MOAB0305 - Oral Abstract
A phase 2 trial of novel anti-tuberculosis regimens with increased efficacy and low potential to interact adversely with antiretroviral therapy
Presented by Stephen Murray (United States).
D. Everitt1, S. Murray2, A. Diacon3, R. Dawson4, J. Hutchings4, C. Van Niekerk5, E. Egizi2, P. Becker6
1TB Alliance, Research & Development, New York, United States, 2TB Alliance, New York, United States, 3Stellenbosch University, Cape Town, South Africa, 4University of Cape Town, Cape Town, South Africa, 5TB Alliance, Pretoria, South Africa, 6Medical Research Council of South Africa, Johannesburg, South Africa
Background: PA-824 (Pa) and
bedaquiline (B) (TMC) are novel compounds in phase 2 development with
established Early Bactericidal Activity (EBA) over 14 days. The study presented is an EBA study that
evaluated these drugs alone or in combination with each other and with
moxifloxacin (M) and pyrazinamide (Z) to identify a regimen with the potential
to shorten treatment of TB in patients without the use of rifamycins or other
drugs that interact adversely with antiretroviral Therapy (ART).
participants enrolled (26% F, 74% M, including 6 HIV+) as five cohorts of 15 TB
patients, each who received daily dosages of B alone, B with Z, B with Pa, Pa
with Z and Pa with M and Z. A cohort of
8 patients received daily standard TB treatment (isoniazid, rifampin, Z and
ethambutol: HRZE) as a control for the EBA quantitative mycobacteriology. The primary
efficacy endpoint was the rate of change in number of colony forming units (CFU)
of Mycobacterium tuberculosis per ml
of sputum incubated on agar plates from serial sputum collections over the
period Day 0 to Day 14.
Results: All cohorts
had decreases in logCFU counts/ml of sputum from Days 0 to 14 that ranged from
1.2 - 2.7 over 14 days. While Z
potentiated the activity of both B and Pa and compared favorably with the HRZE
standard regimen, the cohort with the combination Pa-M-Z had numerically the
greatest effect on CFU reduction.
Conclusions: The combination
regimen of Pa-M-Z has potent bactericidal activity over 14 days in patients
with pulmonary TB and has the potential to treat both Drug Sensitive- and Drug
Resistant-TB (contains no INH or rifampicin) without adverse clinical
interactions with ART. This regimen has
been taken into an 8 week trial to treat DS- and DR-TB in patients with and
without HIV infection.
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