Clinical Trial to Investigate the Safety and Tolerability of EP395 in Patients With COPD

• ClinicalTrials.gov Identifier: NCT05572333
• Recruitment Status: Recruiting
• First Posted: October 7, 2022
• Last Update Posted: December 12, 2022
• Sponsor: EpiEndo Pharmaceuticals
• Collaborator: FGK Clinical Research GmbH
• Information provided by (Responsible Party): EpiEndo Pharmaceuticals

Study Description

Brief Summary:

The aim of this clinical trial is to investigate the safety and tolerability of oral, once-daily EP395 administration in COPD patients for 12 weeks.

Condition or disease	Intervention/treatment	Phase
Chronic Obstructive Pulmonary Disease; COPD	Drug: EP395; Drug: Placebo	Phase 2

Detailed Description:

This is a randomised, double-blind, placebo-controlled, multicentre study to assess the safety and tolerability of EP395 in COPD patients.

In this study, EP395 will be administered to COPD patients for the first time. Patients will receive either EP395 or placebo as oral capsules once-daily for 12 weeks. Safety and tolerability will be assessed, as well as effect on lung function, lung inflammation and systemic inflammation. Patients' symptoms and quality of life will be assessed with questionnaires. In a sub-set of patients, bronchoscopies will be conducted, to investigate exploratory biomarkers in bronchial brushings and bronchoalveolar lavage.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 60 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: The study is double-blind, placebo-controlled and parallel-group in design.
• Masking: Double (Participant, Investigator)
• Masking Description: During the study, study participants, investigators, the sponsor, and all other persons involved in the conduct of the study will be blinded to treatment.
• Primary Purpose: Treatment
• Official Title: A Randomised, Double-blind, Placebo-controlled Study to Investigate the Safety and Tolerability of EP395 in Patients With Chronic Obstructive Pulmonary Disease (COPD)
• Actual Study Start Date: November 22, 2022
• Estimated Primary Completion Date: August 31, 2023
• Estimated Study Completion Date: August 31, 2023

Arms and Interventions

Arm	Intervention/treatment
Experimental: EP395; EP395 in repeated doses. Oral, once-daily administration of 3 EP395 capsules for 12 weeks.	Drug: EP395; Capsule for oral use
Placebo Comparator: Placebo; Matched placebo capsule. Oral, once-daily administration of 3 placebo capsules for 12 weeks.	Drug: Placebo; Capsule for oral use

Outcome Measures

Primary Outcome Measures :

1. Assessment of adverse event (AE) occurrence [ Time Frame: From Screening (Day -28 to Day -1) to Day 100 ]
2. Vital signs: Systolic and diastolic blood pressure [ Time Frame: Screening (Day -28 to Day -1), Day 1, Day 14, Day 28, Day 42, Day 56, Day 70, Day 84, Day 100 ]
   Absolute values and changes from baseline will be summarized for all assessed time points
3. Vital signs: Pulse [ Time Frame: Screening (Day -28 to Day -1), Day 1, Day 14, Day 28, Day 42, Day 56, Day 70, Day 84, Day 100 ]
   Absolute values and changes from baseline will be summarized for all assessed time points
4. Vital signs: Body temperature [ Time Frame: Screening (Day -28 to Day -1), Day 1, Day 14, Day 28, Day 42, Day 56, Day 70, Day 84, Day 100 ]
   Absolute values and changes from baseline will be summarized for all assessed time points
5. Vital signs: Respiratory rate [ Time Frame: Screening (Day -28 to Day -1), Day 1, Day 14, Day 28, Day 42, Day 56, Day 70, Day 84, Day 100 ]
   Absolute values and changes from baseline will be summarized for all assessed time points
6. Assessment of laboratory values (haematology) [ Time Frame: Screening (Day -28 to Day -1), Day 1, Day 14, Day 28, Day 42, Day 56, Day 70, Day 84, Day 100 ]

   Mean corpuscular haemoglobin, mean corpuscular haemoglobin concentration, mean corpuscular volume, haematocrit, haemoglobin, platelet count, white blood cell count with differentials (neutrophils, lymphocytes, monocytes, eosinophils, basophils).

   Absolute values and changes from baseline will be summarized for all assessed time points.

7. Assessment of blood coagulation [ Time Frame: Screening (Day -28 to Day -1), Day 1, Day 14, Day 28, Day 42, Day 56, Day 70, Day 84, Day 100 ]

   International normalized ratio, prothrombin time (quick test), and activated partial thromboplastin time will be assessed.

   Absolute values and changes from baseline will be summarized for all assessed time points.

8. Assessment of laboratory values (biochemistry) [ Time Frame: Screening (Day -28 to Day -1), Day 1, Day 14, Day 28, Day 42, Day 56, Day 70, Day 84, Day 100 ]

   Liver function parameters and fasting lipids (at Screening and Day 84) will be assessed in addition to the following other parameters: bicarbonate, calcium, creatinine, creatine phosphokinase, cystatin C (screening only), fasting glucose (at Screening only), sodium, urea, estimated glomerular filtration rate (at Screening only)

   Absolute values and changes from baseline will be summarized for all assessed time points

9. Urinalysis [ Time Frame: Screening (Day -28 to Day -1), Day 1, Day 28, Day 56, Day 84, Day 100 ]

   pH, glucose, protein, blood (hemoglobin), leukocytes, ketones and nitrite will be assessed.

   Clinical abnormalities will be evaluated

10. ECG heart rate [ Time Frame: Screening (Day -28 to Day -1), Day 1, Day 14, Day 28, Day 56, Day 84, Day 100 ]
    Absolute values and changes from baseline will be summarized for all assessed time points
11. ECG RR interval [ Time Frame: Screening (Day -28 to Day -1), Day 1, Day 14, Day 28, Day 56, Day 84, Day 100 ]
    Absolute values and changes from baseline will be summarized for all assessed time points
12. ECG PR interval [ Time Frame: Screening (Day -28 to Day -1), Day 1, Day 14, Day 28, Day 56, Day 84, Day 100 ]
    Absolute values and changes from baseline will be summarized for all assessed time points
13. ECG QRS duration [ Time Frame: Screening (Day -28 to Day -1), Day 1, Day 14, Day 28, Day 56, Day 84, Day 100 ]
    Absolute values and changes from baseline will be summarized for all assessed time points
14. ECG QT interval (uncorrected) [ Time Frame: Screening (Day -28 to Day -1), Day 1, Day 14, Day 28, Day 56, Day 84, Day 100 ]
    Absolute values and changes from baseline will be summarized for all assessed time points
15. ECG QTcF intervals [ Time Frame: Screening (Day -28 to Day -1), Day 1, Day 14, Day 28, Day 56, Day 84, Day 100 ]
    Absolute values and changes from baseline will be summarized for all assessed time points
16. Standard routine physical examination [ Time Frame: Screening (Day -28 to Day -1), Day 1, Day 28, Day 56, Day 84, Day 100 ]
    A standard routine physical body examination will be performed and abnormal physical examination results will be evaluated. Clinically significant abnormalities will be reported as AEs.

Secondary Outcome Measures :

1. Sputum cells (total and differential) and inflammatory mediators [ Time Frame: Screening (Day -28 to Day -1), Day 1, Day 42, Day 70, Day 84 ]
   Assessment of inflammatory mediators will include mediators including interleukin (IL) 8, tumour necrosis factor (TNF)-α, IL-6, IL 1β, macrophage inflammatory protein (MIP) 1α, MIP-1β, monocyte chemotactic protein (MCP)-1, surfactant protein D (SP-D), granulocyte macrophage colony-stimulating factor (GM-CSF), IL-23, IL-33, IL-25, IL-10, neutrophil elastase (NE), matrix metalloproteinase (MMP)-9, CXC motif chemokine ligand (CXCL)1, myeloperoxidase (MPO)
2. Blood inflammatory markers [ Time Frame: Day 1, Day 42, Day 84 ]
   Including assessment of fibrinogen (FBG), C-reactive protein (CRP), TNF-α, IL-6 and α2 macroglobulin
3. Forced expiratory volume in 1 second (FEV1) [ Time Frame: Screening (Day -28 to Day -1), Day 1, Day 28, Day 56, Day 84 ]
4. Plasma levels of EP395 [ Time Frame: Day 14, Day 28, Day 42, Day 56, Day 70, Day 80, Day 84 ]
5. St George's respiratory questionnaire (SGRQ) [ Time Frame: Screening (Day -28 to Day -1), Day 1, Day 28, Day 56, Day 84 ]
6. Exacerbations of COPD tool (EXACT) respiratory symptoms (E-RS) [ Time Frame: Screening (Day -28 to Day -1), daily from Day 1 to Day 84 ]

Eligibility Criteria

• Ages Eligible for Study: 45 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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:

   1. have a negative pregnancy test (blood) at Screening and (urine) Day 1
   2. 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.
   3. 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, long acting beta-agonist [LABA], long acting muscarinic antagonist [LAMA], LABA/LAMA, LABA/inhaled corticosteroid [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)

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 QT interval by Fredericia (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. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >1.5 x upper limit of normal 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 (substrates, inhibitors, and inducers are listed in https://www.fda.gov/drugs/drug-interactions-labeling/drug-development-and-drug-interactions-table-substrates-inhibitors-and-inducers)
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

Contacts and Locations

Contacts

Contact: Kate Hanrott; +354 454 0090; kate@epiendo.com

Locations

Germany

IKF Pneumologie GmbH & Co. KG; Recruiting

Frankfurt, Germany, 60596

Contact: Marc Oliver Kornmann, Dr. med.

Principal Investigator: Marc Oliver Kornmann, Dr. med.

Pneumologisches Forschungsinstitut an der LungenClinic Grosshansdorf GmbH; Recruiting

Großhansdorf, Germany, 22927

Contact: Henrik Watz, PD Dr. med.

Principal Investigator: Henrik Watz, PD Dr. med.

IKF Pneumologie GmbH & Co. KG Institut für klinische Forschung Pneumologie; Recruiting

Mainz, Germany, 55128

Contact: Stephanie Korn, PD Dr. med.

Principal Investigator: Stephanie Korn, PD Dr. med.

United Kingdom

Bradford Royal Infirmary, Clinical Research Facility; Recruiting

Bradford, United Kingdom, BD9 6RJ

Contact: Dinesh Saralya, Prof.

Principal Investigator: Dinesh Saralya, Prof.

Medicines Evaluation Unit Ltd. (MEU); Recruiting

Manchester, United Kingdom, M23 9QZ

Contact: Sukh Dave Singh, Prof.

Principal Investigator: Sukh Dave Singh, Prof.

Southampton University Faculty of Medicine; Recruiting

Southampton, United Kingdom, SO16 6YD

Contact: Thomas Wilkinson, Prof.

Principal Investigator: Thomas Wilkinson, Prof.

Sponsors and Collaborators

EpiEndo Pharmaceuticals

FGK Clinical Research GmbH

Investigators

• Principal Investigator: Sukh Dave Singh, Prof.; Medicines Evaluation Unit Ltd. (MEU), Manchester, United Kingdom

More Information

• Responsible Party: EpiEndo Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT05572333
• Other Study ID Numbers: EP395-003
• First Posted: October 7, 2022
• Last Update Posted: December 12, 2022
• Last Verified: December 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes