Research & Development
Results from Nix-TB Clinical Trial
The Nix-TB clinical trial demonstrated that a three-drug, six-month, all-oral regimen had a favorable outcome rate of 90 percent in people with highly drug-resistant forms of TB. According to the World Health Organization (WHO), historic treatment success rates for multidrug-resistant (MDR) TB have been about 57 percent and about 43 percent for extensively drug-resistant (XDR) TB. Nix-TB is a Phase 3, open-label trial that enrolled 109 patients at three sites in South Africa. Of the 109 patients included in the clinical trial, 71 (65.1%) were classified as having XDR-TB, 19 (17.4%) as having MDR-TB that was non-responsive to treatment, and 19 (17.4%) as having MDR-TB but could not tolerate their therapy. Of all 109 patients, 56 (51.4%) were HIV positive. The 90 percent favorable outcome rate six months after the completion of therapy was similar for both HIV positive and HIV negative patients. Further results of this pivotal trial were published in the New England Journal of Medicine in March 2020.
TB and HIV are a Deadly Duo
While fortunately more and more people are living with HIV, many of them are dying of TB—TB is the leading killer of people with HIV/AIDS. Because highly resistant forms of TB frequently afflicts HIV positive patients, they comprised just over half of the study population. The results of a HIV subgroup analysis were presented by Dr. Morounfolu Olugbosi, senior director of Clinical Development at TB Alliance, in July 2020 at the AIDS 2020 virtual conference. All 56 HIV positive patients were on antiretroviral (ARV) therapy during the study, and all except two had been receiving ARV therapy before enrolling. The results of the Nix-TB trial demonstrated a 90 percent favorable outcome in patients with highly resistant TB, and these results were consistent regardless of HIV status.
Phase 3 Clinical Research Updates
- The Phase 3 ZeNix clinical trial seeks to optimize the linezolid dosing that was used in the BPaL regimen in the Nix-TB study by evaluating the effects of both lower doses and shorter durations of linezolid administration.
- Patients from Georgia, South Africa, Russia, and Moldova are enrolled in the trial, and primary endpoint results are expected in 2021.
- The Phase 3 SimpliciTB clinical trial is evaluating a new regimen to treat both drug-sensitive (DS) and drug-resistant (DR) TB patients. The trial is testing a novel drug combination of bedaquiline (B), pretomanid (Pa), moxifloxacin (M) and pyrazinamide (Z) (known as the BPaMZ regimen).
- Despite challenges due to the emerging COVID-19 pandemic, and with a great effort from partners at clinical trial sites around the world, enrollment in SimpliciTB was completed in March 2020 with participants enrolled at 26 sites in eight countries on four continents.
Phase 1 Research
- In 2020, TB Alliance completed a SAD (Single Ascending Dose) study for TBI-223, with a MAD (Maximal Tolerated Dose) study to begin in early 2021.
- TB Alliance completed Investigational New Drug enabling studies and began Phase 1 trials for TBAJ-876 in 2020
- Clinical-stage testing began in 2020 for TBAJ-587. The compound was advanced in partnership with the Innovative Medicines Initiative (IMI).
Innovation in the EU
TB Alliance continued its partnership with the Innovative Medicines Initiative (IMI), a public-private partnership between the European Union and the European pharmaceutical industry, in order to facilitate the development of medicines, especially in areas of unmet need.
- As part of this program, the ERA4TB project is focused on developing new TB treatments, and in December 2020 a Phase 1 study of TB Alliance’s new compound (TBAJ-587) began and the first dose was administered.
- EU-PEARL is an IMI program aiming to reimagine how clinical trials are designed by making them more efficient and patient friendly. The project focuses on four disease areas: major depressive disorder, tuberculosis, the liver disease nonalcoholic steatohepatitis, and neurofibromatosis.
Dr. Suzette Oelofse
Suzette Oelofse, MBChB, is a Research Medical Officer at the Lung Institute, a part of the University of Cape Town. Dr. Oelofse provides clinical services and conducts research in the field of respiratory medicines, including TB. During the virtual 51st Annual Union Conference on Lung Health, Dr. Oelofse gave an Oral Abstract Presentation of findings on how the Phase 3 Nix-TB clinical trial compared to a prospectively recruited XDR-TB cohort. “I see many patients with these forms of highly resistant TB. I’ve seen how they’ve had to take thousands of pills over the course of many months, and sometimes years, and seen how the treatment still didn’t work for most of them,” said Dr. Oelofse, who treats TB patients in Cape Town, South Africa. “This three-drug, all-oral, six-month regimen has proven efficacy and offers a reduction in pill burden and duration of treatment that could have a meaningful impact for patients. Ongoing operational research programs and additional clinical studies will continue to generate valuable evidence for its safety and efficacy.”