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PreDiCT-TB

Model-based preclinical development of anti-tuberculosis drug combinations

Summary

 

Tuberculosis (TB) infects over 9 million people worldwide every year and kills 1.7 million. Treatment takes several months, and many patients struggle to take their antibiotics properly, fuelling the rise of drug-resistant strains of the disease. However, putting together a new, shorter treatment regimen could take a quarter of a century using today’s methods. The IMI-funded PreDiCT-TB project aims to speed up the search for new, more effective combinations of treatments to tackle the deadly disease. PreDiCT-TB is one of the world’s only initiatives focused on tackling pre-clinical research barriers to the discovery and development of new TB drug combinations.

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TB is an airborne, infectious disease caused by the bacterium Mycobacterium tuberculosis. It usually affects the lungs, and symptoms include coughing, weight loss, night sweats, fever, and fatigue. Although it is both preventable and curable, it remains a leading cause of disease and death by infection, particularly in developing countries. TB treatment is tough; patients must take four antibiotics for at least six months. The length and complexity of this regimen mean that many patients do not take their treatment properly, or stop taking the drugs before the bacteria have been completely eradicated from the body. Thus poor compliance may well be driving a rise in multidrug-resistant (MDR) strains of TB that simply do not respond to the main first-line antibiotics. If the treatment regimen for standard TB is tough, the regimen for MDR TB is even tougher, taking upwards of two years and involving drugs that often cause severe side effects such as liver, skin and hearing problems. In addition, recent years have seen growing reports of extensively drug resistant (XDR) TB, which does not respond to a number of the core first and second line antibiotics.

There is therefore an urgent need to develop a more potent, yet patient-friendly, combination of drugs to tackle TB. However, very few new TB drugs have been developed in recent decades. Furthermore, to prevent TB from developing resistance, it must be treated with a combination of multiple drugs. Until now, new drug candidates were developed and added to the existing regimen one by one. As it takes at least six years to change one drug in the regimen by either substitution or addition, approving a new four-drug regimen through successive trials would take a quarter of a century.  Shortening this period is a top priority for the fight against TB, but current clinical trial methodologies make it very difficult to evaluate the optimal doses and combinations of drugs.

PreDiCTing the best treatment regimens
We need a way to facilitate the complex decisions around which doses and combinations of new drugs should enter clinical trials, and that’s where the PreDiCT-TB project will focus its combined resources.  PreDiCT-TB aims to develop an integrated set of laboratory-based models that will provide much-needed data to indicate the most appropriate doses and combinations of drugs for patients. In addition, the project will generate a comprehensive database of patient data from previous and on-going clinical trials for use as a reference for evaluating the performance of combination anti-TB drug regimens in these newly developed laboratory models.  Ultimately, they aim to enable researchers to be able to use the information generated by the novel models to design better clinical trials involving TB patients.  Therefore PreDiCT-TB brings together internationally-respected TB scientists and physicians with expertise in the biology, immunology and imaging of the disease, as well as those specialising in the behaviour of drugs in the body (pharmacokinetics), their interactions with one another (pharmacodynamics), and clinical trials.

A boost for TB patients
Today’s long, complex TB treatment regimen is simply not patient-friendly enough and potentially raises the risk of patients developing (and passing on to others) drug-resistant forms of the disease. By speeding up the development of better and shorter treatment regimens, PreDiCT-TB should dramatically increase the likelihood of patients completing the course of treatment successfully in future years.

New leads for the industry
By assessing combinations of new candidate drugs and optimising clinical trial design, PreDiCT-TB is set to revolutionise the speed and effectiveness of drug discovery and development in the field of TB.

Making good on a promise
Tackling TB is a high priority for governments worldwide; the international Stop TB Partnership has set the goal of eliminating TB as a global public health problem by 2050. The results of PreDiCT-TB are set to give a new impetus to efforts to deliver novel treatments against this deadly disease.
 

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Achievements & News

IMI and C-Path tuberculosis projects sign Memorandum of Understanding
IMI’s PreDiCT-TB and C-Path’s CPTR projects have signed a Memorandum of Understanding to coordinate their work in developing new and effective treatment regimens for tuberculosis (TB). ###TB is a leading cause of death worldwide, with nearly 9 million new cases and 1.4 million deaths reported every year. A major challenge for those tackling the disease is the length of TB treatment – even standard cases require at least six months of treatment with a multi-drug regimen, while drug-resistant strains of the disease can take two years to treat. Both PreDiCT-TB and CPTR are working to speed up the development of shorter, more patient-friendly treatment regimens. By working together, the teams will be able to combine their forces to take on the challenges in this area more effectively.
(March 2013)


Participants

 

EFPIA

  • GlaxoSmithKline Investigación y Desarrollo SL, Tres Cantos, Spain
  • Sanofi-Aventis Research & Development, Chilly Mazarin, France
  • Janssen Infectious Diseases – Diagnostics BVBA, Beerse, Belgium

Universities, research organisations, public bodies, non-profit groups

  • University of Liverpool, Liverpool, UK
  • École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland
  • Erasmus University Medical Centre Rotterdam, Rotterdam, the Netherlands
  • Health Protection Agency, London, UK
  • Institut Pasteur, Paris, France
  • Liverpool School of Tropical Medicine, Liverpool, UK
  • Max Planck Gesellschaft zur Förderung der Wissenschaften E.V., Munich, Germany
  • St George’s University of London, London, UK
  • Universidad Carlos III de Madrid, Madrid, Spain
  • University College London, London, UK
  • University of Leicester, Leicester, UK
  • University of St Andrews, St Andrews, UK
  • Uppsala universitet, Uppsala, Sweden

Patients’ organisations

  • Vrije Universiteit Medisch Centrum, Amsterdam, the Netherlands

SMEs

  • Microsens Medtech Ltd, London, UK
  • ZF-Screens BV, Leiden, the Netherlands

Facts & Figures

Start date 01/05/2012
Duration  60 months
   
Contributions    €
IMI funding 14 800 000
EFPIA in kind   9 300 000
Other   4 500 000
Total cost 28 600 000

Links and Documents

Project website: www.predict-tb.eu

IMI funding per project participant

Contact

 

Project Coordinator
Justin Green
GlaxoSmithKline

Tel: +44 20 8990 2092
E-mail: justin.a.green[AT]gsk.com

Managing Entity
Geraint Davies
University of Liverpool

Tel: +44 151 428 0422
E-mail: gerrydavies[AT]doctors.org.uk