20 January 2017 — A pioneering new clinical trial aiming to find a radically improved course of treatment for drug-resistant tuberculosis (TB) began on 17th January 2017, when the first patient took the first pill in Uzbekistan.
The phase II/III trial, called TB PRACTECAL, aims to find a treatment regime for drug resistant TB that is drastically shorter, at six months long, more effective and has less debilitating side effects than current treatment.
The trial is run and sponsored by the international medical humanitarian organisation Médecins Sans Frontières/ Doctors Without Borders (MSF) and is supported by the London School of Hygiene & Tropical Medicine as well as other leaders in medical research1.
It is a full phase III clinical trial combining two new anti-TB drugs (bedaquiline and pretomanid). This will maximise the potential of the trial to develop radically improved treatment for people with either multi drug-resistant TB and the even more resistant, extensively drug-resistant TB. The two new drugs will be given in combination with existing drugs for tackling drug-resistant TB (linezolid, clofazimine and moxifloxacin).
Long treatment and painful side effects
Despite killing more people than HIV2, TB is woefully underfunded.
Medicines for TB have barely improved over the last 50 years. And the number of strains of TB resistant to current medicines is increasing at an alarming rate.
Currently patients with drug-resistant TB are on medicine for almost two years during which time they must swallow more than 10,000 pills and have painful daily injections for at least 8 months. Side effects from treatment are often incapacitating, including nausea, joint pains, psychosis and going permanently deaf.
MSF has been calling on politicians, global health bodies and pharmaceutical companies to address this TB crisis, but in the face of insufficient movement has now decided to take action itself. MSF has played a catalytic role in providing TB and drug resistant TB care for 30 years and is now running two clinical trials. The other, end-TB, is due to start in Georgia later this year.
The first patient on the TB PRACTECAL trial is based at the MSF supported hospital in Karakalpakstan, in North West Uzbekistan. They are the first of 630 patients, to be recruited from Uzbekistan, Belarus and South Africa.
The trial process
The trial will run in two stages. The first stage is a phase II trial finishing in 2018. It will test three different regimes containing new drugs, bedaquiline and pretomanid. The second stage is a phase III trial which will continue to test the two most successful regimes and will end in 2020.
Dr Bern-Thomas Nyang’wa, MSF’s TB specialist and Chief Investigator on the trial says:
“MSF is one of the biggest non-government providers of TB care in the world and we refuse to wait years or even decades for new treatment, while thousands of our patients continue to suffer long, toxic and failing treatments. Despite aggressive treatment, only half of people with drug resistant TB globally are cured3. The current TB regimes are simply inadequate.
“This is an exciting milestone in an important research project that could save hundreds of thousands of lives. The results cannot come sooner.”
On the path to finding a treatment package
Professor David Moore at the London School of Hygiene & Tropical Medicine says:
“We’re thrilled that this crucial large scale clinical trial for the treatment of drug resistant TB has started. “We know these two new drug classes have shown promising signs of tackling drug resistant TB microbes, and there are emerging signals from other therapeutic regimens that we should be able to safely shorten treatment courses and improve patient outcomes.
“If the findings of this trial fulfil the promise of earlier studies, particularly if we are able to effectively treat drug-resistant TB without the need for the tyrannical daily injections, we are on the path to finding a treatment package that could make a huge difference to the hundreds of thousands of multi drug resistant TB patients, and their families, that need treatment every year.”
Building on promising results
Professor Nargiza N Parpieva, Director of the Republican specialised scientific-practical medical centre of physiology and pulmonology in Uzbekistan says:
“Uzbekistan is working hard to address the challenge of drug resistant TB. The Ministry of Health of the Republic of Uzbekistan, the national TB program in partnership with international organizations, including MSF, has cared for, diagnosed and supported thousands of patients over the last 13 years.
“Treatment is long and arduous but if we explain to our patients, their families and medical staff directly involved in the trial the importance of this new approach to treating drug resistant TB we can achieve good results for this complex category of patients.
“It’s invaluable that our patients, doctors and colleagues now have the chance to spearhead better treatment for patients with drug resistant TB in Uzbekistan and around the world.”
Mel Spigelman, Managing Director, President and CEO, TB Alliance says:
“We’re very excited about the launch of TB-PRACTECAL and partnering with MSF. This study will build on the promising results found in two of TB Alliance’s late-stage clinical trials, which have studied bedaquiline and pretomanid in combination with other drugs. Combining novel drugs holds the key to revolutionizing TB treatment in all its forms.”
1 The full list of partners is: London School of Hygiene and Tropical Medicine (LSHTM), University College London (UCL), Drugs for Neglected Diseases initiative (DNDi), Swiss Tropical and Public Health Institute (Swiss TPH), World Health Organization’s Special Programme for research & Training in Tropical Diseases (TDR), Global Alliance for TB Drug Development, Ministry of Health in Republic of Uzbekistan, Ministry of Health of the Republic of Belarus and THINK TB and HIV Investigative Network.
2 Global Tuberculosis Report 2016, WHO, page 5 http://apps.who.int/iris/bitstream/10665/250441/1/9789241565394-eng.pdf?ua=1
3 See MSF’s TB briefing paper https://www.msf.org.uk/sites/uk/files/TB_briefingpaper.pdf