Bactericidal Activity of TBD09 in Combination With Other Drugs in Pulmonary Tuberculosis

Phase 2Not Yet RecruitingNCT07525427

Gates Medical Research Institute150 enrolled

Overview

The purpose of this study is to evaluate if TBD09 in combination with other active agents in adults with drug sensitive pulmonary tuberculosis has potential to be safe and effective.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

150

Conditions

Drug Susceptible Pulmonary Tuberculosis

Interventions

Bedaquiline, pretomanid and TBD09DRUG

Group 1 (30 participants): The combination of TBD09 (100 mg three times weekly, TIW), bedaquiline (200 mg daily, QD), and pretomanid (200 mg QD), 28 days

Bedaquiline, pretomanid and TBD09DRUG

Group 2 (30 participants): The combination of TBD09 (100 mg QD), bedaquiline (200 mg QD), and pretomanid (200 mg QD), 28 days

Bedaquiline, pretomanid and TBD09DRUG

Group 3 (30 participants): The combination of TBD09 (300 mg QD), bedaquiline (200 mg QD), and pretomanid (200 mg QD), 28 days

Eligibility

Sex: ALLMin age: 18 YearsMax age: 65 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Age 18-65 years at consent * Body weight 35-100 kg at screening * Written informed consent obtained * Newly diagnosed rifampicin-sensitive pulmonary TB * Molecular confirmation of M. tuberculosis on Xpert MTB/RIF Ultra * ≥1+ AFB smear or Xpert Ultra low, medium, or high semi-quantitative result * Rifampicin sensitivity on molecular test * Chest X-ray consistent with TB (Investigator assessment) * Able to spontaneously produce sputum * Reproductive requirements met * Women of childbearing potential: 2 approved contraceptive methods or abstinence * Males: contraception or abstinence through 90 days post-dose Exclusion Criteria: * Prior anti-TB treatment for the current TB episode within 60 days * Prior medication active against Mtb within 3 months * Evidence of extra-thoracic TB, per investigator judgement * Prior treatment completion for TB within 3 years * 2 or more prior episodes of TB * Clinically significant history of or current medical condition posing safety risk * If HIV positive: * Not on ARVs or taking ARVs for \<3 months prior to screening OR * CD4+ count \<200cells/uL at screening OR * HIV viral load \>200 copies /mL at screening OR * AIDS infection or malignancies * Meets any of the following laboratory values during screening: * AST, ALT, or ALP ≥2.5× ULN * Total bilirubin ≥1.2× ULN * eGFR \<60 mL/min/1.73 m² * Hemoglobin \<9.0 g/dL (male) or \<8.5 g/dL (female) * White blood cell count \<2,000/mm³ * Absolute neutrophil count \<800/mm³ * Platelet count ≤100,000/mm³ * Positive hepatitis B surface antigen * Positive hepatitis C antibody * HbA1c ≥8.0% * Current or recent systemic immunosuppressive therapy, including corticosteroids * Significant drug or alcohol abuse affecting compliance or safety * Pregnant or breastfeeding, positive pregnancy test, or planning pregnancy shortly after treatment

Locations (13)

Enhancing Care Foundation at Wentworth Hospital

Durban, Bluff, South Africa

TASK Applied Science - Eden

George, Central, South Africa

Clinical Research and HIV Research Unit (CHRU) @ Helen Joseph Hospital

Outcomes

Primary Outcomes

Bactericidal Activity

Average daily change in MGIT sputum culture TTD from baseline to end-of-treatment (EOT)

Time frame: From randomization through Day 28 (EOT)

Safety: SAEs

Proportion of participants with this event

Time frame: Screening through Day 35 (EOS)

Safety: TEAEs

Proportion of participants with this event

Time frame: Screening through Day 35 (EOS)

Safety: AESIs

Proportion of participants with this event

Time frame: Screening through Day 35 (EOS)

Safety: AEs leading to treatment discontinuation

Proportion of participants with this event

Time frame: Screening through Day 35 (EOS)

Secondary Outcomes

Safety: Hematologic Effect

Proportion of participants who meet each of the following binary classifications of platelets, absolute neutrophil count (ANC), total white blood cell count (WBC), absolute lymphocyte count (ALC), and hemoglobin: 1. Post-baseline result \< lower limit of normal (LLN) among participants with baseline result \> LLN (yes/no) 2. Post-baseline result \< 50% of LLN (yes/no) 3. Post-baseline result ≥50% decrease relative to baseline (yes/no)

Time frame: Randomization through Day 35 (EOS)

Safety: Visual Acuity Assessment

Proportion of participants with worsening of postbaseline visual acuity score of 2 lines or more in either eye using Snellen-type charts

Time frame: Randomization through Day 35 (EOS)

Central Contacts

Gates MRI

CONTACT

+1 857 702 2108 clinical.trials@gatesmri.org

Gates MRI

CONTACT

+1-866-789-5757

Data from ClinicalTrials.gov

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