A Phase 1b/2a, Multi-Center, Double-Blind, Randomized, Placebo-Controlled, Single and Multiple Ascending Dose Study to Evaluate the Safety and Tolerability of AP-PA02 Multi-Phage Therapeutic Candidate for Inhalation in Subjects With Cystic Fibrosis and Chronic Pulmonary Pseudomonas Aeruginosa (Pa) Infection
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 29
- 试验地点
- 40
- 主要终点
- Incidence and Severity Treatment Emergent Adverse Events (TEAEs)
研究概览
简要总结
Phase 1b/2a, double-blind, randomized, placebo-controlled, single and multiple ascending dose study to evaluate the safety, tolerability and phage recovery profile of AP-PA02 multi-bacteriophage therapeutic candidate administered by inhalation in subjects with cystic fibrosis and chronic pulmonary Pseudomonas aeruginosa (PA) infection.
详细描述
The study consists of two parts. Subjects with Cystic Fibrosis and chronic pulmonary Pseudomonas aeruginosa (PA) infection will be enrolled in either Part 1 (single-ascending dose cohorts) or Part 2 (multiple-ascending dose cohorts).
Part 1 will evaluate single doses of AP-PA02 at two ascending dose levels, administered by inhalation. Treatment assignment will be randomized, double-blind, placebo-controlled in each of two ascending dose cohorts. Part 2 will also be double-blinded, randomized, placebo controlled, and will evaluate the safety and efficacy of multiple doses of AP-PA02 in each of two ascending dose level cohorts.
Subjects in both Parts 1 and 2 will be followed for approximately 4 weeks and evaluated for safety, tolerability, phage titer profile and immunogenicity.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •≥ 18 years old
- •Body mass index (BMI) of ≥ 18 kg/m2
- •Documented diagnosis of CF
- •Evidence of chronic pulmonary Pseudomonas aeruginosa infection
- •Willing to undergo sputum induction procedures at designated study visits, and willing to provide expectorated sputum samples at all other timepoints (for subjects who are able to expectorate)
- •For SAD: FEV1 ≥ 60% of predicted normal [per Global Lung Function Initiative (GLI) standards] at Screening
- •For MAD: FEV1 ≥ 40% of predicted normal [per Global Lung Function Initiative (GLI) standards] at Screening
- •Adequate renal function
排除标准
- •Recent significant weight loss
- •Abnormal vital signs at Screening
- •History of prolonged QT syndrome
- •Use of supplemental oxygen during the day at rest
- •Abnormal liver function tests greater than 3X the upper limit of normal (ULN)
- •Recent oral or IV antibiotics received for acute pulmonary exacerbation. Inhaled antibiotic use for chronic suppression of P. aeruginosa is acceptable.
- •Recent clinically significant infection requiring systemic antimicrobial therapy
- •Currently receiving anti-pseudomonal antibiotic treatment for acute sinusitis.
- •Currently receiving systemic corticosteroids
- •Currently receiving treatment for active infection with nontuberculous mycobacteria (NTM), Staphylococcus aureus, or Burkholderia cepacia complex lung infection
- •Currently receiving treatment for aspergillosis or ABPA (allergic bronchopulmonary aspergillosis)
- •Initiation of a CFTR potentiator/corrector therapy, such as Trikafta®, less than 90 days prior to Screening
- •Acquired or primary immunodeficiency syndromes
- •Active pulmonary malignancy (primary or metastatic)
- •History of lung transplantation
- •Recent hemoptysis
- •Female pregnant or breastfeeding
- •Heavy smoker
结局指标
主要结局
Incidence and Severity Treatment Emergent Adverse Events (TEAEs)
时间窗: Day 1 pre-dose through End of Study Visit (28 days post last dose of study drug), up to 4 weeks for single ascending dose and up to 5.5 weeks for multiple ascending dose.
Incidence and severity of treatment emergent adverse events of single and multiple doses of AP-PA02 administered by inhalation
次要结局
未报告次要终点