Cape Town, 18 September 2023 – The Unitaid-funded IMPAACT4TB Consortium, led by the Aurum Institute, in collaboration with TASK and the Desmond Tutu Tuberculosis (TB) Centre at Stellenbosch University has launched an important new clinical trial, RPT CRUSH. This innovative study aims to determine whether crushed tablets of rifapentine formulations and isoniazid can maintain the same effectiveness as whole tablets when it comes to treating latent TB infection This pivotal study, which focuses on the three-month weekly Rifapentine and Isoniazid (3HP) regimen, has the potential to significantly improve access to TB preventive treatment for children in high-TB burden TB endemic settings.
This research is part of the broader IMPAACT4TB project, which began in 2017 and is dedicated to the introduction of shorter, rifapentine-based TPT (TB preventive treatment) options with improved adherence, completion rates, and outcomes. The project has successfully supported the introduction of these regimens in 12 countries around the globe, catalysing orders for rifapentine-based TPT regimens in an additional 56 countries. The project also significantly helped reducing the cost of a three-month patient course of weekly rifapentine and isoniazid (3HP), from US$72 to US$14,25 through collaboration with global partners and manufacturers.
The IMPAACT4TB Consortium received additional funding from Unitaid—totalling US$20 million – to support the continued efforts to introduce short course, rifapentine-based TB prevention treatment regimens worldwide, with a particular focus on enhancing access for children. The funding, awarded to the Aurum Institute, builds on the momentum created by the IMPAACT4TB Consortium from 2017-2022, focusing specifically on evidence required to ensure that children and pregnant women, including those living with HIV, and household contacts have access to the latest TB prevention regimens.
Tuberculosis remains a significant global health concern, with millions of individuals at risk of contracting the disease, especially in regions with high prevalence of TB. Children are at high risk of TB and severe manifestations of TB and TB mortality. The 3HP regimen is a crucial component of TB prevention efforts, offering a shorter and more manageable treatment option for children exposed to TB. However, access to child-friendly formulations has been a challenge for children.
The primary objective of this innovative study is to determine whether crushed tablets of rifapentine and isoniazid, sourced from generic manufacturers, maintain the same amount of medicines in the body required to eliminate TB bacteria and therapeutic effectiveness as the whole tablets. By comparing the two methods of administration, the goal is to find a practical solution that will expand the reach of the 3HP regimen to children and others who may struggle with swallowing pills. This is an important practical option for children until a child-friendly dispersible tablets become widely available. In addition, it addresses the challenges of supplying drugs for children in low resource settings.
Professor Anneke Hesseling, the Sponsor Representative of this trial, Stellenbosch University, says that “This study has the potential to break down barriers to accessing TB preventive therapy, especially in young children where giving medications is the most challenging. By exploring the use of crushed tablets, we hope to make this life-saving treatment more accessible and reduce the risk of TB in children, where the vast majority of TB is preventable. Knowing how to use existing adult formulations best and safely in children is a crucial step towards children accessing more optimal treatment in future.”
The clinical trial will involve 24 participants with TB infection, from Cape Town, South Africa. Participants will be closely monitored throughout the study to assess the safety and amount of medicines in the body required to eliminate TB bacteria of the crushed tablet administration compared to whole tablets. Three different generic formulations will be compared to maximize the impact of this study translating into access to TB preventive treatment in the field.
This research initiative is made possible through funding from Unitaid through the IMPAACT4TB project, in collaboration with AURUM, Desmond Tutu Tuberculosis TASK and the University of Uppsala, Sweden, who share our commitment to advancing TB prevention and treatment options worldwide. The results of this clinical trial could have a profound impact on global TB control efforts to prevent TB in children, offering a practical solution to expand the reach of the 3HP regimen in high-burden settings.
Notes to editors
About Unitaid: Unitaid is a global health agency engaged in finding innovative solutions to prevent, diagnose and treat diseases more quickly, cheaply, and effectively, in low- and middle-income countries. Its work includes funding initiatives to address major diseases such as HIV/AIDS, malaria, and tuberculosis, as well as HIV co-infection and co-morbidities such as cervical cancer and hepatitis C, and cross-cutting areas, such as fever management. Unitaid is hosted by the World Health Organization. www.unitaid.org
About IMPAACT4TB: The Increasing Market and Public Health Outcomes Through Scaling Up Affordable Access Models of Short Course Preventive Therapy For TB (IMPAACT4TB) consortium is led by the Aurum Institute and comprised of the Clinton Health Access Initiative (CHAI), Johns Hopkins University, KNCV the Dutch TB Foundation and the Treatment Action Group (TAG).
People living with HIV (PLHIV) and child contacts are at highest risk of contracting TB. The initial IMPAACT4TB grant looked at the safety of co-administering and dosing of 3HP and DTG and, once that was ascertained, the project moved on to introduce and rollout 3HP as an additional TPT option among PLHIV and household contacts of TB patients in 12 low-middle income countries, namely: Brazil, Ethiopia, Cambodia, Indonesia, South Africa, India, Zimbabwe, Kenya, Malawi, Mozambique, Ghana and Tanzania.
Although the project was focused in these 12 countries, efforts were also made to ensure wider access to 3HP. These efforts saw 23 additional countries procuring 3HP for use among eligible populations. The grant also funded studies on the use of 3HP in ART-naive patients on DTG based regimens (DOLPHIN TOO), dosing of 3HP in children from 0-2 years (TBTC Study 35), improved TPT service delivery as well as community advocacy for improved TPT policy and uptake within project countries.
About Aurum: Established in 1998, the Aurum Institute is an African Public Benefit Organization whose mission is to improve the health of people and communities living in poverty through innovation in global health research, systems, and delivery. It is rooted in Africa and is dedicated to researching, supporting, and implementing innovative, integrated approaches to global health with its headquarters in South Africa with offices in the U.S.A, Ghana, and Mozambique. The Aurum Institute has developed itself into a leading player, bridging the worlds of research, policy, and implementation for impact. www.auruminstitute.org
About the Desmond Tutu TB Centre: The Desmond Tutu Tuberculosis Centre (DTTC) is an academic research centre located in the Department of Paediatrics and Child Health, Faculty of Medicine and Health Sciences, Cape Town, South Africa, established in 2003. In 2004, Archbishop Emeritus Desmond Tutu, who suffered from tuberculosis as a child, became its patron and the centre was formally named.
The goals of the centre are designed on a strategy built on basic and applied research, as well as on the training of students and communities in all aspects of tuberculosis (TB). The Centre operates from the premise that grassroots research must never be underestimated; including working with communities and investigations into the everyday challenges of people infected and affected by TB and HIV. Its endeavours are proof that successful treatments in clinics, health centres and even in people’s homes, are not detached from research, but are in fact interdependent on each other. Central to the DTTC’s work is the dissemination of information back to the research communities in addition to other appropriate stakeholders, including health services.
About TASK: TASK is a multinational, multi-site clinical research institute committed to improving global health through testing and progressing novel medicines, vaccines and diagnostics in various therapeutic areas. TASK provides world class clinical trial services through the dedicated Phase I unit in Utrecht in collaboration with UMC Utrecht, as well as 6 clinical sites in South Africa offering Phase I – IV trial services from protocol development through to statistical analysis. TASK’s vision of better healthcare for everyone drives their mission to provide a platform for the development of novelties in healthcare that benefit the community. Established in 2005, to date the company has completed more than 100 projects for both international sponsors as well as consortiums, consisting of top academic and government institutions. TASK is a partner in the biggest Tuberculosis (TB) consortium in history with the ambitious goal of creating a new TB regimen.