A Phase 1, Open-label, Randomized, Pilot and Feasibility Trial to Evaluate the Safety and Tolerability of the Achromobacter-targeting Bacteriophage Cocktail, AchromoPhage, Among Persons With Cystic Fibrosis and Chronic Achromobacter Lung Infections: The AchromoPhage Trial
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 12
- 试验地点
- 2
- 主要终点
- Incidence of treatment-related Grade ≥4 adverse events or treatment-limiting toxicities
研究概览
简要总结
The goal of this clinical trial is to learn if a new treatment called AchromoPhage is safe and well tolerated in adults with cystic fibrosis (CF) who have long-term lung infections caused by Achromobacter bacteria. AchromoPhage is a mixture of four naturally occurring viruses, called phages, that are designed to target and kill Achromobacter.
This study will include 12 participants. People will be randomly assigned to one of three groups to receive AchromoPhage in different ways: by inhalation only, by intravenous (IV) infusion only, or by inhalation followed by IV infusion.
Participants will:
- Receive the study drug during clinic visits over a period of three weeks.
- Provide blood, sputum, nasal, and oral samples so researchers can measure how the phages move through the body, how long they stay, and whether the body develops a response against them.
- Complete breathing tests and quality-of-life questionnaires.
The main question this study will answer is whether AchromoPhage causes any serious or treatment-limiting side effects in the first 42 days after dosing. Researchers will also look at changes in lung function, quality of life, phage levels in the body, and how the treatment affects Achromobacter and other bacteria in the lungs.
The study is being run at the University of Pittsburgh (Pittsburgh, PA) and the University of California San Diego (San Diego, CA).
详细描述
AchromoPhage is a naturally derived bacteriophage cocktail composed of four genetically distinct, obligately lytic phages (phiACH01, phiACH04, phiACH06, and phiACH07) with demonstrated in vitro activity against Achromobacter species. The cocktail showed activity against more than 75% of a panel of 17 genetically diverse Achromobacter isolates collected from adults with cystic fibrosis. This study is designed to evaluate the safety and tolerability of AchromoPhage in adults with cystic fibrosis who have chronic Achromobacter lung infection.
This is an open-label, randomized Phase 1 pilot and feasibility trial conducted at two sites: the University of Pittsburgh, which will serve as the coordinating center, and the University of California San Diego. Eligible participants will be randomized to receive AchromoPhage by one of three delivery routes: inhaled administration, intravenous administration, or sequential inhaled followed by intravenous administration in the same visit. Each participant will receive three weekly administrations with escalating doses.
In addition to evaluating safety and tolerability, the trial will assess lung function and health-related quality of life, characterize pharmacokinetic profiles of AchromoPhage in blood and airway samples, and evaluate the humoral immune response to the administered phages. Exploratory analyses will examine pharmacodynamic effects, including changes in Achromobacter abundance, bacterial community profiles, antibiotic-phage interactions, and phage-pathogen dynamics.
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
- None
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
- •In order to be eligible to participate in this study, an individual must meet all of the following criteria:
- •Adults of any gender, age 18 years or greater at the time of enrollment.
- •Weight of 40 kg or greater.
- •Diagnosed with cystic fibrosis (CF).
- •Stable respiratory symptoms within 30 days prior to screening.
- •Chronic Achromobacter respiratory infection, defined as isolation by culture of Achromobacter species from two or more respiratory, oral, and/or nasopharyngeal samples provided by the participant within 24 months before the date of pre-screening.
- •At least one Achromobacter isolate cultured from a respiratory, oral, and/or nasopharyngeal sample provided by the participant no more than 60 days before the date of planned enrollment must be susceptible to at least 1 phage in AchromoPhage cocktail using study assays.
- •FEV1 ≥ (greater than or equal to) 40% of predicted at time of screening
- •Ability and willingness to provide informed consent or, if applicable, the ability and willingness of legal guardian/representative to provide informed consent.
- •Willingness to comply with study procedures.
- •Ability to travel to the University of Pittsburgh or the University of California San Diego for phage administration and in-person visits.
- •Agreement not to enroll in other bacteriophage studies or receive bacteriophages for clinical care during the study, except in life-saving situations.
- •For females of reproductive potential, a negative urine pregnancy test at the time of consent (before randomization and dosing).
- •Willingness to use highly effective contraception or other preventive measures to avoid conception during the study and for 6 months after the last phage dose.
- •Note, criteria 5 and 6 are the microbiologic criteria.
排除标准
- •An individual who meets any of the following criteria will be excluded from participation in this study:
- •Serious medical illness requiring systemic treatment or hospitalization within 30 days prior to screening (unless medically stable and approved by the PI).
- •Acute pulmonary exacerbation requiring systemic antibiotics within 30 days prior to screening.
- •Acute respiratory illness, including viral infection, within 30 days prior to screening.
- •Grade 3 or higher alanine aminotransferase (ALT) or aspartate aminotransferase (AST) at or within 30 days prior to screening, defined as ALT or AST values >5.0 x upper limit of normal (ULN).
- •Currently breastfeeding, pregnant, or planning to become pregnant within 6 months.
- •Hemoglobin < 8 g/dL
- •Absolute neutrophil count < 1000 cells/uL
- •Intolerance to inhaled therapies.
- •Known allergy or sensitivity to components of the AchromoPhage cocktail.
- •Any other condition that, in the PI's opinion, would interfere with the conduct of the study or would not be in the participant's best interest.
研究组 & 干预措施
Inhaled Alone Arm
Participants will receive a single weekly administration of AchromoPhage via the inhaled route for a total of three administrations. Each weekly administration consists of escalating inhaled doses of the cocktail:
- Day 0 (visit 1, 1st week): 4×10⁷ total PFU
- Day 7 (visit 2, 2nd week): 4×10⁸ total PFU
- Day 14 (visit 3, 3rd week): 4×10⁹ total PFU
干预措施: AchromoPhage (Biological)
Intravenous Alone Arm
Participants will receive a single weekly administration of AchromoPhage via the intravenous route. Each weekly administration consists of escalating intravenous doses of the cocktail.
- Day 0 (visit 1, 1st week): 4×10⁷ total PFU
- Day 7 (visit 2, 2nd week): 4×10⁸ total PFU
- Day 14 (visit 3, 3rd week): 4×10⁹ total PFU
干预措施: AchromoPhage (Biological)
Combination Inhaled + Intravenous Arm
Participants will receive a single weekly administration of AchromoPhage, which will consist of an inhaled dose followed by an intravenous dose given during the same study visit, with a 60-minute wait between doses. Weekly dose escalation will apply to each route, resulting in a total dose that is double that of the single route arms, as follows:
- Day 0 (visit 1, 1st week): 8×10⁷ totalPFU [i.e. 4×10⁷ total PFU inhaled, followed by a 60-minute wait, then 4×10⁷ total PFU intravenous]
- Day 7 (visit 2, 2nd week):8×10⁸ total PFU [i.e. 4×10⁸ total PFU inhaled, followed by a 60-minute wait, then 4×10⁸ total PFU intravenous]
- Day 14 (visit 3, 3rd week): 8×10⁹ total PFU [i.e. 4×10⁹ total PFU inhaled, followed by a 60-minute wait, then 4×10⁹ total PFU intravenous]
干预措施: AchromoPhage (Biological)
结局指标
主要结局
Incidence of treatment-related Grade ≥4 adverse events or treatment-limiting toxicities
时间窗: 42 Days
Incidence of treatment-related Grade 4 or higher adverse events or any treatment-limiting toxicities, assessed overall and by treatment group, from the first dose through Day 42. Severity grading will follow the protocol-specified adverse event definitions.
次要结局
- Change in health-related quality of life measured by the Cystic Fibrosis Questionnaire-(CFQ-R)(42 Days)
- AchromoPhage Concentration by qPCR (Pharmacokinetic Outcome Measure)(Blood: Days 0, 7, 14, 21, 42. Sputum, nasal swabs, and oral swabs: Days 0, 7, 14, 21, 28, 35, and 42.)
- Number of Participants With Treatment-Emergent Serum Phage-Neutralizing Antibody Activity(Days 0, 7, 14, 21, 28, and 42)
研究者
Ghady Haidar
Associate Professor of Medicine; Co-chair, Pittsburgh Phage Program (P3)
University of Pittsburgh