The study is divided into two sections:Part A is a healthy volunteer controlled observational study to determine the course of the disease over time to:- Evaluate disease-related biomarkers in psoriasis when compared with healthy volunteers;-…
ID
Source
Brief title
Condition
- Skin and subcutaneous tissue disorders NEC
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
This study will monitor the change over time in:
• Serum concentration of guselkumab and anti-guselkumab antibodies
• Blood-based biomarkers (whole blood, serum and plasma samples)
o Biomarkers will include, but are not limited to, cellular targets (e.g. T
cells, TH17 cells, γδ T cells) from whole blood, comprehensive metabolomic and
proteomic analysis from serum and/or plasma covering cytokines (e.g. IL-22,
IL21, TNFα), chemokines (e.g. CCL20, CCL17, CXCL8), amines (e.g. amino acids,
neurotransmitters) and inflammatory signalling lipids (e.g. prostaglandins,
leukotrienes, isoprostanes).
• Blister fluid-based biomarkers
o Biomarkers will include, but are not limited to, cellular targets (e.g. T
cells, TH17 cells, γδ T cells) and proteomic analysis covering cytokines (e.g.
IL-22, IL21, TNFα), chemokines (e.g. CCL20, CCL17, CXCL8).
• Skin biopsies for:
o mRNA extraction for next-generation RNA sequencing
o Histology by haematoxylin and eosin staining but might also include
additional immunohistochemical stainings focussing on e.g. proliferation,
complement activation and presence of cellular immune infiltrate.
• Microbiome (skin, faecal)
• Laser Speckle Contrast Imaging (LSCI)*
• Thermography*
• Clinical assessment (PASI, PGA,BSA)*
• Colorimetry*
• Optical coherence tomography (OCT)*
• Multispectral imaging*
• Total body photography (digital PASI)*
• Patient reported outcomes (pruritus, sleeplessness, QoL, activity by
smartwatch, at-home plaque monitoring)*
• Skin surface markers*
• Skin barrier function (TEWL)*
• Lipidomics of stratum corneum by LC-MS*
• Flow-mediated skin fluorescence (FMSF)*
Endpoints marked *** denote non-invasive assessments. Note: if feasible, target
areas for invasive measurements will also be investigated non-invasively over
time. This will allow exploration of the correlation between molecular/cellular
and functional measurements, and evaluation of wound healing.
Secondary outcome
N.A.
Background summary
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 (Boehncke and Schön, 2015).
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 (Dainichi et al., 2018).
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
(figure 1).
Study objective
The study is divided into two sections:
Part A is a healthy volunteer controlled observational study to determine the
course of the disease over time to:
- Evaluate disease-related biomarkers in psoriasis when compared with healthy
volunteers;
- Evaluate the variability of the selected biomarkers between subjects, and
within subjects over time.
Part B is an interventional and placebo controlled study in psoriasis patients
to:
- Evaluate the biomarker for use in disease-monitoring after pharmacological
intervention.
Study design
This is an observational and interventional study in up to 40 patients with
chronic plaque psoriasis and 10 healthy volunteers (observational only). All
volunteers will visit CHDR for a screening and several short visits.
Prior to treatment and following the screening, an initial two-week
observational period is scheduled in order to characterize the natural course
of the disease compared to a cohort of 10 healthy volunteers. Hereafter, only
psoriasis patients will continue with the interventional part. Patients will be
randomized in a 3:1 ratio to 16-week guselkumab treatment or placebo.. During
this 16-week period, the same assessments will be performed with regular
intervals in order to assess the proposed biomarker applicability over a longer
time frame. Patients will be recalled for a follow-up visit 8 weeks after the
end of the treatment period to assess possible recurrence of psoriasis symptoms.
Study assessments will comprise clinical, patient reported, biophysical,
molecular, cellular, and imaging outcomes, of which some require 4 mm skin
biopsies or skin blister induction. For psoriasis patients, both lesional and
non-lesional skin biopsies will be collected. Suction blisters will be induced
on peri-lesional and non-lesional skin.
.
Intervention
Guselkumab (Tremfya, Janssen-Cilag) is an anti-interleukin 23 monoclonal
antibody indicated for the treatment of moderate-to-severe plaque psoriasis in
patients that are candidates for systematic treatment. Guselkumab has been
approved for use by the European Medicine Agency in late 2017 after showing
high efficacy and safety. Patients will receive either the standard therapeutic
dosing regimen of 100 mg guselkumab or placebo administered subcutaneously on
day 0, 28 and 84.
Study burden and risks
Guselkumab has been approved by the European Medicine Agency for the treatment
of moderate to severe plaque psoriasis in patients applicable for systematic
treatment. The European Product Assessment Report states guselkumab shows a
remarkable short- and longer-term efficacy accompanied by a favourable
tolerability and safety profile in over 1500 patients during phase II and phase
III clinical trials. During these trials, the majority of patients treated with
guselkumab obtained a PASI 90 or IGA 0/1 at week 16 (resp. >70.0%, >84.1%),
thereby showing superiority in efficacy over adalimumab. On the other hand,
guselkumab treated patients are more susceptible to infections compared to
placebo (nasopharyngitis; 19.6%, upper respiratory tract infections; 10.2%,
oral herpes; 1.6% and tinea pedis; 1.1%). However, their incidence was similar
compared to the adalimumab treated control group. Overall, treatment of plaque
psoriasis with guselkumab is considered efficacious and safe.
Zernikedreef 8
Leiden 2333CL
NL
Zernikedreef 8
Leiden 2333CL
NL
Listed location countries
Age
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);
during COVID-19 pandemic this is set to 18 to 69 year 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);
during COVID-19 pandemic this is set to 18 to 69 year 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 PASI >=1 and <= 5) (BSA >=1% andPASI <= 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
Healthy volunteers
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; during COVID-19 pandemic only
<= 18.0 or > 33.0 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) and ibuprofen (up to 1 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.
12. During COVID-19 pandemic: presence of high risk comorbidities: such as
cardiovascular, respiratory or immune system disorders
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:
a. < 2 weeks for topical treatment, e.g. retinoids, corticosteroids, vitamin D
analogs
b. < 4 weeks for phototherapy, e.g. PUVA, PDT
c. < 4 weeks for non-biologic systemic treatment, e.g. retinoids, methotrexate,
cyclosporine, fumaric acid esters
d. < 4 weeks for etanercept
e. < 8 weeks for adalimumab
f. < 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; during COVID-19 pandemic only
<= 18.0 or > 30.0 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) and ibuprofen (up to 1 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.
15. During COVID-19 pandemic: presence of high risk comorbidities: such as
cardiovascular, respiratory or immune system disorders other than psoriasis and
psoriasis arthritis
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2019-002383-27-NL |
| CCMO | NL70359.028.19 |