The Simplici-TB study is evaluating a new combination of drugs that could significantly shorten treatment times for both drug-sensitive and drug-resistant TB.

Shorter treatment for drug-resistant TB

TB kills more than 1.5 million people every year. Standard treatment involves six months’ use of multiple antibiotics. In addition, multidrug-resistant TB is on the rise – nearly half a million cases were reported in 2016 – and requires even longer and more arduous treatment, with only a 50% chance of cure.

Shortening and simplifying TB drug treatments are major goals in TB research. Shorter regimens would cost less, be easier to implement and easier for patients to manage.

The challenge

The development of highly effective new drugs – particularly bedaquiline and pretomanid – is raising hopes that shorter duration treatments are a realistic possibility.

A recent trial which showed that bedaquiline and pretomanid, combined with two potent currently used drugs (moxifloxacin and pyrazinamide), cleared TB bacteria from the lungs of patients with multidrug-resistant TB up to three times faster than the standard regimen cleared bacteria from patients with drug-sensitive TB – the fastest rate of clearance ever seen in a clinical trial. Following up these positive findings, the Simplici-TB trial is now comparing a four-month course of the new combination to treat drug-sensitive TB and a six-month course to treat multidrug-resistant TB.

The study is being run in partnership with the TB Alliance, a US-based not-for profit organisation, with the African studies forming part of a wider global trial evaluating the new combination.

The project

The Simplici-TB will provide key data on a highly promising new combination treatment for TB. It could accelerate the introduction of a treatment that has a major impact on treatment of both drug-sensitive and drug-resistant TB in sub-Saharan Africa.

Impact


crucial in

widening African

children’s access

to antiretrovirals

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

TB kills more than 1.5 million people every year. Standard treatment involves six months’ use of multiple antibiotics. In addition, multidrug-resistant TB is on the rise – nearly half a million cases were reported in 2016 – and requires even longer and more arduous treatment, with only a 50% chance of cure.

Shortening and simplifying TB drug treatments are major goals in TB research. Shorter regimens would cost less, be easier to implement and easier for patients to manage.

The development of highly effective new drugs – particularly bedaquiline and pretomanid – is raising hopes that shorter duration treatments are a realistic possibility.

A recent trial which showed that bedaquiline and pretomanid, combined with two potent currently used drugs (moxifloxacin and pyrazinamide), cleared TB bacteria from the lungs of patients with multidrug-resistant TB up to three times faster than the standard regimen cleared bacteria from patients with drug-sensitive TB – the fastest rate of clearance ever seen in a clinical trial. Following up these positive findings, the Simplici-TB trial is now comparing a four-month course of the new combination to treat drug-sensitive TB and a six-month course to treat multidrug-resistant TB.

The study is being run in partnership with the TB Alliance, a US-based not-for profit organisation, with the African studies forming part of a wider global trial evaluating the new combination.

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 Simplici-TB will provide key data on a highly promising new combination treatment for TB. It could accelerate the introduction of a treatment that has a major impact on treatment of both drug-sensitive and drug-resistant TB in sub-Saharan Africa.

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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