Investigation of tissue-resident memory T-cells and disease MEMory in psoriasis during GUSelkumab treatment. The GUSMEM study.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Aarhus University Hospital

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

19 Jun 2023 → ongoing

Decision date (initial)

2023-04-28

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Janssen-Cilag AS as a grant to an investigator initiated study

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacodynamic

The main aim of the project is to investigate whether guselkumab treatment can change the quantity of TRMs in the skin as well as change the protein expression in the microenvironment around these cells in psoriasis patients.

Secondary objectives 1

1. In addition, we will investigate whether the treatment changes the quantity and type of other psoriasis-related cells in the skin.

Conditions and MedDRA coding

Psoriasis vulgaris

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 3

1. History of plaque psoriasis.
2. One target lesion of ~4 cm at its longest axis located on the body (except for the scalp, face, or intertriginous areas), scoring at least 1 for each of redness, thickness, and scaliness on the target plaque severity score (TPSS).
3. Women involved in any sexual intercourse that could lead to pregnancy must agree to use a highly effective contraceptive method from at least 4 weeks before baseline (visit 2). Effective contraceptive methods are: Systemic hormonal contraceptives (oral contraceptive, transdermal patches, vaginal rings, long-acting injectables, or implants), intrauterine devices, vasectomy. This must be used until 12 weeks after EOT. Hormonal contraceptives must be on a stable dose for at least 4 weeks before baseline (visit 2). Women of nonchildbearing potential are as follows: i. Women ≥60 years of age. ii. Women who have had surgical sterilization (hysterectomy, bilateral oophorectomy, bilateral salpingectomy, or bilateral tubal ligation) iii. Women >40 and <60 years of age who have had a cessation of menses for at least 12 months and a follicle-stimulating hormone (FSH) test confirming nonchildbearing potential (FSH ≥40 mIU/mL) or cessation of menses for at least 24 months without FSH levels confirmed. A negative serum pregnancy test at screening and a negative urine pregnancy test at baseline (visit 2) must be presented by women of childbearing potential.

Exclusion criteria 26

1. Age <18.
2. Female participant who is breastfeeding, pregnant, or who is planning pregnancy during the study period.
3. History of concomitant skin disease or presence of skin condition that, in the opinion of the investigator, would interfere with the study assessments and the acquisition of biopsies.
4. Infectious skin lesions on treated areas (e.g., herpes, varicella, fungal, bacterial, and parasitic skin infections, skin manifestations in relation to tuberculosis).
5. Treated skin must not be affected by perioral dermatitis, striae atrophicae, atrophic skin, fragility of skin veins, ichthyosis, acne vulgaris, acne rosacea, rosacea, ulcers, and wounds.
6. Active or latent tuberculosis requiring treatment.
7. History of any known primary immunodeficiency disorder including a positive human immunodeficiency virus (HIV) test at screening, or the subject taking antiretroviral medications as determined by medical history and/or subject’s verbal report.
8. No history of varicella zoster infection and negative varicella antibody test (until varicella vaccination is completed), positive hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (HBsAb), hepatitis B core antibody (HBcAb), or hepatitis C virus antibody (anti-HCV) serology at screening.
9. Other psoriasis subtype that according to investigator may influence any assessments (erythrodermic, guttate, pustular, inverse, drug-induced).
10. History or presence of signs or symptom of progressive or uncontrollable infectious, endocrine, neurological, renal, hepatic, cardiac, vascular, pulmonary, gastrointestinal, hematological rheumatological, psychiatric or metabolic disturbance and/or abnormal blood test or vital signs other paraclinical information, including disorders of calcium metabolism, that, in the opinion of the investigator, may expose the patient to elevated or unnecessary risk or interfere with the interpretation of results.
11. A history of malignancies within the past five years (excluding localized nonmelanoma skin cancer).
12. Known hypersensitivity to any ingredient in the IMP or to components of the container.
13. Participant has had, or is planning, a major surgery within 8 weeks prior to baseline (except minor minimally invasive procedures).
14. Participant has a contraindication to skin biopsies.
15. Participant is currently receiving an investigational product or device or has received one within 4 weeks prior to baseline, that in the opinion of the investigator, might interfere with the results.
16. Participant has used biologic medication 12 weeks prior to baseline visit (Day 0), or 5 half-lives (whichever is longer).
17. Use of any systemic treatment for psoriasis (such as methotrexate, immunosuppressive drugs, corticosteroids, azathioprine, or cyclosporine) within 4 weeks prior to baseline and during the study.
18. Use of any topical medication to treat psoriasis (including salicylic acid, retinoid, calcineurin inhibitors, corticosteroids, vitamin D analogue, or tar) within 2 weeks prior to baseline. Use of moisturizers and emollients are not exclusion criteria.
19. Participant had psoralen and ultraviolet A or narrowband ultraviolet B treatment within 4 weeks prior to baseline.
20. Participant has a history of an allergic reaction or significant sensitivity to lidocaine or other local anesthetics.
21. History of keloid formation or hypertrophic scarring in suture sites or scars.
22. Known inability or unavailability of a participant to complete required study visits during study participation including any condition associated with poor compliance as judged by the investigator.
23. History of intravenous drug use.
24. A psychiatric condition (e.g., suicidal ideation) or chronic alcohol or drug abuse problem, determined from the participant’s medical history, which, in the opinion of the investigator, may obstruct compliance.
25. Participant protected by the law (adult under guardianship or hospitalized in a public or private institution for a reason other than study, or incarcerated).
26. Mental or linguistic incapacity to sign the consent form.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Change in the protein expression using DSP in the microenvironment surrounding TRMs in the epidermis. The following markers in combination will be used to differentiate TRMs: CD3, CD4, CD8, CD103.
2. Change in the number of TRMs in the epidermis and dermis between baseline and EOT using IHC. The following markers in combination will be used to differentiate cells: CD3, CD4, CD8, CD103.

Secondary endpoints 9

1. Change in CD11c+ Dendritic cells over the study duration.
2. Change in CD163+ Macrophages over the study duration.
3. Change in Langerin+/CD207+ Langerhans-cells over the study duration.
4. Change in Myeloperoxidase+ Neutrophils over the study duration.
5. Change in CD4+/FOXP3+ single and double positive cells over the study duration.
6. Change in CD103/RORγt single and double positive cells over the study duration.
7. Change in CD3+, CD4+, CD8+, CD49a+, CD69+, and CD103+ multiple, or single positive cells over the study duration.
8. Change in proliferation assessed using Ki67+ staining over the study duration.
9. Change in epidermal thickness over the study duration.

Investigational products

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

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Aarhus University Hospital

Sponsor organisation

Aarhus University Hospital

Address

Palle Juul-Jensens Boulevard 99

City

Aarhus N

Postcode

8200

Country

Denmark

Scientific contact point

Organisation

Aarhus University Hospital

Contact name

Christian Vestergaard

Public contact point

Organisation

Aarhus University Hospital

Contact name

Christian Vestergaard

Third parties 1

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

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

Documents 15 files

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

Application history

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