Therapeutic Effect of PBF-680 in Patients With COPD

Prior treatment

• COPD exacerbation requiring oral steroids in the 3 months prior to randomization (Visit 2).
• A history of one or more hospitalizations for COPD in the 3 months prior to screening (Visit 1).
• Lower respiratory tract infection treated with antibiotics within 1 months of randomization (Visit 2).
• Previous lung resection or lung reduction surgery.
• Oral therapies for COPD (e.g., theophylline, and roflumilast) in 1 month prior to screening (Visit 1) and throughout the study.
• Pulmonary rehabilitation, unless such treatment has been stable for 4 weeks prior to Visit 1) and remains stable during the trial.
• Received an experimental drug within 30 days or five half-lives of Visit 2, whichever is longer.
• Documented cardiovascular disease: arrhythmias, unstable angina, recent or suspected myocardial infarction within 6 months prior to screening, congestive heart failure, a history of unstable or uncontrolled hypertension, or has been diagnosed with hypertension in last 3 months.

Other illness

• Participants with a significant COVID-19 illness ≥ OMS-4 within 6 months of enrolment
• A history of life-threatening COPD including Intensive Care Unit admission and requiring intubation.
• Evidence of cor pulmonale or clinically significant pulmonary hypertension.
• Other respiratory disorders: Patients with a current diagnosis of asthma, active tuberculosis, lung cancer, bronchiectasis, sarcoidosis, lung fibrosis, interstitial lung diseases, known alpha-1 antitrypsin deficiency or other active pulmonary diseases.
• A history of, or reason to believe a subject has, drug or alcohol abuse within the past 3 years.
• Patients with a history of chronic uncontrolled disease including, but not limited to, endocrine, active hyperthyroidism, neurological, hepatic, gastrointestinal, renal, hematological, urological, immunological, or ophthalmic diseases that the Investigator believes are clinically significant.

Other

• Participants who have not been Vaccinated against SARS-CoV-2 and after performing a diagnostic nucleic acid test at screening visit, this would produce a positive result
• Increased pre-BD FEV1 at randomization visit (V2) compared to Screening (V1) of ≥ 400 mL or ≥ 20% of V1 FEV1.
• Women who are pregnant or breast-feeding.

• Sign an informed consent document indicating they understand the purpose of and procedures required for the study and are willing to participate in the study.
• Male or female aged between 40 and 80 years inclusive, at the time of informed consent.
• Have a 12-lead ECG recording at screening (Visit 1) showing the following (and no changes at Visit 2 deemed clinically significant by the Investigator):
  • Heart rate between 50 and 90 beats per minute QT interval corrected for heart rate using Fridericia's formula (QTcF) interval ≤ 450 msec for males and ≤ 470 msec for females. QRS complex ≤ 120 msec PR interval ≤ 200 msec
• No clinically significant abnormality including morphology (e.g. left bundle branch block, atrioventricular nodal dysfunction, ST segment abnormality consistent with ischemia).
• Capable of complying with all study restrictions and procedures.
• Body mass index (BMI) between 20 and 35 kg/m2 (inclusive)
• COPD diagnosis: Patients with a clinical diagnosis of COPD as defined by Global Initiative for Chronic Obstructive Lung Disease - GOLD 20201 with symptoms compatible with COPD for at least 1 year prior to screening (Visit 1).
• Background triple therapy (ICS + LABA + LAMA) or double therapy (ICS + LABA or ICS + LAMA) for 3 months prior to randomization with a stable dose of medication for ≥1 month prior to Visit 1.
• Patient with blood eosinophils \>100 cells/µL
• Ability to perform acceptable and reproducible spirometry. Post- bronchodilator (albuterol/salbutamol four puffs) spirometry at screening (Visit 1) must demonstrate a:
  • Post-bronchodilator FEV1/FVC ratio ≤ 0.70 Post-bronchodilator FEV1 ≥ 30 % and: ≤ 75 % of predicted normal.
• Clinically stable COPD in the 4 weeks prior to screening (Visit 1) and randomization (Visit 2).
• Meet the concomitant medication restrictions and be expected to do so for the rest of the study.
• Current and former smokers with a smoking history of ≥ 10 pack years.