Ensayos clínicos

Key Inclusion Criteria:

• Are able and willing to comply with the Protocol and provide signed informed consent prior to any study-specific procedures.
• Are male or female ≥ 18 years old.
• Have a body mass index of ≥ 16.5 kg/m^2.
• Have findings consistent with bronchiectasis per computerized tomography (CT) (or high-resolution CT [HRCT]).
  • Note: A CT or HRCT that demonstrates the above criterion is required during Screening or the Screening Period unless such an examination has been performed within the last 5 years and meets the above criterion.
• Have microbiological evidence of pulmonary P. aeruginosa infection from a sputum sample within the last 24 months. Sputum cultures may be repeated on up to 3 occasions during the Screening Period to document P. aeruginosa presence if the initial sputum culture is negative.
• Are willing and able to provide an induced sputum sample at Screening or during the Screening Period and at designated time points during the study and are willing and able to provide a spontaneously expectorated or induced sputum at all other time points.
• Have ≥ 104 colony-forming units of P. aeruginosa per gram of induced sputum obtained at Screening or during the Screening Period. Up to 3 specimens may be collected to meet this criterion.
• Have forced expiratory volume (FEV1) ≥ 35% of predicted normal for age, gender, race, and height (using Global Lung Function Initiative standards) at Screening (regardless of the timing of the most recent prior administration of short-acting bronchodilator) or during the Screening Period.
• Have, at the Baseline Visit, stable lung function, as determined by the Investigator, provided that the FEV1 at the Baseline Visit has not decreased by more than 10% compared to the FEV1 measured at Screening or during the Screening Period.
• Have no acute infection or exacerbation of primary disease, as determined by the Investigator, prior to randomization and first dose of study drug.
• Are able to reproducibly perform spirometry per American Thoracic Society/European Respiratory Society Standards.
• Have past experience administering inhaled antibiotics and/or feel comfortable administering inhaled antibiotics and/or have a caregiver that is comfortable administering inhaled antibiotics to the subject.
• For Cohort A, have not received chronic inhaled antipseudomonal antibiotic regimen for at least 3 months prior to Visit 1. For Cohort B, have received chronic inhaled antipseudomonal antibiotic regimen for at least 3 months prior to Visit 1.
• Are able to comply with study visits and study procedures as judged by the Investigator.
• Have a negative serum pregnancy test at Screening and a negative urine pregnancy test at the Baseline Visit, with results known prior to randomization and first dose of study drug, if a woman of childbearing potential.
• Must agree to use a highly effective method of birth control (defined as those, alone or in combination, that result in a low failure rate [ie, less than 1% per year]) from Screening through 60 days following the last dose of study drug if female or female partner of male subjects, of childbearing potential; and
• Must agree to use barrier contraception (ie, condoms) from Day 1 through 60 days following the last dose of study drug if male. Male subjects must refrain from donating sperm throughout the study and until 60 days after the last dose of study drug.

Exclusion Criteria:

• Have previously received 1 or more doses of AP-PA02 in any context, including, but not limited to, prior participation in study AP-PA02-101, prior enrollment in this study, or emergency use (with or without prior authorization).
• Have a history of lung transplantation.
• Have a history of primary or acquired immunodeficiency syndromes, including, but not limited to, hypogammaglobulinemia and common variable immunodeficiency.
• Have a history of cystic fibrosis.
• Have a history of α1-antitrypsin deficiency.
• Have a history of pulmonary malignancy (primary or metastatic) or any other malignancy requiring treatment (including, but not limited to, chemotherapy, radiation therapy, or immunotherapy) within 1 year prior to Screening or anticipated during the study period (Exceptions: Basal cell carcinoma of the skin and carcinoma in situ of the cervix surgically excised and assessed as definitely removed).
• Have, at Screening or during the Screening Period, either of the following findings:
  • A personal history or subject-reported family history of prolonged QT syndrome; or
  • Severe cardiovascular disease such as severe uncontrolled hypertension, unstable ischemic heart disease or cardiac arrhythmia and any other cardiac conditions that would confound the evaluation of safety in the opinion of the Investigator.
• Have a history of hemoptysis meeting either of the following criteria:
  • Within the 6 months prior to Screening, was hospitalized for management or evaluation of hemoptysis; or
  • Within the 3 months prior to Screening, had hemoptysis totaling greater than 30 mL in a single day.
• Have, within the 3 months prior to Screening, used supplemental oxygen during the day while at rest.
• Have, within the 3 months prior to Screening, lost more than 10% of their body weight.
• Have, within the 2 months prior to Screening, participated in any clinical study involving an investigational drug, an investigational device, or any systemic antibiotic.
• Note: For systemic drugs or antibiotics with a half-life > 12 days, the exclusion period is 5 half-lives.
• Have, within the 30 days prior to Screening, received any intravenous, intramuscular, or oral antipseudomonal antibiotic (Exception: Chronic oral macrolide treatment with a stable dose is permitted).
  • Note: Inhaled antibiotic use for chronic suppression of P. aeruginosa is acceptable for subjects enrolling in Cohort B.
• Have, within 30 days prior to Screening, had changes in either the treatment regimen or initiation of treatment with any of the following medications: oral macrolides (e.g., azithromycin, erythromycin, or clarithromycin), hypertonic saline, mucolytics, bronchodilator medications, or oral corticosteroids.
• Have, within the 30 days prior to Screening, received a course of any systemic antibiotics (by any route) for a new active infection at any site, unless assessed as fully resolved and not clinically significant by the Investigator with concurrence of the Medical Monitor.
• Are, at Screening or during the Screening Period, receiving treatment for active pulmonary infection due to any of the following pathogens: nontuberculous mycobacteria, Staphylococcus aureus, Burkholderia cepacia complex, Aspergillus species, or endemic mycoses.
• Are receiving treatment for allergic bronchopulmonary aspergillosis.
• Have, within 30 days prior to Screening, received either a systemic corticosteroid at a dose equivalent to > 20 mg/day of prednisone (including every other day dosing of > 40 mg equivalent) or any immunosuppressive medication or biologic for the treatment of inflammatory or autoimmune disease.
• Have history of AIDS (human immunodeficiency virus positive with AIDS-defining condition and/or CD4 count 3 × ULN or total bilirubin ≥ 2 × ULN at Screening.
  • Note: Abnormal laboratory results may be repeated once and only once at the discretion of the Investigator. Subjects with values outside the normal range may be permitted if the value is not clinically significant in the opinion of the Investigator with concurrence from the study Medical Monitor and/or Sponsor designee.
• Have, in the opinion of the Investigator, any acute or chronic medical, psychiatric, or behavioral condition or laboratory abnormality such that any of the following apply: the subject is considered not medically stable or in any other way not suitable for the study; participation in the study is not in the subject’s best interest, including, but not limited to, concern that participation in the study has the potential to put the subject at undue risk or to interfere with the results of the study or the outcome measures.

Eligibility last updated 12/20/23. Questions regarding updates should be directed to the study team contact.