An Explorative Psoriasis Biomarker Study

NCT04394936 | Terminated

• 3 other identifiers: CHDR18062019-002383-27NL70359.028.19
• Study Type: interventional
• Target: 37
• Locations: 1 country
• Sites: 1

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

Conditions

Psoriasis Vulgaris

Keywords

Psoriasis; Biomarker; Guselkumab

Outcome Measures

Primary Outcomes (25)

• Psoriasis Area and Severity Index (PASI) Assessment

  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).

  from day -14 to day 168

• Physicians Global Assesment (PGA) Assessment

  Physicians Global Assesment (PGA) is a 4-point scale ranging from 0 (no disease) to 4 (maximal disease).

  from day -14 to day 168

• Percentage body surface affected (%BSA) Assessment

  Percentage body surface affected (%BSA) is the area of lesional skin as a percentage of the total body surface

  from day -14 to day 168

• digital PASI

  Digital Psoriasis Area and Severity Index (dPASI) calculated from standardized total body photography

  from day -14 to day 168

• Erythema measurement of the skin

  Redness of the skin will be determined using a colorimeter

  from day -14 to day 168

• Multispectral imaging

  The redness and superficial morphology of (non-)lesional skin sites will be determined using a multispectral imaging system

  from day -14 to day 168

• Laser Speckle Contrast imaging

  The cutaneous microcirculation of (non-)lesional skin sites will be monitored over a 30 second timespan with a laser speckle contrast imager

  from day -14 to day 168

• Thermography

  Body surface temperature of (non-)lesional skin will be determined using a thermal imaging infrared camera

  from day -14 to day 168

• Patient reported outcomes

  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.

  from day -14 to day 168

• Activity Tracking Heartrate

  Subjects are requested to wear a smartwatch at all times which heart rate (beats per minute)

  from day -14 to day 168

• Activity Tracking Steps

  Subjects are requested to wear a smartwatch at all times which register steps (amount of steps taken)

  from day -14 to day 168

• Activity Tracking Sleep

  Subjects are requested to wear a smartwatch at all times which register sleep (hrs, minutes, seconds of rest)

  from day -14 to day 168

• Cells/ml; Circulating immune cell subsets

  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

  from day -14 to day 168

• Circulating protein biomarkers

  Blood be drawn during using a venipuncture during visits and analyzed for the presence of various chemokines and cytokines (e.g. CCL20, CCL17, CXCL8)

  from day -14 to day 168

• Anti-drug antibodies

  The occurrence of antibodies directed against guselkumab will be monitored during the treatment period (ng/ml)

  from day 0 to day 168

• Blister immune cell subsets

  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

  from day 0 to day 112

• Blister protein biomarkers

  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)

  from day 0 to day 112

• Immunohistochemistry of biopsies

  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).

  day 0 to day 112

• Transcriptome of biopsies

  Biopsies will be analyzed with an untargeted next-generation sequencing approach.

  day 0 to day 112

• Cutaneous microbiome

  The microbiome is collected by swabbing. The abundance of bacteria is thereafter determined using next-generation sequencing.

  from day -14 to day 112

• Fecal microbiome

  The bacterial composition of stool samples is determined using next-generation sequencing.

  from day 0 to day 112

• Skin surface biomarkers

  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.

  from day -14 to day 112

• Lipidomics of the stratum corneum

  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)

  from day -14 to day 112

• Skin barrier function

  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)

  from day -14 to day 168

• Patient genotyping

  A whole blood sample will be used to scan for common mutations in genes implicated in psoriasis using next-generation sequencing.

  day -14

Study Arms (3)

Guselkumab

EXPERIMENTAL

Guselkumab 100 mg/ml in prefilled syringe, subcutaneous injection, administered on day 0, 28 and 84.

Drug: Guselkumab

Placebo

PLACEBO COMPARATOR

Sodiumchloride 0,9% solution for injection, subcutaneous injection, administered on day 0, 28 and 84.

Drug: Placebos

Healthy volunteers

NO INTERVENTION

Healthy volunteer cohort (observational)

Interventions

Guselkumab DRUG

100 mg guselkumab administered subcutaneously

Guselkumab

Placebos DRUG

Sodiumchloride 0,9% solution for injection

Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or non-pregnant female subjects, 18 to 75 years of age (inclusive);
• 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;
• Willing to give written informed consent and willing and able to comply with the study protocol; Psoriasis patients
• Male or non-pregnant female subjects, 18 to 75 years of age (inclusive);
• Diagnosed with plaque psoriasis at least 6 months prior to study participation
• Willing to discontinue any psoriasis therapy other than emollients.
• Having mild (PASI ≥1 and ≤ 5) or moderate-to-severe (PASI ≥ 10) plaque psoriasis;

You may not qualify if:

• 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;
• History of immunological abnormality (e.g., immune suppression, severe allergy or anaphylaxis) that may interfere with study objectives, in the opinion of the Investigator;
• Known infection requiring antibiotic therapy within the last three months prior to the study;
• Immunosuppressive or immunomodulatory treatment within 30 days prior to the study;
• Body mass index (BMI) ≤ 18.0 or ≥ 40.0 kg/m2;
• Participation in an investigational drug study within 3 months prior to screening or more than 4 times a year;
• Previous participation in an investigational drug study involving the dosing of an investigational compound targeting an immune pathway within one year prior to screening;
• Loss or donation of blood over 500 mL within three months prior to screening;
• 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;
• 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;
• Any other condition that could interfere with the conduct of the study or the study objectives, in the opinion of the Investigator.
• Psoriasis patients
• Having primarily erythrodermic, pustular or guttate psoriasis;
• Having medication-induced psoriasis;
• Having previously failed on anti-IL23 therapy;

Sponsors & Collaborators

• Centre for Human Drug Research, Netherlands: lead
• Janssen Pharmaceuticals: collaborator

Study Sites (1)

Centre for Human Drug Research

Leiden, 2333 CL, Netherlands

Location

Related Publications (1)

• Rousel J, Mergen C, Bergmans ME, Bruijnincx LJ, de Kam ML, Klarenbeek NB, Niemeyer-van der Kolk T, van Doorn MBA, Bouwstra JA, Rissmann R; Next-Generation ImmunoDermatology Consortium (NGID). Guselkumab treatment normalizes the stratum corneum ceramide profile and alleviates barrier dysfunction in psoriasis: results of a randomized controlled trial. J Lipid Res. 2024 Aug;65(8):100591. doi: 10.1016/j.jlr.2024.100591. Epub 2024 Jul 9.

  PMID: 38992724 DERIVED

MeSH Terms

Conditions

Psoriasis

Interventions

guselkumab

Condition Hierarchy (Ancestors)

Skin Diseases, Papulosquamous; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Robert Rissmann, PhD

  Centre for Human Drug Research

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is an observational and interventional study in up to 40 patients with chronic plaque psoriasis and 10 healthy volunteers (observational only).

Study Record Dates

• First Submitted: April 8, 2020
• First Posted: May 20, 2020
• Study Start: September 1, 2020
• Primary Completion: February 22, 2023
• Study Completion: March 27, 2023
• Last Updated: June 15, 2025

Record last verified: 2025-06

Locations

NL (1)