Chronic Obstructive Pulmonary Disease (COPD)
Conditions
Keywords
Chronic Obstructive Pulmonary Disease, COPD, Bronchitis, DPP, DPP1, DPP Inhibitor, DPP1 Inhibitor
Brief summary
This is a Phase 2 study of the efficacy, safety, tolerability and pharmacokinetics of two doses of EXPD-101 in participants with COPD. Study participants will be randomized to receive either study drug or placebo administered once daily for 52 weeks.
Interventions
DRUGEXPD-101/FXS7553 Dose 1
Oral tablet
DRUGEXPD-101/FXS7553 Dose 2
Oral tablet
DRUGPlacebo
EXPD-101/FXS7553 - matching oral tablet.
Sponsors
Expedition Therapeutics, Inc
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
40 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
1. Provided written informed consent for the study 2. Body mass index (BMI) ≥ 18.5 kg/m2 and \< 35 kg/m2 at screening (weight ≥ 50 kg for males and ≥ 45 kg for females) 3. Diagnosis of COPD for at least 1 year 4. COPD with physician-confirmed diagnosis of chronic bronchitis (persistent, productive cough and sputum for at least 3 months in the past year) 5. At least 2 moderate or \> 1 severe exacerbation within 12 months prior to screening 6. Current or ex-tobacco smokers with history of ≥ 10 pack-years (1 pack year = 20 cigarettes smoked per day for 1 year); 7. Stable maintenance therapy with either dual or triple inhaled therapy for ≥ 3 months prior to enrollment per below: 1. Dual therapy: long-acting beta-2 agonist/muscarinic antagonist (LABA/LAMA) or inhaled corticosteroids (ICS)/LAMA, or ICS/LABA OR 2. Triple therapy: ICS/LAMA/LABA 8. Post-BD FEV1/FVC \< 0.7 and post-BD FEV1(% predicted) ≥ 40% at Screening 9. COPD Assessment Test (CAT) score ≥ 10 at Screening 10. If participant is of childbearing potential, must commit to practicing highly effective methods of birth control and not donating eggs during the study and at least 14 days after the last dose. 11. Male participants commit to the following during the study and for at least 14 days after the last dose: 1. Practice true sexual abstinence (refrain from heterosexual intercourse) 2. Use a condom with any female partner of childbearing potential and ensure that the partner uses a highly effective contraceptive method (eg, IUD/IUS, combined hormonal contraception, progestogen-only contraception, or bilateral tubal occlusion). 3. Be vasectomized (≥ 3 months prior to screening) 4. Refrain from donating sperm during the Treatment Period and for at least 14 days after the last dose of the IP
Exclusion criteria
1. COPD exacerbation within the 4 weeks prior to randomization. 2. Clinically important pulmonary disease other than COPD (eg, asthma, active lung infection, clinically significant bronchiectasis, pulmonary fibrosis, cystic fibrosis, lung cancer, alpha-1 antitrypsin deficiency, tuberculosis). 3. Significant immunodeficiency and/or positive serological tests for hepatitis B, hepatitis C, or known human immunodeficiency virus (HIV) infection. 4. Pneumonia requiring antibiotics or antiviral medication within 28 days prior to Visit 1. 5. History of clinically significant infection (excluding pneumonia), acute upper or lower respiratory infection, requiring antibiotics or antiviral medication within 14 days prior to Visit 1. 6. Evidence of active liver disease (with or without ongoing treatment) 7. Participants with a QT interval, from the ECG conducted at Screening Visit 1, corrected with Fridericia's formula (QTcF) \> 450 msec (or QTcF \> 480 msec in participants with bundle branch block). 8. Current or history, within the past year of Visit 1, of substance and/or alcohol abuse. 9. History of cancer except: 1. Participants who have had basal cell carcinoma, localized squamous cell carcinoma of the skin or in situ carcinoma of the cervix are eligible to participate in the study provided that curative therapy was completed at least 12 months prior to Visit 1 2. Participants who have had other malignancies are eligible provided that curative therapy was completed at least 5 years prior to Visit 1 10. Any clinically significant abnormal findings in physical examination, vital signs, hematology, clinical chemistry, or urinalysis during Screening Period, which in the opinion of the investigator, may put the participant at risk because of his/her participation in the study, or may influence the results of the study, or the participant's ability to complete the entire duration of the study. 11. Known history of allergy or reaction to any component of the investigational product formulation 12. Current treatment with biologic drugs for COPD (eg, dupilumab, mepolizumab) or use of Therapeutics, biologics within 5 half-lives or 4 months, whichever is longer, from randomization 13. Current long-term treatment with oxygen therapy \> 12 hours per day 14. Use of immunoglobulin or blood products in 30 days prior to Screening 15. Received a live attenuated vaccine within 30 days prior to Screening 16. Participants who are participating in the acute phase of a pulmonary rehabilitation program, i.e. who started rehabilitation \< 4 weeks prior to screening (Note: participants in the maintenance phase of a rehabilitation program can be included). 17. History or active conditions associated with the onset of non-hereditary palmoplantar keratosis: 18. Have any tooth that can potentially cause pain or infection as noted in the oral exam unless they are corrected before the study 19. Has active periodontal disease and are either: 1. Currently treated by a dentist for this condition or 2. Expected to have periodontal disease-related procedures within the study period 20. Are scheduled to have tooth extraction that will occur during the study period
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Annualized rate of moderate and severe COPD exacerbations | Over 52 Weeks | Effect of EXPD-101/FXS7553 compared with placebo on rate of moderate and severe COPD exacerbations. Moderate COPD exacerbation is defined as acute exacerbations of COPD that require either systemic corticosteroids (intramuscular (IM), intravenous, or oral) and/or antibiotics. Severe COPD exacerbation is defined as acute exacerbation of COPD requiring hospitalization or emergency room / urgent care visit ≥ 24 hours. |
| The number of participants experiencing an adverse events (AEs) | Over 52 weeks | The number of participants experiencing an AE (an AE is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship) will be presented. |
| Changes in vital sign parameters | Over 52 weeks | Vital signs, including systolic and diastolic BP (mmHg), heart rate (beats per minute), body temperature (°C), and respiratory rate will be listed and summarized. |
| Changes in electrocardiogram (ECG) parameters | Over 52 weeks | ECG (graphical tracing that records the electrical signals of your heartbeat) parameters will be summarized. |
| Number of Participants with Clinically Significant Changes in Physical Examination Findings | Over 52 weeks | Physical examination will be performed at each study visit by a qualified investigator. The following body systems will be assessed: ears, nose, throat, skin, cardiovascular, respiratory, musculoskeletal, and neurological. |
| Number of participants with clinically significant abnormalities | Over 52 weeks | Clinical laboratory assessments including hematology, serum chemistry, and urinalysis will be performed at each study visit. |
| Changes in Physical Exam Parameters - Body Weight | Over 52 weeks | Body weight measured using a calibrated scale at each study visit |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to first moderate or severe COPD exacerbation | Over 52 Weeks | Effect of EXPD-101/FXS7553 compared with placebo on time to first moderate or severe COPD exacerbation. |
| Change From Baseline in Quality of Life Questionnaire - St. George's Respiratory Questionnaire (SGRQ) | Baseline, Week 52 | The SGRQ is a validated, self-administered patient-reported outcome (PRO) that assesses symptoms, functioning, and health-related quality of life for participants with Chronic Obstructive Pulmonary Disease (COPD). It contains 50 items in 2 parts. Part 1 has 8 items for assessing the severity of respiratory symptoms (cough, sputum production, wheeze, breathlessness, and the duration and frequency of attacks of breathlessness or wheeze). Part 2 has 42 items across 2 components (Activity and Impacts) related to daily activities and psychosocial impacts of the participant's respiratory condition. The SGRQ total score is calculated as the sum of scores across symptoms, activity, and effects, with 0 indicating the best possible health status and 100 indicating the worst possible health status. A decrease in 4 units in the total score corresponds to a clinically significant improvement in the quality of life. |
| Change From Baseline at Week 52 in Postbronchodilator Forced Expiratory Volume in 1 Second (FEV1) and forced vital capacity (FVC) | Baseline, Week 52 | FEV1 is used to assess lung function and is the maximum amount of air that can be forced out in one second after first second after taking a forced expiration as measured by a spirometer. Postbronchodilator FEV1 tests included spirometry tests performed after administration of bronchodilator. FVC is used to assess lung function and is the total volume of air that can be forced out after taking a deep breath as measured by a spirometer. |
| Change From Baseline at Week 52 in Quality of Life Questionnaire - Evaluating Respiratory Symptoms (E-RS): COPD | Baseline, Week 52 | The E-RS:COPD™ scale, a part of the EXACT tool, is a derivative instrument used to measure the effect of treatment on the severity of respiratory symptoms in stable COPD. The E-RS is an 11-item participant-reported diary to measure respiratory symptom items contained in the 14-item EXACT. Summation of E-RS: COPD item responses produces a total score ranging from 0 to 40, with higher scores indicating greater severity. In addition to the total score, symptom domain scores can be calculated for breathlessness (5 items; score range: 0-17), cough and sputum (3 items; score range: 0-11) and chest symptoms (3 items; score range: 0-12) by summing the responses of items within a respective domain. As with the total score, higher domain scores indicate greater severity. |
| Annualized rate of severe COPD exacerbations | Over 52 Weeks | Effect of EXPD-101/FXS7553 compared with placebo on rate of severe COPD exacerbations. |
| Plasma Concentration and metabolites of EXPD-101/FXS755 | Pre-dose at baseline, and Weeks 2, 4, 12, 28, 52 and 56. | — |
| Change from Baseline in sputum neutrophil elastase (NE) activity | Over 52 Weeks | Effect of EXPD-101/FXS7553 compared with placebo on sputum neutrophil elastase (NE) activity. |
| Annualized rate of COPD exacerbations requiring Emergency Department visit and/or hospitalization | Over 52 Weeks | Effect of EXPD-101/FXS7553 compared with placebo on rate of COPD exacerbations requiring Emergency Department visit and/or hospitalization. |
Countries
United States
Contacts
CONTACTGeoffrey Gilmartin, MD
STUDY_CHAIRJames Duncan Chalmers, MBChB, PhD
Radcliffe Department of Medicine, University of Oxford
Outcome results
None listed