Risankizumab Long-term Remission Study

Study Overview
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Brief Summary
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Although the newly developed biologics (drugs derived from living cells cultured in a laboratory) are highly effective in controlling psoriasis, all the biologics should be continuously injected to suppress recurrence of the disease. In this regard, the observation in the phase II clinical trial conducted by us (Laboratory for Investigative Dermatology at the Rockefeller University) was groundbreaking that just a single dose of anti-IL-23p19 antibody (risankizumab, trade name: Skyrizi, study drug in this clinical trial) administration produced disease clearance up to 66 weeks in 46% (6 of 13) of patients. However, there is a lack of understanding about immune regulation in human skin induced by anti-IL-23p19 antibody injection, and there is a need to conduct a psoriasis clinical trial for single-cell sequencing immune cells in human psoriasis skin before and after anti-IL-23p19 antibody administration, and to correlate regulatory immune cell alterations with clinical disease progression. The overall objective of the clinical trial is to study regulatory immune cell alterations induced by anti-IL-23p19 antibody administration in psoriasis patients who achieve long-term disease clearance off drugs.

Detailed Description
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Although the newly developed biologics targeting IL-23/Th17 axis are highly effective in controlling psoriasis, all the biologics should be continuously injected to suppress recurrence of the disease. In this regard, the observation in our phase I psoriasis clinical trial was groundbreaking that just a single dose of anti-IL-23p19 antibody administration produced disease clearance up to 66 weeks in 46% (6 of 13) of patients. Since FoxP3 mRNA levels remained high in posttreatment biopsy specimens of these patients, we hypothesized that IL-23p19 inhibition increased regulatory T-cell levels or function in resolved psoriatic skin. However, there is a lack of understanding about regulatory immune cell promotion by IL-23p19 inhibition in human skin. Our overall objectives of the study, are to (i) identify regulatory immune cell alterations induced by anti-IL-23p19 antibody administration in the skin of patients whose psoriasis is cleared without recurrence and (ii) develop pre-treatment predictive models for psoriasis patients that anticipate disease clearance and recurrence after short-term anti-IL-23p19 antibody injection. The rationale for this project is that molecular evidence of immune tolerance induction by IL-23p19 inhibition in human skin is likely to offer a strong clinical framework whereby new strategies to prevent recurrence of chronic inflammatory diseases can be developed. In this study, subjects with moderate-to-severe psoriasis will receive FDA-approved anti-IL-23p19 antibody (Generic name: Risankizumab, Product name: SKYRIZI™ or risankizumab-rzaa) up to 4 months following the FDA-approved indications, usage, dosage, and administration in the FDA-approved dosage forms and strengths through week 16, after which, dosing stops.

Official Title
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Immune Modification of Psoriasis by Selective IL-23 Blockade Using Risankizumab

Conditions
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Psoriasis

Intervention / Treatment
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* Drug: Risankizumab-Rzaa
* Procedure: Punch biopsies of the skin at baseline visit
* Procedure: Punch biopsies of the skin at week 28 visit


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult males or females with a diagnosis of plaque psoriasis for at least 6 months. Baseline Psoriasis Area Severity Index (PASI) score > 12. More than 10% body surface area has plaque psoriasis involvement. Willingness to forgo other available psoriasis therapies, live vaccines, and pregnancy during the trial. Ability and willingness to provide informed consent and comply with study requirements. Exclusion Criteria: Non-plaque forms of psoriasis. Any previous treatment with agents targeting IL-12 or IL-23, including ustekinumab. Treatment with biologic agents within previous 3 months prior to visit 0, including adalimumab, etanercept, and infliximab. Treatment with immunosuppressive medications, including methotrexate, cyclosporine, oral retinoids, prednisone, or phototherapy within previous 4 weeks prior to visit 0. Topical psoriasis treatment within previous 2 weeks prior to visit 0, including topical corticosteroids, vitamin D analogues, retinoids, calcineurin inhibitors, salicylic acid, and coal tar. Any investigational study medication within previous 6 months prior to visit 0. History of recent or ongoing uncontrolled bacterial, viral, fungal, or other opportunistic infections. Positive QuantiFERON-TB Gold test. PPD tuberculin test may be substituted for QuantiFERON-TB Gold test. Receipt of a live vaccine (e.g., varicella, measles, mumps, rubella, cold-attenuated intranasal influenza vaccine, and smallpox) in the previous 6 weeks prior to visit 0. Females who are pregnant, lactating, planning on pregnancy during the study period, or unwilling to use a medically acceptable method of birth control. Severe, progressive, or uncontrolled renal, hepatic, hematological, gastrointestinal, pulmonary, cardiac, or neurological disease, or any other medical condition that, in the investigator's opinion, places the participant at risk by participating in this study. Any medical history, including laboratory results, deemed by the investigator to be likely to interfere with their participation in the study, or to interfere with the interpretation of the results, or any social condition that, in the opinion of the Investigator, might pose additional risk to the participant or confound the results of the study.

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
Intervention Model: Single Group Assignment
Interventional Model Description: The interventional study model is to treat moderate-to-severe psoriasis patients with risankizumab for 4 months and analyze pre- and post-treatment skin biopsy samples to (i) identify regulatory immune cell alterations induced by risankizumab administration in the skin of patients whose psoriasis is cleared without recurrence and (ii) develop pre-treatment predictive models for psoriasis patients that anticipate disease clearance and recurrence.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Psoriasis treatment with risankizumab<br>Moderate-to-severe psoriasis treatment with risankizumab for 16 weeks | Drug: Risankizumab-Rzaa<br>* Risankizumab at a dose of 150 mg with injections administered at baseline, week 4 and week 16 following FDA-approved dosage and time periods<br>* Other names: SKYRIZI;Procedure: Punch biopsies of the skin at baseline visit<br>* Two 6 mm punch biopsies of the skin at baseline visit<br>Procedure: Punch biopsies of the skin at week 28 visit<br>* One 6 mm punch biopsy of the skin at week 28 visit<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determination of regulatory immune cell changes induced by risankizumab | Changes of regulatory immune cell proportions in total immune cells harvested from the skin biopsy tissues of subjects who have a reduction of 90% or more from baseline in the Psoriasis Area and Severity Index (PASI; range from 0 to 72) at week 12 and also maintain the 90% reduction in PASI at week 52. | week 52 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Validation of predictive models that anticipate disease recurrence after risankizumab treatment | Sensitivity (range from 0 to 100%) and specificity (range from 0 to 100%) of statistical prediction models with single-cell genomic data from the skin biopsy tissues that predict subjects who have a reduction of 90% or more from baseline in the Psoriasis Area and Severity Index (PASI; range from 0 to 72) at week 12 and also maintain the 90% reduction in PASI at week 52. | week 52 | 

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