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

20 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing higher doses of risankizumab to see if it can better treat plaque psoriasis by removing immune cells that make the condition last longer. Risankizumab is a medication approved for the treatment of moderate-to-severe chronic plaque psoriasis.

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.

What data supports the effectiveness of the drug Risankizumab (Skyrizi) for treating psoriasis?

Research shows that Risankizumab is effective in treating moderate-to-severe plaque psoriasis, with patients experiencing significant improvements in skin condition and quality of life. Clinical trials have demonstrated that it works better than other treatments like placebo, ustekinumab, and adalimumab, and its benefits are maintained over the long term. ^{1 2 3 4 5}

Is risankizumab safe for humans?

Risankizumab, also known as Skyrizi, has been shown to be safe in humans based on multiple clinical trials for moderate-to-severe plaque psoriasis, with no serious safety issues reported. ^{2 3 5 6 7}

How is the drug Risankizumab unique for treating psoriasis?

Risankizumab is unique because it specifically targets the p19 subunit of interleukin-23 (IL-23), a protein involved in inflammation, making it highly effective for moderate-to-severe plaque psoriasis. It has shown superior results compared to other treatments like ustekinumab and adalimumab in clinical trials, with more patients achieving significant skin clearance. ^{1 2 3 5 6}

Research Team

Benjamin D Ehst, MD, PhD

Principal Investigator

Oregon Medical Research Center

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

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

2. New Zealand pubmed.ncbi.nlm.nih.gov

Risankizumab: First Global Approval. [2020]

3. England pubmed.ncbi.nlm.nih.gov

Long-term safety of risankizumab from 17 clinical trials in patients with moderate-to-severe plaque psoriasis. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Long-term, durable, absolute Psoriasis Area and Severity Index and health-related quality of life improvements with risankizumab treatment: a post hoc integrated analysis of patients with moderate-to-severe plaque psoriasis. [2022]

5. New Zealand pubmed.ncbi.nlm.nih.gov

Clinical Evaluation of Risankizumab-rzaa in the Treatment of Plaque Psoriasis. [2020]

6. United States pubmed.ncbi.nlm.nih.gov

Risankizumab for the Treatment of Moderate to Severe Plaque Psoriasis. [2020]

7. United States pubmed.ncbi.nlm.nih.gov

Risankizumab for the treatment of moderate-to-severe psoriasis: A multicenter, retrospective, 1 year real-life study. [2022]