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

Influenza, Human Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05765955
• Other study ID #: CHDR2149
• Status: Completed
• Phase: Phase 1
• Start date: July 22, 2022
• Est. completion date: December 16, 2022

Study information

• Verified date: March 2023
• Source: Poolbeg Pharma plc
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 36
• Est. completion date: December 16, 2022
• Est. primary completion date: December 14, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 55 Years

Eligibility

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

Related Conditions & MeSH terms

• Influenza, Human

Intervention

Drug:
• POLB 001
Investigational Medicinal Product
• Placebo
Matching Placebo

Locations

Country	Name	City	State
Netherlands	Centre for Human Drug Research	Leiden

Sponsors (1)

Lead Sponsor	Collaborator
Poolbeg Pharma plc

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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-1ß) (pg/mL)	16 days
Primary	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-1ß) (pg/mL)	16 days