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

• ClinicalTrials.gov Identifier: NCT05516316
• Recruitment Status: Recruiting
• First Posted: August 25, 2022
• Last Update Posted: October 17, 2022
• Sponsor: EpiEndo Pharmaceuticals
• Collaborator: FGK Clinical Research GmbH
• Information provided by (Responsible Party): EpiEndo Pharmaceuticals

Study Description

Brief 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.

Condition or disease	Intervention/treatment	Phase
Chronic Obstructive Pulmonary Disease; COPD	Drug: EP395; Drug: Placebo	Phase 1

Detailed 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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 48 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 Proof-of-pharmacology Study of EP395 in Healthy Adults
• Actual Study Start Date: October 11, 2022
• Estimated Primary Completion Date: May 2023
• Estimated Study Completion Date: May 2023

Arms and Interventions

Arm	Intervention/treatment
Experimental: EP395 high dose; EP395 in repeated doses. Orally, once-daily administration of 3 EP395 capsules for 21 days	Drug: EP395; Capsule for oral use
Experimental: EP395 low dose; EP395 in repeated doses. Orally, once-daily administration of 1 EP395 capsule and 2 placebo capsules for 21 days	Drug: EP395; Capsule for oral use
Placebo Comparator: Placebo; Matched placebo capsule, once-daily administration of 3 placebo capsules for 21 days	Drug: Placebo; Capsule for oral use

Outcome Measures

Primary Outcome Measures :

1. Bronchoalveolar lavage fluid interleukin 8 at Day 21 [ Time Frame: Day 21 ]

Secondary Outcome Measures :

1. ECG ventricular rate [ Time Frame: Screening (Day -21 to Day -1), Days 1, 7 (±2 days), 14 (±2 days), Day 21 (±2 days), Day 37 (±3 days) ]
   Absolute values and changes from baseline will be summarized for all assessed time points
2. ECG RR interval [ Time Frame: Screening (Day -21 to Day -1), Days 1, 7 (±2 days), 14 (±2 days), Day 21 (±2 days), Day 37 (±3 days) ]
   Absolute values and changes from baseline will be summarized for all assessed time points
3. ECG PR interval [ Time Frame: Screening (Day -21 to Day -1), Days 1, 7 (±2 days), 14 (±2 days), Day 21 (±2 days), Day 37 (±3 days) ]
   Absolute values and changes from baseline will be summarized for all assessed time points
4. ECG QRS duration [ Time Frame: Screening (Day -21 to Day -1), Days 1, 7 (±2 days), 14 (±2 days), Day 21 (±2 days), Day 37 (±3 days) ]
   Absolute values and changes from baseline will be summarized for all assessed time points
5. ECG QT interval (uncorrected) [ Time Frame: Screening (Day -21 to Day -1), Days 1, 7 (±2 days), 14 (±2 days), Day 21 (±2 days), Day 37 (±3 days) ]
   Absolute values and changes from baseline will be summarized for all assessed time points
6. ECG QTcF intervals [ Time Frame: Screening (Day -21 to Day -1), Days 1, 7 (±2 days), 14 (±2 days), Day 21 (±2 days), Day 37 (±3 days) ]
   Absolute values and changes from baseline will be summarized for all assessed time points
7. Assessment of laboratory values (haematology) [ Time Frame: Screening (Day -21 to Day -1), Days 1, 7 (±2 days), 14 (±2 days), Day 21 (±2 days), Day 37 (±3 days) ]
   Absolute values and changes from baseline will be summarized for all assessed time points
8. Assessment of laboratory values (blood biochemistry) [ Time Frame: Screening (Day -21 to Day -1), Days 1, 7 (±2 days), 14 (±2 days), Day 21 (±2 days), Day 37 (±3 days) ]
   Absolute values and changes from baseline will be summarized for all assessed time points
9. Assessment of blood coagulation [ Time Frame: Screening (Day -21 to Day -1), Days 1, 7 (±2 days), 14 (±2 days), Day 21 (±2 days), Day 37 (±3 days) ]
   Absolute values and changes from baseline will be summarized for all assessed time points
10. Urinalysis [ Time Frame: Screening (Day -21 to Day -1), Days 1, 7 (±2 days), 14 (±2 days), Day 21 (±2 days), Day 37 (±3 days) ]
    Absolute values and changes from baseline will be summarized for all assessed time points
11. Vital signs: Systolic and diastolic blood pressure [ Time Frame: Screening (Day -21 to Day -1), Days 1, 7 (±2 days), 14 (±2 days), Day 21 (±2 days) ]
    Absolute values and changes from baseline will be summarized for all assessed time points
12. Vital signs: Pulse [ Time Frame: Screening (Day -21 to Day -1), Days 1, 7 (±2 days), 14 (±2 days), Day 21 (±2 days) ]
    Absolute values and changes from baseline will be summarized for all assessed time points
13. Vital signs: Body temperature [ Time Frame: Screening (Day -21 to Day -1), Days 1, 7 (±2 days), 14 (±2 days), Day 21 (±2 days) ]
    Absolute values and changes from baseline will be summarized for all assessed time points
14. Height and weight [ Time Frame: Screening (Day -21 to Day -1), Day 37 (±3 days) ]
    BMI will be calculated from height and weight measurements
15. Standard routine physical examination [ Time Frame: Screening (Day -21 to Day -1), Days 1, Day 21 (±2 days), Day 37 (±3 days) ]
    A standard routine physical body examination will be performed and abnormal physical examination results will be evaluated and reported as AEs.
16. Assessment of adverse event (AE) occurrence [ Time Frame: From Screening (Day -21 to Day -1), to Day 37 (±3 days) ]
17. BALF cell count (total and differential) and mediators [ Time Frame: Day 21 (±2 days) ]
    Including tumour necrosis factor (TNF)-α, IL-6, IL-1β, macrophage inflammatory protein (MIP)-1α, MIP-1β, 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
18. Exhaled particles IL-6 and IL-8 [ Time Frame: Day 21 (±2 days) ]
19. Blood inflammatory markers including C-reactive protein, TNF-α, IL-6, IL-8, and α2-macroglobulin [ Time Frame: Day 21 (±2 days) ]
20. Plasma EP395 [ Time Frame: Day 7 (±2 days) [only applicable for trough levels of EP395], Day 14 (±2 days) and Day 21 (±2 days) ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 55 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

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

Contacts and Locations

Contacts

Contact: Kerstin Danielson; +354 454 0090; Kerstin@epiendo.com

Locations

Germany

Fraunhofer Institute for Toxicology and Experimental Medicine ITEM; Recruiting

Hannover, Germany, 30625

Principal Investigator: Jens Hohlfeld, Prof. Dr.

Sponsors and Collaborators

EpiEndo Pharmaceuticals

FGK Clinical Research GmbH

Investigators

• Principal Investigator: Jens Hohlfeld, Prof. Dr.; Fraunhofer Institute for Toxicology and Experimental Medicine ITEM

More Information

• Responsible Party: EpiEndo Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT05516316
• Other Study ID Numbers: EP395-002; 2021-005867-28 ( EudraCT Number )
• First Posted: August 25, 2022
• Last Update Posted: October 17, 2022
• Last Verified: October 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, Obstructive; Pulmonary Disease, Chronic Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes