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

NCT05003089 | Completed Phase 1

• 2 other identifiers: 213292020-003138-18
• Study Type: interventional
• Target: 51
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Immune Mediated Inflammatory Diseases

Outcome Measures

Primary Outcomes (4)

• Average change of perfusion/basal flow

  The change from baseline will be averaged over the changes at 24 hour / 48 hour / 72 hour assessments

  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.

  Pre-challenge and at 24 hour / 48 hour / 72 hour after start of skin challenge

• Average change in TNF-α

  From pre-challenge up to 6 hour after the systemic challenge

• Average change in IL-6

  From pre-challenge up to 6 hour after the systemic challenge

Secondary Outcomes (13)

• Change of perfusion/basal flow

  Pre-challenge and at 24 hour / 48 hour / 72 hour after start of skin challenge

• Change of erythema score

  Pre-challenge and at 24 hour / 48 hour / 72 hour after start of skin challenge

• Average change of Clinician Erythema Assessment (CEA) score

  Pre-challenge and at 24 hour / 48 hour / 72 hour after first administration of skin challenge

• Changes in cytokines cells of skin suction blisters

  From baseline up to 72 hour after first administration of skin challenge

• Changes in immune cells of skin suction blisters

  From baseline up to 72 hour after first administration of skin challenge

Study Arms (4)

BAY1834845 arm

EXPERIMENTAL

BAY1834845 will be administered twice daily for 7 consecutive days (Days 1 - 7).

Drug: BAY1834845

BAY1830839 arm

EXPERIMENTAL

BAY1830839 will be administered twice daily for 7 consecutive days (Days 1 - 7).

Drug: BAY1830839

Prednisolone arm

ACTIVE COMPARATOR

Prednisolone will be administered twice daily for 7 consecutive days (Days 1 - 7).

Drug: Prednisolone

Placebo arm

PLACEBO COMPARATOR

Placebo will be administered twice daily for 7 consecutive days (Days 1 - 7).

Drug: Placebo

Interventions

BAY1834845 DRUG

Tablet, oral.

BAY1834845 arm

BAY1830839 DRUG

Tablet, oral.

BAY1830839 arm

Prednisolone DRUG

Tablet, oral.

Prednisolone arm

Placebo DRUG

Tablet, oral.

Placebo arm

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Participant must be 18 to 55 years of age inclusive, at the time of signing the informed consent.
• Overtly healthy as determined by medical evaluation including medical and surgical history, physical examination, laboratory tests, ECG and vital signs.
• Participant has Fitzpatrick skin phototypes I (very fair), II (fair), or III (darker white skin).
• 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.
• Male.

You may not qualify if:

• 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
• 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.
• Unintended weight loss or gain of at least 5 kg in 4 weeks at screening.
• Any serious concomitant illness that anticipates the need of systemic medication interfering with the study medication.
• A history of trauma with likely damage to the spleen, surgery to spleen or congenital abnormalities of the spleen.
• Hemorrhagic diathesis (easy bruising, epistaxis, gastro-intestinal bleeding).
• History of known pulmonary embolism or known anti-phospholipid syndrome.
• Previous participation in a systemic (i.v./inhalative) lipopolysaccharide (LPS) challenge trial within one year before start of treatment.
• 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).
• 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.
• 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.
• Febrile illness within 30 days before the start of the first study intervention.
• 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 \[HIV\]).
• 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)
• 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).

Sponsors & Collaborators

• Bayer: lead

Study Sites (1)

Center for Human Drug Research

Leiden, 2333 CL, Netherlands

Location

MeSH Terms

Interventions

zabedosertib; Prednisolone

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Double blind for BAY1834845, BAY1830839 and placebo (participant and investigator) with unblinded active control (prednisolone), rater-blinded for skin reaction assessments (all 4 study interventions).
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 16, 2021
• First Posted: August 12, 2021
• Study Start: June 28, 2021
• Primary Completion: December 16, 2021
• Study Completion: January 20, 2022
• Last Updated: December 16, 2022

Record last verified: 2022-12

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1)