High Dose Risankizumab for Psoriasis

(KNOCKOUT Trial)

Overseen By Molly Blauvelt

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Oregon Medical Research Center

Must not be taking: Topical medications, Oral medications, Biologics

Disqualifiers: HIV, Hepatitis, Cancer, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 16 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests higher doses of the drug risankizumab (also known as Skyrizi) to determine if it can more effectively clear plaque psoriasis, a skin condition that causes itchy, red patches. Researchers aim to discover how these doses affect specific immune cells in the skin. Participants will receive risankizumab injections at varying strengths to compare results. The trial seeks individuals who have had chronic plaque psoriasis for at least six months and have not found success with other treatments. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial requires that you stop taking topical medications for psoriasis 2 weeks before, oral medications for psoriasis 4 weeks before, and biologic medications for psoriasis (other than Risankizumab) 4 months before joining the study.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that risankizumab is generally safe for treating psoriasis. Studies have monitored patients using risankizumab for up to five years and found it well-tolerated, with no new safety issues. Common side effects include mild upper respiratory infections, headaches, tiredness, and injection site reactions, occurring in less than 1% of users. This study examines higher doses, but current evidence suggests risankizumab is safe for long-term use. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatments for psoriasis, which often involve topical applications or systemic therapies like methotrexate and cyclosporine, risankizumab targets a specific part of the immune system known as interleukin-23 (IL-23). This targeted approach can potentially lead to better control of the inflammatory process that causes psoriasis, with fewer side effects. Researchers are particularly excited about the high doses being tested — 300 mg and 600 mg — as they may offer more robust and quicker results compared to existing options. This could mean more effective relief for patients with moderate to severe psoriasis.

What evidence suggests that high-dose risankizumab might be an effective treatment for psoriasis?

Research shows that risankizumab effectively treats plaque psoriasis. Studies have found that a standard dose of 150 mg can significantly improve skin and reduce symptoms for many people. In this trial, participants will receive either a 300 mg or 600 mg dose of risankizumab. Previous studies demonstrated that these higher doses quickly reduce certain immune cells contributing to psoriasis. Additionally, risankizumab has kept skin clearer for longer periods. Overall, evidence supports its effectiveness, especially with higher doses. ^{3 6 7 8 9}

Who Is on the Research Team?

Benjamin D Ehst, MD, PhD

Principal Investigator

Oregon Medical Research Center

Are You a Good Fit for This Trial?

This trial is for adults with chronic stable plaque psoriasis, having a body surface area (BSA) involvement of at least 10% and a Psoriasis Area Severity Index (PASI) score of 12 or more. Participants must be able to follow the study plan and women should use birth control if they can have children. People who've had certain treatments recently, those with other serious illnesses, drug or alcohol abuse history, suicidal behavior in the past six months, active infections like HIV or tuberculosis, pregnant or breastfeeding women cannot join.

Inclusion Criteria

I am a woman who cannot become pregnant, confirmed by tests or because I am postmenopausal, surgically sterile, or using birth control.

Subject has provided written consent

Subject has the ability to comply with all study visits and procedures

Exclusion Criteria

I have previously been treated with Risankizumab.

I have not had any active cancer except for skin or cervical cancer in the last 3 years.

I have taken biologic medications for psoriasis, but not Risankizumab, in the last 4 months.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive risankizumab subcutaneous injections at Weeks 0, 4, and 16 with either 300 mg or 600 mg doses

16 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment, with assessments at Weeks 28, 40, and 52

36 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Risankizumab

Trial Overview The study tests whether higher initial doses of risankizumab (300 mg and 600 mg) are more effective than standard doses at clearing skin by targeting immune cells called resident memory T cells in psoriatic lesions. The goal is to see if this leads to completely clear skin that lasts longer after stopping treatment.

How Is the Trial Designed?

Group I: risankizumab subcutaneous injection 600 mg (4x dosing) at Weeks 0, 4, and 16 Experimental Treatment 1 Intervention

Group II: risankizumab subcutaneous injection 300 mg (2x dosing) at Weeks 0, 4, and 16 Experimental Treatment 1 Intervention

Risankizumab is already approved in Canada, United States, European Union for the following indications:

Approved in Canada as Skyrizi for:

• Moderate-to-severe Crohn's disease

Approved in United States as Skyrizi for:

• Moderate-to-severe Crohn's disease
• Moderate-to-severe plaque psoriasis

Approved in European Union as Skyrizi for:

• Moderate-to-severe Crohn's disease
• Moderate-to-severe plaque psoriasis
• Psoriatic arthritis

Who Is Running the Clinical Trial?

Oregon Medical Research Center

Lead Sponsor

Trials

1

Recruited

20+

AbbVie

Industry Sponsor

Trials

1,079

Recruited

535,000+

Founded

2013

Headquarters

North Chicago, USA

Known For

Immunology treatments

Top Products

Humira (adalimumab), Skyrizi (risankizumab), Rinvoq (upadacitinib)

Dr. Roopal Thakkar

AbbVie

Chief Medical Officer since 2023

MD from Wayne State University School of Medicine

Robert A. Michael

AbbVie

Chief Executive Officer

Bachelor's degree in Finance from the University of Illinois

Published Research Related to This Trial

Risankizumab, a monoclonal antibody targeting IL-23, received its first global approval in March 2019 in Japan for treating various forms of psoriasis, including psoriasis vulgaris and psoriatic arthritis.

The drug is currently approved in multiple regions, including the USA and EU, for moderate-to-severe plaque psoriasis and is undergoing further clinical trials for other conditions like Crohn's disease and ulcerative colitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risankizumab: First Global Approval. McKeage, K., Duggan, S.[2020]

Risankizumab-rzaa (Skyrizi®) is an effective treatment for moderate-to-severe psoriasis, as demonstrated in four pivotal Phase III trials involving adult patients, showing both efficacy and safety.

The drug works by targeting interleukin-23p19 (IL-23p19), a key player in the inflammatory process of psoriasis, which helps reduce the symptoms of the disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Evaluation of Risankizumab-rzaa in the Treatment of Plaque Psoriasis. Reddy, V., Yang, EJ., Myers, B., et al.[2020]

Risankizumab is a monoclonal antibody that effectively targets IL-23, showing superior efficacy compared to placebo and other treatments like ustekinumab and adalimumab in pivotal phase III trials involving adults with moderate to severe plaque psoriasis.

In long-term studies, risankizumab demonstrated durable efficacy and improved quality of life for patients, with a favorable safety profile over more than 2.5 years of continuous treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risankizumab: A Review in Moderate to Severe Plaque Psoriasis. Blair, HA.[2021]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05283135

NCT05283135 | High Dose Risankizumab for Psoriasis 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 ...

2. skyrizihcp.com skyrizihcp.com/dermatology/psoriasis-efficacy

SKYRIZI® Efficacy In Moderate to Severe Plaque Psoriasis ... The efficacy and safety of SKYRIZI (150 mg) vs placebo over 16 weeks and biologic active control (45 mg or 90 mg, based on screening weight) over 52 weeks.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12436474/

Final LIMMitless Phase 3, Open-Label Extension Trial Results In previous interim analyses of patients after 3 and 5 years of treatment, risankizumab 150 mg was well tolerated and demonstrated sustained and ...

4. skyrizihcp.com skyrizihcp.com/gastroenterology/crohns-disease/efficacy

Efficacy Data - SKYRIZI® (risankizumab-rzaa) for Crohn's Results at 52 weeks are among 382 patients who achieved clinical response‡ after 12 weeks of treatment with SKYRIZI in induction trials. bContinuous placebo ...

5. hcplive.com hcplive.com/view/risankizumab-dose-clears-psoriasis-resident-memory-cells

High Risankizumab Induction Dose Rapidly Clears ... Data from the phase 2 KNOCKOUT study show risankizumab's sustained benefit in reducing memory cells over 52 weeks in psoriasis patients.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11393270/

Long-Term Safety of Risankizumab in Patients with ... The results support the favourable safety profile of risankizumab for long-term treatment of psoriatic disease with no new safety concerns.

7. skyrizihcp.com skyrizihcp.com/dermatology/pso-psa-safety-profile

SAFETY PROFILE ESTABLISHED IN Ps AND PsA 1 Most common adverse reactions (≥1%) associated with SKYRIZI include upper respiratory infections, headache, fatigue, injection site reactions, and tinea ...

8. sciencedirect.com sciencedirect.com/science/article/pii/S0190962223024167

Long-term safety and efficacy of risankizumab for the ... Long-term continuous risankizumab treatment for up to 5 years was well tolerated and demonstrated high and durable efficacy.

9. news.abbvie.com news.abbvie.com/2020-06-12-AbbVie-Presents-New-Late-Breaking-Data-Showing-SKYRIZI-R-risankizumab-rzaa-Achieves-Superior-Rates-of-Complete-Skin-Clearance-Versus-COSENTYX-R-secukinumab-at-52-Weeks

Jun 12, 2020 Particularly, 66 percent of psoriasis patients receiving SKYRIZI achieved completely clear skin—100 percent clearance in the Psoriasis Area and ...