High Dose Risankizumab for Psoriasis (KNOCKOUT)
October 9, 2025 updated by: Oregon Medical Research Center
Decreasing Resident Memory T Cells While Increasing Clinical Durability: Higher Induction Doses of Risankizumab for Moderate-to-severe Plaque Psoriasis
This pilot study explores higher than standard doses of risankizumab for plaque psoriasis, to see effects on resident memory T cells and skin clearance.
Study Overview
Detailed Description
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).
Study Type
Interventional
Enrollment (Actual)
20
Phase
- Phase 2
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Oregon
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Portland, Oregon, United States, 97201
- Oregon Medical Research Center
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
14 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Description
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
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Triple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
|---|---|
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Experimental: risankizumab subcutaneous injection 600 mg (4x dosing) at Weeks 0, 4, and 16
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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.
Other Names:
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Experimental: risankizumab subcutaneous injection 300 mg (2x dosing) at Weeks 0, 4, and 16
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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.
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
CD8+ Trm1 Cells in Lesional Skin at Baseline and Week 52
Time Frame: 52 weeks
|
The number of lesional CD8+ Trm1 cells at baseline and Week 52 was calculated by longitudinal single-cell RNA-sequencing of full-thickness skin biopsy samples.
Uniform Manifold Approximation Projection (UMAP) was used for T cell subtype visualization and CD8+ Trm1 cells were identified as IFNγ+/CD8+/CD69+ T cells.
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52 weeks
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CD8+ Trm17 Cells in Lesional Skin at Baseline and Week 52
Time Frame: 52 weeks
|
The number of lesional CD8+ Trm17 cells at baseline and Week 52 was calculated by longitudinal single-cell RNA-sequencing of full-thickness skin biopsy samples.
Uniform Manifold Approximation Projection (UMAP) was used for T cell subtype visualization and CD8+ Trm17 cells were identified as IFNγ+/CD8+/CD69+ T cells.
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52 weeks
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
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PASI 100 Results in Patients Receiving 4X Standard Induction Doses of Risankizumab vs. Those Receiving 2X Standard Induction Doses of Risankizumab.
Time Frame: Enrollment to Week 52
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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.
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Enrollment to Week 52
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Safety Events
Time Frame: Enrollment to Week 52
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Safety events over 52 weeks in patients receiving 4X standard induction doses of risankizumab vs. those receiving 2X standard induction doses of risankizumab.
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Enrollment to Week 52
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Collaborators
Investigators
- Principal Investigator: Benjamin D Ehst, MD, PhD, Oregon Medical Research Center
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
General Publications
- Gordon KB, Strober B, Lebwohl M, Augustin M, Blauvelt A, Poulin Y, Papp KA, Sofen H, Puig L, Foley P, Ohtsuki M, Flack M, Geng Z, Gu Y, Valdes JM, Thompson EHZ, Bachelez H. Efficacy and safety of risankizumab in moderate-to-severe plaque psoriasis (UltIMMa-1 and UltIMMa-2): results from two double-blind, randomised, placebo-controlled and ustekinumab-controlled phase 3 trials. Lancet. 2018 Aug 25;392(10148):650-661. doi: 10.1016/S0140-6736(18)31713-6. Epub 2018 Aug 7.
- Blauvelt A, Leonardi CL, Gooderham M, Papp KA, Philipp S, Wu JJ, Igarashi A, Flack M, Geng Z, Wu T, Camez A, Williams D, Langley RG. Efficacy and Safety of Continuous Risankizumab Therapy vs Treatment Withdrawal in Patients With Moderate to Severe Plaque Psoriasis: A Phase 3 Randomized Clinical Trial. JAMA Dermatol. 2020 Jun 1;156(6):649-658. doi: 10.1001/jamadermatol.2020.0723.
- Reich K, Gooderham M, Thaci D, Crowley JJ, Ryan C, Krueger JG, Tsai TF, Flack M, Gu Y, Williams DA, Thompson EHZ, Paul C. Risankizumab compared with adalimumab in patients with moderate-to-severe plaque psoriasis (IMMvent): a randomised, double-blind, active-comparator-controlled phase 3 trial. Lancet. 2019 Aug 17;394(10198):576-586. doi: 10.1016/S0140-6736(19)30952-3. Epub 2019 Jul 4.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
March 1, 2022
Primary Completion (Actual)
August 7, 2023
Study Completion (Actual)
July 10, 2024
Study Registration Dates
First Submitted
February 3, 2022
First Submitted That Met QC Criteria
March 8, 2022
First Posted (Actual)
March 16, 2022
Study Record Updates
Last Update Posted (Estimated)
October 24, 2025
Last Update Submitted That Met QC Criteria
October 9, 2025
Last Verified
October 1, 2025
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- B20-433
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
NO
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Yes
Studies a U.S. FDA-regulated device product
No
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