Safety and Efficacy of Secukinumab in Mild Psoriasis

James G. Krueger, MD, PhD23 enrolled

Overview

Mild psoriasis not only progresses to moderate-to-severe psoriasis but also precedes systemic inflammation that leads to psoriatic arthritis and cardiovascular comorbidities. By curing mild psoriasis with a short-term anti- interleukin (IL)-17A treatment, investigators may reduce the costs of treating psoriasis and associated medical conditions, including psoriatic arthritis, cardiovascular disease, and diabetes.

Psoriasis is an immune-mediated disease of the skin that, even in mild disease, increases the risk of comorbidities such as cardiovascular disease and metabolic derangements. Mild psoriasis tends to be treated with topical drugs, while moderate-to-severe disease is optimally treated with systemic immune modulators. However, the treatment of "mild" psoriasis needs to be re-thought because recent studies have revealed that mild psoriasis is characterized by stronger expression of pathogenic molecules, such as interleukin (IL)-17A, and higher numbers of T cells in the skin, compared to severe psoriasis. A key distinction between mild and severe psoriasis is now discovered to be the higher expression of negative immune regulatory genes in mild lesions. Therefore, targeted immune therapy with anti-IL-17A, which is highly effective in severe psoriasis, might be equally (or even more) effective in mild disease. Also, restoration of immune tolerance might be more easily achieved in mild disease. Thus, short-term anti-IL-17A treatment of mild psoriasis might prevent the recurrence and eventually cure the disease. The aim of study is to test this hypothesis by exploring whether 3 months or 6 months of anti-IL17A treatment will prevent relapses after medication has been discontinued in mild psoriasis patients.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

Conditions

Psoriasis

Interventions

SecukinumabDRUG

Arms: Group 1 - Group 1 will receive Secukinumab at a dose of 300 mg with injections administered once weekly at baseline and at weeks 1, 2, 3, and 4 and then every 4 weeks for 6 months of period. In order to maintain the blind for the Group 2, Group 1 will receive placebo injections at weeks 13, 14, and 15. Group 1 will discontinue Secukinumab after 6 months of period being observed from week 25 to week 72 (48 weeks).

Placebo followed by SecukinumabDRUG

Arms: Group 2 - Group 2 will receive placebo injections corresponding to the Group 1 regimen until week 8 in order to maintain a double-dummy design until week 12. From week 12, Group 2 will receive Secukinumab with injections administered once weekly at week 12 and at weeks 13, 14, 15, and 16 and then every 4 weeks for 3 months of period. Group 2 will discontinue Secukinumab after 6 months of period being observed from week 25 to week 72 (48 weeks).

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. Written informed consent must be obtained before any assessment is performed 2. 18 years of age or older 3. Chronic plaque-type psoriasis for at least 6 months 4. Negative PPD (negative chest w-ray if positive) or negative QuantiFERON-TB Gold 5. Have a PASI between 6 and 12 and Body Surface Area (BSA) affected by plaque-type psoriasis less than 10% at screening and baseline 6. Willing to wash off steroid creams and ultraviolet B light (UVB) therapy for 2 weeks prior to the baseline visit Exclusion Criteria: 1. Has a nonplaque form of psoriasis (eg, erythrodermic, guttate, or pustular) 2. Has previously received Secukinumab or other biologics 3. History of Inflammatory Bowel Disease (IBD) 4. History of Rheumatoid Arthritis 5. Use of topical treatments for psoriasis, including steroids, vitamin D derivatives, vitamin A derivatives, salicylic acid, tar (except moisturizers) and/or ultraviolet A light (UVA)/UVB phototherapy within the last 2 weeks (if these have used them, the participant needs to wash off of them for at least 2 weeks after signing consent prior to baseline) 6. Is pregnant, nursing, or planning a pregnancy (both men and women) within 5 months following the last administration of study drug 7. Has recently received or is planning to receive a vaccination while on the study 8. HIV positive 9. Chronic untreated hepatitis C, positive hepatitis B surface antigen and acute hepatitis A infection 10. Known tuberculosis (TB) or evidence of TB infection. Subjects with a positive QuantiFERON; TB test or a positive purified protein derivate (PPD) skin test result may participate in the study if further work up (according to local practice/guidelines) establishes conclusively that the subject has no evidence of active TB. 11. Any severe, progressive or uncontrolled medical condition at screening that in the judgment of the investigator prevents the subject from participating in the study.

Locations (1)

The Rockefeller Univesity

New York, New York, United States

Outcomes

Primary Outcomes

Percentage of Subjects Who Have 75% or More Reduction in [Psoriasis Area-and-severity Index Score (PASI)] (PASI75)

The percentage of subjects who have a reduction of 75% or more from baseline in the Psoriasis Area and Severity Index (PASI) at week 12 (PASI 75). Psoriasis Area and Severity Index (PASI) combines the assessment of the severity of lesions and the area affected into a single score in the range 0 (no disease) to 72 (maximal disease)

Time frame: week 12

Secondary Outcomes

Percentage of Subjects Who Have 90% or More Reduction in [Psoriasis Area-and-severity Index Score (PASI)] (PASI90)

The percentage of subjects who have a reduction of 90% or more from baseline in the Psoriasis Area and Severity Index (PASI) at week 12 (PASI 90). Psoriasis Area and Severity Index (PASI) combines the assessment of the severity of lesions and the area affected into a single score in the range 0 (no disease) to 72 (maximal disease)

Time frame: week 12

Percentage of Subjects Who Achieve a Physician Global Assessment (PGA) Score of 0 or 1 With at Least a 2-step Improvement From Baseline (PGA 0/1 Response Rate).

Percentage of Subjects Who Achieve a Physician Global Assessment (PGA) score of 0 or 1 with at least a 2-step improvement from baseline (PGA 0/1 response rate). Physician Global Assessment (PGA) is a global assessment of all psoriasis lesions scored on a scale of 0-5, with 0 representing clear skin, 1 almost clear skin, and 5 representing severe psoriasis

Time frame: week 12

Percentage of Subjects Who Experience Psoriasis Relapse

The percentage of subjects who experience a psoriasis relapse at any time between week 24 and week 72. Psoriasis relapse is defined as loss of \> 50% of the initial Psoriasis Area and Severity Index (PASI) improvement measured at week 24. Psoriasis Area and Severity Index (PASI) combines the assessment of the severity of lesions and the area affected into a single score in the range 0 (no disease) to 72 (maximal disease)

Data from ClinicalTrials.gov

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