PanACEA - STEP2C -01

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.

Conditions

• Pulmonary Tuberculosis
• Other Specified Pulmonary Tuberculosis

Interventions

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.

Sponsors & Collaborators

• Radboud University Medical Center

  collaborator OTHER

• University of California, San Francisco

  collaborator OTHER

• University College, London

  collaborator OTHER

• GlaxoSmithKline

  collaborator INDUSTRY

• LigaChem Biosciences, Inc.

  collaborator INDUSTRY

• Michael Hoelscher

  lead OTHER

Principal Investigators

• Michael Hoelscher, Prof Dr. · LMU University Hospital

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

SINGLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

65 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2023-04-14

Primary Completion

2027-10-31

Completion

2027-12-30

FDA Drug

Yes

Countries

• Gabon
• Malawi
• Mozambique
• South Africa
• Tanzania
• Uganda

Study Locations