Health Trials

PanACEA - STEP2C -01

ConditionsPulmonary TuberculosisOther Specified Pulmonary Tuberculosis
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18-65
SponsorMichael Hoelscher

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Provide written, informed consent prior to all trial-related procedures including HIV testing.

Male or female, aged between 18 and 65 years, inclusive.

Body weight (in light clothing and with no shoes) between 40 and 90 kg, inclusive.

had a good treatment response in the opinion of the investigator; i.e. TB symptoms improved sufficiently or resolved suggesting a cure of the past episode; AND

Disqualifiers

Circumstances that raise doubt about free, unconstrained consent to study participation (e.g., person in detention or person with mental disability)

Poor general condition where delay in treatment cannot be tolerated or death within four months is likely.

Circumstances (in the opinion of the investigator) that raise doubt about ability to complete the follow-up during the study period.

The participant is pregnant or breast-feeding or planning to become pregnant in the study period.

Trial design

Design model

Parallel

Treatments tested in this trial

  • BTZ-043

    Drug

    BTZ-043 1000mg once daily in arms 4 and 6.

  • Rifampicin

    Drug

    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.

  • Isoniazid

    Drug

    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.

  • Pyrazinamide

    Drug

    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.

  • Moxifloxacin

    Drug

    Moxifloxacin will be dosed at 600 mg orally once daily in arms 1-2.

  • Alpibectir (GSK3729098)

    Drug

    Alpibectir 45 mg OD plus Ethionamide 500 mg OD combined with rifampicin pyrazinamide and ethambutol at standard weight-banded doses in arm 5.

  • Ganfeborole (GSK3036656)

    Drug

    Ganfeborole 20 mg OD in arm 6

  • Delpazolid (LCB01-0371)

    Drug

    Delpazolid 1200mg OD in arm 6

  • Pretomanid (Pa)

    Drug

    Pretomanid 20mg OD in arm 6.

  • Ethambutol (E)

    Drug

    Ethambutol 20mg/Kg OD in arm 3, 5 and 7

  • Ethionamide

    Drug

    Ethionamide 500mg OD in arm 5.

Treatment groups

390 Participants
are divided into 7 treatment groups

7

Treatment groups

See each treatment group below.

Group A: Arm 1 (Stage 1)Experimental treatment 4 interventions
Group B: Arm 2 (Stage 1)Experimental treatment 4 interventions
Group C: Arm 3Active comparator 4 interventions
Group D: Arm 4 (Stage 2)Experimental treatment 4 interventions
Group E: Arm 5 (Stage 3)Experimental treatment 5 interventions
Group F: Arm 6 (Stage 3)Experimental treatment 4 interventions
Group G: Arm 7 (Stage 3)Active comparator 4 interventions

Trial outcomes

Primary outcomes

1

Time to stable culture conversion to negative in liquid media

The primary efficacy endpoint of arms 1 and 2 will be time to stable culture conversion to negative in liquid media defined as the time from enrolment to the first of two negative weekly sputum cultures without an intervening positive culture in liquid media, in comparison to arm 3. The efficacy of BTZ-043 will be evaluated by measuring the change in mycobacterial load over time on treatment as quantified by time to positivity in BD MGIT 960® liquid culture described by non-linear mixed-effects methodology, in comparison to arm 3.

Time frame
Day 01- Week 26
2

Change in Mycobacterial load (Stage 3)

The efficacy of the arms 5 and 6 (Stage 3) will be evaluated by measuring the change in mycobacterial load over time on treatment as quantified by time to positivity in BD MGIT 960® liquid culture described by non-linear mixed-effects methodology, in comparison to arm 7 using the TTP0-8 or 12 weeks slope.

Time frame
Baseline until week 12 of treatment.

Secondary outcomes

1

Relapse - free survival at 12 months after randomization

To assess treatment efficacy based on proportion of patients with relapse free outcome at 12 months after randomization. Sustained cure at 12 months (52 weeks) after randomization without a failure or relapse event is achieved when all the following criteria are met: * known to be alive at or after 48 weeks after randomization; * having Sustained Culture Negativity at 48 weeks after randomization; * not having met criteria for Failure or Relapse event (see below); * not in need of TB treatment and having had no substantial treatment modifications or additional treatment for TB outside of the pre-specified treatment strategies.

Time frame
Day 01-364
2

Frequency of all adverse events (serious and non-serious)

To assess the frequency, severity, and type of adverse events (AEs), and AE related treatment discontinuations.

Time frame
Day 01-182
3

Frequency of adverse events of Grade 3 severity (severe) or higher

Severity of AEs will be classified following the U.S. National Institutes of Health Common Terminology Criteria for Adverse Events 5.0 (CTCAE). The minimum grade is 1 (Mild) and the maximum grade is 5 (Death related to AE). Higher scores mean a worse outcome.

Time frame
Day 01-182
4

Frequency of adverse events possibly, probably or definitely related to study drug

To assess the frequency, severity, and type of adverse events (AEs), and AE related treatment discontinuations.

Time frame
Day 01-182

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Michael Hoelscher

Lead sponsor

Ludwig-Maximilians - University of Munich

Sponsor institution

Radboud University Medical Center

Collaborator

University of California, San Francisco

Collaborator

University College, London

Collaborator

GlaxoSmithKline

Collaborator

LigaChem Biosciences, Inc.

Collaborator

Source ClinicalTrials.gov
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