CoViD-19 treatment by Aloxistatin-Inhalation – a phase I trial to evaluate the safety of inhalable aloxistatin (E64d)

Phase 1

• Conditions: Phase-I trial with healthy subjects

• Registration Number: DRKS00028033
• Lead Sponsor: niversitätsklinikum Freiburg vertreten durch den Leitenden Ärztlichen Direktor und die Kaufmännische Direktorin

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2023-04-13
• Study Completion: 2024-06-07
• Last Update Posted: 19 August 2024

Recruitment & Eligibility

• Status: Complete
• Sex: Male
• Target Recruitment: 48

Inclusion Criteria

1. Signed Informed Consent Form (ICF), including consent to use effective contraceptive methods (sexual abstinence or condoms) during the trial and for three months after the end of the study
2. Male subjects
3. Electrocardiogram (ECG) without clinically significant abnormalities (including QTc < 450 ms)
4. Age = 18 and < 65 years at the time of signing ICF
5. Body mass index (BMI) = 18 and = 30
6. Normally active and in good health by medical history and physical examination
7. FEV1 (one-second capacity) must be greater than or equal to the
Lower Limit of Normal, which corresponds to the 5% percentile (zscore
of -1.645)

Exclusion Criteria

1. Enrollment in any interventional clinical trial in the previous 6 months
2. Healthy volunteers being unable to follow study instructions and not understanding basics and risks of the study
3. Underlying condition that may interfere with inhalation of the IMP
4. Current acute or chronic condition (including airway infection (cough, purulent sputum), fever, chronic obstructive pulmonary disease (COPD), asthma, or other severe respiratory disease, cardiovascular disease, diabetes mellitus, obesity, malignant and autoimmune diseases) unless considered clinically irrelevant and stable by the investigator
5. History of allergies
6. Renal insufficiency (estimated glomerular filtration rate [eGFR] < 60 mL/min/1·73m²) or hepatic impairment (as judged by the investigator)
7. The presence of a condition which renders the subject vulnerable as defined by good clinical practice (GCP) or of a condition the investigator believes would interfere with the ability to provide informed consent, or comply with study procedures/instructions, or that might confound the interpretation of the study results or put the subject at undue risk
8. Anamnestic smoke or regular use of any form of nicotine product including e-cigarette, snuff, chewing tobacco, nicotine gum, etc.,
during the study period and for the previous 6 months
9. Healthy volunteers unable to abstain from alcoholic drinks during the study, prehistory of or current alcohol or drug abuse
10. Known difficulty undergoing venipuncture or poor venous access
11. Whole blood donation or loss (> 400 mL) within 90 days before the dosing of Investigational medicinal product (IMP)
12. Consumed alcohol in the 4 days prior to dosing
13. Anamnestic any therapies within 90 days prior to dosing. Nonprescriptive
drugs within 90 days prior to dosing are allowed by investigators judgement.
14. Failure to provide contact details of a person with unimpeded access to the trial participant for 24h after inhalation of IMP, who can call for help in case of emergency situations caused by adverse reactions occurring after discharge from the clinic.

Study & Design

• Study Type: interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Safety and tolerability of single dosing of inhaled E64d in comparison to placebo:<br>- Number and severity of adverse events (AE), serious AEs (SAEs), treatment emergent AEs (TEAEs), AEs of special interest (AESI) after<br>start of treatment for all dose-levels of E64d solution for inhalation and placebo until day 4.<br>- Change from baseline and frequency of out of range values for all safety variables measured for all dose-levels from signing of ICF until End of Study (EOS).

Secondary Outcome Measures

Name	Time	Method
Pharmacokinetics (PK):<br>The following PK parameters will be determined for the active drug molecules (E64d and E64c (loxistatin)) in plasma at all applied dose levels:<br>Cmax, tmax, AUC0-t, AUC0-inf, Cl/f*, Vz/f*, terminal elimination rate (lambda_z), terminal elimination half-life (t1/2).<br><br>E64d and E64c concentration in plasma will be determined 0 -2 h predose, and 3, 10, 20, 30, 40, 50 minutes, 1, 1.5, 2, 4, 6 and 8 h after start<br>of single dose inhalation of E64d solution.