Study on Doses of Inhaled ALX1 in Adults With Bronchiectasis

Официальное название

A Phase 2a, Placebo-Controlled, Single-Blind, Dose Range-Finding Study of Inhaled ALX1 in Adults With Bronchiectasis

Обзор

This study will evaluate the safety and effects of ALX1, an inhaled investigational treatment, in adults with bronchiectasis. Participants will receive either ALX1 or a placebo (a treatment with no active medicine) for 14 days. The study will compare different dose levels of ALX1 to help identify appropriate doses for future research based on safety, tolerability, and changes in predictive biomarkers.

Подробное описание

This is a Phase 2a, multicentre, placebo-controlled, single-blind, dose range-finding study will assess the safety, tolerability, pharmacodynamics (PD), and preliminary efficacy of inhaled ALX1 or placebo administered for 14 days in adult participants with bronchiectasis. 28 participants will be enrolled and assigned to one of four cohorts. The total duration of study participation will be up to 53 days, including Pre-screening and Screening of approximately 32 days, a Treatment Period of approximately 14 days, and a Follow-up of approximately 1 day following the last dose.

Вмешательства

• Препарат ALX1
  Dose Formulation: Solution for inhalation Dose Strength: 28 mg/mL Route of Administration: Inhalation via nebulizer
• Препарат Placebo
  Dose Formulation: Solution for inhalation Dose Strength: 0.9% sodium chloride Route of Administration: Inhalation via nebulizer

Первичные конечные точки

• Proportion of participants with a metHb value ≥ 5% per dose level [Срок оценки: From Day 1 to Day 14 (EOT visit)]

Вторичные конечные точки (10)

• Incidence of TEAEs [Срок оценки: From Day 1 to Day 14 (EOT visit)]
• Incidence of SAEs [Срок оценки: From Day 1 to Day 14 (EOT visit)]
• Proportion of participants with abnormal vital signs [Срок оценки: From Day 1 to Day 14 (EOT visit)]
• Proportion of participants with abnormal Laboratory parameters [Срок оценки: From Day 1 to Day 14 (EOT visit)]
• Proportion of participants with abnormal ECG readings [Срок оценки: From Day 1 to Day 14 (EOT visit)]
• Proportion of participants with abnormal SpO2 [Срок оценки: From Day 1 to Day 14 (EOT visit)]
• Proportion of participants with abnormal Spirometry Value [Срок оценки: From Day 1 to Day 14 (EOT visit)]
• Mean change in sputum inflammatory biomarkers per dose level [Срок оценки: From Day 1 to Day 14 (EOT visit)]
• Mean change in total bacterial load of pathogens per dose level [Срок оценки: From Day 1 to Day 14 (EOT visit)]
• Proportion of participants achieving a microbiological culture of pathogens change of at least 1-log CFU/g per dose level [Срок оценки: From Day 1 to Day 14 (EOT visit)]

Критерии участия

Критерии включения

• Current sputum producer with a history of chronic expectoration that, in the opinion of the Investigator, will be able to continue to reliably provide sputum throughout the study.
• Confirmed diagnosis of BE per high-resolution computed tomography (HRCT) prior to Screening due to any of the following: NCFB, CF, primary ciliary dyskinesia, or COPD.
• Clinical history consistent with BE (cough, daily chronic sputum production, and/or recurrent respiratory infections).
• FEV1 ≥ 40% of predicted values at Screening.
• Able to reproducibly perform spirometry manoeuvres (i.e., able to perform at least 3 acceptable forced expiratory curves based on the PI's assessment).
• History of at least one exacerbation treated with a course of antibiotics (inhaled, oral or intravenous \[IV\]) within the 24 months prior to Screening
• Woman of childbearing potential (WOCBP) or fertile man (see definitions in Section 5.3) agrees to use an acceptable method of contraception from the start of Screening until 90 days after the last dose of IP.

Критерии исключения

• Negative sputum NEATstik result for neutrophil elastase at Pre-screening.
• History of Burkholderia cepacia complex within 2 years prior to Pre-screening and/or detection of any Burkholderia spp. in sputum culture or by polymerase chain reaction (PCR) at Screening.
• History of Aspergillus fumigatus requiring treatment within 12 months prior to Pre-screening.
• History of non-tuberculosis mycobacteria (NTM) infection requiring treatment within 12 months prior to Screening, or detection of one or more NTM species in sputum by PCR at Screening.
• History of bronchospasm with inhaled antibiotics or hypertonic saline.
• Haemoptysis exceeding 50 mL of blood from the respiratory tract at any time within 30 days prior to IP administration (Day 1).
• Initiated macrolide therapy within 90 days before Screening. Existing stable maintenance with inhaled macrolides is permitted if initiated more than 90 days prior to Screening.
• Received inhaled anti-pseudomonal therapy within the last 14 days before Pre-screening. Must be willing to refrain from use of inhaled anti-pseudomonal therapy during the study until completion of the Follow-up video/telephone call.
• Received oral antibiotics other than macrolide within 30 days prior to Screening. Must be willing to refrain from use of oral antibiotics during the study until completion of the Follow-up video/telephone call.
• Received IV antibiotics within 60 days prior to Screening
• Initiation of, or increase in the dose of, inhaled corticosteroids within 90 days prior to Screening. Note: participants may be taking stable inhaled corticosteroids at the time of enrolment but must have initiated treatment more than 90 days prior to Screening
• Started any of the following muco-corrective therapies (e.g., nebulised saline, N-acetyl cysteine, Pulmozyme®, etc.) within 30 days prior to Screening. Maintenance with these muco-corrective therapies is permitted if initiated 30 days prior to Screening.
• Any of the following laboratory abnormalities at Screening:

• Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 2.5 × upper limit of normal (ULN)
• Creatinine > 1.5 × ULN
• QT interval corrected by Fridericia's formula (QTcF) interval > 450 ms for males or > 470 ms for females at Screening, or history of prolonged QT syndrome. PR interval < 200 ms at Screening. Out-of-range values may be repeated twice for confirmation. The mean QTcF and PR intervals of the triplicate ECG recordings will be used to determine qualification.
• Positive test for hepatitis C antibody (HCV), hepatitis B surface antigen (HBsAg), or human immunodeficiency virus (HIV) antibody at Screening

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

Простое слепое

Основная цель

Лечение

Центры проведения

Список центров уточняется — проверьте первичный протокол.

Идентификаторы

NCT: NCT07731919 · VST-201

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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