A71-04 Novel 4-month Pan-TB Regimens Promoting Recovery of Lung Function: Preliminary Findings of the PanTB-HM Phase 2c Trial
R S Wallis, D Mudzengi, S Mashatole, N Glover, T Ngwanto, S Boniface, W Brumskine, A Bhoola, M Rassool, N Ntinginya, J Lalashowi, M Moyo, Q Xiang, L Paramo, E Basson, I Sabi, T Nielson, E Fumane, J Horne, R Macuiana, J Bennet, R Kunambi, D Mapamba, T Beattie, S Charalambous, L Zurba, V Maphossa, J Mdluli, M Spigelman, C Nacy, M Nell, N Heinrich, C Khosa, C Venter, J Booth, D Schoeman, R Keyter, E Svensson, S Koele, S Rajaram, E Sichone, L Botha, C Barker, S Foraida, A RachowAbstract
Rationale
There is an urgent need for safer, shorter treatments for pulmonary tuberculosis that do not require drug susceptibility testing and that aid lung function recovery.
Methods
panTB-HM compared 3 novel 4-month pan-TB regimens to standard 6-month treatment (HRZE) in a phase IIC trial. The regimens included the investigational oxazolidinone sutezolid (S) 1200 or 1600mg daily, bedaquiline (B), pretomanid (P), and N-acetylcysteine (N) 1800mg BID. Participants had culture-confirmed RIF-S-TB and met predefined chemistry and hematology entry criteria. HIV+ individuals with ≥100 CD4+ T cells/ul were eligible if they were either receiving antiretroviral therapy or willing to start during the trial. Participants were randomly assigned to S1200BP, S1600BP, S1600BPN, or HRZE (1:1:1:1). The primary endpoint was durable cure. Secondary endpoints included lung function and safety. All participants provided written informed consent prior to screening. The protocol was approved by relevant ethics and regulatory authorities and was registered on clinicaltrials.gov (NCT05686356). The Aurum Institute served as Sponsor. Adverse events were reported to USFDA with the assistance of the TB Alliance. Oversight was provided by an external safety and data monitoring board.
Results
378 adults in ZA, TZ, and MZ were enrolled from 28-Jul-23 to 3-Feb-25. The median age was 33. The mean FEV1 on entry was 72% of predicted. The last participant visit occurred on 14-Jan-26. 334 adverse events (AEs) occurred during HRZE treatment of control participants vs 212-221 in each experimental arm. There were no differences in the distributions of AE severity. 5 serious AEs (SAEs) occurred that were attributable or possibly attributable to HRZE treatment, vs 1-2 for each experimental treatment. There were no typical oxazolidinone SAEs. Linear mixed effects modelling in participants with impaired baseline lung function (FEV1≤62%, n = 106) showed superior recovery of FEV1% in S1600BPN recipients during days 1-14 (arm*day interaction indicating difference in slope vs HRZE, P=.004). The resulting 10.6 point difference vs HRZE at day 14 (P=.003) was largely maintained through day 168. Other experimental arms showed similar but smaller effects. As of 21-Jan-26, 5, 11, 6 and 6 relapses had been reported in the S1200BP, S1600BP, S1600BPN, and HRZE arms, respectively.
Conclusion
Novel 4-month regimens containing sutezolid and N-acetylcysteine appear poised to meet WHO target regimen profiles for a pan-TB indication and to provide the additional benefit of superior recovery of lung function.
Funding
EDCTP2 RIA2019AMR-2647.
This abstract is funded by: EDCTP RIA2019AMR-2647