Effects of p38 MAPK Inhibitor POLB 001 on in Vivo LPS Challenge Responses

NCT05765955 | Completed Phase 1

• 1 other identifier: CHDR2149
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief Summary

A single center trial to evaluate the effect of POLB 001 on inflammatory responses following an intradermal LPS challenge in healthy volunteers.

Conditions

Influenza, Human

Outcome Measures

Primary Outcomes (4)

• Effect of intradermal LPS challenge

  To evaluate the effect of POLB 001 on inflammatory responses following an intradermal LPS challenge in healthy volunteers Endpoints: Skin response by imaging \- Erythema (multispectral imaging) (Clinician's Erythema Assessment (CEA) Scale)

  16 days

• Effect of intradermal LPS challenge

  To evaluate the effect of POLB 001 on inflammatory responses following an intradermal LPS challenge in healthy volunteers Endpoints: Blister exudate analysis \- Flow cytometry (neutrophils, monocyte subsets, T cells, B cells, NK cells, dendritic cells) (10\*9/L)

  16 days

• Effect of intradermal LPS challenge

  To evaluate the effect of POLB 001 on inflammatory responses following an intradermal LPS challenge in healthy volunteers Endpoints: Blister exudate analysis \- Cytokines (IL-6, IL-8, TNF, IL-1β) (pg/mL)

  16 days

• Effect of intravenous LPS challenge

  To evaluate the effect of POLB 001 on inflammatory responses following an intravenous LPS challenge in healthy volunteers Endpoints: Blood \- Cytokines (IL-6, IL-8, IL-10, TNF, IL-1β) (pg/mL)

  16 days

Study Arms (4)

POLB 001 30 mg

ACTIVE COMPARATOR

Drug: POLB 001

POLB 001 70 mg

ACTIVE COMPARATOR

Drug: POLB 001

POLB 001 150 mg

ACTIVE COMPARATOR

Drug: POLB 001

Placebo

PLACEBO COMPARATOR

Drug: Placebo

Interventions

POLB 001 DRUG

Investigational Medicinal Product

POLB 001 150 mg; POLB 001 30 mg; POLB 001 70 mg

Placebo DRUG

Matching Placebo

Placebo

Eligibility Criteria

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

You may qualify if:

• Healthy male volunteers aged 18 to 55 years, inclusive.
• BMI in the range of 18 to 32 kg/m2 a minimum body weight of 50 kg.
• Fitzpatrick skin type I-III.
• Able to give written informed consent and willing to comply with all study-related procedures.
• Has the ability to communicate well with the Investigator in the Dutch language and willing to comply with the study restrictions.

You may not qualify if:

• (A history of) any clinically significant medical condition or abnormalities, as judged by the investigator.
• History of sepsis, cardiovascular disease or malignancy.
• History of trauma with likely damage to the spleen or surgery to spleen.
• History of alcohol or drug abuse.
• Any clinically significant febrile illness 30 days preceding study Day 1.
• History of serious bleeding.
• Clinical evidence of significant or unstable medical illness including neurological, hematological, cardiovascular (including clinically significant arrhythmia), hepatic, pulmonary, metabolic, gastrointestinal, renal, psychiatric, endocrine, or infectious diseases or malignancies. Subjects who have had splenectomy.
• Previous participation in a systemic (i.v./inhaled) LPS challenge trial within a year before the first study day.
• Have any current and / or recurrent pathologically, clinically significant skin condition at the lower forearms (i.e., atopic dermatitis) including tattoos.
• Antibiotic use, operation or intervention by surgeon/dentist within one month before the first study day.
• Subjects who have used any prescribed or non-prescribed systemic or topical medication (including herbal remedies) within 7 days of the first dose administration, or less than 5 half-lives (whichever is longer), and during the study (except for vitamin/mineral supplements) unless, in the opinion of the Investigator, the medication will not interfere with the study procedures or compromise safety.
• Subjects who have received any medications, including St John's Wort, known to chronically alter drug absorption or elimination processes within 30 days of the first dose administration unless, in the opinion of the Investigator, the medication will not interfere with the study procedures or compromise safety.
• Any active inflammatory or infectious disease (e.g., periodontitis).
• Known immunodeficiency.
• Positive test results for Hepatitis B, Hepatitis C, HIV antibody.

Sponsors & Collaborators

• Poolbeg Pharma plc: lead

Study Sites (1)

Centre for Human Drug Research

Leiden, 2333 CL, Netherlands

Location

MeSH Terms

Conditions

Influenza, Human

Condition Hierarchy (Ancestors)

Respiratory Tract Infections; Infections; Orthomyxoviridae Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 28, 2022
• First Posted: March 13, 2023
• Study Start: July 22, 2022
• Primary Completion: December 14, 2022
• Study Completion: December 16, 2022
• Last Updated: March 14, 2023

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1)