Clinical trial NCT06677918: Clinical Trial Investigating the Effects of EP395 Following an Inhaled Endotoxin Challenge in Healthy Adults
Official title: A Randomised, Double-blind, Placebo-controlled Trial to Assess the Effects of EP395 Following an Inhaled Endotoxin Challenge in Healthy Adults
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Healthy Volunteer
Lead sponsor: EpiEndo Pharmaceuticals
Sponsor class: INDUSTRY
Collaborators: name: FGK Clinical Research GmbH
First posted: 2024-11-07
Enrollment: 65
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

Brief summary: The aim of this clinical trial is to assess the effect of EP395 in a model of lung inflammation (inhaled lipopolysaccharide, which causes temporary inflammation in the airways). In addition, further information on the safety and tolerability of EP395 will be collected.

Detailed description: This is a randomized, double-blind, placebo-controlled trial in healthy adults. The study will assess the effect of repeated doses of EP395 on blood and lung markers of inflammation after inhaled lipopolysaccharide (LPS). It will also assess the safety, tolerability and systemic exposure of EP395.

Participants will be randomized to receive EP395 or placebo (taken orally) for 21 days. On Day 21, participants will inhale LPS to induce airway inflammation. Blood and sputum (phlegm) samples will be taken before and after the LPS challenge to measure inflammatory markers. A final safety follow-up visit will be performed on Day 37.

Depending on the results from the first cohort of participants (Cohort A), a second cohort may be recruited to test a lower dose of EP395 (Cohort B).

Eligibility criteria: Inclusion Criteria:

1. Willing and able to understand the requirements and restrictions of the study, and to provide voluntary, written informed consent.
2. Aged ≥18 and ≤55 years at the time of signing the consent form.
3. Body mass index (BMI) of ≥19.0 and ≤31.0 kg/m\^2 at Screening.
4. Medically healthy without abnormal clinically significant medical history, physical findings, vital signs, ECG and laboratory values at the time of Screening, as judged by the investigator.
5. Non-smoker, or former smoker with less than 10 pack years who stopped smoking (including e-cigarettes) at least 6 months before Screening.
6. Normal pulmonary function test (spirometry) adjusted for sex, height, and age.
7. Women of childbearing potential (WOCBP) must have a negative pregnancy test at Screening (blood) and Day 1 (urine) and must agree to use, highly effective measures of contraceptive control during trial participation and until 90 days after the last intake of study drug.

Women defined as of non-childbearing potential are postmenopausal (no menses for at least 1 year without alternative medical cause or surgically sterile women (tubal ligation, hysterectomy, or bilateral oophorectomy).

Men must agree to use a condom during sexual intercourse with WOCBP during treatment and for 90 days after the last IMP intake and should not donate sperm during this time.

Exclusion Criteria:

1. History of any clinically significant disease or disorder which, in the opinion of the investigator, may either put the participant at risk because of participation in the trial, or influence the results, or the participant's ability to participate in the trial.
2. Any clinically significant illness, medical/surgical procedure or trauma within 4 weeks of the first administration of study drug.
3. Recent infection, including but not limited to SARS-CoV-2, within 14 days prior to the sputum screening collection or Day 1.
4. Presence or history of lung disease, e.g., asthma or COPD.
5. History of or active tuberculosis at the time of Screening based on participant anamnesis. Participants who have been living together with another person with active tuberculosis at any time over the past 10 years will also be excluded.
6. Clinically significant abnormality on 12-lead ECG at Screening or Day 1 pre-dose.
7. Abnormal renal function at Screening.
8. Elevated liver values of Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) greater than 1.5 x upper limit of normal at Screening.
9. Use of prescription or non-prescription medications or herbal remedies within 28 days prior to Day 1, or unable to refrain from prescription or non-prescription medications or herbal remedies during the trial, with the exception of hormone replacement therapy, contraception and occasional use of paracetamol.
10. Live vaccine within 28 days or any other vaccine within 14 days prior to Day 1 until 28 days after the final dose.
11. Any positive result at Screening for serum hepatitis B, hepatitis C or human immunodeficiency virus (HIV).
12. Positive drugs of abuse, smoking, or alcohol test at Screening or Day 1.
13. History of alcohol abuse or excessive intake of alcohol, as judged by the investigator.
14. Presence or history of drug abuse, as judged by the investigator.
15. Pregnant, currently breastfeeding, or intend to become pregnant during the course of the trial.
16. Known hypersensitivity to LPS, macrolides or EP395 or any of the study products.
17. Any clinically significant allergy, as judged by the investigator.
18. Planned treatment or treatment with another investigational drug within 5 half-lives or 3 months before the first administration of study drug, whichever is longer. Participants consented and screened, but not dosed in a previous clinical trial are not excluded.
19. Blood donation (or corresponding blood loss) greater than 400 mL, during the 3 months before the first administration of study drug.
20. Employees of the sponsor or employees or relatives of the investigator.
21. The investigator considers the participant unlikely to comply with trial procedures, restrictions and requirements.
22. Withdrawal of consent before randomisation (despite meeting the other eligibility criteria).

Primary outcomes:
measure: Blood surfactant protein-D (SP-D)
timeFrame: Day 21
Secondary outcomes:
measure: Blood biomarkers of immune response and systemic inflammation
timeFrame: Day 21
measure: Lung inflammatory markers in exhaled particles (PEx)
timeFrame: Day 21
measure: Plasma levels of EP395
timeFrame: Day 1, 7, 13, 21 and 22
measure: Assessment of adverse event (AE) occurrence
timeFrame: Day 1 to Day 37
measure: Electrocardiogram (ECG) recording
timeFrame: Screening, Day 1, 7, 13, 21, 22 and 37
measure: Assessment of laboratory values (haematology)
timeFrame: Screening, Day 1, 7, 13, 21, and 37
measure: Assessment of laboratory values (blood biochemistry)
timeFrame: Screening, Day 1, 7, 13, 21, and 37
measure: Vital signs - Heart rate
timeFrame: Screening, Day 1, 7, 13, 21, and 37
measure: Vital signs: Systolic and diastolic blood pressure
timeFrame: Screening, Day 1, 7, 13, 21, and 37
measure: Vital signs - Body temperature
timeFrame: Screening, Day 1, 7, 13, 21, and 37
measure: Physical Examination
timeFrame: Screening, Day 1, 13, 21, and 37
Other outcomes:
Locations:
city: Hanover
country: Germany
facility: Fraunhofer Institute for Toxicology and Experimental Medicine ITEM, Division of Clinical Airway Research
Study officials:
References: