Clinical trial to study the safety and tolerability of EP395 in comparison with placebo in patients with chronic obstructive pulmonary disease (COPD)

Phase 1

Active, not recruiting

• Conditions: Chronic obstructive pulmonary disease (COPD); MedDRA version: 21.1Level: LLTClassification code 10010952Term: COPDSystem Organ Class: 100000004855; Therapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]

• Registration Number: EUCTR2021-005787-22-DE
• Lead Sponsor: EpiEndo Pharmaceuticals

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2022-06-07
• Last Update Posted: 29 July 2024

Recruitment & Eligibility

• Status: Not Recruiting
• Sex: All
• Target Recruitment: 60

Inclusion Criteria

1. Willing and able to understand the information on the nature, the scope, and the relevance of the study, and to provide voluntary, written informed consent to participate in the study before any study-related procedures
2. Men and women, aged =45 years
3. Women of childbearing potential must:
a. have a negative pregnancy test (blood) at Screening and (urine) Day 1
b. agree to use, and be able to comply with, highly effective measures of contraceptive control (failure rate less than 1% per year when used consistently and correctly) without interruption, during study participation and until 90 days after the last investigational product (IP) intake.
c. agree to abstain from breast feeding during the study participation and for 90 days after the last IP intake.
4. Men must agree to use a condom during sexual intercourse with women of childbearing potential during treatment and for 90 days after the last IP intake and should not donate sperm during this time
5. Diagnosed with COPD for at least 2 years with FEV1/forced vital capacity (FVC) ratio <0.70 and FEV1 <70% (post bronchodilator) at Screening
6. Receiving at least one maintenance inhaled therapy (ie, LABA, LAMA, LABA/LAMA, LABA/ICS, LAMA/ICS, or LABA/LAMA/ICS) for at least 3 months before Screening
7. Able to tolerate the sputum induction procedure and to produce an adequate (volume and sufficient quality for cell count) sputum sample
8. Body mass index of =19 and =35 kg/m2
9. History of sputum production (bronchitic phenotype) for approximately 3 months (minimum, not consecutive) in a year
10. Up to date COVID-19 vaccination (according to local law and guidelines)

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 30
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 30

Exclusion Criteria

1. History or presence of any clinically relevant medical condition including laboratory test abnormality or planned surgery that in the investigator’s opinion could affect the patient’s safety or interfere with the objectives of the study
2. Exacerbation of COPD in the 3 months before Screening
3. Change in medication for COPD in the 3 months before Screening
4. Lung function at Screening that in the investigator’s opinion would indicate not safe to perform sputum induction or bronchoscopy (bronchoscopy applicable only in a subset of patients)
5. History of or active tuberculosis
6. Malignancy within the past 5 years, except removed basal cell carcinoma and resected benign colonic polyps
7. Clinically significant abnormality on 12-lead ECG including prolonged corrected QTcF (>450 msec in men or >470 msec in women); based on triplicate) at Screening and Day 1 pre-dose
8. Absolute estimated glomerular filtration rate ([eGFR cystatin C + eGFR creatinine]/2) <60mL/min according to Lund-Malmö equation at Screening
9. AST or ALT >1.5 x ULN at Screening
10. Use (including prescription, over-the-counter, herbal or dietary) of cytochrome P450 (CYP) inducers within 28 days before first dosing, or strong or moderate inhibitors of CYP3A4 (including dietary eg, grapefruit juice) or P-glycoprotein (Pgp) inhibitors or oral narrow therapeutic index (TI) Pgp substrates (eg, digoxin) within 14 days before first dosing
11. Use of macrolide, roflumilast, or oral corticosteroid (OCS) within 28 days before Screening
12. Ongoing antibiotic treatment at Screening
13. Use of home oxygen or home-based non-invasive ventilation 3 months before Screening
14. Use of a biological therapy within 3 months before Screening
15. Use of herbal remedies within 28 days before first dose until follow up
16. Live vaccine within 28 days or any other vaccine within 14 days before first dose until 28 days after final dose of the IP (with the exception of COVID-19 booster and flu vaccination; see Previous and concomitant medications and therapies)
17. Positive hepatitis B surface antigen, hepatitis C antibodies, or human immunodeficiency virus 1 or 2 antibodies at Screening
18. Positive test result for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) on Day 1
19. Positive drugs of abuse test at Screening, including cotinine only in ex-smokers for at least 3 months
20. Use of e-cigarettes and vapes
21. History of alcohol or drug misuse within 12 months before Screening
22. Pregnant and lactating women
23. Prior recovery from recent infection, including but not limited to COVID 19 within the last 30 days before first dosing with IP
24. Known hypersensitivity to macrolides or EP395 or any of the excipients (dicalcium phosphate, croscarmellose sodium, magnesium stearate, microcrystalline cellulose)
25. Participation in a study of an experimental drug within 5 half-lives or 3 months before Screening, whichever is longer
26. Dependent subjects of the sponsor or investigator (eg, employees, relatives)
27. Patients without the capacity to understand the nature and risks of the study

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To assess the safety and tolerability of repeat doses of EP395 in patients with COPD;Secondary Objective: Secondary objectives: <br><br>• To assess the effect of EP395 on lung inflammation<br>• To assess the effect of EP395 on systemic inflammation<br>• To assess the effect of EP395 on lung function<br>• To assess the systemic exposure to EP395<br>• To assess the effect of EP395 on quality of life<br><br>Exploratory objectives: <br>• To assess the effect of EP395 on mechanistic biomarkers<br>• To assess the effects of EP395 on the microbiome<br>;Primary end point(s): Adverse events (AEs), vital signs, laboratory safety tests, 12-lead electrocardiograms (ECGs), physical examinations;Timepoint(s) of evaluation of this end point: Throughout treatment phase and follow-up