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.
Overview
- Phase
- Not Applicable
- Intervention
- Guselkumab
- Conditions
- Psoriasis Vulgaris
- Sponsor
- Centre for Human Drug Research, Netherlands
- Enrollment
- 37
- Locations
- 1
- Primary Endpoint
- Erythema measurement of the skin
- Status
- Terminated
- Last Updated
- 10 months ago
Overview
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
Investigators
Eligibility Criteria
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Arms & Interventions
Guselkumab
Guselkumab 100 mg/ml in prefilled syringe, subcutaneous injection, administered on day 0, 28 and 84.
Intervention: Guselkumab
Placebo
Sodiumchloride 0,9% solution for injection, subcutaneous injection, administered on day 0, 28 and 84.
Intervention: Placebos
Outcomes
Primary Outcomes
Erythema measurement of the skin
Time Frame: from day -14 to day 168
Redness of the skin will be determined using a colorimeter
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
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).
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)
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
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).
Fecal microbiome
Time Frame: from day 0 to day 112
The bacterial composition of stool samples is determined using next-generation sequencing.
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
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
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.
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.
digital PASI
Time Frame: from day -14 to day 168
Digital Psoriasis Area and Severity Index (dPASI) calculated from standardized total body photography
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
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)
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)
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.
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)
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)
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
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)
Transcriptome of biopsies
Time Frame: day 0 to day 112
Biopsies will be analyzed with an untargeted next-generation sequencing approach.
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)
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).
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)
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.