| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Inflammatory Onset and Resolution |
|
| E.1.1.1 | Medical condition in easily understood language |
| Blister induction and effect of PL8177 on inflammation |
|
| E.1.1.2 | Therapeutic area | Body processes [G] - Immune system processes [G12] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 20.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10053414 |
| E.1.2 | Term | Application site blister |
| E.1.2 | System Organ Class | 100000004867 |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| To determine whether subcutaneous PL8177 compared to placebo alters blister fluid volume and blister fluid differential leukocyte numbers. |
|
| E.2.2 | Secondary objectives of the trial |
• Determine whether PL8177 alters blister fluid cytokine analysis
• Determine whether PL8177 alters markers of inflammation resolution
• Determine whether PL8177 alters peripheral markers of inflammation |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Healthy male participants on the Fitzpatrick scale of 1 to 3, between 18 and 45
years of age, inclusive, at screening.
2. Body mass index between 18.0 and 30.0 kg/m2, inclusive, with body weight not
less than 50 kg, at screening.
3. In good health, determined by no clinically significant findings from
medical/surgical history, physical examination, vital sign measurements, 12-lead
ECG, and clinical laboratory evaluations (congenital nonhemolytic
hyperbilirubinemia (e.g. Gilbert’s syndrome) is not acceptable at screening), as
assessed by the Investigator (or designee).
4. A 12-lead ECG consistent with normal cardiac conduction and function at screening, including; HR between 45 and 100 bpm, QTcF interval less than or equal to 450 ms , QRS interval <120 ms, PR interval <220 ms and morphology consistent with healthy cardiac conduction and function.
5. Has clinical chemistry, haematology, coagulation and complete urinalysis (fasted for at least 4 hours) results at screening within the reference range for the testing laboratory, unless the out of range results are deemed not clinically significant by the Investigator.
6. A male volunteer with sexual partners who could become pregnant must meet the following criteria:
a. Participants who are sexually active agree to use one of the accepted contraceptive regimens from first drug administration until 3 months (90 days) after the drug administration. An acceptable method of contraception includes one of the following; abstinence from vaginal intercourse, condom with spermicide or condom with intra-vaginally applied spermicide.
b. Male participants must agree to provide any requested information about the pregnancy should contraception fail and a pregnancy occurs within the 90 days after the drug administration.
c. Male participants subjects must agree to not donate sperm during the study and for 3 months (90 days) after receiving the last dose of study drug.
7. Able to comprehend and willing to sign an Informed Consent Form (ICF) and to abide by the study restrictions. |
|
| E.4 | Principal exclusion criteria |
1. Significant history or clinical manifestation of any medical illness including (but not limited to); metabolic, dermatological, hepatic, renal, haematological, pulmonary, cardiovascular, coagulation disorder, lipid abnormality, gastrointestinal (GI), immunologic, neurological, respiratory, endocrine, psychiatric disorder, or infectious disease (including tuberculosis), any other current physical condition that the Investigator considers should exclude the participant, or that could interfere with the interpretation of the study results as determined by the Investigator (or designee).
2. Participants with significant history of or clinical manifestation of a dermatologic disorder, including but not limited to psoriasis, severe acne, seborrhoea, and eczema. Mild to moderate acne limited to the face, chest, and shoulders is acceptable. The skin of the forearms must not be affected.
3. Has any clinically significant physical examination finding, ECG abnormality, or clinically significant abnormal value for clinical chemistry, haematology, coagulation, or urinalysis at screening or any significant physical exam finding, clinically significant abnormal value for clinical chemistry, haematology or urinalysis at baseline, as determined by the Investigator.
4. Has any of the following:
a. Systolic blood pressure <90 mmHg or >140 mmHg at screening (measured in seated position)
b. Diastolic blood pressure of <50mmHg or >90 mmHg at screening
(measured in seated position)
c. Heart rate <45 bpm or >100 bpm
5. Currently suffers from clinically significant systemic allergic disease as determined by the Investigator, or has a history of significant drug allergies,
6. Current systemic infection.
7. History or current manifestation of herpes infection of the eye.
8. History or current manifestation of galactose or lactose intolerance or glucosegalactose malabsorption.
9. History or current manifestation of severe depression or manic-depression (bipolar disorder), or if any close family member (parent, sibling, or offspring) has had severe depression or manic-depression, steroid psychosis, emotional instability, or psychotic tendencies.
10. Receipt of any live vaccine within 30 days prior to screening or intent to receive any live vaccine within 90 days following completion of the study.
11. History of adverse reaction to corticosteroid, including fluid retention, alteration in glucose tolerance, elevation in blood pressure, behavioural and mood changes, increased appetite and weight gain.
12. History or presence of malignancy within the past 5 years with the exception of adequately treated localised skin cancer (basal cell or squamous cell carcinoma) which is allowed.
13. Personal history or family history of melanoma (for the purposes of this study family history is defined as history in first-degree relatives i.e. parents or siblings).
14. History of hyperplastic, dysplastic or atypical nevi.
15. Has had an acute or clinically significant illness as determined by the Investigator, within 30 days prior to Day 1, or has had a recent febrile illness with an abnormal body temperature within 72 hours before dosing on Day 1.
16. History of alcoholism or drug/chemical abuse within 2 years prior to screening.
17. Has a positive test for hepatitis B surface antigen, hepatitis C antibody, or human immunodeficiency virus (HIV) at screening or has been previously treated for hepatitis B, hepatitis C or HIV infection.
18. Participation in a clinical study involving administration of an investigational drug (new chemical entity) in the past 60 days prior to screening.
19. Use or intent to use any prescription medications/products within 30 days prior to screening, unless deemed acceptable by the Investigator (or designee).
20. Use of NSAIDs or pain medication within 7 days prior to screening.
21. Use or intent to use any non-prescription medications/products including vitamins, minerals, within 7 days prior to screening, unless deemed acceptable by the Investigator (or designee).
22. Consumption of alcoholic beverages or foods that contain alcohol or poppy seeds from 1 day prior to baseline visit on Day 1 through Day 11 assessments
23. Use of tobacco or nicotine-containing products within 6 months prior to screening or positive cotinine test at screening or is unwilling to abstain from these products for the duration of the study.
24. Receipt of blood products within 2 months prior to screening.
25. Donation of more than 100 mL of blood from 56 days prior to screening, plasma from 2 weeks prior to screening, platelets from 6 weeks prior to screening, acute loss of blood (>500 mL) during the 3 months before study drug administration or intent to donate blood or blood products within 3 months after the completion of the study.
26. Poor peripheral venous access
27. Have previously received PL8177
28. Participants who, in the opinion of the Investigator (or designee), should not participate in this study |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
• Difference in volume of blister fluid, as compared to placebo.
• Difference in WBC count and differential in blister fluid, as compared to placebo. |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
Blister fluid collection will occur on Day 4.
|
|
| E.5.2 | Secondary end point(s) |
• Proportion of participants with reduced blister volume, blister fluid WBC count, and altered fluid differential, as compared to placebo.
• Proportion of subjects with reduced inflammatory response to blister induction, compared with placebo, as indicated by:
o Reduced blister fluid markers of cell activation
o Altered blister fluid lipid mediator profile
o Reduced blister and plasma cytokines/chemokines
• Change of the following parameters, as compared to placebo:
o Levels of blister fluid markers of cell activation
o Change of blister fluid lipid mediator profile
o Change of levels of blister and plasma cytokines/chemokines |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
Blister fluid collection will occur on Day 4.
Inflammatory Markers, peripheral blood samples (cytokines/chemokines) will be collected on Day 1, 4, 11.
|
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | No |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | Yes |
| E.8.1.7.1 | Other trial design description |
|
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Yes |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 3 |
| E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
| E.8.4 | The trial involves multiple sites in the Member State concerned | No |
| E.8.5 | The trial involves multiple Member States | No |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | No |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.7 | Trial has a data monitoring committee | Yes |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 0 |
| E.8.9.1 | In the Member State concerned months | 6 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 0 |
| E.8.9.2 | In all countries concerned by the trial months | 6 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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