A clinical trial will examine an investigational drug's early bacteria-killing activity in patients newly diagnosed with drug-sensitive pulmonary tuberculosis. The clinical trial-sponsored by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health-is being led by researchers at the Tuberculosis Research Unit at Case Western Reserve University in Cleveland. The study to take place in Cape Town, South Africa, will enroll 75 men and women with TB ages 18 to 65, including individuals who are also infected with HIV but not yet taking antiretroviral treatment.
In 2011, 8.7 million people worldwide became infected with TB, and 1.4 million people died, according to the World Health Organization. Co-infection with TB causes one quarter of all deaths among those infected with HIV. South Africa has the highest TB infection rate in the world and accounts for 5 percent of the global TB burden. The country also has the highest TB/HIV co-infection rate, 73 percent.
"New, simplified treatments that cure TB infection more quickly are desperately needed," said NIAID Director Anthony S. Fauci, M.D. "It has been nearly 50 years since a new drug specifically developed for TB was licensed. This is a relatively small study, but we hope it yields insights into whether this investigational drug shows promise in people who are newly diagnosed with TB, as laboratory and earlier clinical safety trials indicate it might."
The clinical trial will assess the investigational TB drug developed by AstraZeneca, based in London. In laboratory testing, the drug proved active against a wide range of drug-sensitive and drug-resistant strains of Mycobacterium tuberculosis (Mtb), the bacterium that causes TB disease. In two preliminary human studies in the United States, testing multiple doses, the oral drug was generally well-tolerated. Some study participants experienced gastrointestinal and blood-related adverse events at higher doses, but these effects were reversible and not serious.
To be eligible to participate in the new trial, patients must have newly diagnosed pulmonary TB as confirmed through a positive sample of mucus and saliva (sputum). HIV-infected patients who are not currently taking antiretrovirals and who have a CD4+ T-cell count of greater than 350 cells per cubic millimeter are eligible for the study. CD4+ T-cells are a key marker of immune system health.
Study volunteers will be randomly assigned to one of five study groups, each with 15 participants. In four groups, all participants will receive a 14-day regimen of the experimental drug, but at different dosages and frequencies: 500 milligrams (mg) once daily; 500 mg twice daily; 800 mg twice daily; and 1200 mg twice daily.
The study lasts only 14 days because of the potential risk of drug resistance emerging in TB patients receiving a single drug for a prolonged period of time.
Participants in the fifth study group will receive the standard TB treatment of 14 days of rifafour-a four-drug combination pill containing isoniazid, rifampin, ethambutol and pyrazinamide-dosed according to the study participants' body weight. After the 14-day study, all participants will receive standard TB drugs to treat their disease.
Researchers will examine daily sputum samples from the study participants to determine whether the investigational drug is reducing their TB bacteria counts, and if so, to what extent.