Clinical Trial Comparing the Pharmacological Effects of EP395 With Placebo in Healthy Adults

Chronic Obstructive Pulmonary Disease Clinical Trial

Official title:

A Randomised, Double-blind, Placebo-controlled Proof-of-pharmacology Study of EP395 in Healthy Adults

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05516316
• Other study ID #: EP395-002
• Secondary ID: 2021-005867-28
• Status: Completed
• Phase: Phase 1
• Start date: October 11, 2022
• Est. completion date: June 21, 2023

Study information

• Verified date: June 2023
• Source: EpiEndo Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study aims to assess the effect of EP395 against an induced inflammation of the lung. In addition, further data about the safety and tolerability of EP395 will be collected.

To investigate the efficacy of EP395 at the end of the treatment with EP395 or placebo (dummy), all participants will inhale a lipopolysaccharide (a molecule composed of sugar and fat) that artificially induces an acute inflammation of the airways. It is assumed that participants who received EP395 will show less inflammation of the airways than participants who received placebo.

Description:

This is a study to assess the pharmacological effect of repeated doses of EP395 in healthy subjects with the aim to assess the effects of EP395 on lung and blood markers of inflammation after inhaled lipopolysaccharide (LPS), and the safety, tolerability, and systemic exposure of EP395.

The study will be randomised in a 1:1 ratio to take either high dose EP395 or placebo as oral capsules once daily for 21 days starting on Day 1 with scheduled visits at Days 7, 14, and 21 for assessments of safety and tolerability and systemic exposure of EP395. At Day 21, 2 hours after the last investigational product (IP) intake, participants will undergo an inhaled LPS challenge to induce airway inflammation, which will be followed by bronchoscopy and BAL 6 hours later. A final safety follow-up visit will be performed at Day 37.

If the data from the high dose EP395 arm (variability, effect size) indicate that it may be possible to detect effects on IL-8 at a lower dose of EP395, an additional lower dose EP395 arm will be added.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 49
• Est. completion date: June 21, 2023
• Est. primary completion date: June 21, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

1. Willing and able to understand the information on the nature, the scope and the relevance of the clinical study, and to provide voluntary, written informed consent to participate in the study before any study-related procedures

2. Men and women, aged =18 and =55 years

3. Women of childbearing potential must:

1. have a negative pregnancy test (blood) at Screening.

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, from Screening until 90 days after the last IP intake.

4. Men must agree to use contraception (barrier method) during sexual intercourse with women of childbearing potential during treatment until 90 days after the last IP intake and should not donate sperm during this time.

5. In good health as determined by medical history and screening investigations, as judged by the investigator

6. Body mass index of =19 and =33 kg/m2

7. Normal spirometry (forced expiratory volume in 1 second [FEV1] >80% predicted and FEV1/forced vital capacity >70%)

8. Non-smoker or former smoker with <10 pack years who had stopped smoking (including e-cigarettes) for at least 6 months before Screening.

Exclusion Criteria:

1. History or presence of any clinically relevant medical condition that could affect the participant's safety or interfere with the objectives of the study

2. Presence or history of lung disease, eg, asthma, chronic obstructive pulmonary disease

3. Clinically significant abnormality on 12-lead ECG including prolonged corrected QT interval by Fredericia (>450 msec men or >470 msec women)

4. Use of prescribed or nonprescribed medications or herbal remedies within 28 days of first dosing and during the study with the exception of

1. hormone replacement therapy (HRT)

2. contraception

3. occasional use of paracetamol

5. Positive hepatitis B surface antigen, hepatitis C antibodies, HIV-1 or -2 antibodies

6. Positive drugs of abuse, smoking, or alcohol test at Screening

7. History of alcohol or drug misuse

8. Pregnant and lactating women

9. Prior recovery from recent infection, including but not limited to COVID-19, within the last 14 days before first dosing with IP

10. History of hypersensitivity to any constituents of the IMP or LPS

11. Any clinically significant allergy

12. Participation in a clinical study with an IP within 3 months or 5 half-lives before first dosing, whichever is longer

13. Employees of the sponsor or employees or relatives of the investigator

Related Conditions & MeSH terms

• Chronic Obstructive Pulmonary Disease
• COPD
• Lung Diseases, Obstructive
• Pulmonary Disease, Chronic Obstructive

Intervention

Drug:
• EP395
Capsule for oral use
• Placebo
Capsule for oral use

Locations

Country	Name	City	State
Germany	Fraunhofer Institute for Toxicology and Experimental Medicine ITEM	Hannover

Sponsors (2)

Lead Sponsor	Collaborator
EpiEndo Pharmaceuticals	FGK Clinical Research GmbH

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Bronchoalveolar lavage fluid interleukin 8 at Day 21		Day 21
Secondary	ECG ventricular rate	Absolute values and changes from baseline will be summarized for all assessed time points	Screening (Day -21 to Day -1), Days 1, 7 (±2 days), 14 (±2 days), Day 21 (±2 days), Day 37 (±3 days)
Secondary	ECG RR interval	Absolute values and changes from baseline will be summarized for all assessed time points	Screening (Day -21 to Day -1), Days 1, 7 (±2 days), 14 (±2 days), Day 21 (±2 days), Day 37 (±3 days)
Secondary	ECG PR interval	Absolute values and changes from baseline will be summarized for all assessed time points	Screening (Day -21 to Day -1), Days 1, 7 (±2 days), 14 (±2 days), Day 21 (±2 days), Day 37 (±3 days)
Secondary	ECG QRS duration	Absolute values and changes from baseline will be summarized for all assessed time points	Screening (Day -21 to Day -1), Days 1, 7 (±2 days), 14 (±2 days), Day 21 (±2 days), Day 37 (±3 days)
Secondary	ECG QT interval (uncorrected)	Absolute values and changes from baseline will be summarized for all assessed time points	Screening (Day -21 to Day -1), Days 1, 7 (±2 days), 14 (±2 days), Day 21 (±2 days), Day 37 (±3 days)
Secondary	ECG QTcF intervals	Absolute values and changes from baseline will be summarized for all assessed time points	Screening (Day -21 to Day -1), Days 1, 7 (±2 days), 14 (±2 days), Day 21 (±2 days), Day 37 (±3 days)
Secondary	Assessment of laboratory values (haematology)	Absolute values and changes from baseline will be summarized for all assessed time points	Screening (Day -21 to Day -1), Days 1, 7 (±2 days), 14 (±2 days), Day 21 (±2 days), Day 37 (±3 days)
Secondary	Assessment of laboratory values (blood biochemistry)	Absolute values and changes from baseline will be summarized for all assessed time points	Screening (Day -21 to Day -1), Days 1, 7 (±2 days), 14 (±2 days), Day 21 (±2 days), Day 37 (±3 days)
Secondary	Assessment of blood coagulation	Absolute values and changes from baseline will be summarized for all assessed time points	Screening (Day -21 to Day -1), Days 1, 7 (±2 days), 14 (±2 days), Day 21 (±2 days), Day 37 (±3 days)
Secondary	Urinalysis	Absolute values and changes from baseline will be summarized for all assessed time points	Screening (Day -21 to Day -1), Days 1, 7 (±2 days), 14 (±2 days), Day 21 (±2 days), Day 37 (±3 days)
Secondary	Vital signs: Systolic and diastolic blood pressure	Absolute values and changes from baseline will be summarized for all assessed time points	Screening (Day -21 to Day -1), Days 1, 7 (±2 days), 14 (±2 days), Day 21 (±2 days)
Secondary	Vital signs: Pulse	Absolute values and changes from baseline will be summarized for all assessed time points	Screening (Day -21 to Day -1), Days 1, 7 (±2 days), 14 (±2 days), Day 21 (±2 days)
Secondary	Vital signs: Body temperature	Absolute values and changes from baseline will be summarized for all assessed time points	Screening (Day -21 to Day -1), Days 1, 7 (±2 days), 14 (±2 days), Day 21 (±2 days)
Secondary	Height and weight	BMI will be calculated from height and weight measurements	Screening (Day -21 to Day -1), Day 37 (±3 days)
Secondary	Standard routine physical examination	A standard routine physical body examination will be performed and abnormal physical examination results will be evaluated and reported as AEs.	Screening (Day -21 to Day -1), Days 1, Day 21 (±2 days), Day 37 (±3 days)
Secondary	Assessment of adverse event (AE) occurrence		From Screening (Day -21 to Day -1), to Day 37 (±3 days)
Secondary	BALF cell count (total and differential) and mediators	Including tumour necrosis factor (TNF)-a, IL-6, IL-1ß, macrophage inflammatory protein (MIP)-1a, MIP-1ß, monocyte chemotactic protein-1, intercellular adhesion molecule-1, surfactant protein (SP)-D, granulocyte macrophage colony-stimulating factor, IL-23, IL-33, IL-25, IL-10, albumin, and protein	Day 21 (±2 days)
Secondary	Exhaled particles IL-6 and IL-8		Day 21 (±2 days)
Secondary	Blood inflammatory markers including C-reactive protein, TNF-a, IL-6, IL-8, and a2-macroglobulin		Day 21 (±2 days)
Secondary	Plasma EP395		Day 7 (±2 days) [only applicable for trough levels of EP395], Day 14 (±2 days) and Day 21 (±2 days)