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

NCT05572333 | Completed Phase 2

• 1 other identifier: EP395-003
• Study Type: interventional
• Target: 61
• Locations: 2 countries
• Sites: 6

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.

Conditions

Chronic Obstructive Pulmonary Disease; COPD

Outcome Measures

Primary Outcomes (16)

• Assessment of adverse event (AE) occurrence

  From Screening (Day -28 to Day -1) to Day 100

• Vital signs: Systolic and diastolic blood pressure

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

  Screening (Day -28 to Day -1), Day 1, Day 14, Day 28, Day 42, Day 56, Day 70, Day 84, Day 100

• Vital signs: Pulse

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

  Screening (Day -28 to Day -1), Day 1, Day 14, Day 28, Day 42, Day 56, Day 70, Day 84, Day 100

• Vital signs: Body temperature

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

  Screening (Day -28 to Day -1), Day 1, Day 14, Day 28, Day 42, Day 56, Day 70, Day 84, Day 100

• Vital signs: Respiratory rate

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

  Screening (Day -28 to Day -1), Day 1, Day 14, Day 28, Day 42, Day 56, Day 70, Day 84, Day 100

• Assessment of laboratory values (haematology)

  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.

  Screening (Day -28 to Day -1), Day 1, Day 14, Day 28, Day 42, Day 56, Day 70, Day 84, Day 100

• Assessment of blood coagulation

  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.

  Screening (Day -28 to Day -1), Day 1, Day 14, Day 28, Day 42, Day 56, Day 70, Day 84, Day 100

• Assessment of laboratory values (biochemistry)

  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

  Screening (Day -28 to Day -1), Day 1, Day 14, Day 28, Day 42, Day 56, Day 70, Day 84, Day 100

• Urinalysis

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

  Screening (Day -28 to Day -1), Day 1, Day 28, Day 56, Day 84, Day 100

• ECG heart rate

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

  Screening (Day -28 to Day -1), Day 1, Day 14, Day 28, Day 56, Day 84, Day 100

• ECG RR interval

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

  Screening (Day -28 to Day -1), Day 1, Day 14, Day 28, Day 56, Day 84, Day 100

• ECG PR interval

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

  Screening (Day -28 to Day -1), Day 1, Day 14, Day 28, Day 56, Day 84, Day 100

• ECG QRS duration

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

  Screening (Day -28 to Day -1), Day 1, Day 14, Day 28, Day 56, Day 84, Day 100

• ECG QT interval (uncorrected)

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

  Screening (Day -28 to Day -1), Day 1, Day 14, Day 28, Day 56, Day 84, Day 100

• ECG QTcF intervals

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

  Screening (Day -28 to Day -1), Day 1, Day 14, Day 28, Day 56, Day 84, Day 100

• Standard routine physical examination

  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.

  Screening (Day -28 to Day -1), Day 1, Day 28, Day 56, Day 84, Day 100

Secondary Outcomes (6)

• Sputum cells (total and differential) and inflammatory mediators

  Screening (Day -28 to Day -1), Day 1, Day 42, Day 70, Day 84

• Blood inflammatory markers

  Day 1, Day 42, Day 84

• Forced expiratory volume in 1 second (FEV1)

  Screening (Day -28 to Day -1), Day 1, Day 28, Day 56, Day 84

• Plasma levels of EP395

  Day 14, Day 28, Day 42, Day 56, Day 70, Day 80, Day 84

• St George's respiratory questionnaire (SGRQ)

  Screening (Day -28 to Day -1), Day 1, Day 28, Day 56, Day 84

Study Arms (2)

EP395

EXPERIMENTAL

EP395 in repeated doses. Oral, once-daily administration of 3 EP395 capsules for 12 weeks.

Drug: EP395

Placebo

PLACEBO COMPARATOR

Matched placebo capsule. Oral, once-daily administration of 3 placebo capsules for 12 weeks.

Drug: Placebo

Interventions

EP395 DRUG

Capsule for oral use

EP395

Placebo DRUG

Capsule for oral use

Placebo

Eligibility Criteria

• Age: 45 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• Men and women, aged ≥45 years
• Women of childbearing potential must:
• have a negative pregnancy test (blood) at Screening and (urine) Day 1
• 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.
• agree to abstain from breast feeding during the study participation and for 90 days after the last IP intake.
• 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
• Diagnosed with COPD for at least 2 years with FEV1/forced vital capacity (FVC) ratio \<0.70 and FEV1 \<70% (post bronchodilator) at Screening
• 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
• Able to tolerate the sputum induction procedure and to produce an adequate (volume and sufficient quality for cell count) sputum sample
• Body mass index of ≥19 and ≤35 kg/m2
• History of sputum production (bronchitic phenotype) for approximately 3 months (minimum, not consecutive) in a year
• Up to date COVID-19 vaccination (according to local law and guidelines)

You may not qualify if:

• 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
• Exacerbation of COPD in the 3 months before Screening
• Change in medication for COPD in the 3 months before Screening
• 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)
• History of or active tuberculosis
• Malignancy within the past 5 years, except removed basal cell carcinoma and resected benign colonic polyps
• 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
• Absolute estimated glomerular filtration rate (\[eGFR cystatin C + eGFR creatinine\]/2) \<60mL/min according to Lund-Malmö equation at Screening
• Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \>1.5 x upper limit of normal at Screening
• 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)
• Use of macrolide, roflumilast, or oral corticosteroid (OCS) within 28 days before Screening
• Ongoing antibiotic treatment at Screening
• Use of home oxygen or home-based non-invasive ventilation 3 months before Screening
• Use of a biological therapy within 3 months before Screening
• Use of herbal remedies within 28 days before first dose until follow-up

Sponsors & Collaborators

• EpiEndo Pharmaceuticals: lead
• FGK Clinical Research GmbH: collaborator

Study Sites (6)

IKF Pneumologie GmbH & Co. KG

Frankfurt, 60596, Germany

Location

Pneumologisches Forschungsinstitut an der LungenClinic Grosshansdorf GmbH

Großhansdorf, 22927, Germany

Location

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

Mainz, 55128, Germany

Location

Bradford Royal Infirmary, Clinical Research Facility

Bradford, BD9 6RJ, United Kingdom

Location

Medicines Evaluation Unit Ltd. (MEU)

Manchester, M23 9QZ, United Kingdom

Location

Southampton University Faculty of Medicine

Southampton, SO16 6YD, United Kingdom

Location

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Sukh Dave Singh, Prof.

  Medicines Evaluation Unit Ltd. (MEU), Manchester, United Kingdom

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: During the study, study participants, investigators, the sponsor, and all other persons involved in the conduct of the study will be blinded to treatment.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: The study is double-blind, placebo-controlled and parallel-group in design.

Study Record Dates

• First Submitted: September 30, 2022
• First Posted: October 7, 2022
• Study Start: November 22, 2022
• Primary Completion: November 24, 2023
• Study Completion: November 24, 2023
• Last Updated: November 29, 2023

Record last verified: 2023-11

Data Sharing

• IPD Sharing: Will not share

Locations

GB (3); DE (3)