info.mycology@witshealth.co.za

Our 5FC
PROTECT Project

Population-pharmacokinetics, safety and tolerability of sustained-release flucytosine pellets for the treatment of asymptomatic cryptococcal antigen-positive individuals.

Our 5FC
PROTECT Project

Population-pharmacokinetics, safety and tolerability of sustained-release flucytosine pellets for the treatment of asymptomatic cryptococcal antigen-positive individuals.

Project Overview

Project title: Population-pharmacokinetics, safety and tolerability of sustained-release flucytosine pellets for the treatment of asymptomatic cryptococcal antigen-positive individuals: a single-arm trial.

Abbreviation: 5FC-PROTECT (5FC Pharmacokinetics, Risk assessment, Outcomes, Tolerability in Early Cryptococcal Treatment)

ISRCTN: ISRCTN18180872

The 5FC-PROTECT trial is a phase II single-arm PK study which aims to investigate a new sustained-release (SR) formulation of flucytosine (5FC) administered twice daily. The trial will be conducted in adults with advanced HIV infection and cryptococcal antigenaemia without symptoms of meningitis in Cape Town, Durban and Johannesburg, South Africa. This trial aims to build on the work of the EFFECT trial, in the pursuit of improving the management of cryptococcal infection in individuals with advanced HIV disease.

Key Objectives

Primary Outcomes
  • To characterise the population-pharmacokinetic parameters of SR 5FC pellets
Additional Outcomes
  • Safety and tolerability of SR-5FC
  • Development of symptomatic cryptococcal meningitis within the first 4 weeks
  • Acceptability and tolerability of SR-5FC
  • All-cause mortality at 2 and 4 weeks
  • Change in CrAg titre/CrAg semi-quantitative assay score from baseline to 2 weeks post-treatment

Achievements

SAHPRA, UCT HREC, UKZN BREC, Wits HREC and LSHTM REC, along with Western Cape, KwaZulu-Natal and Gauteng Department of Health approvals in place.

Current Status

October 2025

Site Initiation Visits and training completed at all sites

Q1 or Q2 2026

Trial has not yet opened to recruitment; anticipated start in Q1 or Q2 2026

Recruitment / Site Participation

Recruitment target: 36 participants overall

This trial will be conducted at the following 3 sites:
  • UCT: Clinical Research Centre, Cape Town, with participants recruited from the Khayelitsha and Mitchells Plain districts
  • UKZN: Clinical Trials Unit, Durban, with participants recruited from Victoria Mxenge Hospital and surrounding clinics
  • Wits: Ezintsha, Johannesburg, with participants recruited from Helen Joseph Hospital and surrounding clinics

Team Members

  • Prof. Nelesh Govender
  • Dr Sile Molloy
  • Cape Town: Dr Kyla Murphy (National PI) and Dr Teagan van Wyk (UCT site co-PI)
  • Durban: Prof. Yunus Moosa
  • Johannesburg: Prof. Jeremy Nel
  • Dr Isabella Ribiero
  • Dr David Lawrence
  • Dr Angela Loyse
  • Dr Rachel Wake
  • Prof. Joseph Jarvis
  • Prof. Thomas Harrison
  • Dr Thomas Dorlo
    Protocol Pharmacometrician
  • Thabang Ngwaile
    Pharmacy Assistant
  • Lebogang Raisibe Makhubele
    Pharmacy Manager
  • Nceba Mtshaki
    Pharmacy Assistant
  • Philadelphia Macholo
    Pharmacist
  • Dipole Motsepe
    Pharmacist
  • Dr Jonathan Falconer
  • Dr Bernadett Gosnell
  • Dr Merika Tsitsi (CHBAH)
  • Dr Monicah Mbonani (Wits Mycology)
  • Dr Asha Thombrayil
  • Dr Tappie Cairns
  • Dr Lauren Richards (HJH)
  • Dr Heilisha Dehaloo (Wits Mycology)
  • Dr Juliet Rundogo
  • Dr Evette Moodley (UKZN CTU)
  • Dr Sharon Sunny (HJH)
  • Dr Shashmika Bridgmohan (Wits Mycology)
  • Dr Lia Edkins
  • Dr Ntombeziningi Phungula (UKZN CTU)
  • Dr Monique da Fonseca (Wits Mycology)
  • Sr Pauline Mbutuma
  • Sr Abigail Selotole (Wits Mycology)
  • Sr Mmaphenya Raphadu (Wits Mycology)
  • Sr Ntombizanele Nkomo (Wits Donald Gordon Medical Centre)
  • Sr Lethu Zondi
  • Sr Brenda Montsho (Wits Mycology)
  • Sr Precious Ndebele (Wits Mycology)
  • Sr Ntwenhle Makhaza
  • Sr Harriet Molokwane (Wits Mycology)
  • Sr Tumelo Dlamini (Wits Mycology)
  • Sr Mandisa Msomi (UKZN CTU)
  • Sr Matsiliso Mokhali (Wits Mycology)
  • Sr Gloria Matomela (Wits Donald Gordon Medical Centre)
  • Jack Adams
    Trial Manager
  • Michelle Eriksson
    Trial Coordinator
  • Justine Jelagat Odionyi (Coordinator for DnDi)
  • Ms Phume Ngcobo
  • Cherissa Thobela (UKZN CTU)
  • Zolwazi Manzi (UKZN CTU)
  • Nkuli Mashabane
    Director of Research Operations
  • Ineeleng Taukobong
    Snr Clinical Trial Manager
  • Simpiwe Dladla
    Site co-ordinator
  • Evette Moodley
    Sub-Investigator
  • Simphiwe Dladla
    Site Administrator
  • Siyabonga Maziya
    Data Manager
  • Mandisa Msomi
    Research Nurse
  • Siyabonga Maziya
    Data Manager
  • Bhavna Maharaj
    Pharmacist
  • Siphesihle Gumede
    Research Nurse
  • Cherissa Thobela
    Research Assistant
  • Babalwa Gxumisa
    Lab technician
  • Zolwazi Manzi
    Research Assistant
  • Bhavna Maharaj
    Pharmacist
  • Annemie Stewart (CRC Operations Manager)
  • Sherisce Govender (CRC Pharmacists)
  • Annemie Stewart (CRC Operations Manager)
  • Lindolwethu Mayiya (Research Assistant)
  • A/Prof. Charlotte Schutz (CRC Director)
  • Sivuyile Buhlungu (Research Assistant)
  • Fathima Docrat (CRC Pharmacists)
  • Lethabo Ramoshaba (Research Assistant)

Media

WITS Site Initiation Visit

WITS Site Initiation Visit

UCT Site Initiation Visit

UKZN Site Initiation Visit

UKZN Site Initiation Visit