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

Официальное название

A Phase 2, Open-Label, Multi-Group, Controlled, Randomized Trial of the Safety, Bactericidal Activity, and Pharmacokinetics of TBD09 in Combination With Other Active Agents in Adults With Drug-Sensitive Pulmonary Tuberculosis

Обзор

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.

Вмешательства

• Препарат Bedaquiline, pretomanid and TBD09
  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
• Препарат Bedaquiline, pretomanid and TBD09
  Group 2 (30 participants): The combination of TBD09 (100 mg QD), bedaquiline (200 mg QD), and pretomanid (200 mg QD), 28 days
• Препарат Bedaquiline, pretomanid and TBD09
  Group 3 (30 participants): The combination of TBD09 (300 mg QD), bedaquiline (200 mg QD), and pretomanid (200 mg QD), 28 days
• Препарат Bedaquiline, pretomanid and TBD09
  Group 4 (30 participants): The combination of TBD09 (500 mg QD), bedaquiline (200 mg QD), and pretomanid (200 mg QD), 28 days
• Препарат Bedaquiline, pretomanid and linezolid
  Group 5 (30 participants): The combination of linezolid (600 mg QD), bedaquiline (200 mg QD), and pretomanid (200 mg QD), 28 days

Первичные конечные точки

• Bactericidal Activity [Срок оценки: From randomization through Day 28 (EOT)]
• Safety: SAEs [Срок оценки: Screening through Day 35 (EOS)]
• Safety: TEAEs [Срок оценки: Screening through Day 35 (EOS)]
• Safety: AESIs [Срок оценки: Screening through Day 35 (EOS)]
• Safety: AEs leading to treatment discontinuation [Срок оценки: Screening through Day 35 (EOS)]

Вторичные конечные точки (12)

• Safety: Hematologic Effect [Срок оценки: Randomization through Day 35 (EOS)]
• Safety: Visual Acuity Assessment [Срок оценки: Randomization through Day 35 (EOS)]
• Safety: Colour Vision Assessment [Срок оценки: Randomization through Day 35 (EOS)]
• Safety: Brief Peripheral Neuropathy Screen (BPNS) score [Срок оценки: Randomization through Day 35 (EOS)]
• Safety: Brief Peripheral Neuropathy Screen (BPNS) score [Срок оценки: Randomization through Day 35 (EOS)]
• Safety: Brief Peripheral Neuropathy Screen (BPNS) score [Срок оценки: Randomization through Day 35 (EOS)]
• Bactericidal activity [Срок оценки: Day 28 (EOT)]
• Maximum plasma concentration (Cmax) of TBD09 [Срок оценки: Day 1 and Day 28]
• Time to maximum plasma concentration (Tmax) of TBD09 [Срок оценки: Day 1 and Day 28]
• Area under the curve from 0 to 24 hours (AUC0-24) of plasma concentration of TBD09 [Срок оценки: Day 1]
• Area under the curve from 0 to infinity (AUC0-inf) of plasma concentration of TBD09 [Срок оценки: Day 28]
• Area under the curve over the dosing interval on day 28 (AUCtau) of plasma concentration of TBD09 [Срок оценки: Day 28]

Критерии участия

Критерии включения

• 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

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

ЮАР · 13 центров

• Enhancing Care Foundation at Wentworth Hospital — Durban
• TASK Applied Science - Eden — George
• Clinical Research and HIV Research Unit (CHRU) @ Helen Joseph Hospital — Johannesburg
• The Aurum Institute Tembisa — Tembisa
• CHRU @ Isango Lethemba — Bethelsdorp
• Madibeng Centre for Research — Brits
• Setshaba Research Center — Pretoria
• ONE MRI — Cape Town
• … и ещё 5 центров

Идентификаторы

NCT: NCT07525427 · Gates MRI-TBD09-201

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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