EDCTP

EDCTP funded studies

 

 

 

 

The European & Developing Countries Clinical Trials Partnership (EDCTP) http://www.edctp.org/   funds clinical research to accelerate the development of new or improved drugs, vaccines, microbicides and diagnostics against HIV/AIDS, tuberculosis and malaria as well as other poverty-related infectious diseases in sub-Saharan Africa, with a focus on phase II and III clinical trials. The EDCTP is funding two major CAPRISA studies: CAPRISA 012 and CAPRISA 018  studies. These projects are part of the EDCTP2 programme supported by the European Union.
 

CAPRISA 097 Study https://www.caprisa.org/Pages/CAPRISAStudies

To assess post removal implant insertion site healing, implant acceptability and pre-exposure prophylaxis (PrEP) product user preferences in previous CAPRISA 018 trial participants. 
This prospective, cohort study enrolled consenting participants previously enrolled in Group 1 and Group 2 from the CAPRISA 018 trial. After enrolment, participants attended study visits quarterly and exited the study at the month 12 visit. This post-trial cohort study was conducted at the CAPRISA eThekwini Clinical Research Site (ECRS) in Durban, KwaZulu-Natal South Africa. This study was completed in December 2023.

CAPRISA 012 trial  https://www.caprisa.org/Pages/CAPRISAStudies
is a phase I/II trial conducted in three parts. The first part of the study, CAPRISA 012A, is a double blinded, randomized, placebo- controlled phase I trial assessing the safety and pharmacokinetic profile of the monoclonal antibodies,  PGT121 and VRC07-523.LS administered subcutaneously in HIV negative women and is currently underway. All 45 participants have now been enrolled into the study, with 100% retention to date. Part B is a phase I study that will assess the safety, pharmacokinetics and acceptability of CAP256V2LS as well as the combination of the two bNAbs (CAP256V2LS + VRC07-523LS and CAP256V2LS + PGT121). Based on the phase I data from both CAPRISA 012A and CAPRISA 012B, one or both bNAb combinations will then be selected, based on matched pharmacokinetics, to proceed to the phase II trial, CAPRISA 012C, which will assess extended safety and obtain an estimate of efficacy in preventing HIV infection, in 606 (909 if both combinations go forward) young South African and Zambian women.  The overall goal of the CAPRISA 012 trial is to develop a combination of two anti-HIV monoclonal antibodies as a new, safe and effective long-acting HIV prevention technology, principally for women, in order to alter the course of the HIV epidemic in Africa. This trial is co-funded by the South African Medical Research Council, the South African Department of Health, the Department of Science and Innovation and the National Research Foundation.

CAPRISA 018 study https://www.caprisa.org/Pages/CAPRISAStudies
was a phase I/II trial to assess the safety, acceptability, tolerability and pharmacokinetics of a sustained-release tenofovir alafenamide (TAF) sub-dermal implant for HIV prevention in women. This implant combines two well-established elements; a) TAF, which is a licenced antiretroviral drug widely used in HIV treatment, and b) a sub-dermal implant, which is widely used as a route of administration for contraception. This trial was co-funded by the South African Medical Research Council, the South African Department of Health, and the Department of Science and Innovation. Cipla Ltd provide an in-kind contribution through the donation of study drug and Gilead Sciences Inc provided the active pharmaceutical ingredients for the TAF implants.

 

New Studies

1. Study: Natural History and Laboratory Tests for COVID-19 in South Africa (HALT_COVID-19)

Participating Organisations: 

1. Amsterdam Institute for Global Health and Development (AIGHD), Netherlands 
2. Medical Department, Division of Infectious Diseases and Pneumology - Charité- Universitätsmedizin, Germany 
3. Statens Serum Institut (SSI), Denmark

Study duration : 24 months

For any study related questions or data access please contact Prof Ayesha Kharsany (email: ayesha.kharsany@caprisa.org)

This study will build on existing global research but fill an important gap in characterizing COVID-19 disease in the sub-Saharan African region. The research will enhance and refine our understanding of SARS-CoV-2 transmission dynamics, natural history and disease progression in a setting that has a high burden of HIV and TB. In addition, the comprehensive laboratory validation testing studies will supplement the gold standard RTPCR testing and provide options for rapid diagnosis COVID-19. Combined, this study will help guide the South African response to the COVID-19 outbreak.

Investigators

Prof Ayesha Kharsany (PI)
Dr Aida Sivro (co-PI)
Ms Natasha Samsunder (Director, Laboratories)

 

Publications

• Samsunder N, Lustig G, Ngubane S, Maseko TG, Rambaran S, Ngcapu S, Magini SN,Lewis L, Cawood C, Kharsany ABM, Karim QA, Karim SA, Naidoo K, Sivro A. Field evaluations of four SARS-CoV-2 rapid antigen tests during SARS-CoV-2 Delta variant wave in South Africa. Diagn Progn Res. 2023 Jul 25;7(1):14. doi: 10.1186/s41512-023-00151-3. PMID: 37491317; PMCID: PMC10369830. https://pubmed.ncbi.nlm.nih.gov/37491317/
• Samsunder N, Lustig G, de Vos M, Ngcapu S, Giandhari J, Tshiabuila D, San EJ, Lewis L, Kharsany AB, Cawood C, de Oliveira T, Abdool Karim Q, Abdool Karim S,Escadafal C, Naidoo K, Sivro A. Performance of rapid antigen tests in identifying Omicron BA.4 and BA.5 infections in South Africa. J Clin Virol. 2023 Aug;165:105498. doi: 10.1016/j.jcv.2023.105498. Epub 2023 Jun 2. PMID: 37329842; PMCID: PMC10236920.
  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10236920/
• Samsunder N, de Vos M, Ngcapu S, Giandhari J, Lewis L, Kharsany ABM, Cawood C, de Oliveira T, Karim QA, Karim SA, Naidoo K, Escadafal C, Sivro A. Clinical Evaluation of Severe Acute Respiratory Syndrome Coronavirus 2 Rapid Antigen Tests During the Omicron Wave in South Africa. J Infect Dis. 2022 Oct 17;226(8):1412-1417. doi: 10.1093/infdis/jiac333. PMID: 35921539; PMCID:PMC9384653.
  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9384653/

2. Study: PrEP- Underlying Mucosal Immunity Before and After (PUMBA) PUMBA focuses on unravelling the immune correlates of risk or protection for HIV acquisition in the genital tracts and systemically in young African women who used antivirals as pre-exposure prophylaxis (PrEP) to prevent HIV. With the likely advent of combination HIV prevention strategies that include both vaccines and PrEP, understanding the effect that PrEP may have on the humoral immunity, inflammatory profiles and the microbiome in the genital tract and systemically may have important implications for efficacy of candidate HIV vaccines (Dr Desh Archary, Senior Fellowship)

3. CAPRISA 094 TRIAD Study, is a phase IV multi-centre, multi-country operational study to assess the effectiveness, feasibility, acceptability, and cost effectiveness of the GeneXpert MTB/XDR (Xpert MTB/XDR; Cepheid) assay for rapid triage-and-treatment with short, all- oral drug-resistant TB (DR-TB) treatment.

The study will enrol 1280 participants across 9 clinical research study sites in South Africa, Nigeria and Ethiopia.  The Xpert XDR assay is a rapid genotypic test which will be implemented as a reflex test  to detect resistance to isoniazid, fluoroquinolones and second-line injectable agents to provide rapid genotypic susceptibility testing for DR-TB. The Xpert XDR assay will guide the selection of appropriate, all-oral DR-TB treatment regimens of the shortest possible duration. The tuberculosis molecular bacterial load assay (TB-MBLA) will be used as an adjunct to  provide bacillary load monitoring over the course of treatment and assess real-time treatment response. 

Operational research will provide information about the feasibility, acceptability and cost-effectiveness to inform policies and guidelines for programmatic implementation of the triage-and-treat model. Collectively, the study will leverage on recent novel developments in the DR-TB diagnostic and treatment arena ensuring rapid delivery and uptake of these innovations into clinical practice in settings most afflicted by the disease.

Investigators:

1. Professor Kogie Naidoo
2. Dr Navisha Dookie

Participating Organisations: 

1. WITS Health Consortium, South Africa
2. Koninklijke Nederlandse Centrale Vereniging tot bestrijding der Tuberculose (KNCV), Netherlands
3.  Amsterdam Institute for Global Health and Development (AIGHD), Netherlands
4. Ospedale San Raffaele (OSR), Italy
5. Global TB Alliance, New York
6. Institute of Human Virology Nigeria LTDGTE (IHVN), Nigeria
7. Foundation for New Diagnostics (FIND), Switzerland
8. University Court of St Andrews (USTAN), United Kingdom
9. National Institute for Medical Research (NIMR), Tanzania
10. Ethiopian Public Health Institute (EPHI), Ethiopia

EDCTP- funded Senior Fellowship Grants & Career Development Fellowships
HIVDR-MIT is a study that is embedded in the CAPRISA HIV/TB Treatment Research Program, and is funded by the European and Developing Countries Clinical Trials Partnership (EDCTP). This study aims to design innovative methods for HIV-1 drug resistance testing that are affordable, accessible, and applicable to the changes in HIV treatment guidelines in most low and middle-income countries, such as South Africa. Moreover, the study aims to develop a database platform that captures near "real-time" HIV drug resistance data from KwaZulu-Natal province, in South Africa, for longitudinal monitoring of HIVDR, through drug resistance genotyping requests from the public health facilities in the province. This study will inform on the public health approach to HIV treatment and will provide a next generation of HIVDR diagnostic tools that are streamlined to meet the changes in ART programmes.

Two CAPRISA scientists have been awarded EDCTP Senior Grant Fellowships and four Career Development Fellowships http://www.edctp.org/call/senior-fellowships-4/

They are:

• Professor Nesri Padayatchi (MBChB) (PhD) - Senior Fellow. Study: The individualised multi-/extensively drug-resistant tuberculosis treatment strategy study.
• Dr Desh Archary (PhD) - Senior Fellow. Study: Effect of pre-exposure prophylaxis (PrEP) on immune responses systematically and mucosally in healthy individuals in the CAPRISA 082 study (PrEP Underlying Mucosal-immunity Before/After).
• Dr Aida Sivro (PhD) - Career Development Fellow. Study: Mucosal type I IFN desensitization and the risk of HIV acquisition study examines the effect of chronic interferon expression in the female genital tract on interferon responsiveness and subsequent susceptibility of HIV target cells in the mucosa. 
• Dr Navisha Dookie (PhD) - Career Development Fellow. Study: Optimizing the Clinical Utility of Whole Genome Sequencing to enhance Drug-Resistant Tuberculosis outcomes (Optim-TB) study aims to optimize the extraction of DNA directly from sputum for the rapid detection of drug-resistance and study the effects of evolving drug-resistance and mycobacterial factors on treatment outcomes in patients with drug-resistant TB.
• Dr Nikita Naicker (PhD) - Career Development Fellow. The project titled Evaluating the Impact of Metformin on Mycobacterium tuberculosis Growth in Macrophages (TMA2019CDF-2709) is part of the EDCTP2 programme supported by the European Union.
• Dr Benjamin Chimukangara (PhD) - Career Development Fellow. Study:  Monitoring of HIV drug resistance in South Africa and innovative approaches to HIV drug resistance testing (HIVDR-MIT). HIVDR-MIT is a study that is embedded in the CAPRISA HIV/TB Treatment Research Program, and is funded by the European and Developing Countries Clinical Trials Partnership (EDCTP). This study aims to design innovative methods for HIV-1 drug resistance testing that are affordable, accessible, and applicable to the changes in HIV treatment guidelines in most low and middle-income countries, such as South Africa. Moreover, the study aims to develop a database platform that captures near "real-time" HIV drug resistance data from KwaZulu-Natal province, in South Africa, for longitudinal monitoring of HIVDR, through drug resistance genotyping requests from public health facilities in the province. This study will inform on the public health approach to HIV treatment and will provide a next generation of HIVDR diagnostic tools that are streamlined to meet changes in ART programmes.
   

Co-funders of the CAPRISA 012 and CAPRISA 018 Trials: