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

• Sponsor: Poolbeg Pharma plc (Industry)
• Overall Status: Completed
• CT.gov ID: NCT05765955
• Collaborator: (none)
• Enrollment: 36
• Location: 1
• Arms: 4
• Actual Duration (Months): 4.8
• Patients Per Site Per Month: 7.5

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Influenza, Human	Drug: POLB 001; Drug: Placebo	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 36 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: Jul 22, 2022
• Actual Primary Completion Date: Dec 14, 2022
• Actual Study Completion Date: Dec 16, 2022

Arms and Interventions

Arm	Intervention/Treatment
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
Placebo Comparator: Placebo	Drug: Placebo; Matching Placebo

Outcome Measures

Primary Outcome Measures

1. Effect of intradermal LPS challenge [16 days]

   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)

2. Effect of intradermal LPS challenge [16 days]

   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)

3. Effect of intradermal LPS challenge [16 days]

   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)

4. Effect of intravenous LPS challenge [16 days]

   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)

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 55 Years
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: Yes

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Centre for Human Drug Research	Leiden		Netherlands	2333 CL

Sponsors and Collaborators

• Poolbeg Pharma plc

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Poolbeg Pharma plc
• ClinicalTrials.gov Identifier: NCT05765955
• Other Study ID Numbers: CHDR2149
• First Posted: Mar 13, 2023
• Last Update Posted: Mar 14, 2023
• Last Verified: Mar 1, 2023

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• 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
• Additional relevant MeSH terms: Influenza, Human

Study Results

No Results Posted as of Mar 14, 2023