Bacteriophages for Adults With Cystic Fibrosis and Chronic Achromobacter Lung Infection
Trial statusRecruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age18+
SponsorGhady Haidar
About this trial
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).
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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), including transplant recipients
Stable respiratory symptoms within 30 days prior to screening, with no change in CF maintenance medications (including cystic fibrosis transmembrane conductance regulator (CFTR) modulators) within 30 days prior to screening.
Disqualifiers
Serious medical illness requiring systemic treatment or hospitalization within 30 days prior to screening (unless medically stable and approved by the investigator).
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).
Trial design
Design model
Parallel
Treatments tested in this trial
AchromoPhage
Biological/VaccineAchromoPhage is a cocktail of four genetically distinct, obligately lytic bacteriophages (phiACH01, phiACH04, phiACH06, phiACH07) with in vitro activity against \>75% of a panel of 17 genetically diverse Achromobacter isolates from persons with cystic fibrosis. In this study, AchromoPhage will be administered by inhaled, intravenous, or sequential inhaled + intravenous routes with weekly dose escalation. Each participant will receive three weekly administrations, with escalating total doses of 4×10⁷ PFU, 4×10⁸ PFU, and 4×10⁹ PFU per route (double the total dose in the combination arm).
Treatment groups
12 Participants
are divided into 3 treatment groupsGroup A: Inhaled Alone ArmExperimental treatment 1 intervention
Group B: Intravenous Alone ArmExperimental treatment 1 intervention
Group C: Combination Inhaled + Intravenous ArmExperimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
Incidence of treatment-related Grade ≥4 adverse events or treatment-limiting toxicities
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.
Time frame
42 DaysSecondary outcomes
1
Change in health-related quality of life measured by the Cystic Fibrosis Questionnaire-(CFQ-R)
Change in health-related quality of life from baseline to Day 42 measured using the Cystic Fibrosis Questionnaire-(CFQ-R), a validated, disease-specific instrument assessing physical, emotional, social, and respiratory health domains in cystic fibrosis. Construct measured: Health-related quality of life. Score range: Each domain generates a score from 0 to 100, where higher scores indicate better quality of life. Scoring: Domain scores are computed as linear transformations of raw responses; domains are not summed into a single composite score. Interpretation: Increases in domain scores represent improvement.
Time frame
42 Days2
AchromoPhage Concentration by qPCR (Pharmacokinetic Outcome Measure)
Quantitative serum concentrations of each phage component of AchromoPhage will be measured by qPCR using primers that will amplify each of the 4 phages in the cocktail at predefined time points, following inhaled, intravenous, or combined administration. Blood PCR: Collected at 0-, 10-, 30-, 60-, 120-, 180-, and 240-minute intervals following AchromoPhage administration during dosing visits (Days 0, 7, and 14) and once on Days 21 and 42. Sputum, nasal swabs, and oral swabs: Collected weekly (Days 0, 7, 14, 21, 28, 35, and 42).
Time frame
Blood: Days 0, 7, 14, 21, 42. Sputum, nasal swabs, and oral swabs: Days 0, 7, 14, 21, 28, 35, and 42.3
Number of Participants With Treatment-Emergent Serum Phage-Neutralizing Antibody Activity
Quantitative phage-neutralizing antibody activity will be measured in serum samples to assess treatment-emergent humoral immune responses following AchromoPhage administration.
Time frame
Days 0, 7, 14, 21, 28, and 42Sponsors and contacts
Click on the lead sponsor to view all of their trials.
Ghady Haidar
Lead sponsor
University of Pittsburgh
Sponsor institution
Cystic Fibrosis Foundation
Collaborator
Source ClinicalTrials.gov