NCT05807399

PanACEA - STEP2C -01

A Multiple-arm, Multiple-stage (MAMS), Phase 2B/C, Open-label, Randomized, Controlled Platform Trial to Evaluate Experimental Arms Including Optimised Use of Existing and Introduction of Novel Anti-tuberculosis Drugs, in Adults With Newly Diagnosed, Drug-sensitive, Smear-positive Pulmonary Tuberculosis

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 390 (estimated)
• Sponsor: Michael Hoelscher · Academic / Other
• Sex: All
• Age: 18 Years – 65 Years
• Healthy volunteers: Not accepted

Summary

This is a phase 2B/C, open label platform study that will compare the efficacy, safety of experimental regimens with a standard control regimen in participants with newly diagnosed, drug sensitive pulmonary tuberculosis. In stage 1, participants will be randomly allocated to the control or one of the 2 rifampicin-containing experimental regimens in the ratio 1:1:1. In stage 2, the experimental arm 4 containing BTZ-043 will be added. The allocation ratio will be changed to co-enrol the remaining participants in arms 1- 3 simultaneously with arm 4 in a ratio of 1:1:1:2. When arms 1-2 are fully enrolled and arm 4 is not, further participants will be randomized 1:1 to control and experimental arm 4. Not all countries will participate in stage 2. In stage 3, participants will be allocated in parallel to control arm treatment (now designated arm 7) or the experimental arms 5 and 6, favouring arm 5, 2:1:1 over arms 6 and control. This stage will start after completion of recruitment in the stages 1 and 2. Enrolment of participants into arm 5 will proceed following review of data from the ENABLE/UNITE-03 (NCT06748937), non-clinical safety data and after endorsement by the DSMB. Thus, arm 5 recruitment might start after arms 6 and 7, which may require an increase in the control arm sample size to ensure controls are recruited concomitantly.

Detailed description

This open label, phase 2B/C , randomized, controlled platform trial, will evaluate experimental arms including regimens with optimized doses of rifampicin, pyrazinamide, and moxifloxacin; a regimen with BTZ-043 combined first-line anti-TB drugs; a regimen with alpibectir-boosted ethionamide replacing isoniazid in combination with first-line anti-TB durgs, and a bedaquiline sparing regimen containing new anti-TB drugs (ganfeborole, BTZ-043 and delpazolid) in adults with newly diagnosed, drug sensitive, smear-positive pulmonary tuberculosis A total of up to 390 (270 for stage 1 and 2, and 120 for stage 3, respectively) adult (≥ 18 years of age) participants will be enrolled. In case of a high number of dropouts or non-evaluable participants, it may be necessary to recruit more participants into the study. Also, if the stage 2 starts later than stage 1, it may be necessary to increase the number of control arm participants to achieve a 1:1 ratio of concomitantly recruited control and arm 4 participants until the recruitment for arm 4 is completed (see sample size considerations). Stage 3 will start after stages 1 and 2 complete recruitment.

Conditions

• Pulmonary Tuberculosis
• Other Specified Pulmonary Tuberculosis

Interventions

Type	Name	Description
DRUG	BTZ-043	BTZ-043 1000mg once daily in arms 4 and 6.
DRUG	Rifampicin	Rifampicin will be dosed in a fixed high-dose (2100 mg for arms 1 and 2) or a weight-banded regular dose (10 mg/kg) in arm 3, 5 and 7.
DRUG	Isoniazid	Isoniazid will be dosed at fixed dose of 300mg in arms 1 and 2, and regular dose of 5 mg/kg in arm 3 and 7.
DRUG	Pyrazinamide	Pyrazinamide will be dosed in a fixed regular dose in arm 1 (1600 mg), a weight banded high dose in arm 2 (2000/2400 mg) or a weight-banded regular dose (25 mg/kg) in arm 3, 5 and 7.
DRUG	Moxifloxacin	Moxifloxacin will be dosed at 600 mg orally once daily in arms 1-2.
DRUG	Alpibectir (GSK3729098)	Alpibectir 45 mg OD plus Ethionamide 500 mg OD combined with rifampicin pyrazinamide and ethambutol at standard weight-banded doses in arm 5.
DRUG	Ganfeborole (GSK3036656)	Ganfeborole 20 mg OD in arm 6
DRUG	Delpazolid (LCB01-0371)	Delpazolid 1200mg OD in arm 6
DRUG	Pretomanid (Pa)	Pretomanid 20mg OD in arm 6.
DRUG	Ethambutol (E)	Ethambutol 20mg/Kg OD in arm 3, 5 and 7
DRUG	Ethionamide	Ethionamide 500mg OD in arm 5.

Timeline

• Start date: 2023-04-14
• Primary completion: 2027-10-31
• Completion: 2027-12-30
• First posted: 2023-04-11
• Last updated: 2025-10-07

Locations

10 sites across 6 countries: Gabon, Malawi, Mozambique, South Africa, Tanzania, Uganda

Regulatory

• FDA-regulated drug study