An Explorative Psoriasis Biomarker Study

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.

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

Study Overview

• Status: Recruiting
• Conditions: Psoriasis Vulgaris
• Intervention / Treatment: Drug: Guselkumab; Drug: Placebos

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

• Study Type: Interventional
• Enrollment (Anticipated): 50
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Robert Rissmann, PhD; Phone Number: +31 71 5246 438; Email: clintrials@chdr.nl
• Study Contact Backup: Name: Jannik Rousel, MSc; Phone Number: +31 71 7517 197; Email: clintrials@chdr.nl

Study Locations

• Netherlands
  • Leiden, Netherlands, 2333 CL
    • Recruiting
    • Centre for Human Drug Research
    • Contact: Robert Rissmann, PharmD, PhD; Phone Number: +31 71 5246 400; Email: clintrials@chdr.nl
    • Contact: Diana Noort; Phone Number: +31 71 5246 400; Email: clintrials@chdr.nl

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Healthy volunteers; Healthy volunteer cohort (observational)
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Collaborators and Investigators

• Sponsor: Centre for Human Drug Research, Netherlands
• Collaborators: Janssen Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2020
• Primary Completion (Anticipated): October 1, 2022
• Study Completion (Anticipated): December 1, 2022

Study Registration Dates

• First Submitted: April 8, 2020
• First Submitted That Met QC Criteria: May 14, 2020
• First Posted (Actual): May 20, 2020

Study Record Updates

• Last Update Posted (Actual): June 14, 2021
• Last Update Submitted That Met QC Criteria: June 11, 2021
• Last Verified: June 1, 2021

More Information

Terms related to this study

• Keywords: Biomarker; Psoriasis; Guselkumab
• Additional Relevant MeSH Terms: Skin Diseases; Skin Diseases, Papulosquamous; Psoriasis
• Other Study ID Numbers: CHDR1806; 2019-002383-27 (EudraCT Number); NL70359.028.19 (Other Identifier: Regulatory registration number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• 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