Clinical trial NCT04394936: An Explorative Psoriasis Biomarker Study
Official title: An Exploratory, Single-center, Double-blinded, Healthy Volunteer Controlled Study to Characterize Psoriasis Patients and Explore Novel Biomarkers for the Treatment Response of Psoriasis With a Multimodal Patient Profiling Approach.
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Psoriasis Vulgaris
Keywords: Psoriasis
Biomarker
Guselkumab
Lead sponsor: Centre for Human Drug Research, Netherlands
Sponsor class: OTHER
Collaborators: name: Janssen Pharmaceuticals
First posted: 2020-05-20
Enrollment: 37
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This is an observational and interventional study in up to 40 patients with chronic plaque psoriasis and 10 healthy volunteers (observational only).
Primary purpose: TREATMENT

Brief summary: Plaque psoriasis may be an ideal model disease to explore potential therapeutic effects of immunosuppressive agents, given the easy accessibility of inflammatory lesions. In this study, the applicability of a systems dermatology approach is investigated in order to better assess the efficacy of psoriasis treatments at an early clinical stage. Up to this point, the clinical manifestation and regression of psoriasis is not yet sufficiently characterized with a multimodal state-of-the-art evaluation tool. The in-house developed 'DermaToolbox' enables the determination and subsequent integration of different diseaserelated biomarkers, including clinical, biophysical, molecular, cellular, and imaging markers as well as patient reported outcomes

Detailed description: Psoriasis is a common skin disorder affecting up to an estimated 3% of the world's population. The most prevalent form of psoriasis, called psoriasis vulgaris or plaque psoriasis, is characterized by the presence of sharply demarcated erythematous plaques covered with white scales. These lesions can occur all over the body, but are most often seen on the extensor surface of the joints, nether regions and on the scalp. Patients can experience excessive itch, pain and sometimes bleeding of the lesions. Moreover, the visual appearance of psoriatic lesions can severely impact the patients psychological state and quality of life. An abundancy of different factors contributes to the pathogenesis of psoriasis. However, aberrant inflammatory reactions in the skin are thought to be the underlying cause. Excessive infiltration of immune cells in the skin and their interactions with cutaneous resident cells results in the hyper proliferation of keratinocytes and subsequent thickening of the epidermis. Indeed, more and more immunosuppressive biologicals targeting specific components of the immune system, like tumor necrosis factor alpha (TNFα), interleukin (IL-)17 and IL-23, have shown excellent efficacy in treating psoriasis Plaque psoriasis may be an ideal model disease to explore potential therapeutic effects of immunosuppressive agents, given the easy accessibility of inflammatory lesions and the good willingness of patients to participate in clinical studies. In this study, the applicability of a systems dermatology approach is investigated in order to better assess the efficacy of psoriasis treatments at an early clinical stage. Up to this point, the clinical manifestation and regression of psoriasis is not yet sufficiently characterized with a multimodal state-of-the-art evaluation tool. The in-house developed 'DermaToolbox' enables the determination and subsequent integration of different disease-related biomarkers, including clinical, biophysical, molecular, cellular, and imaging markers as well as patient-reported outcomes

Eligibility criteria: Inclusion Criteria Healthy volunteers

Eligible healthy volunteers must meet all of the following inclusion criteria at screening:

1. Male or non-pregnant female subjects, 18 to 75 years of age (inclusive);
2. Healthy as defined by the absence of any uncontrolled active or uncontrolled chronic disease following a medical and surgical history, documentation of general symptoms, and a symptom-directed physical examination including vital signs;
3. Willing to give written informed consent and willing and able to comply with the study protocol; Psoriasis patients

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

1. Male or non-pregnant female subjects, 18 to 75 years of age (inclusive);
2. Diagnosed with plaque psoriasis at least 6 months prior to study participation
3. Willing to discontinue any psoriasis therapy other than emollients.
4. Having mild (PASI ≥1 and ≤ 5) or moderate-to-severe (PASI ≥ 10) plaque psoriasis;
5. Currently not using psoriasis medication and ≥ 2 plaques suitable for repeated biopsies and target lesion assessments. At least one of these lesions must be located on the extremities, preferably on the elbow or knee, with a minimal target lesion score between 6 and 9. Or, when currently using psoriasis medication and insufficient lesional skin is present, willing to discontinue treatment awaiting rescreening (see also exclusion criteria 3 for psoriatic patients);
6. Willing to give written informed consent and willing and able to comply with the study protocol; Exclusion Criteria

Eligible healthy volunteers must meet none of the following exclusion criteria at screening:

1. History or symptoms of any uncontrolled, significant disease including (but not limited to), neurological, psychiatric, endocrine, cardiovascular, respiratory, gastrointestinal, hepatic, or renal disorder that may interfere with the study objectives, in the opinion of the Investigator;
2. History of immunological abnormality (e.g., immune suppression, severe allergy or anaphylaxis) that may interfere with study objectives, in the opinion of the Investigator;
3. Known infection requiring antibiotic therapy within the last three months prior to the study;
4. Immunosuppressive or immunomodulatory treatment within 30 days prior to the study;
5. Body mass index (BMI) ≤ 18.0 or ≥ 40.0 kg/m2;
6. Participation in an investigational drug study within 3 months prior to screening or more than 4 times a year;
7. Previous participation in an investigational drug study involving the dosing of an investigational compound targeting an immune pathway within one year prior to screening;
8. Loss or donation of blood over 500 mL within three months prior to screening;
9. The use of any medication or vitamin/mineral/herbal/dietary supplement within less than 5 half-lives prior to study participation, if the Investigator judges that it may interfere with the study objectives. The use of paracetamol (up to 4 g/day) is allowed;
10. History of alcohol consumption exceeding 5 standard drinks per day on average within 3 months of screening. Alcohol consumption will be prohibited from at least 12 hours preceding each study visit;
11. Any other condition that could interfere with the conduct of the study or the study objectives, in the opinion of the Investigator.

Psoriasis patients

Eligible psoriasis patients must meet none of the following exclusion criteria at screening:

1. Having primarily erythrodermic, pustular or guttate psoriasis;
2. Having medication-induced psoriasis;
3. Having previously failed on anti-IL23 therapy;
4. Having received treatments for psoriasis within the following intervals prior to the start of the study:

   1. \< 2 weeks for topical treatment, e.g. retinoids, corticosteroids, vitamin D analogs
   2. \< 4 weeks for phototherapy, e.g. PUVA, PDT
   3. \< 4 weeks for non-biologic systemic treatment, e.g. retinoids, methotrexate, cyclosporine, fumaric acid esters
   4. \< 4 weeks for etanercept
   5. \< 8 weeks for adalimumab
   6. \< 3 months for anti-IL17, anti-IL12(/23) and anti-IL23 treatments
5. History or symptoms of any significant uncontrolled disease including (but not limited to), neurological, psychiatric, endocrine, cardiovascular, respiratory, gastrointestinal, hepatic, or renal disorder that may interfere with the study objectives, in the opinion of the Investigator, excluding psoriasis and conditions that are related to psoriasis;
6. History of immunological abnormality (e.g., immune suppression, severe allergy or anaphylaxis) that may interfere with study objectives, in the opinion of the Investigator;
7. Known infection requiring antibiotic therapy within the last 3 months prior to the study, including latent tuberculosis;
8. Systemic immunosuppressive or immunomodulatory treatment within 30 days prior to the study;
9. Body mass index (BMI) ≤ 18.0 or ≥ 40.0 kg/m2;
10. Participation in an investigational drug study within 3 months prior to screening or more than 4 times a year;
11. Loss or donation of blood over 500 mL within three months prior to screening;
12. The use of any medication or vitamin/mineral/herbal/dietary supplement within less than 5 half-lives prior to study participation, if the Investigator judges that it may interfere with the study objectives. The use of paracetamol (up to 4 g/day) is allowed;
13. History of alcohol consumption exceeding 5 standard drinks per day on average within 3 months of screening. Alcohol consumption will be prohibited from at least 12 hours preceding each study visit;
14. Any other condition that could interfere with the conduct of the study or the study objectives, in the opinion of the Investigator.

Primary outcomes:
measure: Psoriasis Area and Severity Index (PASI) Assessment
timeFrame: from day -14 to day 168
measure: Physicians Global Assesment (PGA) Assessment
timeFrame: from day -14 to day 168
measure: Percentage body surface affected (%BSA) Assessment
timeFrame: from day -14 to day 168
measure: digital PASI
timeFrame: from day -14 to day 168
measure: Erythema measurement of the skin
timeFrame: from day -14 to day 168
measure: Multispectral imaging
timeFrame: from day -14 to day 168
measure: Laser Speckle Contrast imaging
timeFrame: from day -14 to day 168
measure: Thermography
timeFrame: from day -14 to day 168
measure: Patient reported outcomes
timeFrame: from day -14 to day 168
measure: Activity Tracking Heartrate
timeFrame: from day -14 to day 168
measure: Activity Tracking Steps
timeFrame: from day -14 to day 168
measure: Activity Tracking Sleep
timeFrame: from day -14 to day 168
measure: Cells/ml; Circulating immune cell subsets
timeFrame: from day -14 to day 168
measure: Circulating protein biomarkers
timeFrame: from day -14 to day 168
measure: Anti-drug antibodies
timeFrame: from day 0 to day 168
measure: Blister immune cell subsets
timeFrame: from day 0 to day 112
measure: Blister protein biomarkers
timeFrame: from day 0 to day 112
measure: Immunohistochemistry of biopsies
timeFrame: day 0 to day 112
measure: Transcriptome of biopsies
timeFrame: day 0 to day 112
measure: Cutaneous microbiome
timeFrame: from day -14 to day 112
measure: Fecal microbiome
timeFrame: from day 0 to day 112
measure: Skin surface biomarkers
timeFrame: from day -14 to day 112
measure: Lipidomics of the stratum corneum
timeFrame: from day -14 to day 112
measure: Skin barrier function
timeFrame: from day -14 to day 168
measure: Patient genotyping
timeFrame: day -14
Secondary outcomes:
Other outcomes:
Locations:
city: Leiden
country: Netherlands
facility: Centre for Human Drug Research
Study officials:
affiliation: Centre for Human Drug Research
name: Robert Rissmann, PhD
role: PRINCIPAL_INVESTIGATOR
References: