What side effects are associated with this type of intervention?

Common treatments for psoriasis, such as TNF-alpha inhibitors, IL-17 inhibitors, and IL-23 inhibitors like Risankizumab, have various side effects. TNF-alpha inhibitors can reduce the risk of myocardial infarction but may cause infections and injection site reactions. IL-17 inhibitors, such as secukinumab and ixekizumab, are associated with infections, including upper respiratory infections, and may exacerbate inflammatory bowel disease. Risankizumab, an IL-23 inhibitor, can cause upper respiratory infections, headache, arthralgia, and potential liver injury. Monitoring for infections and liver function is recommended with these treatments.

What prior FDA approvals exist?

The FDA has approved several biologic agents for the treatment of moderate to severe psoriasis, particularly those targeting interleukin pathways. Risankizumab, an IL-23 inhibitor, is one such drug. Other similar biologics include Ustekinumab, which targets IL-12/23, and Secukinumab and Ixekizumab, which target IL-17. These agents have shown efficacy in reducing the symptoms of psoriasis by modulating the immune response involved in the disease's pathogenesis.

What other types of research exist?

Promising alternatives to Risankizumab for psoriasis treatment include: 1) Ixekizumab (anti-IL-17A), which has shown long-term efficacy in erythrodermic and generalized pustular psoriasis. 2) Secukinumab (anti-IL-17A), which has demonstrated high efficacy and a favorable safety profile in both plaque and erythrodermic psoriasis. 3) Guselkumab (anti-IL-23), which has shown efficacy and safety in generalized pustular and erythrodermic psoriasis. 4) Brodalumab (anti-IL-17 receptor), which has shown positive results in generalized pustular psoriasis and psoriatic erythroderma.

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Monoclonal Antibodies

High Dose Risankizumab for Psoriasis (KNOCKOUT Trial)

Phase 2

Waitlist Available

Led By Andrew Blauvelt, MD, MBA

Research Sponsored by Oregon Medical Research Center

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

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

Must not have

Any prior treatment with Risankizumab

History of known active cancer, other than non-melanoma skin cancer or cervical carcinoma in situ, in the past 3 years

Timeline

Screening 3 weeks

Treatment Varies

Follow Up enrollment to week 52

Awards & highlights

All Individual Drugs Already Approved

Approved for 5 Other Conditions

No Placebo-Only Group

Summary

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.

Who is the study for?

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.

What is being tested?

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.

What are the potential side effects?

Risankizumab may cause side effects such as infections due to lowered immunity, allergic reactions where the medicine is injected into the skin, headaches, fatigue and digestive issues. It's important for participants to report any unusual symptoms they experience during the trial.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I am 18 years old or older.

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I have had stable plaque psoriasis for over 6 months, covering more than 10% of my body.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have previously been treated with Risankizumab.

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

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

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I have had light therapy for psoriasis in the last month.

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I have not had thoughts or attempts of suicide in the last 6 months.

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I do not have an active infection with HIV, hepatitis B, or hepatitis C.

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I do not have an active or untreated latent tuberculosis infection.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ enrollment to week 52

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~enrollment to week 52

This trial's timeline: 3 weeks for screening, Varies for treatment, and enrollment to week 52 for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

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

Secondary study objectives

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.

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

Side effects data

From 2020 Phase 3 trial • 18 Patients • NCT03022045

25%

Urticaria

25%

Erythema

25%

Viral upper respiratory tract infection

25%

Aspartate aminotransferase increased

25%

Gamma-glutamyltransferase increased

25%

Rash

25%

Osteoarthritis

25%

Hepatic function abnormal

25%

Alanine aminotransferase increased

25%

Intervertebral disc protrusion

100%

80%

60%

40%

20%

Study treatment Arm

GPP Risankizumab 75 mg

EP Risankizumab 150 mg

GPP Risankizumab 150 mg

EP Risankizumab 75 mg

Awards & Highlights

All Individual Drugs Already Approved

Therapies where all constituent drugs have already been approved are likely to have better-understood side effect profiles.

Approved for 5 Other Conditions

This treatment demonstrated efficacy for 5 other conditions.

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

2Treatment groups

Experimental Treatment

Group I: risankizumab subcutaneous injection 600 mg (4x dosing) at Weeks 0, 4, and 16Experimental Treatment1 Intervention

Group II: risankizumab subcutaneous injection 300 mg (2x dosing) at Weeks 0, 4, and 16Experimental Treatment1 Intervention

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Isopropyl alcohol

FDA approved

0 / 9Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Psoriasis treatments often target specific components of the immune system to reduce inflammation and skin cell proliferation. Biologic agents, such as Interleukin-23 (IL-23) inhibitors like Risankizumab, work by blocking the action of IL-23, a cytokine involved in the inflammatory process of psoriasis. By inhibiting IL-23, these treatments can reduce the activity of T-helper 17 (Th17) cells, which are responsible for producing other inflammatory cytokines that contribute to the symptoms of psoriasis. This targeted approach is significant for patients as it can lead to more effective and sustained clearance of psoriatic lesions with potentially fewer side effects compared to broader immunosuppressive therapies.