Shobha Shukla, CNS (Citizen News Service)
(CNS) Taking the encouraging results of its N-005 study one step forward, TB Alliance has initiated SimpliciTB a pivotal clinical study to evaluate the efficacy, safety and tolerability of a novel and potentially shorter 4 drug regimen for patients with drug-sensitive (DS) as well as multi drug-resistant (MDR) pulmonary TB.
The new drug regimen BPaMZ comprising four different antibiotics Bedaquiline (B), Pretomanid (Pa), Moxifloxacin (M) and Pyrazinamide (Z) will be administered for 4 months to patients of DS-TB, and for 6 months to patients with MDR-TB with mono-resistance to rifampicin or isonaizid.
What is SimpliciTB?
SimpliciTB is a pivotal, multi-centric, open-label partially randomized clinical study targeting at least 26 centres in 10 countries in Africa, Asia, Europe and South America. A total of 450 participants (150 per treatment group) will be enrolled and assigned to the following treatment arms:
- Participants with DS-TB will receive BPaMZ daily for 4 months;
- Participants with DS-TB will receive HRZE/HR combination tablets daily for 6 months; and
- Participants with DR-TB (MDR-TB as well as mono-resistance to isonaizid or rifampicin) will receive BPaMZ daily for 6 months.
The study would evaluate if an all-oral BPaMZ drug regimen has the potential to shorten and simplify treatment for both DS-TB and MDR-TB. It will test and compare the efficacy of a 4 month treatment with the BPaMZ regimen, in people with DS-TB, to that of the current 6 month treatment regimen of isoniazid, rifampicin, pyrazinamide and ethambutol (HRZE), to determine whether BPaMZ can shorten the duration of therapy. The study will also assess BPaMZ's potential to treat DR-TB (with mono-resistance to rifampicin or isonaizid) in 6 months. Currently, treatment for MDR-TB is complicated, expensive, and lengthy- lasting for 9 to 24 months- involving a wide variety of medicines that have debilitating side-effects.
The N-005 study
As mentioned earlier, the BPaMZ regimen has been previously studied in a 2 month long Phase 2b N-005 clinical study conducted on 240 patients (180 patients with DS-TB and 60 patients with DR-TB) at 10 sites in 3 countries (Uganda, South Africa, and Tanzania). Study results showed that the best regimen was a combination of all four drugs- BPaMZ-, that resulted in the highest level of bactericidal activity among all its four parallel treatment arms. At the end of 2 months, participants receiving BPaMZ cleared TB bacteria from their sputum 3 times faster than those on the standard (HRZE) treatment regimen, with almost all of them having culture conversion after 2 months of treatment. The study also found that a daily dose of Bedaquiline (200 mg) is at least as active and safe as the labelled dose. This could lead to a simpler daily dosing with fewer pills and an overall less complicated treatment for patients.