Clinical trial NCT03131570: Safety and Efficacy of Secukinumab in Mild Psoriasis
Official title: Safety and Efficacy of Secukinumab in Adults With Chronic Plaque Type Psoriasis With a PASI Score of 6 to 12
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Psoriasis
Keywords: Psoriasis
Chronic Plaque Psoriasis
Secukinumab
Lead sponsor: Rockefeller University
Sponsor class: OTHER
Collaborators: name: Novartis
First posted: 2017-04-27
Enrollment: 23
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: To compare the secukinumab-receiving mild psoriasis subjects (Group 1) and the placebo-receiving mild psoriasis subjects (Group 2).
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Percentage of Subjects Who Have 75% or More Reduction in [Psoriasis Area-and-severity Index Score (PASI)] (PASI75)
timeFrame: week 12
Secondary outcomes:
measure: Percentage of Subjects Who Have 90% or More Reduction in [Psoriasis Area-and-severity Index Score (PASI)] (PASI90)
timeFrame: week 12
measure: 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).
timeFrame: week 12
measure: Percentage of Subjects Who Experience Psoriasis Relapse
timeFrame: week 24 through week 72
measure: Percentage of Subjects Who Experience Severe Psoriasis Relapse
timeFrame: Observation Period: week 24 through week 72.
measure: Percentage of Subjects Who Experience Psoriasis Relapse After Psoriasis is Cleared
timeFrame: Observation Period: week 24 through week 72
measure: Elapsed Time Until Relapse
timeFrame: week 24 until week 72
measure: Percentage of Subjects Who Have 100% Reduction in [Psoriasis Area-and-severity Index Score (PASI)] (PASI100)
timeFrame: week 12
measure: Frequency of Adverse Events
timeFrame: week 0 through week 72
measure: Frequency of Serious Adverse Events
timeFrame: week 0 through week 72
Other outcomes:
Locations:
city: New York
country: United States
facility: The Rockefeller Univesity
state: New York
Study officials:
affiliation: Rockefeller University
name: James G Krueger, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Kim J, Bissonnette R, Lee J, Correa da Rosa J, Suarez-Farinas M, Lowes MA, Krueger JG. The Spectrum of Mild to Severe Psoriasis Vulgaris Is Defined by a Common Activation of IL-17 Pathway Genes, but with Key Differences in Immune Regulatory Genes. J Invest Dermatol. 2016 Nov;136(11):2173-2182. doi: 10.1016/j.jid.2016.04.032. Epub 2016 May 13.
citation: Kim J, Oh CH, Jeon J, Baek Y, Ahn J, Kim DJ, Lee HS, Correa da Rosa J, Suarez-Farinas M, Lowes MA, Krueger JG. Molecular Phenotyping Small (Asian) versus Large (Western) Plaque Psoriasis Shows Common Activation of IL-17 Pathway Genes but Different Regulatory Gene Sets. J Invest Dermatol. 2016 Jan;136(1):161-172. doi: 10.1038/JID.2015.378.
citation: Kim J, Nadella P, Kim DJ, Brodmerkel C, Correa da Rosa J, Krueger JG, Suarez-Farinas M. Histological Stratification of Thick and Thin Plaque Psoriasis Explores Molecular Phenotypes with Clinical Implications. PLoS One. 2015 Jul 15;10(7):e0132454. doi: 10.1371/journal.pone.0132454. eCollection 2015.
citation: Kim J, Krueger JG. The immunopathogenesis of psoriasis. Dermatol Clin. 2015 Jan;33(1):13-23. doi: 10.1016/j.det.2014.09.002.