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An Explorative Psoriasis Biomarker Study

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ClinicalTrials.gov Identifier: NCT04394936
Recruitment Status : Not yet recruiting
First Posted : May 20, 2020
Last Update Posted : May 21, 2020
Sponsor:
Collaborator:
Janssen Pharmaceuticals
Information provided by (Responsible Party):
Centre for Human Drug Research, Netherlands

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

Condition or disease Intervention/treatment Phase
Psoriasis Vulgaris Drug: Guselkumab Drug: Placebos Not Applicable

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

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 50 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
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).
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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.
Estimated Study Start Date : June 1, 2020
Estimated Primary Completion Date : October 2021
Estimated Study Completion Date : December 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Psoriasis
Drug Information available for: Guselkumab

Arm Intervention/treatment
Experimental: Guselkumab
Guselkumab 100 mg/ml in prefilled syringe, subcutaneous injection, administered on day 0, 28 and 84.
Drug: Guselkumab
100 mg guselkumab administered subcutaneously

Placebo Comparator: Placebo
Sodiumchloride 0,9% solution for injection, subcutaneous injection, administered on day 0, 28 and 84.
Drug: Placebos
Sodiumchloride 0,9% solution for injection

No Intervention: Healthy volunteers
Healthy volunteer cohort (observational)



Primary Outcome Measures :
  1. Psoriasis Area and Severity Index (PASI) Assessment [ Time Frame: from day -14 to day 168 ]
    Psoriasis Area and Severity Index (PASI) combines the assessment of the severity of lesions and the area affected into a single score in the range 0 (no disease) to 72 (maximal disease).

  2. Physicians Global Assesment (PGA) Assessment [ Time Frame: from day -14 to day 168 ]
    Physicians Global Assesment (PGA) is a 4-point scale ranging from 0 (no disease) to 4 (maximal disease).

  3. Percentage body surface affected (%BSA) Assessment [ Time Frame: from day -14 to day 168 ]
    Percentage body surface affected (%BSA) is the area of lesional skin as a percentage of the total body surface

  4. digital PASI [ Time Frame: from day -14 to day 168 ]
    Digital Psoriasis Area and Severity Index (dPASI) calculated from standardized total body photography

  5. Erythema measurement of the skin [ Time Frame: from day -14 to day 168 ]
    Redness of the skin will be determined using a colorimeter

  6. Multispectral imaging [ Time Frame: from day -14 to day 168 ]
    The redness and superficial morphology of (non-)lesional skin sites will be determined using a multispectral imaging system

  7. Laser Speckle Contrast imaging [ Time Frame: from day -14 to day 168 ]
    The cutaneous microcirculation of (non-)lesional skin sites will be monitored over a 30 second timespan with a laser speckle contrast imager

  8. Thermography [ Time Frame: from day -14 to day 168 ]
    Body surface temperature of (non-)lesional skin will be determined using a thermal imaging infrared camera

  9. Patient reported outcomes [ Time Frame: from day -14 to day 168 ]
    Patients will be asked to report on their condition through an NRS scale (0 (better)- 10 (worse)) for sleeplessness, itch and quality of life. Additionally, patients image their lesions on a daily basis using a mobile device.

  10. Activity Tracking Heartrate [ Time Frame: from day -14 to day 168 ]
    Subjects are requested to wear a smartwatch at all times which heart rate (beats per minute)

  11. Activity Tracking Steps [ Time Frame: from day -14 to day 168 ]
    Subjects are requested to wear a smartwatch at all times which register steps (amount of steps taken)

  12. Activity Tracking Sleep [ Time Frame: from day -14 to day 168 ]
    Subjects are requested to wear a smartwatch at all times which register sleep (hrs, minutes, seconds of rest)

  13. Cells/ml; Circulating immune cell subsets [ Time Frame: from day -14 to day 168 ]
    Blood be drawn during using a venipuncture during visits and analyzed for the presence of immune cells (e.g. CD4+ and CD8+ T-Cells) using flow cytometry

  14. Circulating protein biomarkers [ Time Frame: from day -14 to day 168 ]
    Blood be drawn during using a venipuncture during visits and analyzed for the presence of various chemokines and cytokines (e.g. CCL20, CCL17, CXCL8)

  15. Anti-drug antibodies [ Time Frame: from day 0 to day 168 ]
    The occurrence of antibodies directed against guselkumab will be monitored during the treatment period (ng/ml)

  16. Blister immune cell subsets [ Time Frame: from day 0 to day 112 ]
    Blisters will be induced on the non-lesional skin and the blister exudate aspirated. Blister exudate will be analyzed for the presence of immune cells (e.g. CD4+ and CD8+ T-Cells) using flow cytometry

  17. Blister protein biomarkers [ Time Frame: from day 0 to day 112 ]
    Blisters will be induced on the non-lesional skin and blister fluid aspirated. Blister fluid will be analyzed for the presence of various chemokines and cytokines (e.g. CCL20, CCL17, CXCL8) (ng/ml)

  18. Immunohistochemistry of biopsies [ Time Frame: day 0 to day 112 ]
    Biopsies will be sectioned and stained for the determination of the epidermal homeostasis (proliferation, differentiation and thickness) and infiltration of cellular immune subsets (e.g. presence of CD4 and CD8).

  19. Transcriptome of biopsies [ Time Frame: day 0 to day 112 ]
    Biopsies will be analyzed with an untargeted next-generation sequencing approach.

  20. Cutaneous microbiome [ Time Frame: from day -14 to day 112 ]
    The microbiome is collected by swabbing. The abundance of bacteria is thereafter determined using next-generation sequencing.

  21. Fecal microbiome [ Time Frame: from day 0 to day 112 ]
    The bacterial composition of stool samples is determined using next-generation sequencing.

  22. Skin surface biomarkers [ Time Frame: from day -14 to day 112 ]
    Superficial protein biomarkers are samples using a FibroTx Patch. Afterwards, these patches are extracted and the presence of protein biomarkers (e.g. HBD-3) determined using ELISA.

  23. Lipidomics of the stratum corneum [ Time Frame: from day -14 to day 112 ]
    Tape stripping will be performed on (non-)lesional skin and lipids are subsequently extracted from the tape and analyzed using Liquid Chromatogrpahy-Mass Spectormetry. (ng/cm2)

  24. Skin barrier function [ Time Frame: from day -14 to day 168 ]
    The trans epidermal water loss of (non-)lesional skin will be determined as function of the inside-out barrier function of the skin. (g/m2/h)

  25. Patient genotyping [ Time Frame: day -14 ]
    A whole blood sample will be used to scan for common mutations in genes implicated in psoriasis using next-generation sequencing.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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 (BSA ≥1% and ≤ 5%) or moderate-to-severe (BSA ≥ 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04394936


Contacts
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Contact: Robert Rissmann, PhD +31 71 5246 438 clintrials@chdr.nl
Contact: Jannik Rousel, MSc +31 71 7517 197 clintrials@chdr.nl

Locations
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Netherlands
Centre for Human Drug Research
Leiden, Netherlands, 2333 CL
Sponsors and Collaborators
Centre for Human Drug Research, Netherlands
Janssen Pharmaceuticals
Investigators
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Principal Investigator: Robert Rissmann, PhD Centre for Human Drug Research
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Responsible Party: Centre for Human Drug Research, Netherlands
ClinicalTrials.gov Identifier: NCT04394936    
Other Study ID Numbers: CHDR1806
2019-002383-27 ( EudraCT Number )
NL70359.028.19 ( Other Identifier: Regulatory registration number )
First Posted: May 20, 2020    Key Record Dates
Last Update Posted: May 21, 2020
Last Verified: May 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by Centre for Human Drug Research, Netherlands:
Psoriasis
Biomarker
Guselkumab
Additional relevant MeSH terms:
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Psoriasis
Skin Diseases, Papulosquamous
Skin Diseases