High Dose Risankizumab for Psoriasis

Study Overview
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Brief Summary
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This is a pilot study that explores whether higher initial doses of risankizumab (300 mg and 600 mg, 2 times and 4 times the standard initial doses for plaque psoriasis) can more effectively target resident memory T cells, a type of immune cell within psoriatic lesions, and whether this results in higher levels of completely clear skin and for longer periods of time following withdrawal of drug. It is believed that resident memory T cells in psoriatic skin contribute to the persistence of psoriasis. It is believed that if the study drug can more effectively eliminate these cells, better clearance of psoriasis may be achieved (when compared to standard initial doses of study drug).

Official Title
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Decreasing Resident Memory T Cells While Increasing Clinical Durability: Higher Induction Doses of Risankizumab for Moderate-to-severe Plaque Psoriasis

Conditions
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Psoriasis

Intervention / Treatment
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* Drug: risankizumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject has provided written consent Subject has the ability to comply with all study visits and procedures Subject is at least 18 years of age Subject has chronic stable plaque psoriasis for at least 6 months and with a severity of BSA greater than or equal to 10 and PASI greater than or equal to 12 Female subjects of child-bearing potential must have a negative urine test at screening and baseline. Female subjects must be either postmenopausal, or permanently surgically sterile, or for women of child-bearing potential practicing at least one form of birth control Exclusion Criteria: Breastfeeding or pregnant women, or women who plan to become pregnant during study period Participation in any other clinical trial Active infection with HIV, hepatitis B virus, or hepatitis C virus Active infection with tuberculosis or untreated latent tuberculosis History of known active cancer, other than non-melanoma skin cancer or cervical carcinoma in situ, in the past 3 years History of drug or alcohol abuse in the past 6 months, as per investigator's assessment History of suicidal ideation or attempts in the past 6 months Presence of any concurrent illness, which in the opinion of the investigator, would place the patient at unnecessary safety risk during the trial or interfere with completion of the trial Treatment with topical medications for psoriasis in the past 2 weeks Treatment with oral medications for psoriasis in the past 4 weeks Phototherapy for psoriasis in the past 4 weeks Any prior treatment with Risankizumab Treatment with biologic medications for psoriasis (other than Risankizumab) in the past 4 months

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: risankizumab subcutaneous injection 600 mg (4x dosing) at Weeks 0, 4, and 16<br> | Drug: risankizumab<br>* Risankizumab (Skyrizi) is an anti-IL-23 antibody being investigated for the treatment of multiple inflammatory diseases, including psoriasis, Crohn's disease, ulcerative colitis, and psoriatic arthritis.<br>* Other names: Skyrizi;|
| Experimental: risankizumab subcutaneous injection 300 mg (2x dosing) at Weeks 0, 4, and 16<br> | Drug: risankizumab<br>* Risankizumab (Skyrizi) is an anti-IL-23 antibody being investigated for the treatment of multiple inflammatory diseases, including psoriasis, Crohn's disease, ulcerative colitis, and psoriatic arthritis.<br>* Other names: Skyrizi;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Primary Endpoint: The number and effector function of epidermal CD8+CD103+ Trm cells at Week 52 (compared to baseline) in psoriasis patients treated with 4X standard induction doses of risankizumab or 2X standard induction doses of risankizumab | The number and effector function of epidermal CD8+CD103+ Trm cells at Week 52 (compared to baseline numbers) in psoriasis patients treated with 4X standard induction doses of risankizumab (600 mg at Weeks 0, 4, and 16) or 2X standard induction doses of risankizumab (300 mg at Weeks 0, 4, and 16). Please note, these are laboratory parameters that do not have units of measurement and will be reported together. | Enrollment to Week 52 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Secondary Endpoint 1: The percentage of patients with Psoriasis Area and Severity Index (PASI) 100 at Weeks 28, 40, and 52 in patients receiving 4X standard induction doses of risankizumab vs. those receiving 2X standard induction doses of risankizumab. | The percentage of patients with Psoriasis Area and Severity Index (PASI) 100 (complete clearance) at Weeks 28, 40, and 52 in patients receiving 4X standard induction doses of risankizumab vs. those receiving 2X standard induction doses of risankizumab. | Enrollment to Week 52 | 
| Secondary Endpoint 2: Safety events over 52 weeks in patients receiving 4X standard induction doses of risankizumab vs. those receiving 2X standard induction doses of risankizumab | Safety events over 52 weeks in patients receiving 4X standard induction doses of risankizumab vs. those receiving 2X standard induction doses of risankizumab. | Enrollment to Week 52 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Psoriasis, Risankizumab, Plaque, Skyrizi