High Dose Risankizumab for Psoriasis (KNOCKOUT)

• ClinicalTrials.gov Identifier: NCT05283135
• Recruitment Status: Active, not recruiting
• First Posted: March 16, 2022
• Last Update Posted: March 15, 2024
• Sponsor: Oregon Medical Research Center
• Collaborator: AbbVie
• Information provided by (Responsible Party): Oregon Medical Research Center

Tracking Information

• First Submitted Date: February 3, 2022
• First Posted Date: March 16, 2022
• Last Update Posted Date: March 15, 2024
• Actual Study Start Date: March 1, 2022
• Actual Primary Completion Date: December 1, 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 8, 2022)

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 [ Time Frame: Enrollment to Week 52 ]

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.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: March 8, 2022)

• 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. [ Time Frame: Enrollment to Week 52 ]
  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 [ Time Frame: Enrollment to Week 52 ]
  Safety events over 52 weeks in patients receiving 4X standard induction doses of risankizumab vs. those receiving 2X standard induction doses of risankizumab.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: High Dose Risankizumab for Psoriasis
• Official Title: Decreasing Resident Memory T Cells While Increasing Clinical Durability: Higher Induction Doses of Risankizumab for Moderate-to-severe Plaque Psoriasis
• 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).
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Triple (Participant, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Psoriasis

Intervention

Drug: risankizumab

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 Name: Skyrizi

Study Arms

• Experimental: risankizumab subcutaneous injection 600 mg (4x dosing) at Weeks 0, 4, and 16
  Intervention: Drug: risankizumab
• Experimental: risankizumab subcutaneous injection 300 mg (2x dosing) at Weeks 0, 4, and 16
  Intervention: Drug: risankizumab

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.
• 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;:
• 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.

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: March 8, 2022): 20
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: July 2024
• Actual Primary Completion Date: December 1, 2022 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT05283135
• Other Study ID Numbers: B20-433
• Has Data Monitoring Committee: Not Provided

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Oregon Medical Research Center
• Original Responsible Party: Same as current
• Current Study Sponsor: Oregon Medical Research Center
• Original Study Sponsor: Same as current
• Collaborators: AbbVie

Investigators

• Principal Investigator: Benjamin D Ehst, MD, PhD; Oregon Medical Research Center

• PRS Account: Oregon Medical Research Center
• Verification Date: March 2024