Early Bactericidal Activity, Safety & Tolerability of Oral GSK3036656 in a Dual Combination With Novel and Established Antitubercular Agents, or Standard of Care in Adults With Rifampicin Susceptible Pulmonary Tuberculosis

Launched by GLAXOSMITHKLINE · May 16, 2022

Keywords

ClinConnect Summary

This clinical trial is studying a new medication called GSK3036656 to see how well it works when combined with other existing treatments for pulmonary tuberculosis (TB) that can be treated with rifampicin. The goal is to understand how effective this new treatment is at killing the bacteria causing TB, as well as to check how safe and tolerable it is for patients. Participants in the study will receive the treatment for 14 days and then switch back to standard TB medication afterward.

To be eligible for this trial, participants must be between 18 and 65 years old and have a new case of drug-sensitive pulmonary TB, confirmed by tests. They also need to have a normal heart function and meet certain health criteria. Throughout the trial, participants will be closely monitored to ensure their safety and to measure how well the treatment is working. This study is currently recruiting participants, and anyone considering joining should discuss it with their healthcare provider to understand the potential benefits and risks.

Gender

ALL

Eligibility criteria

• Inclusion Criteria:
• • Participants must be 18 to 65 years of age inclusive, at the time of signing the informed consent.
• * Participants who have:
• • 1. New episode of untreated, rifampicin-susceptible pulmonary tuberculosis (TB)
• • 2. A chest X-ray picture consistent with pulmonary TB
• • 3. 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)
• • 4. Normal echocardiogram or echocardiogram with normal left ventricular function with at most trace to mild valvular regurgitation is allowed and no valvular stenosis.
• • 5. A creatinine clearance greater than or equal to (\>=)90 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 breast feeding 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).
• • Arterial hypertension with Systolic BP \>=160 mm Hg or diastolic BP \>=100 nm Hg. Participants with well-controlled hypertension may be included if they are using amlodipine for the duration of the study.
• • Participants with vitiligo.
• • Participants receiving any QT prolonging drugs, including but not limited to fluoroquinolones, macrolides and clofazimine.
• * HIV infected participants:
• • 1. having a cluster of differentiation (CD)4+ count \<350 cells/microliters;
• • 2. having received any antiretroviral therapy medication within the last 30 days;
• • 3. or having received oral or intravenous antifungal medication within the last 30 days;
• • 4. 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).