Sorfequiline-based Regimens in Adults With Newly Diagnosed Drug-sensitive Pulmonary TB

Официальное название

A Phase 2b, Randomised, Multi-center, Partially Blinded Trial Assessing the Safety and Efficacy of Regimens Containing Sorfequiline, Pretomanid and Linezolid in Adults With Newly Diagnosed, Drug-sensitive, Smear Positive Pulmonary Tuberculosis

Обзор

The goal of this interventional trial is to evaluate the safety and efficacy of the loading dose regimen 200/100SPaL-4/13 weeks, and the 100SPaL -17 weeks regimen in adults with newly diagnosed, drug-sensitive, smear-positive pulmonary tuberculosis. Participants (18-65 years) will be randomised 1:1, stratified by country and disease severity, to receive either : 1. a sorfequiline loading-dose regimen (200 mg daily for 4 weeks followed by 100 mg daily for 13 weeks) plus pretomanid 200 mg and linezolid 600 mg daily, or 2. sorfequiline 100 mg daily for 17 weeks plus pretomanid 200 mg and linezolid 600 mg daily. Study treatment is administered orally once daily with food. The primary objective is to assess safety through 17 weeks of treatment, including treatment-emergent adverse events, ECG findings, vital signs, laboratory assessments, visual acuity, and peripheral neuropathy. Secondary objectives include assessments of efficacy (time to stable sputum culture conversion; favorable outcome and treatment failure/relapse at 26 and 52 weeks after end of treatment) and pharmacokinetics of trial drugs, with exploratory analyses including predictors of culture conversion, exposure-response relationships, and quality of life.

Подробное описание

This is a phase 2, randomised, multi-center, partially blinded, clinical trial conducted in 2 treatment arms.

The trial will be performed at multiple centers in South Africa and Tanzania in at approximately 100 participants with DS-TB who meet all the inclusion criteria and none of the exclusion criteria, aged 18 to 65, inclusive. Participants will be randomised to one of the 2 sorfequiline, pretomanid and linezolid containing regimens and will be randomised in 1:1 ratio based on country and severity of disease (AFB 3+ and/or bilateral cavitation). T

The trial will consist of the following periods:

1. Screening period: Screening visit, up to 11 days prior to randomisation (Day 1) 2. Treatment Period: approximately 100 participants will be randomised equally to the 2 treatment arms below:

* Sorfequiline 200 mg + pretomanid 200 mg + linezolid 600 mg for 4 weeks followed by sorfequiline 100 mg for 13 weeks * Sorfequiline 100 mg + pretomanid 200 mg + linezolid 600 mg for 17 week 3. Follow-up Period: 52 weeks after end of treatment

Вмешательства

• Препарат sorfequiline
  Two sorfequiline 100mg tablets taken once daily for 4 weeks then one sorfequiline taken once daily for 13 weeks OR one sorfequiline 100mg tablet taken once daily for 17 weeks (with one 100mg sorfequiline placebo tablet for the first 4 weeks)
• Препарат Pretomanid
  one 200mg tablet taken once daily for 17 weeks
• Препарат Linezolid
  one 600mg tablet taken once daily for 17 weeks

Первичные конечные точки

• Incidence and characterization of treatment-emergent adverse events (TEAEs) [Срок оценки: Through 17 weeks of treatment]

Вторичные конечные точки (2)

• Time to stable sputum culture conversion (SSCC) to negative [Срок оценки: Through 17 weeks of treatment]
• Proportion with favorable outcome [Срок оценки: 26 weeks after EOT; 52 weeks after EOT]

Критерии участия

Критерии включения

• DS-TB as defined as sensitive to rifampicin and isoniazid by rapid sputum-based test AND either newly diagnosed for TB or have a history of being untreated for at least 3 years after cure from a previous episode of TB
• Of non-childbearing potential OR using effective birth control methods
• Body weight ≥ 35 k

Критерии исключения

• Karnofsky score < 60 at screening
• Any evidence of extrapulmonary TB
• Cardiovascular or QT prolongation risk factors Pregnant or breast-feeding
• Laboratory abnormalities as defined in the protocol. • For participants living with HIV only:

• CD4+ count<200 cells/μL.
• WHO Clinical Stage 4 HIV disease
• Participant does not agree to use DTG/TFV/3TC during study treatment if ARV therapy is indicated
• If initiation of ARV therapy is indicated, participants who are known to be intolerant, non-responsive to DTG/TFV/3TC or have DTG/TFV/3TC as a contraindication.

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

Тройное слепое

Основная цель

Лечение

Центры проведения

ЮАР · 7 центров

• Isango Lethemba TB Research Unit — Port Elizabeth
• Setshaba Research Centre — Pretoria
• University of Capetown Lung Institute — Cape Town
• The Aurum Institute, Rustenburg — Rustenburg
• Madiberg Centre for Research — Brits
• Durban International Clinical Research Site, Enhancing Care Foundation — Durban
• Synergy Biomed Research Institute — East London

Tanzania · 4 центра

• INUKA Africa — Dar es Salaam
• Mbeya Referral Hospital — Mbeya
• Kilimanjaro Clinical Research Instuute — Moshi
• National Instittute for Medical Research — Mwanza

Публикации

• Olugbosi M, Beumont M, Lombard L, Nedelman J, Timm J, Black T, Bruning-Barry R, Hickman D, Lombardi A, Betteridge M, Egizi E, Marcopulos L, Henderson J, Seidel S, Foraida S, Benhayoun M, Sun E. Protocol for a phase 2, partially blinded, randomized trial assessing the safety and efficacy of sorfequiline or bedaquiline in combination with pretomanid and linezolid in adult participants with newly dia PMID 41495827

Идентификаторы

NCT: NCT07672405 · NC-010

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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