Dr Hadija Hamisi Semvua

Tanzania

EDCTP portfolio: Career Development Fellowships

Dr Hadji Hamisi Semvua is evaluating the pharmacokinetics and safety/tolerability of higher doses of rifampicin in children with newly diagnosed, uncomplicated tuberculosis.

Dosing drugs for children with uncomplicated TB

Tuberculosis (TB) treatment outcome is not only impaired by co-morbidities such as HIV infection, but also by insufficient consideration of the relationship between the dosing of the administered TB drugs, the concentrations achieved, and eventually, the desirable and undesirable responses. Especially dosing of TB drugs for children is not well substantiated and the concept of using higher doses of rifampicin has not been translated to the treatment of children.

The challenge

Dr Semvua proposed to conduct a phase IIa dose-finding clinical study to find the rifampicin dose in children that yields plasma concentrations similar to those achieved in adults after a 35 mg/kg daily dose. This will answer an important scientific question of direct public benefit.

As regards capacity development, the fellow will receive hands-on training from a mentor of the Radboudumc, an academic research hospital in the Netherlands, during all parts of the study. Skills to perform bio-analysis of TB drugs will be obtained through the pharmacokinetic laboratory at Radboudumc. The fellow will also attend courses on bioanalytical method validation and pharmacokinetic data analysis as well as relevant conferences. All this will enable the development and validation of bioanalytical methods for TB drugs at the Biotechnology Laboratory in the Kilimanjaro region. The fellow will mentor two next-generation scientists on the principles of bio-analysis of drugs and pharmacokinetic data analysis through PhD and Master training at the Kilimanjaro Christian Medical University College.

The project

The team of experts developed through this proposal will continue to design and conduct pharmacokinetic studies focused on infectious disease threats in Tanzania and contribute to the global effort to fight poverty-related infectious diseases.

Impact


test the safety and efficacy of this new formulation in young children

Bringing antiretroviral drugs to children

The CHAPAS trials have ensured that many more children with HIV have benefited
from life-saving antiretrovirals.

EDCTP portfolio: HIV & HIV-associated infections

The challenge

Tuberculosis (TB) treatment outcome is not only impaired by co-morbidities such as HIV infection, but also by insufficient consideration of the relationship between the dosing of the administered TB drugs, the concentrations achieved, and eventually, the desirable and undesirable responses. Especially dosing of TB drugs for children is not well substantiated and the concept of using higher doses of rifampicin has not been translated to the treatment of children.

Dr Semvua proposed to conduct a phase IIa dose-finding clinical study to find the rifampicin dose in children that yields plasma concentrations similar to those achieved in adults after a 35 mg/kg daily dose. This will answer an important scientific question of direct public benefit.

As regards capacity development, the fellow will receive hands-on training from a mentor of the Radboudumc, an academic research hospital in the Netherlands, during all parts of the study. Skills to perform bio-analysis of TB drugs will be obtained through the pharmacokinetic laboratory at Radboudumc. The fellow will also attend courses on bioanalytical method validation and pharmacokinetic data analysis as well as relevant conferences. All this will enable the development and validation of bioanalytical methods for TB drugs at the Biotechnology Laboratory in the Kilimanjaro region. The fellow will mentor two next-generation scientists on the principles of bio-analysis of drugs and pharmacokinetic data analysis through PhD and Master training at the Kilimanjaro Christian Medical University College.

The project

The later CHAPAS-3 trial compared the efficacy and safety of three fixed-dose combinations including two without stavudine (found to have some long-term side effects in adults, leading to a recommendation that its use be discontinued in children). The trial the first of its kind in Africa studied nearly 500 children at four sites in two African countries.

The team of experts developed through this proposal will continue to design and conduct pharmacokinetic studies focused on infectious disease threats in Tanzania and contribute to the global effort to fight poverty-related infectious diseases.

ratios forfixed-dose combinations and on appropriatedosage according to weight. 

The CHAPAS-3 trial confirmed the effectiveness of fixed-dose combinations, providing further impetus to the rollout of antiretrovirals to children. Its evidence on abacavir informed the WHO recommendation of abacavir-containing combinations for first-line therapy in children. Trial data have also been used to support applications for regulatory approval for new scored efavirenz tablets.

Impact

L’homme RF et al. Nevirapine, stavudine and lamivudine pharmacokinetics in African children on paediatric fixed-dose combination tablets. AIDS. 2008;22(5):557–65.

Mulenga V et al. Abacavir, zidovudine, or stavudine as paediatric tablets for African HIVinfected children (CHAPAS-3): an open-label, parallel-group, randomised controlled trial. Lancet Infect Dis. 2016;16(2):169–79.

WHO. Guidelines on the use of antiretroviral drugs for treating and preventing HIV infection: recommendations for a public health approach. 2010.

WHO. Consolidated guidelines on the use of antiretroviral drugs
for treating and preventing

HIV infection: Recommendations for a public health approach
(second edition). 2016

Projects: Children with HIV in Africa Pharmacokinetics and Adherence of Simple Antiretroviral Regimens (CHAPAS): CHAPAS-1 and -3

Project lead: Professor Chifumbe Chintu, University Teaching Hospital, Zambia (CHAPAS-1); Dr Veronica Mulenga, University Teaching Hospital, Zambia (CHAPAS-3)

Target population(s): Children with HIV

Sample size: 71 (CHAPAS-1); 480 (CHAPAS-3)

Countries involved: Ireland, the Netherlands, the UK, the USA, Zambia (CHAPAS-1); Uganda, Zambia (CHAPAS-3)

Project duration: 2005–2009 (CHAPAS-1); 2010 –2011 (CHAPAS-3)

EDCTP funding: €1.2M (CHAPAS-1); €4.6M (CHAPAS-3)

Total project funding: €1.2M (CHAPAS-1); €5.0M

About us

The European & Developing Countries Clinical Trials Partnership (EDCTP) is a public–public partnership between 14 European and 16 African countries, supported by the European Union. EDCTP’s vision is to reduce the individual, social and economic burden of poverty-related infectious diseases by affecting sub-Saharan Africa. EDCTP’s mission is to accelerate the development of new or improved medicinal products for the identification, treatment and prevention of infectious diseases, including emerging and re-emerging diseases, through pre- and postregistration clinical studies, with emphasis on phase II and III clinical trials. Our approach integrates conduct of research with development of African clinical research capacity and networking. The second EDCTP programme is implemented by the EDCTP Association supported under Horizon 2020, the European Union’s Framework Programme for Research and Innovation.

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