check_circleStudy Completed

Immune mediated inflammatory diseases

A trial to learn how BAY1834845 and BAY1830839 affect inflammation when taken by mouth twice a day for 7 days in a row in healthy male participants

Trial purpose

The immune system helps protect the body from diseases. But, sometimes the immune system can be too sensitive and overreact to very small allergens, like dust and pet dander. This can cause skin conditions like dermatitis and eczema. People with these skin conditions have inflammation that can cause dry, red, and itchy skin. These symptoms often “flare up”, meaning that the symptoms come back after being gone for some time.
Researchers are looking for a different way to treat people who have skin conditions caused by an overreaction of the immune system. Before a treatment is available to all patients, researchers study it in trials to better understand its safety and how well it works.
In this trial, the researchers will learn more about how BAY1834845 and BAY1830839 work and how safe they are in healthy male participants.
The trial will include about 72 healthy male participants who are between the ages of 18 and 55.
The researchers will use a computer program to randomly choose the treatment each participant will take. This will help make sure the treatments are chosen fairly. Researchers do this so that comparing the results of the treatments is accurate as possible. The participants will be randomly put into 1 of 4 groups. The participants will take their trial treatment 2 times a day for 7 days in a row.
- Group 1: BAY1834845 as tablets by mouth
- Group 2: BAY1830839 as tablets by mouth
- Group 3: A placebo as tablets by mouth
- Group 4: Prednisolone as tablets by mouth
A placebo looks like a treatment but does not have any medicine in it. Prednisolone is a steroid treatment that is already available for doctors to prescribe to people with skin conditions caused by an overreaction of the immune system.
All the participants will also receive imiquimod applied as a cream to their back. All participants will also receive lipopolysaccharide as an intravenous infusion. Imiquimod and lipopolysaccharide will be used to cause irritation and inflammation of the skin and in the blood. The researchers want to see if treatment with BAY1834845 and BAY1830939 can then help reduce these symptoms of irritation and inflammation.
In this trial, the researchers will look at:
- the change in the amount of blood flow in the participants after imiquimod
- the change in how red the participants’ skin is after imiquimod
- the change in the amount of inflammation applying the participants have after receiving lipopolysaccharide infusion

Key Participants Requirements

Sex

Male

Age

18 - 55 Years

Trial summary

Enrollment Goal
51
Trial Dates
June 2021 - January 2022
Phase
Phase 1
Could I Receive a placebo
Yes
Products
Zabedosertib (BAY1834845)
Accepts Healthy Volunteer
Yes

Where to participate

StatusInstitutionLocation
Completed
Center for Human Drug ResearchLeiden, 2333 CL, Netherlands

Primary Outcome

  • Average change of perfusion/basal flow
    The change from baseline will be averaged over the changes at 24 hour / 48 hour / 72 hour assessments
    date_rangeTime Frame:
    Pre-challenge and at 24 hour / 48 hour / 72 hour after start of skin challenge
  • Average change of erythema score
    The change from baseline will be averaged over the changes at 24 hour / 48 hour / 72 hour assessments. Erythema score will be measured by Antera 3D camera.
    date_rangeTime Frame:
    Pre-challenge and at 24 hour / 48 hour / 72 hour after start of skin challenge
  • Average change in TNF-α
    date_rangeTime Frame:
    From pre-challenge up to 6 hour after the systemic challenge
  • Average change in IL-6
    date_rangeTime Frame:
    From pre-challenge up to 6 hour after the systemic challenge

Secondary Outcome

  • Change of perfusion/basal flow
    date_rangeTime Frame:
    Pre-challenge and at 24 hour / 48 hour / 72 hour after start of skin challenge
  • Change of erythema score
    Erythema score will be measured by Antera 3D camera.
    date_rangeTime Frame:
    Pre-challenge and at 24 hour / 48 hour / 72 hour after start of skin challenge
  • Average change of Clinician Erythema Assessment (CEA) score
    Clinician Erythema Assessment (CEA) scale: 0 - Clear skin with no signs of erythema; 1 - Almost clear, slight redness; 2 - Mild erythema, defined redness; 3 - Moderate erythema, marked redness; 4 - Severe erythema, fiery redness.
    date_rangeTime Frame:
    Pre-challenge and at 24 hour / 48 hour / 72 hour after first administration of skin challenge
  • Changes in cytokines cells of skin suction blisters
    Skin suction blisters will be induced on the tape stripping and/or treated skin areas, allowing the collection of blister exudate for cytokine cell analysis.
    date_rangeTime Frame:
    From baseline up to 72 hour after first administration of skin challenge
  • Changes in immune cells of skin suction blisters
    Skin suction blisters will be induced on the tape stripping and/or treated skin areas, allowing the collection of blister exudate for immune cell analysis.
    date_rangeTime Frame:
    From baseline up to 72 hour after first administration of skin challenge
  • Changes in immune cells of blood samples
    date_rangeTime Frame:
    From pre-challenge up to 24 hour after systemic challenge
  • Changes in C-reactive protein (CRP) of blood samples
    date_rangeTime Frame:
    From pre-challenge up to 24 hour after systemic challenge
  • Changes in Procalcitonin (PCT) of blood samples
    date_rangeTime Frame:
    From pre-challenge up to 24 hour after systemic challenge
  • Changes in other inflammation markers of blood samples
    date_rangeTime Frame:
    From pre-challenge up to 24 hour after systemic challenge
  • Changes in temperature
    date_rangeTime Frame:
    From pre-challenge to 0.5 hour / 1 hour / 2 hour / 4 hour / 6 hour and 8 hour after systemic challenge
  • Changes in pulse rate
    date_rangeTime Frame:
    From pre-challenge to 0.5 hour / 1 hour / 2 hour / 4 hour / 6 hour and 8 hour after systemic challenge
  • Changes in systolic blood pressure
    date_rangeTime Frame:
    From pre-challenge to 0.5 hour / 1 hour / 2 hour / 4 hour / 6 hour and 8 hour after systemic challenge
  • Changes in diastolic blood pressure
    date_rangeTime Frame:
    From pre-challenge to 0.5 hour / 1 hour / 2 hour / 4 hour / 6 hour and 8 hour after systemic challenge

Trial design

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
Trial Type
Interventional
Intervention Type
Drug
Trial Purpose
Basic Science
Allocation
Randomized
Blinding
N/A
Assignment
Parallel Assignment
Trial Arms
4