SKINERGY: deep biomarker profiling of immune-driven skin diseases in dermatology clinics

A Prospective, Multi-Center, Observational Biomarker Real-World Evidence Study for In-Depth Profiling of Patients With Chronic Immune-Mediated Inflammatory Skin Diseases in Daily Practice

This project will test whether detailed blood, tissue, imaging, and patient-reported biomarker profiles in adults with several immune-related skin conditions can find patterns that distinguish disease types and predict who responds to treatment.

Quick facts

• Study type: Observational
• Enrollment: 840 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Leiden University Medical Center (Academic / other)
• Drugs / interventions: dupilumab, tralokinumab, lebrikizumab, omalizumab, secukinumab, bimekizumab, abrocitinib, upadacitinib, radiation, methotrexate, guselkumab, risankizumab, tildrakizumab, ixekizumab, brodalumab, adalimumab, certolizumab, deucravacitinib, remibrutinib, rilzabrutinib
• Locations: 8 sites (Nijmegen, Gelderland and 7 other locations)
• Trial ID: NCT07021495 on ClinicalTrials.gov

What this trial studies

SKINERGY is an observational, multi-center effort to collect clinical data, patient-reported outcomes, imaging, biophysical measurements, microbiological samples, blood, and tissue from adults with atopic dermatitis, plaque psoriasis, hidradenitis suppurativa, chronic spontaneous urticaria, cutaneous T-cell lymphoma (mycosis fungoides), and cutaneous lupus erythematosus, alongside healthy volunteers. Samples and multi-omics analyses will be used to define disease endotypes, compare patients to healthy controls, and look for biomarkers associated with disease subtype and treatment response. The protocol emphasizes real-world dermatology practice workflows and longitudinal sampling to capture treatment outcomes over time. Results will feed the Next Generation ImmunoDermatology infrastructure to support personalized care decisions in the future.

Who should consider this trial

Good fit: Adults (≥18) with a confirmed diagnosis of one of the listed immune-mediated skin conditions who can provide informed consent, follow study procedures, agree to sample collection and visits, and avoid pregnancy during the study period are ideal candidates.

Not a fit: Patients seeking immediate therapeutic benefit from a trial drug, those unable to attend in-person visits at participating sites, or those unwilling to provide biological samples or follow-up are unlikely to benefit directly from this observational effort.

Why it matters

Potential benefit: If successful, the work could help clinicians choose treatments more precisely by identifying biomarkers that predict which patients will respond to specific therapies.

How similar studies have performed: Biomarker research in individual diseases such as psoriasis and atopic dermatitis has produced promising candidates, but broad multi-omics profiling across multiple dermatoses in routine practice remains relatively novel and not yet validated.

Eligibility criteria

Inclusion Criteria:

Patients:

1. Able to understand and provide a written informed consent prior to any study procedures
2. Male or non-pregnant female, ≥18 years of age
3. Patient is willing to refrain from extensively washing (including bathing, swimming) the target lesional skin 12 hours before every study visit day.
4. Patient is willing and able to comply with the study protocol
5. Female participants are willing to not get pregnant between M0 until M12, from study entry to the last study visit
6. The patient is willing to start the prescribed treatment.

Disease-specific inclusion criteria

For patients with AD:

To be eligible to participate in this study, a subject must meet all of the following criteria:

6\. Diagnosis and history of chronic, moderate-to-severe AD (by the Eichenfield revised criteria of Hanifin and Rajka for at least 3 years before baseline visit.

7\. Documented recent history (last 6 months) of eligibility for (local or systemic) treatment with immunosuppressants, biologics or JAK-inhibitors.

8\. When applicable, documented recent history (last 6 months) of inadequate response to treatment with topical therapy, immunosuppressants, biologics or JAK-inhibitors.

9\. Current treatment can include moisturizers, topical treatment and/or systemic treatments with preferable wash-out (see exclusion criterion #9). On-study treatment is at physician and patient discretion but must include eligibility to starting new systemic treatment.

10\. EASI≥7 (moderate-to-severe disease) 11. At least one suitable target lesion at the discretion of the investigator 12. Intention to start treatment with cyclosporine A, dupilumab, tralokinumab, lebrikizumab or a JAK1-inhibitor (abrocitinib or upadacitinib)

For patients with CLE:

Participants must have a diagnosis of CLE, including SCLE, CDLE or LET that fulfil the following:

6\. Confirmed CLE diagnosis by clinicopathological correlation. 7. An overall CLE Disease Area and Severity Index Activity (CLASI-A) Score ≥3 without counting any diffuse alopecia or oral ulcers.

8\. Intention to start treatment with TCS, hydroxychloroquine or methotrexate (combination or mono-treatment).

If participating in the exploratory study with the skin biopsy: location of the lesion(s) selected for biopsy preferably outside the facial area (possible are e.g., neck, chest, back, limbs, scalp, ear etc.).

For patients with CSU:

6\. Diagnosis of CSU (moderate to severe according to international guidelines (Zuberbier et al, 2022)) for ≥3 months and symptomatic disease despite treatment with second generation H1 antihistamines (up to fourfold the approved dose).

7.Patients currently on an antihistamine (up to fourfold the approved dose) must be on a stable dose for at least 2 weeks prior to day 1 and must maintain the same stable dose throughout the treatment period.

8\. Intention to start (add-on to antihistamine) treatment of omalizumab, cyclosporine A or BTK inhibitor\*. (\*when approved and reimbursed in NL)

For patients with HS:

6\. Patient with a history of signs and symptoms consistent with moderate-to-severe HS, based on IHS4 score (Zouboulis et al., 2017), for at least 1 year prior to baseline 7. Current treatment can include topical treatment. On-study treatment is at physician and patient discretion but must include eligibility to starting systemic treatment 8. Intention to start treatment with anti-TNF or anti-IL17 (secukinumab, bimekizumab\*) \*when approved and reimbursed in NL.

For patients with MF:

6\. A confirmed diagnosis of CTCL MF type and stage classification via histology or clinicopathological correlation 7. For the stage IA-IIA CTCL patients: at least one patch and/or one plaque lesion is present 8. Intention to start treatment with topical chlormethine, topical corticosteroids or phototherapy (PUVA / UV-B).

For patients with PSO:

6\. Diagnosed with chronic plaque psoriasis at least 6 months prior to study participation 7. PASI≥5 with at least one suitable target lesion at the discretion of the investigator 8. Current treatment can include moisturizers, topical treatment and/or systemic treatments with preferable wash-out. On-study treatment is at physician and patient discretion but must include eligibility to starting new systemic treatment 9. Intention to start treatment with biologics: anti-TNF, anti-IL23, anti-IL17 or anti-TYK2

Healthy volunteers:

All healthy volunteers must meet all of the following inclusion criteria:

1. Signed informed consent before any study-mandated procedure.
2. Male or non-pregnant female volunteers, ≥18 years of age
3. Subject is in stable good health as per judgement of the investigator based upon the results of medical history and assessments performed at baseline.
4. No clinically significant skin disease as judged by the investigator.
5. No history of hypertrophic scarring or keloid.
6. Subject is willing to refrain from extensively washing (including bathing, swimming) the skin 12 hours before every study visit.
7. Subject is willing and able to wash out and withhold any topical treatment (prescription and over-the-counter products) in the investigational area for 2 weeks prior to Day 1.
8. Subject is willing to refrain from application of any topical product (e.g. ointments, cream, or washing lotions) on the skin 24 hours prior to every study visit day.
9. Subject is willing and able to wash out any antibiotic therapy for 14 days prior to Day 1.
10. Subject is willing and able to comply with the study protocol.
11. Female participants are willing to not get pregnant from study entry to the last study visit

Exclusion Criteria:

Patients:

1. Have any other relevant skin infection/disease in the treatment area other than the investigated skin disease.
2. Subjects who have received treatment with any non-marketed drug substance (that is, an agent which has not yet been made available for clinical use following registration) within 4 weeks prior to the baseline visit.
3. Any other condition, disease, or known factor that could interfere with the study conduct or the study objectives as per judgement of the investigator. 4. Having received treatments for the investigated skin disease within the following intervals prior to the start of the study is not a strict exclusion criterion since this is a real-world study. However, preferred intervals for washout are as follows:

   * 1 week for topical treatment, e.g. corticosteroids, retinoids, vitamin D analogs, calcineurin inhibitors
   * 4 weeks for phototherapy, e.g. UVB, PUVA, PDT
   * 4 weeks for non-biologic systemic treatment, e.g. retinoids, methotrexate, cyclosporine, JAK inhibitors
   * 8 weeks for radiotherapy or surgery in the treatment area
   * 8 weeks for biologics
   * 3 months for any systemic chemotherapeutical treatment

Disease specific exclusion criteria for patients with CLE:

5\. Diagnosed with SLE

Disease specific exclusion criteria for patients with CSU:

5\. Treatment with omalizumab within 8 weeks prior to Day 1 6. Urticarial or angioedema symptoms such as urticarial vasculitis, erythema multiforme, cutaneous mastocytosis (urticaria pigmentosa) and hereditary, acquired angioedema or drug-induced (e.g., due to C1 esterase inhibitor deficiency, ACE-inhibitor induced).

Disease specific exclusion criteria for patients with MF:

5\. Ongoing uncontrolled active skin infection, other than secondary impetiginized CTCL lesions as judged by the investigator

Disease specific exclusion criteria for patients with PSO:

5\. Having primarily erythrodermic, pustular or guttate psoriasis; 6. Having drug-induced psoriasis;

Healthy volunteers:

All healthy volunteers must meet none of the following exclusion criteria:

1. History of immunological abnormality (e.g. immune suppression, severe allergy, or anaphylaxis) that may interfere with study objectives as per judgement of the investigator.
2. History or symptoms of any uncontrolled, significant disease including (but not limited to), a neurological, psychiatric, endocrine, cardiovascular, respiratory, gastrointestinal, hepatic, or renal disorder that may interfere with the study objectives as per judgement of the investigator.
3. The use of systemic antibiotic therapy for \>2 months in the past 12 months.
4. The use of any immunosuppressive or immunomodulatory therapy within the past 30 days prior to Day 1.

6\. Loss or donation of blood over 500mL within three months prior to baseline. Participation in an investigational drug study within 3 months prior to baseline visit or more than 4 times a year.

7\. History of alcohol consumption exceeding 5 standard drinks per day on average within 3 months prior to baseline. Alcohol consumption will be prohibited for at least 24 hours preceding each study visit.

8\. Positive urine test for drugs or history of abuse at baseline. 9. Exposure to high doses of UV radiation is not permitted within 3 weeks of the first study visit until the end of the study 10. Extreme physical activities are not permitted within 48 hours before each study visit 11. Any other condition, disease, or known factor that could interfere with the study conduct or the study objectives as per judgement of the investigator.

Where this trial is running

Nijmegen, Gelderland and 7 other locations

• Radboud University Medical Center — Nijmegen, Gelderland, Netherlands (Not_yet_recruiting)
• Maastricht University Medical Center+ — Maastricht, Limburg, Netherlands (Not_yet_recruiting)
• Amsterdam University Medical Center — Amsterdam, North Holland, Netherlands (Not_yet_recruiting)
• University Medical Center Groningen — Groningen, Provincie Groningen, Netherlands (Not_yet_recruiting)
• Leiden University Medical Center — Leiden, South Holland, Netherlands (Not_yet_recruiting)
• Centre for Human Drug Research — Leiden, South Holland, Netherlands (Not_yet_recruiting)
• Erasmus Medical Center — Rotterdam, South Holland, Netherlands (Not_yet_recruiting)
• University Medical Center Utrecht — Utrecht, Utrecht, Netherlands (Recruiting)

Study contacts

• Study coordinator: Robert Rissmann, Professor

Conditions Chronic Spontaneous Urticaria; Hidradenitis Suppurativa; Psoriasis; Atopic Dermatitis; CTCL/ Mycosis Fungoides; Urticaria; Hives; Mast cells