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

Prior treatment

• Participant has had, or is planning, a major surgery within 8 weeks prior to baseline (except minor minimally invasive procedures).
• 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.
• Participant has used biologic medication 12 weeks prior to baseline visit (Day 0), or 5 half-lives (whichever is longer).
• 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.
• 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.
• Participant had psoralen and ultraviolet A or narrowband ultraviolet B treatment within 4 weeks prior to baseline.
• 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.
• Other psoriasis subtype that according to investigator may influence any assessments (erythrodermic, guttate, pustular, inverse, drug-induced).

Other illness

• A history of malignancies within the past five years (excluding localized nonmelanoma skin cancer).
• Known hypersensitivity to any ingredient in the IMP or to components of the container.
• Participant has a history of an allergic reaction or significant sensitivity to lidocaine or other local anesthetics.
• History of keloid formation or hypertrophic scarring in suture sites or scars.
• 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.
• History of intravenous drug use.
• 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.
• Infectious skin lesions on treated areas (e.g., herpes, varicella, fungal, bacterial, and parasitic skin infections, skin manifestations in relation to tuberculosis).
• Active or latent tuberculosis requiring treatment.
• 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.
• 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.

Lab values

• 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.

Age

• Age <18.

Other

• Participant has a contraindication to skin biopsies.
• Female participant who is breastfeeding, pregnant, or who is planning pregnancy during the study period.
• Participant protected by the law (adult under guardianship or hospitalized in a public or private institution for a reason other than study, or incarcerated).
• Mental or linguistic incapacity to sign the consent form.
• 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.

• History of plaque psoriasis.
• 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).
• 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.