A large clinical trial to assess the efficacy of delamanid in preventing people from developing multidrug-resistant tuberculosis (MDR-TB) has commenced.
The study will compare the efficacy and safety of the new drug, which used in the treatment of active MDR-TB, with the decades-old TB drug isoniazid for preventing active MDR-TB disease in children, adolescents and adults at high risk who are exposed to adult household members with MDR-TB.
Isoniazid is the standard drug for TB prevention in many of the study’s host countries.
The study investigators hypothesise that prophylactic treatment with delamanid will prove better than isoniazid at reducing the likelihood that at-risk household members of individuals with MDR-TB will develop active TB disease.
Study participants are at high risk for MDR-TB because they either have latent TB infection, immune systems suppressed by HIV or other factors, or are younger than age 5 years and therefore have a weak immune system.
The phase 3 clinical trial is called PHOENIx MDR-TB, short for Protecting Households on Exposure to Newly Diagnosed Index Multidrug-Resistant Tuberculosis Patients.
“We urgently need to halt the spread of MDR-TB,” said Gavin Churchyard, MBBCh., MMed., PhD., founder and chief executive officer of the Aurum Institute for Health Research in Johannesburg, who leads the study.
The PHOENIx MDR-TB study will take place at more than 27 sites in at least 12 countries, including Botswana, Brazil, Haiti, India, Kenya, Peru, the Philippines, South Africa, Tanzania, Thailand, Uganda and Zimbabwe.
The study team will enroll approximately 5,610 participants, including 2,158 adults ages 18 and older who are being treated for confirmed active MDR-TB through their country’s national TB treatment programme and 3,452 members of their households who are at high risk for developing active TB disease.
The participating household members will be assigned at random to receive either oral delamanid daily for 26 weeks or oral isoniazid plus vitamin B6 daily for 26 weeks. All at-risk members of the same household will receive the same drug regimen.
Both delamanid and isoniazid have minimal potential for interacting with the antiretroviral drugs used to treat HIV.
The study team will follow participants for 96 weeks to see if they are protected from active TB disease. Final results from the trial are expected in 2024.
“A highly effective preventive TB therapy for vulnerable household members of people with active MDR-TB disease would be a game-changer in TB care,” said Dr Hesseling, who chairs the International Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT) Network’s Tuberculosis Scientific Committee said in a statement.
IMPAACT Network and the AIDS Clinical Trials Group (ACTG), both funded by NIH, are conducting the PHOENIx MDR-TB study.
The study is co-funded by NIAID and the Eunice Kennedy Shriver National Institute of Child Health and Human Development, also part of NIH. The manufacturer of delamanid, Otsuka Pharmaceutical Co., Ltd. of Tokyo, is donating the drug to the trial.