A randomized, controlled, partial-blind, parallel-group study evaluating the effect of oral administration of BAY 1834845 and BAY 1830839 twice daily for 7 consecutive days on local and systemic IRAK4 pathway-related challenges in healthy male participants

Completed

• Conditions: Contact dermatitis; 10014982

• Registration Number: NL-OMON50967
• Lead Sponsor: Bayer AG

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 2022-11-30
• Last Update Posted: 15 April 2024

Recruitment & Eligibility

• Status: Completed
• Sex: Not specified
• Target Recruitment: 48

Inclusion Criteria

1. Participant must be 18 to 55 years of age inclusive, at the time of signing
the informed consent.
2. Overtly healthy as determined by medical evaluation including medical and
surgical history, physical examination, laboratory tests, ECG and vital signs.
3. Participant has Fitzpatrick skin phototypes I (very fair), II (fair), or III
(darker white skin).
4. Body weight must be above 50 kg and body mass index (BMI) above or equal
18.5 and lower or equal 28 kg/m2 at the screening visit.
5. Male.

Exclusion Criteria

1. Medical disorder, condition or history of such that would impair the
participant's ability to take part in or complete this study in the opinion of
the investigator
2. A history of relevant diseases of vital organs, of the central nervous
system including neuropsychiatric illness or other organs, previous syncope or
autoimmune disease such as multiple sclerosis, inflammatory bowel disease,
rheumatoid arthritis or other immune-inflammatory diseases.
3. Unintended weight loss or gain of at least 5 kg in 4 weeks at screening.
4. Any serious concomitant illness that anticipates the need of systemic
medication interfering with the study medication.
5. A history of trauma with likely damage to the spleen, surgery to spleen or
congenital abnormalities of the spleen.
6. Hemorrhagic diathesis (easy bruising, epistaxis, gastro-intestinal bleeding).
7. History of known pulmonary embolism or known anti-phospholipid syndrome.
8. Previous participation in an i.v./systemic LPS challenge trial or prior
exposure to endotoxin within one year before start of treatment.
9. Diseases for which it can be assumed that the absorption, distribution,
metabolism, elimination and effects of the study intervention(s) will not be
normal (cholecystectomy permitted).
10. Any infection requiring hospitalization, systemic antimicrobial therapy
within 60 days, or as otherwise judged to be an opportunistic infection or
clinically significant by the investigator, within the past 6 months prior to
treatment period.
11. Any active or ongoing chronic infectious disease including periodontitis
with the exception of common viral or fungal skin infections such as plantar
warts or athlete's foot.
12. Febrile illness within 30 days before the start of the first study
intervention.
13. Medical history of sepsis, tuberculosis, increased frequency of infections,
immunodeficiency diseases, with recent febrile diseases and anamnestic and/or
laboratory signs of an impaired immune status or latent infections (hepatitis
B, hepatitis C, and human immunodeficiency virus [HIV]).
14. History of COVID-19 within 6 months prior to treatment period or in case of
clinically relevant sequela of former COVID-19 (such as fatigue or exercise
dyspnea)
15. Contact with SARS-CoV-2- positive or COVID-19 patient within the last 2
weeks prior to SARS-CoV-2 viral PCR test (at visit 2).
16. History of major surgery within 8 weeks prior to treatment period or
scheduled (elective) surgery, planned hospitalization and surgical dental
treatment within study and 4 weeks after final follow-up.
17. History of or acute atopic dermatitis with active eczematous lesions,
bronchial asthma or allergic rhino-conjunctivitis symptomatic during screening
period.
18. History of other concomitant skin conditions (chronic inflammatory
dermatoses) that would interfere with the evaluation of the effect of the study
medication on contact dermatitis.
19. History of hypersensitivity to any of the components of the study
interventions.
20. History of malignant tumors (except treated basal cell carcinoma).
21. Any clinical contraindications to treatment with steroids, such as
uncontrolled hypertension, chronic liver disease (Child*Pugh scores B or C),
latent diabetes mellitus, history of gastrointestinal bleeding.
22. Use of topical and systemic

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>1. Average change of perfusion/basal flow and erythema<br /><br>2. Average change in systemic inflammation markers (TNF-*, IL-6)</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>1. Change of perfusion/basal flow and erythema at individual timepoints<br /><br>2. Average change of Clinician Erythema Assessment (CEA) score<br /><br>3. Measurement of molecular changes (cytokines and immune cells)<br /><br>4. Changes in immune cells, immune phase reactants such as CRP and other<br /><br>inflammation markers caused by the systemic challenge<br /><br>5. Changes in temperature, pulse rate, systolic and diastolic blood pressure</p><br>