Cutaneous lupus erythematosus (CLE) lupus affecting the skin
Conditions
Interventions
Aldara 5% is a cream containing the active ingredient imiquimod (50 mg/g).
Imiquimod is registered for various indications including the treatment of
basal cell carcinoma, actinic keratosis, and per
Sponsors
Centre for Human Drug Research
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: Eligible healthy volunteers must meet all the following inclusion criteria at screening: 1. Signed informed consent prior to any study-mandated procedure. 2. Male or female subjects, 18 years of age or older at the time of signing informed consent; in general, stable good health as per judgement of the investigator based upon the results of a medical history, physical examination, vital signs, ECG, and laboratory assessments performed at screening. Repeated laboratory testing may be performed at the discretion of the clinical investigator. 3. Body mass index (BMI) > 18.0 and 18.0 and =3 without counting any diffuse alopecia or oral ulcers.
Exclusion criteria
Exclusion criteria: Eligible healthy volunteers must meet none of the following exclusion criteria at screening: 1. (History of) immunological abnormality (e.g., immune suppression) that may interfere with study objectives, in the opinion of the investigator. 2. Have any current and/or recurrent clinically significant skin condition, including tattoos. 3. Antibiotic use, operation, or clinically significatn intervention by surgeon/dentist within one month before Day 1. 4. Positive hepatitis B surface antigen (HbsAg), hepatitis C antibody (HCV ab), or human immunodeficiency virus antibody (HIB ab) at screening. 5. Participation in an investigational drug study within 3 months prior to screening or more than 4 times a year. 6. Loss or donation of blood over 500mL within three months prior to screening. 7. Subject is willing to refrain from the use of any medication within 28 days prior to Day 1, if the investigator judges it may interfere with the study objectives. 8. History of alcohol abuse or consumption exceeding 5 standard drinks per day on average within 3 months of screening. 9. Positive urine test for drugs or history of abuse at screening. Urine drug test may be repeated at the discretion of the investigator. 10. Pregnant, a positive pregnancy test, intending to become pregnant during the study conduct, or breastfeeding. 11. (A history of) any clinically significant medical condition, factor or abnormality that might interfere with study conduct or interpretation, as judged by the investigator. 12. Previous use of Aldara (imiquimod cream) 3 months prior to the Day 1 visit in part B. 13. Any active or chronic and/or uncontrolled condition that, in the opinion of the investigator, may influence study conduct or interpretation. 14. Increased risk of delirium based on the delirium screening (meaning that at least one of the delirium risk questions was answered with *yes* at the screening visit, only applicable for participants > 70 years old). Eligible CLE patients must meet none of the abovementioned and following exclusion criteria at screening: 1. Presence of a relevant skin infection or disease in the target areas other than the observational disease (CLE), inclusively, but not limited to atopic dermatitis, psoriasis vulgaris and dermatomycosis. 2. Having received treatments for CLE or any other disease within the following intervals prior to Day 1: a. <2 weeks for topical treatment, e.g., corticosteroids at target area(s) b. <6 weeks for systemic therapy with immunosuppressive agents (other than the permitted systemic treatments with stable use for a minimum of 8 weeks) c. <12 weeks for biologics d. <8 weeks procedure or surgery in or close to the target areas e. <3 months for chemotherapeutical treatment 3. Presence of severe lupus-associated renal disease. 4. Presence of antiphospholipid syndrome. 5. Active or unstable lupus-associated neuropsychiatric disease. 6. Severe organ SLE manifestation(s) (e.g., active myocarditis) or unstable disease as judged by the investigator. 7. Diagnosis of systemic lupus erythematosus (SLE) according to the EULAR-ACR criteria (2019) or substantial indication for systemic involvement (part B only). 8. Low complement (C3 and/or C4) levels at screening (< ULN) (Part B only). 9. Positive ANA and anti-dsDNA and/or
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Tolerability / safety endpoints Part A: not applicable. Part B safety and tolerability upon topical IMQ challenge will be assessed in the following endpoints: - Application site assessment (LIGS), including Erythema grading scale - Vital signs (HR, BP) - Body temperature - Patient-reported outcomes (itch, pain) Observational and pharmacodynamic endpoints - Skin suction blisters (cells and micro-environment proteomics) - Skin punch biopsies o Histology o RNA-sequencing - Imaging: o Laser Speckle Contrast Imaging* (microcirculation) o Antera 3D multispectral imaging* (3D skin morphology, erythema, haemoglobin level) o Optical Coherence Tomography* (skin morphology, epidermal thickness, blood perfusion) o AquaFlux and GPSkin Barrier Pro-1* (trans-epidermal water loss, stratum corneum hydration) o 2D photography* - Tape stripping (lipidomics, OLINK)* - Skin swabs (microbiome)* - Faecal microbiota* - Laboratory (blood): o IFN signature o Ex vivo imiquimod o Cytokines o Complement o Autoantibodies - Patient reported outcomes (DLQI, 5D-itch, NRS itch and pain, sleeplessness)* - Patient satisfaction of imaging and non-imaging tools/interventions* Endpoints marked with *** denote non-invasive assessments. | — |
Countries
Netherlands
Outcome results
None listed