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

A Randomized, Double-blind, Placebo-controlled, Multiple Ascending Dose Study to Evaluate Safety, PK and the Immunosuppressive Effects of p38 MAPK Inhibitor POLB 001 on the Intradermal and Intravenous LPS Challenge Response in Healthy Volunteers

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

Study Overview

• Status: Completed
• Conditions: Influenza, Human
• Intervention / Treatment: Drug: Placebo; Drug: POLB 001

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Phase 1

Contacts and Locations

Study Locations

• Netherlands
  • Leiden, Netherlands, 2333 CL
    • Centre for Human Drug Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

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

Exclusion Criteria:

1. (A history of) any clinically significant medical condition or abnormalities, as judged by the investigator.
2. History of sepsis, cardiovascular disease or malignancy.
3. History of trauma with likely damage to the spleen or surgery to spleen.
4. History of alcohol or drug abuse.
5. Any clinically significant febrile illness 30 days preceding study Day 1.
6. History of serious bleeding.
7. 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.
8. Previous participation in a systemic (i.v./inhaled) LPS challenge trial within a year before the first study day.
9. Have any current and / or recurrent pathologically, clinically significant skin condition at the lower forearms (i.e., atopic dermatitis) including tattoos.
10. Antibiotic use, operation or intervention by surgeon/dentist within one month before the first study day.
11. 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.
12. 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.
13. Any active inflammatory or infectious disease (e.g., periodontitis).
14. Known immunodeficiency.
15. Positive test results for Hepatitis B, Hepatitis C, HIV antibody.
16. Subjects who consume on average more than 3 units of alcohol per day (one alcohol unit =1 beer [12 oz] =1 wine [5 oz] =1 spirits [1.5 oz]) or are unable to abstain from using alcohol during the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; Matching Placebo
Active Comparator: POLB 001 30 mg	Drug: POLB 001; Investigational Medicinal Product
Active Comparator: POLB 001 70 mg	Drug: POLB 001; Investigational Medicinal Product
Active Comparator: POLB 001 150 mg	Drug: POLB 001; Investigational Medicinal Product

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Collaborators and Investigators

• Sponsor: Poolbeg Pharma plc

Study record dates

Study Major Dates

• Study Start (Actual): July 22, 2022
• Primary Completion (Actual): December 14, 2022
• Study Completion (Actual): December 16, 2022

Study Registration Dates

• First Submitted: July 28, 2022
• First Submitted That Met QC Criteria: March 9, 2023
• First Posted (Actual): March 13, 2023

Study Record Updates

• Last Update Posted (Actual): March 14, 2023
• Last Update Submitted That Met QC Criteria: March 13, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Orthomyxoviridae Infections; Influenza, Human
• Other Study ID Numbers: CHDR2149

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No