High Dose Risankizumab for Psoriasis (KNOCKOUT)
Primary Purpose
Psoriasis
Status
Active
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
risankizumab
Sponsored by
About this trial
This is an interventional treatment trial for Psoriasis focused on measuring Psoriasis, Risankizumab, Plaque, Skyrizi
Eligibility Criteria
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
Sites / Locations
- Oregon Medical Research Center
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
risankizumab subcutaneous injection 600 mg (4x dosing) at Weeks 0, 4, and 16
risankizumab subcutaneous injection 300 mg (2x dosing) at Weeks 0, 4, and 16
Arm Description
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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.
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.
Full Information
NCT ID
NCT05283135
First Posted
February 3, 2022
Last Updated
August 15, 2022
Sponsor
Oregon Medical Research Center
Collaborators
AbbVie
1. Study Identification
Unique Protocol Identification Number
NCT05283135
Brief Title
High Dose Risankizumab for Psoriasis
Acronym
KNOCKOUT
Official Title
Decreasing Resident Memory T Cells While Increasing Clinical Durability: Higher Induction Doses of Risankizumab for Moderate-to-severe Plaque Psoriasis
Study Type
Interventional
2. Study Status
Record Verification Date
August 2022
Overall Recruitment Status
Active, not recruiting
Study Start Date
March 1, 2022 (Actual)
Primary Completion Date
June 2023 (Anticipated)
Study Completion Date
December 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Oregon Medical Research Center
Collaborators
AbbVie
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
Brief Summary
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).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Psoriasis
Keywords
Psoriasis, Risankizumab, Plaque, Skyrizi
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
20 (Actual)
8. Arms, Groups, and Interventions
Arm Title
risankizumab subcutaneous injection 600 mg (4x dosing) at Weeks 0, 4, and 16
Arm Type
Experimental
Arm Title
risankizumab subcutaneous injection 300 mg (2x dosing) at Weeks 0, 4, and 16
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
risankizumab
Other Intervention Name(s)
Skyrizi
Intervention Description
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.
Primary Outcome Measure Information:
Title
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
Description
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.
Time Frame
Enrollment to Week 52
Secondary Outcome Measure Information:
Title
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.
Description
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.
Time Frame
Enrollment to Week 52
Title
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
Description
Safety events over 52 weeks in patients receiving 4X standard induction doses of risankizumab vs. those receiving 2X standard induction doses of risankizumab.
Time Frame
Enrollment to Week 52
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Andrew Blauvelt, MD, MBA
Organizational Affiliation
Oregon Medical Research Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Oregon Medical Research Center
City
Portland
State/Province
Oregon
ZIP/Postal Code
97223
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
30097359
Citation
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.
Results Reference
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PubMed Identifier
31280967
Citation
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. Erratum In: Lancet. 2019 Jul 16;:
Results Reference
background
PubMed Identifier
32267471
Citation
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.
Results Reference
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High Dose Risankizumab for Psoriasis
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