CoViD-19 treatment by Aloxistatin-Inhalation – a phase I trial to evaluate the safety of inhalable aloxistatin (E64d)
Organizational Data
- DRKS-ID:
- DRKS00028033
- Recruitment Status:
- Recruiting ongoing
- Date of registration in DRKS:
- 2023-04-13
- Last update in DRKS:
- 2024-03-13
- Registration type:
- Prospective
Acronym/abbreviation of the study
COALITION-I
URL of the study
No Entry
Brief summary in lay language
The trial has been designed with the intention to provide reliable evidence about the safety and pharmacokinetics of inhalable aloxistatin (E64d)
Brief summary in scientific language
Double-blind, randomized, placebo-controlled single-ascending-dose (SAD) phase-I study to evaluate safety and pharmacokinetics of single ascending doses of inhalable aloxistatin (E64d) in healthy individuals.
Health condition or problem studied
- Free text:
- Phase-I trial with healthy subjects
- Healthy volunteers:
- Yes
Interventions, Observational Groups
- Arm 1:
- E64d Solution for Inhalation, 0.4 ml in ascending doses, single-dose: Dose-level 1: 0.0136 mg, Dose-level 2: 0.136 mg, Dose-level 3: 0.340 mg, Dose-level 4: 0.850 mg, Dose-level 5: 2.176 mg, Dose-level 5: 5.44 mg
- Arm 2:
- single-dose of placebo solution for inhalation: 0.4 ml 96% EtOH
Endpoints
- Primary outcome:
- Safety and tolerability of single dosing of inhaled E64d in comparison to placebo: - Number and severity of adverse events (AE), serious AEs (SAEs), treatment emergent AEs (TEAEs), AEs of special interest (AESI) after start of treatment for all dose-levels of E64d solution for inhalation and placebo until day 4. - 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:
- Pharmacokinetics (PK): The following PK parameters will be determined for the active drug molecules (E64d and E64c (loxistatin)) in plasma at all applied dose levels: Cmax, tmax, AUC0-t, AUC0-inf, Cl/f*, Vz/f*, terminal elimination rate (lambda_z), terminal elimination half-life (t1/2). 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 of single dose inhalation of E64d solution.
Study Design
- Purpose:
- Other
- Allocation:
- Randomized controlled study
- Control:
-
- Placebo
- Phase:
- I
- Study type:
- Interventional
- Mechanism of allocation concealment:
- No Entry
- Blinding:
- Yes
- Assignment:
- Parallel
- Sequence generation:
- No Entry
- Who is blinded:
-
- Caregiver
- Investigator/therapist
- Patient/subject
Recruitment
- Recruitment Status:
- Recruiting ongoing
- Reason if recruiting stopped or withdrawn:
- No Entry
Recruitment Locations
- Recruitment countries:
-
- Germany
- Number of study centers:
- Monocenter study
- Recruitment location(s):
-
- Medical center Universitätsklinikum Freiburg Freiburg im Breisgau
Recruitment period and number of participants
- Planned study start date:
- 2023-06-05
- Actual study start date:
- 2023-06-05
- Planned study completion date:
- No Entry
- Actual Study Completion Date:
- No Entry
- Target Sample Size:
- 48
- Final Sample Size:
- No Entry
Inclusion Criteria
- Sex:
- Male
- Minimum Age:
- 18 Years
- Maximum Age:
- 64 Years
- Additional 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.
Addresses
Primary Sponsor
- Address:
- Universitätsklinikum Freiburg vertreten durch den Leitenden Ärztlichen Direktor und die Kaufmännische DirektorinBreisacher Str. 15379110 Freiburg im BreisgauGermany
- Telephone:
- No Entry
- Fax:
- No Entry
- Contact per E-Mail:
- Contact per E-Mail
- URL:
- https://www.uniklinik-freiburg.de/de.html
- Investigator Sponsored/Initiated Trial (IST/IIT):
- Yes
Contact for Scientific Queries
- Address:
- Universitätsklinikum Freiburg, Department Innere Medizin, Klinik für PneumologiePD Dr. Sebastian FähndrichKillianstraße 579106 FreiburgGermany
- Telephone:
- 0761 270 37130
- Fax:
- 0761 270 37040
- Contact per E-Mail:
- Contact per E-Mail
- URL:
- https://www.uniklinik-freiburg.de/pneumologie.html
Contact for Public Queries
- Address:
- Universitätsklinikum Freiburg, Department Innere Medizin, Klinik für PneumologiePD Dr. Sebastian FähndrichKillianstraße 579106 FreiburgGermany
- Telephone:
- 0761 270 37130
- Fax:
- 0761 270 37040
- Contact per E-Mail:
- Contact per E-Mail
- URL:
- https://www.uniklinik-freiburg.de/pneumologie.html
Principal Investigator
- Address:
- Universitätsklinikum Freiburg, Department Innere Medizin, Klinik für PneumologiePD Dr. Sebastian FähndrichKillianstraße 579106 FreiburgGermany
- Telephone:
- 0761 270 37130
- Fax:
- 0761 270 37040
- Contact per E-Mail:
- Contact per E-Mail
- URL:
- https://www.uniklinik-freiburg.de/pneumologie.html
Sources of Monetary or Material Support
Public funding institutions financed by tax money/Government funding body (German Research Foundation (DFG), Federal Ministry of Education and Research (BMBF), etc.)
- Address:
- Bundesministerium für Bildung und Forschung Dienstsitz BerlinFriedrichstraße 130 B10117 BerlinGermany
- Telephone:
- No Entry
- Fax:
- No Entry
- Contact per E-Mail:
- Contact per E-Mail
- URL:
- http://www.bmbf.de
Ethics Committee
Address Ethics Committee
- Address:
- Ethik-Kommission der Albert-Ludwigs-Universität FreiburgEngelberger Str. 2179106 FreiburgGermany
- Telephone:
- +49-761-27072600
- Fax:
- +49-761-27072630
- Contact per E-Mail:
- Contact per E-Mail
- URL:
- No Entry
Vote of leading Ethics Committee
- Vote of leading Ethics Committee
- Date of ethics committee application:
- 2022-09-29
- Ethics committee number:
- 22-1395-AMG-ff mono
- Vote of the Ethics Committee:
- Approved
- Date of the vote:
- 2022-12-01
Further identification numbers
- Other primary registry ID:
- No Entry
- EudraCT Number:
- 2022-000705-27
- Other secondary IDs:
- Förderkennzeichen 01KI20386 - BMBF
IPD - Individual Participant Data
- Do you plan to make participant-related data (IPD) available to other researchers in an anonymized form?:
- No
- IPD Sharing Plan:
- No Entry
Study protocol and other study documents
- Study protocols:
- No Entry
- Study abstract:
- COALITION-I
- Other study documents:
- No Entry
- Background literature:
- No Entry
- Related DRKS studies:
- No Entry
Publication of study results
- Planned publication:
- No Entry
- Publikationen/Studienergebnisse:
- No Entry
- Date of first publication of study results:
- No Entry
- DRKS entry published for the first time with results:
- No Entry
Basic reporting
- Basic Reporting / Results tables:
- No Entry
- Brief summary of results:
- No Entry