The priMe study will reveal whether a promising alternative to BCG is safe and effective for use in newborn infants.

Building a successor to BCG

The BCG (Bacillus Calmette-Guérin) vaccine has been used to vaccinate against TB since the 1920s. It is reasonably effective at preventing serious disease, but many vaccinated infants still develop TB meningitis and it appears to have little impact on the spread of pulmonary TB. Modelling studies suggest that, despite BCG, around 7.5 million children were infected with Mycobacterium tuberculosis in 2010 and 650,000 developed TB disease.

BCG is a weakened or attenuated version of Mycobacterium bovis, a relative of M. tuberculosis that causes TB in cattle. Researchers have recently revisited M. bovis and introduced precise genetic changes that cause it to stimulate stronger immune responses and make it safer for use in individuals with HIV, who sometimes suffer reactions to conventional BCG.

The challenge

The large-scale phase III priMe study will build on promising preliminary trials, in adults and children, of this updated version of BCG, known as VPM1002. Aiming to recruit around 7000 newborns, it will provide definitive evidence of the safety and efficacy of VPM1002 in both HIV-free and HIV-infected newborn infants.

The project

Positive findings would indicate that VPM1002 is a suitable alternative to BCG, widely recognised to be an imperfect vaccine but included in most countries’ routine immunisation programmes; it would also provide a suitable vaccine for infants with HIV. Furthermore, production methods for VPM1002 are relatively simple and straightforward to scale up, so the vaccine could meet global demand and overcome some of the supply difficulties recently experienced with BCG. The priMe study will also generate important data on the immune responses associated with good protection against M. tuberculosis, to enhance the design of future vaccines.

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

The BCG (Bacillus Calmette-Guérin) vaccine has been used to vaccinate against TB since the 1920s. It is reasonably effective at preventing serious disease, but many vaccinated infants still develop TB meningitis and it appears to have little impact on the spread of pulmonary TB. Modelling studies suggest that, despite BCG, around 7.5 million children were infected with Mycobacterium tuberculosis in 2010 and 650,000 developed TB disease.

BCG is a weakened or attenuated version of Mycobacterium bovis, a relative of M. tuberculosis that causes TB in cattle. Researchers have recently revisited M. bovis and introduced precise genetic changes that cause it to stimulate stronger immune responses and make it safer for use in individuals with HIV, who sometimes suffer reactions to conventional BCG.

The large-scale phase III priMe study will build on promising preliminary trials, in adults and children, of this updated version of BCG, known as VPM1002. Aiming to recruit around 7000 newborns, it will provide definitive evidence of the safety and efficacy of VPM1002 in both HIV-free and HIV-infected newborn infants.

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.

Positive findings would indicate that VPM1002 is a suitable alternative to BCG, widely recognised to be an imperfect vaccine but included in most countries’ routine immunisation programmes; it would also provide a suitable vaccine for infants with HIV. Furthermore, production methods for VPM1002 are relatively simple and straightforward to scale up, so the vaccine could meet global demand and overcome some of the supply difficulties recently experienced with BCG. The priMe study will also generate important data on the immune responses associated with good protection against M. tuberculosis, to enhance the design of future vaccines.

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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