Early Bactericidal Activity, Safety & Tolerability of Oral GSK3036656 in Combination With Delamanid or Bedaquiline, Delamanid in Combination With Bedaquiline, or Standard of Care in Male and Female Participants Aged 18 to 65 Years With Pulmonary Tuberculosis

Sponsor

GlaxoSmithKline (Industry)

Overall Status

Not yet recruiting

CT.gov ID

NCT05382312

Collaborator

Click-TB Consortium (Other)

Enrollment

Arms

13.9

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

This study aims to measure the early bactericidal activity (EBA), safety, tolerability and pharmacokinetics with GSK3036656 in combination with either delamanid or bedaquiline, delamanid in combination with bedaquiline or standard of care for 14 days in participants with newly diagnosed sputum smear positive drug-sensitive pulmonary tuberculosis. Participants will revert to the standard treatment (RIFAFOUR® e-275) once the study treatment (Day 1 to Day 14) has been completed.

RIFAFOUR e-275 is a registered trademark of Sanofi-Aventis

Condition or Disease	Intervention/Treatment	Phase
Tuberculosis	Drug: GSK3036656 Drug: Bedaquiline Drug: Delamanid Drug: RIFAFOUR e-275	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

55 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Single (Outcomes Assessor)

Masking Description:

All laboratory staff involved in analyzing and reporting the microbiological endpoints (logarithm to base10 [log10] colony forming units [CFU] counts and time to sputum culture positivity) will be unaware of treatment assignments.

Primary Purpose:

Other

Official Title:

A Parallel Group, Phase 2A, Randomised, Open Label, 4 Treatment Arm Study to Assess the Early Bactericidal Activity, Safety and Tolerability of Oral GSK3036656 in Combination With Either Oral Delamanid or Oral Bedaquiline, Oral Delamanid in Combination With Oral Bedaquiline, or Standard of Care in Males and Females Aged 18 to 65 Years Inclusive With Drug-sensitive (Rifampicin-susceptible) Pulmonary Tuberculosis

Anticipated Study Start Date :

Jul 25, 2022

Anticipated Primary Completion Date :

Sep 21, 2023

Anticipated Study Completion Date :

Sep 21, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Participants receiving GSK3036656+bedaquiline	Drug: GSK3036656 GSK3036656 will be administered. Drug: Bedaquiline Bedaquiline will be administered.
Experimental: Participants receiving GSK3036656+delamanid	Drug: GSK3036656 GSK3036656 will be administered. Drug: Delamanid Delamanid will be administered.
Experimental: Participants receiving bedaquiline+delamanid	Drug: Bedaquiline Bedaquiline will be administered. Drug: Delamanid Delamanid will be administered.
Experimental: Participants receiving RIFAFOUR e-275	Drug: RIFAFOUR e-275 RIFAFOUR e-275 will be administered.

Outcome Measures

Primary Outcome Measures

Change from Baseline in log10 CFU of Mycobacterium tuberculosis (MTB) (per milliliters of respiratory sputum samples) [Baseline and up to Day 14]
The extended early bactericidal activity of each treatment group will be determined by the change from Baseline to Day 14 in log10CFU.

Secondary Outcome Measures

Change from Baseline in time to sputum culture positivity [Baseline and up to Day 14]
Time to sputum-culture positivity is the time between sample inoculation and detection of mycobacterial growth in the mycobacterium growth indicator tube.
Number of participants with serious adverse events [Up to Day 28]
Number of participants with adverse events of Grade 3 severity or higher [Up to Day 28]
Number of participants with adverse events related to study drug [Up to Day 28]
Number of participants withdrawn from the treatment due to adverse events [Up to Day 28]
Number of participants withdrawn from the study due to adverse events [Up to Day 28]
Number of participants with electrocardiogram (ECG) values of potential clinical importance (PCI) [Up to Day 28]
Number of participants with hematology laboratory values of PCI [Up to Day 28]
Number of participants with clinical chemistry laboratory values of PCI [Up to Day 28]
Number of participants with vital signs of PCI [Up to Day 28]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion criteria:

Participants must be 18 to 65 years of age inclusive, at the time of signing the informed consent.
Participants who have:

New episode of untreated, rifampicin-susceptible pulmonary tuberculosis (TB)
A chest X-ray picture consistent with pulmonary TB
At least one sputum sample positive on direct microscopy for acid-fast bacilli (at least 1+ on the International Union Against Tuberculosis and Lung Disease [IUATLD]/World Health Organization [WHO] scale) or positive on a molecular test (at least medium positive for MTB on Xpert MTB/Rif)
Normal echocardiogram or echocardiogram with normal left ventricular function with at most trace to mild valvular regurgitation is allowed and no valvular stenosis.
A creatinine clearance greater than or equal to (>=)75 mL/minute (Cockroft-Gault formula).

Male participants are eligible to participate if they agree to barrier precautions until 90 days after last dose.
A female participant is eligible to participate if she is not pregnant or breastfeeding, and is a woman of non-childbearing potential (WONCBP) or a woman of childbearing potential (WOCBP) using a contraceptive method that is highly effective. A WOCBP must have a negative pregnancy test urine or serum as required by local regulations before the first dose of study intervention. Only participants who are at least 25 years of age (and females of non-childbearing potential) will be eligible for the positron emission tomography-computed tomography (PET-CT) assessments.
Capable of giving signed informed consent.

Exclusion Criteria:

Evidence of a clinically significant (as judged by the Investigator) condition or abnormality (other than the indication being studied) that might compromise safety or the interpretation of trial efficacy or safety endpoints.
Clinically significant evidence of extrathoracic TB as judged by the Investigator.
QTc interval corrected for heart rate by Fridericia's formula (QTcF) greater than (>)450 milliseconds (msec).
Participants with vitiligo.
Participants receiving any QT prolonging drugs, including but not limited to fluoroquinolones, macrolides and clofazimine.
HIV infected participants:

having a cluster of differentiation (CD)4+ count <350 cells/microliters;
or having received efavirenz or lopinavir-boosted ritonavir as antiretroviral therapy medication within the last 30 days;
or having received oral or intravenous antifungal medication within the last 30 days;
or with an acquired immunodeficiency syndrome (AIDS)-defining opportunistic infection or malignancies in the last 12 months (except pulmonary TB).

Presence of Hepatitis B surface antigen (HBsAg) or Positive Hepatitis C antibody test result at screening.
Participants with diabetes (Type 1 or 2), point of care glycated hemoglobin (HbA1c) above 6.5%, or random glucose over 11.1 millimoles (mmol)/L
Any diseases or conditions in which use of delamanid or bedaquiline is contraindicated.
Participants with abnormal laboratory values at screening as graded by the enhanced Common Terminology Criteria for Adverse Events (CTCAE version 5 2017).