytical Research Corporation
name: Dis-Chem Pharmacy
name: BioVac
name: Biocair
name: Right to Care
name: Clinical Laboratory Services
First posted: 2021-04-09
Enrollment: 477102
Sex: ALL
Minimum age (years): 18
Maximum age (years): 105
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Open-label, single-arm phase 3B vaccine implementation study
Primary purpose: PREVENTION

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

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

Eligibility criteria: 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

Primary outcomes:
measure: Number of severe COVID, hospitalizations and deaths in HCWs as compared with the general unvaccinated population in South Africa
timeFrame: 24 Months
Secondary outcomes:
measure: The number of symptomatic SARSCoV-2 infections among vaccinated HCWs
timeFrame: 24 Months
measure: The measure of genetic diversity of breakthrough SARSCoV-2 infections
timeFrame: 24 months
measure: Monitoring for asymptomatic infection in a sub-set (10 000) of HCWs
timeFrame: 24 Months
measure: Monitor for safety and any unexpected adverse effects of the vaccine administration -pharmacovigilance
timeFrame: 24 Months
measure: The vaccine uptake among HCWs in South Africa
timeFrame: 12 Months
Other outcomes:
measure: To monitor for safety and any unexpected adverse effects of the vaccine administration
timeFrame: 24 Months
Locations:
city: Mthatha
country: South Africa
facility: Nelson Mandela Academic Clinical Research Unit (NeMACRU)
state: Eastern Cape
city: Port Elizabeth
country: South Africa
facility: PHOENIX Pharma Pty Ltd
state: Eastern Cape
city: Bloemfontein
country: South Africa
facility: Josha Research
state: Free State
city: Johannesburg
country: South Africa
facility: The Aurum Institute: Tembisa Clinical Research Centre
state: Gauteng - South
city: Johannesburg
country: South Africa
facility: Perinatal HIV Research Unit Kliptown
state: Gauteng - South
city: Germiston
country: South Africa
facility: CRISMO Research Centre, Dr Bhekithemba
state: Gauteng
city: Johannesburg
country: South Africa
facility: Perinatal HIV Research Unit (PHRU), SOWETO
state: Gauteng
city: Johannesburg
country: South Africa
facility: Wits RHI: Shandukani Research Centre
state: Gauteng
city: Johannesburg
country: South Africa
facility: Themba Lethu HIV Research Unit (CHRU), Dr
state: Gauteng
city: Pretoria
country: South Africa
facility: Synexus SA - Stanza Clinical Research Centre
state: Gauteng
city: Pretoria
country: South Africa
facility: Setshaba Research Centre,
state: Gauteng
city: Pretoria
country: South Africa
facility: Synexus Watermeyer Clinical Research Centre,
state: Gauteng
city: Pretoria
country: South Africa
facility: Ndlovu Research Centre
state: Gauteng
city: Bothas Hill
country: South Africa
facility: Botha's Hill Clinical Research Site
state: KWA ZULU Natal
city: Durban
country: South Africa
facility: CAPRISA eThekwini Clinical Research Site, Dr
state: KWA ZULU Natal
city: Durban
country: South Africa
facility: Chatsworth Clinical Research Site
state: Kwa Zulu Natal
city: Durban
country: South Africa
facility: CAPRISA Vulindlela Clinical Research Site, Dr
state: KWA ZULU Natal
city: Ladysmith
country: South Africa
facility: Qhakaza Mbokodo Research Clinic
state: KWA ZULU Natal
city: Tongaat
country: South Africa
facility: Tongaat Clinical Research Site, Dr
state: Kwa Zulu Natal
city: Middleburg
country: South Africa
facility: Mzansi Ethical Research Centre
state: Mpumalanga
city: Klerksdorp
country: South Africa
facility: The Aurum Institute Klerksdorp Clinical Research Centre
state: North WEST Province
city: Cape Town
country: South Africa
facility: FAMCRU (Family Clinical Research Unit),
state: Western Cape
city: Cape Town
country: South Africa
facility: TASK Central
state: Western Cape
city: Cape Town
country: South Africa
facility: TASK Clinical Research Centre
state: Western Cape
city: Cape Town
country: South Africa
facility: Emavundleni Research Centre
state: Western CAPE
city: Cape Town
country: South Africa
facility: Khayelitsha CRS, Dr Amy Ward / Dr Graeme Meintjes
state: Western CAPE
city: Cape Town
country: South Africa
facility: Desmond Tutu Health Foundation CTU J52 Old Main Building Groote SchuurHospital
state: Western Cape
city: Somerset West
country: South Africa
facility: Synexus Helderberg Clinical Research Centre, Dr Vera
state: Western CAPE
city: Worcester
country: South Africa
facility: South African Vaccine Initiative (SATVI), Dr Angelique Kany Kany
state: Western Cape
city: Cape Town
country: South Africa
facility: Desmond Tutu Health Foundation - Masiphumelele Research Office
city: Rustenburg
country: South Africa
facility: The Aurum Institute: Rustenburg Clinical Research Centre, Dr Lawrence
Study officials:
affiliation: Non-Executive Director
name: Glenda E Gray, MBChB
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.