Deep phenotyping of cutaneous lupus erythematosus

An Exploratory, Single-center, Two-part Study to Characterize Cutaneous Lupus Erythematosus and Investigate the Effect of an Immune Challenge by Comparing CLE Patients With Healthy Volunteers

This study is testing how a cream called IMIQUIMOD affects different types of skin lupus to help researchers better understand the disease and improve treatments.

Quick facts

• Phase: NA
• Study type: Interventional
• Enrollment: 40 (estimated)
• Ages: 18 Years to 65 Years
• Sex: All
• Sponsor: Centre for Human Drug Research, Netherlands (other)
• Locations: 1 site (Leiden, South Holland)
• Trial ID: NCT06411106 on ClinicalTrials.gov

What this trial studies

This study aims to better understand cutaneous lupus erythematosus (CLE), an autoimmune disease with various subtypes that complicate diagnosis and treatment. By employing a deep phenotyping approach, the researchers will investigate the role of TLR7 activation in the disease's pathophysiology and identify specific biomarkers for different CLE subtypes. The study will involve healthy volunteers who meet specific eligibility criteria and will assess the effects of IMIQUIMOD cream on disease characteristics. The goal is to enhance the understanding of CLE and improve future treatment strategies.

Who should consider this trial

Good fit: Ideal candidates for this study are healthy volunteers aged 18 to 65 with Fitzpatrick skin types I-III and no significant skin diseases.

Not a fit: Patients with existing skin diseases or those with a history of hypertrophic scarring or keloids may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could lead to more accurate diagnosis and targeted therapies for patients with cutaneous lupus erythematosus.

How similar studies have performed: While there is ongoing research into the pathogenesis of CLE, this deep phenotyping approach is relatively novel and has not been extensively tested in prior studies.

Eligibility 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 to 65 years of age 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 \< 32.0 kg/m2
4. Fitzpatrick skin type I-III (Caucasian).
5. Subjects and their partners of childbearing potential must use effective contraception for the duration of the study.
6. No clinically significant skin disease as judged by the investigator.
7. No history of hypertrophic scarring or keloid.
8. Subject is willing to refrain from application of any topical product (e.g., ointments, cream or washing lotions) on the target lesion(s)skin 24 hours prior to every study visit day.
9. Subject has the ability to communicate well with the investigator in the Dutch language and is willing to comply with the study requirements.

Eligible CLE patients must meet all the following inclusion criteria at screening:

1. Signed informed consent prior to any study-mandated procedure.
2. Male or female CLE patients, 18 to 65 years of age 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 investigators.
3. Body mass index (BMI) \> 18.0 and \< 35.0 kg/m2.
4. Only applicable for CDLE patients who will also participate in part B: Fitzpatrick skin type I-III (Caucasian).
5. Subjects and their partners of childbearing potential must use effective contraception for the duration of the study.
6. Patient has the ability to communicate well with the investigator in the Dutch language and is willing to comply with the study requirements.
7. Subject is willing to refrain from application of any topical product (e.g., ointments, cream or washing lotions) on the target lesion(s) 24 hours prior to every study visit day.
8. Participants must have a diagnosis of SCLE, CDLE or LET that fulfils the following:

   * Confirmed CLE diagnosis by clinicopathological correlation.
   * At least one CLE skin lesion of at least 3x3 cm suitable as assessed by the investigator for measurements performed in the study.
   * Location of the lesion(s) selected for biopsy outside the face (possible are e.g., neck, chest, back, limbs, scalp, ear etc.).
   * Receiving one of the following systemic treatments for CLE (stable for a minimum of 8 weeks):

     * None
     * Hydroxychloroquine
   * An overall CLE Disease Area and Severity Index Activity (CLASI-A) Score ≥3 without counting any diffuse alopecia or oral ulcers

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 significant 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 (HIV 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

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:

   1. \<2 weeks for topical treatment, e.g., corticosteroids at target area(s)
   2. \<6 weeks for systemic therapy with immunosuppressive agents (other than hydroxychloroquine stable use for a minimum of 8 weeks)
   3. \<12 weeks for biologics
   4. \<8 weeks procedure or surgery in or close to the target areas
   5. \<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 anti-SM at screening (part B only).

Where this trial is running

Leiden, South Holland

• Centre for Human Drug Research — Leiden, South Holland, Netherlands (RECRUITING)

Study contacts

• Principal investigator: R. Rissmann, RPh, PhD — Centre for Human Drug Research
• Study coordinator: R. Rissmann, RPh, PhD

Conditions: Cutaneous Lupus Erythematosus, CLE, Cutaneous lupus erythematosus, Deep phenotyping, Immune challenge, Healthy volunteers