Molecular effects of deucravacitinib on plaque psoriasis and hard-to-treat psoriasis sites.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Charite Universitaetsmedizin Berlin KöR

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Skin and Connective Tissue Diseases [C17]

Trial duration

completed 5 May 2025

Decision date (initial)

2025-01-17

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2023-508948-22-00

WHO UTN

U1111-1303-4802

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

Assess the immunological response based on the gene expression signature in classic and hard to-treat plaques comparing baseline with 16 weeks of treatment

Secondary objectives 7

1. Assess the effects of TYK2 inhibition at baseline (before treatment) and at weeks 4 and 16 in comparison to healthy controls.
2. Assess the immune cell infiltrate by immune histochemistry
3. Assess keratinocyte proliferation and the extent of hyperplasia by immune histochemistry
4. Evaluate the phosphorylation state of the signal transducer and activator of transcription
5. Investigate the frequency and activation state of T cells and monocytes in peripheral blood by flow cytometry
6. Assess the therapeutic success of Sotyktu® in moderate to severe plaque psoriasis
7. Assess patient-reported outcomes

Conditions and MedDRA coding

moderate to severe plaque psoriasis

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. Patient has been prescribed the drug Sotyktu in routine clinical practice
2. Prescription is independent of the study
3. Subjects is willing to participate in the study and sign the informed consent form (ICF)
4. Men or women, ≥18 years old
5. The patient has moderate to severe psoriasis as defined by the German S3 guideline, characterized by: a. Body-surface area (BSA) of 10% or more and Dermatological Life Quality Index (DLQI) score of 10 or higher, OR b. Psoriasis Area and Severity Index (PASI) score of 10 or higher and Dermatological Life Quality Index (DLQI) score of 10 or higher, OR c. Meeting any of the following upgrade criteria according to the German S3 guidelines for systemic treatment: i. Severe disease in visual areas, ii. Severe disease of the scalp, iii. Genital psoriasis, iv. Palmoplantar psoriasis, v. Onycholysis or onychodystrophy of at least 2 fingernails, vi. Experience pruritus and associated itching, vii. Therapy-resistant plaques.
6. Patient has a disease history of 6 months or longer
7. In addition to plaque psoriasis, disease manifestation is present at at least one hard-to-treat area body site (scalp, palmoplantar (non-pustular) or inverse) with a minimum total plaque size of 2x2cm. Multiple smaller lesions may add up to that size. Biopsies of the hands are preferred over biopsies taken from feet.

Exclusion criteria 22

1. Participation in any other clinical trial or treatment with investigational medicinal products (IMPs) or previous therapies with known or potential overlapping toxicities with the IMP and its relevant metabolites, within a period equivalent to five times the half-life of the IMP or its relevant metabolites (whichever is longer) prior to screening.
2. Patient has permanent severe diseases, especially those affecting the immune system other than psoriasis • (Example: Systemic lupus erythematodes, autoimmune blistering diseases (AIBD), myasthenia gravis, multiple sclerosis, seropositive rheumatoid arthritis, Crohn´s disease, ulcerative colitis)
3. Patient has pustular psoriasis or other forms of psoriasis • Exception: plaques, palmoplantar, inverse and scalp
4. History of lymphoproliferative disorders
5. Patients is considered potentially unreliable or may not consistently attend scheduled study visits
6. History of allergy to any component of deucravacitinib
7. Patients has prior exposure to deucravacitinib or other JAK-inhibitors
8. Patients has prior exposure to more than one biologic
9. Patients has prior exposure to systemic treatments targeting IL-23 or IL-12
10. Patients receiving biologics (IL-17) within 3 months of first visit of study
11. Patients receiving biologics (TNF-alpha) within 3 months of first visit of study
12. Patients receiving any systemic immunosuppressants or anakinra within 4 weeks of the first visit of the study • Example immunosuppressants: MTX, azathioprine, cyclosporine, 6-thioguanine, mercaptopurine, mycophenolate mofetil, hydroxyurea and tacrolimus
13. Patients receiving phototherapy or any systemic medications/treatments that could affect psoriasis or PGA evaluation within 4 weeks of the first visit of the study • Including, but not limited to, oral or injectable corticosteroids, retinoids, 1,25dihydroxy vitamin D3 and analogues, psoralens, sulfasalazine, hydroxyurea, or fumaric acid derivatives
14. Patients receiving topical medications/treatments that could affect psoriasis or PGA evaluation • Including, but not limited to, corticosteroids, anthralin, calcipotriene, topical vitamin D derivatives, retinoids, tazarotene, methoxsalen, trimethylpsoralens, pimecrolimus, and tacrolimus. within 2 weeks of the first visit of the study
15. Patient is deprived of freedom, detained or commited to psychiatric ward, prison or state institution by court or legal authority
16. Patient has at least one parameter of blood works outside of defined range at screening • Absolute white blood cell count <3000/mm3 • Absolute lymphocyte count <500/mm3 • Absolute neutrophil count <1000/mm3 • Platelet count <100,000/mm3 • Hemoglobin <9 g/dL • Renal impairment based on an estimated glomerular filtration rate <45 mL/min • Alanine and/or aspartate aminotransferase >3 × upper limit of normal (ULN)
17. Patient has allergies to local anesthetics
18. Pateint has a dependence on the sponsor
19. Pregnant or breastfeeding women
20. Female subjects of childbearing potential who are not using a highly effective method of contraception as recommended by the “CTCG Recommendations related to contraception and pregnancy testing in clinical trials, Version 1.2."
21. Subjects who are unwilling or unable to comply with the pregnancy testing requirements during the study period
22. Contraindications to Deucravacitinib: • a. Known hypersensitivity to Deucravacitinib or any of its excipients, • b. Active tuberculosis, untreated latent tuberculosis, or serious chronic infections, • c. Active or chronic hepatitis B or C, or HIV infection, • d. Severe hepatic impairment, • e. Severe renal impairment (glomerular filtration rate <30 mL/min), • f. History of malignancies, including lymphoproliferative disorders, except successfully treated non-metastatic basal cell carcinoma, squamous cell carcinoma of the skin, or carcinoma in situ of the cervix, • g. Use of live vaccines within 4 weeks prior to baseline or planned during the trial.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary endpoint is a change in the expression of the genes IL-17A, IL-17F, IL-22, ß-defensin4A/b and KRT16 compared to baseline in both the classic and hard-to-treat plaques following the treatment with 6 mg Sotyktu® QD for 16 weeks.

Secondary endpoints 7

1. • based on the expression of IL-17A, IL-17F, IL-19, IL-22, and IL-36A, the interleukin receptor IL-23R as well as ß-defensine-2 (DEFB4A/B), S100A8/9, KRT16, OASL, MX1, CXCL10, iNOS, CXCR3 and CCL20 as well as IL-31.
2. • CD3 • CD4 • CD11c.
3. • Ki67 • KRT16 • H&E
4. • STAT-1, • STAT-3 • STAT-4 • STAT-5
5. • Th1 • Th2 • Th17 • Th17.1 • Treg • DCs • MDSCs
6. • overall PASI • body site specific local PASI • inverse • scalp • palmoplantar
7. • Overall • pruritus, pain NRS

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 8

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Charite Universitaetsmedizin Berlin KöR

Sponsor organisation

Charite Universitaetsmedizin Berlin KöR

Address

Chariteplatz 1, Mitte Mitte

City

Berlin

Postcode

10117

Country

Germany

Scientific contact point

Organisation

Charite Universitaetsmedizin Berlin KöR

Contact name

Psoriasis-Forschungs- und BehandlungsCentrum (PFBC)

Public contact point

Organisation

Charite Universitaetsmedizin Berlin KöR

Contact name

Psoriasis-Forschungs- und BehandlungsCentrum (PFBC)

Third parties 2

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 12 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications