None MedDRA version: 21.0 Level: LLT Classification code 10062249 Term: Skin inflammation System Organ Class: 100000004858
Conditions
Interventions
Trade Name: Aldara 5%
Product Name: Aldara
Pharmaceutical Form: Ointment
INN or Proposed INN: IMIQUIMOD
CAS Number: 99011-02-6
Concentration unit: mg/g milligram(s)/gram
Concentration type: equal
Conc
Sponsors
Centre for Human Drug Research
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Healthy male or female subjects (Part B males only), 18 to 45 years of age, inclusive. Healthy status is defined by absence of evidence of any active or chronic disease following a detailed medical and surgical history, a complete physical examination including vital signs, 12-lead ECG, hematology, blood chemistry, blood serology and urinalysis. In the case of uncertain or questionable results, tests performed during screening may be repeated before randomization to confirm eligibility or judged to be clinically irrelevant for healthy subjects; 2. Body mass index (BMI) between 18 and 30 kg/m2 and a maximum weight of 100 kg, inclusive; 3. Fitzpatrick skin type I-III (Caucasian); 4. Subjects and their partners of childbearing potential must use effective contraception for the duration of the study; 5. Able and willing to give written informed consent and to comply with the study restrictions. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 60 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Eligible subjects must meet none of the following exclusion criteria at screening: 1. Any vaccination within the last 3 months; COVID19 vaccination is allowed up until 4 weeks prior to the first prednisolone/placebo dosing, and from 2 weeks after the last prednisolone/placebo dosing. 2. Family history of psoriasis; 3. History of pathological scar formation (keloid, hypertrophic scar); 4. Have any current and / or recurrent pathologically, clinical significant skin condition at the treatment area (i.e. atopic dermatitis); inlcuding tattoos 5. Previous use of Aldara (IMQ cream) 3 weeks prior to the baseline visit (part A only) 6. Known hypersensitivity to the (non)investigational drug, drugs of the same class, or any of their excipients; 7. Hypersensitivity for dermatological marker at screening; 8. Requirement of immunosuppressive or immunomodulatory medication within 30 days prior to enrollment or planned to use during the course of the study; 9. Use of topical medication (prescription or over-the-counter [OTC]) within 30 days of study drug administration, or less than 5 half-lives (whichever is longer) in local treatment area 10. Tanning due to sunbathing, excessive sun exposure or a tanning booth within 3 weeks of enrollment; 11. Participation in an investigational drug or device study within 3 months prior to screening or more than 4 times a year. 12. Loss or donation of blood over 500 mL within three months prior to screening (part A and B), or donation of plasma withing 14 days of screening (part B only) . 13. Any (medical) condition that would, in the opinion of the investigator, potentially compromise the safety or compliance of the patient or may preclude the patient’s successful completion of the clinical trial. 14. Latent Diabetes Mellitus 15. Volunteers with clinically relevant infections 16. Current smoker and/or regular user of other nicotine-containing products (e.g., patches); or positive urine cotinine test at screening (part B only) 17. History of or current drug or substance abuse considered significant by the PI (or medically qualified designee), including a positive urine drug screen. 18. Subjects that test positive for a SARS-CoV-2 infection 19. Subjects with a BMI > 30 and/or cardiovascular, respiratory or immune system disorders
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: • To assess the pharmacodynamic effects of systemic prednisolone on the LPS or IMQ-induced inflammatory response • To assess safety & tolerability of intradermal LPS and topical IMQ in combination with prednisolone ;Secondary Objective: • To explore pharmacodynamic biomarkers determined in blister exudate compared to skin punch biopsies in LPS- or IMQ-induced inflammation.;Primary end point(s): Tolerability / safety endpoints • Adverse events (AEs) • Vital signs • 12-leads ECGs • Local tolerance (erythema grading scale, numeric rating scale (NRS) pruritus and pain) Pharmacodynamic endpoints Non-invasive measures: • Perfusion by Laser speckle contrast imaging (LSCI) • Erythema by Antera 3D camera • Erythema by clinical evaluation (erythema grading scale) • Optical Coherence Topography (OCT) (part A only) • 2D photography by ATBM for photo documentation only (part A only) Invasive measures: • Suction blister exudates, including but not limited to o Cytokines and chemokines o Flow cytometry (for example: neutrophils, monocytes/macrophages, CD4+ lymphocytes, CD8+ lymphocytes, CD56+ lymphocytes, CD1c dendritic cells) • Skin punch biopsies, may include, but is not limited to o Local biomarkers, : IL-8, IFN-a, IL-1ß, IFN-?, MXA, MX1, IL-6, IL-10, CCL20 and HBD-2) o Immunohistochemistry: CD1a, HLADR, CD8+, CD4+, CD14+, CD11c, complement factors, iNOS, NETs, gasdermin, IRAK4. o Histology (HE) • Ex vivo blood assay o Ex vivo cytokine release assay (imiquimod, part A only) o Ex vivo cytokine release assay (LPS, part B only) o Ex vivo NET assay (Part B only) ;Timepoint(s) of evaluation of this end point: Day 0 - EOS | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): NA;Timepoint(s) of evaluation of this end point: NA | — |
Countries
Netherlands
Contacts
Public ContactPrincipal Investigator
Centre for Human Drug Research
Outcome results
None listed