Safety and Efficacy of Secukinumab in Mild Psoriasis

Psoriasis Clinical Trial

Official title:

Safety and Efficacy of Secukinumab in Adults With Chronic Plaque Type Psoriasis With a PASI Score of 6 to 12

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03131570
• Other study ID #: JKR-0937
• Status: Completed
• Phase: Phase 2
• Start date: May 23, 2017
• Est. completion date: June 21, 2021

Study information

• Verified date: September 2022
• Source: Rockefeller University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 23
• Est. completion date: June 21, 2021
• Est. primary completion date: January 8, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Psoriasis

Intervention

Drug:
• Secukinumab
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 Secukinumab
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).

Locations

Country	Name	City	State
United States	The Rockefeller Univesity	New York	New York

Sponsors (2)

Lead Sponsor	Collaborator
James G. Krueger, MD, PhD	Novartis

Country where clinical trial is conducted

United States, 

References & Publications (4)

Kim J, Bissonnette R, Lee J, Correa da Rosa J, Suárez-Fariñas 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. — View 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. Review. — View Citation

Kim J, Nadella P, Kim DJ, Brodmerkel C, Correa da Rosa J, Krueger JG, Suárez-Fariñas 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. — View Citation

Kim J, Oh CH, Jeon J, Baek Y, Ahn J, Kim DJ, Lee HS, Correa da Rosa J, Suárez-Fariñas 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)	week 12
Secondary	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)	week 12
Secondary	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	week 12
Secondary	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)	week 24 through week 72
Secondary	Percentage of Subjects Who Experience Severe Psoriasis Relapse	The percentage of subjects who experience a severe psoriasis relapse at any time between week 24 and week 72. Severe psoriasis relapse is defined as loss of > 75% 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)	Observation Period: week 24 through week 72.
Secondary	Percentage of Subjects Who Experience Psoriasis Relapse After Psoriasis is Cleared	The percentage of subjects who experience a psoriasis relapse at any time between week 24 and week 72 among the subjects whose psoriasis is cleared between week 0 and week 24. Psoriasis relapse is defined as loss of > 50% of the initial Psoriasis Area and Severity Index (PASI) improvement measured at week 24. Psoriasis clearance is defined as the achievement of PASI100, which is a reduction of 100% from baseline in the Psoriasis Area and Severity Index (PASI) score. 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).	Observation Period: week 24 through week 72
Secondary	Elapsed Time Until Relapse	Elapsed time from week 24 until relapse occurs before week 72, measured in weeks.	week 24 until week 72
Secondary	Percentage of Subjects Who Have 100% Reduction in [Psoriasis Area-and-severity Index Score (PASI)] (PASI100)	The percentage of subjects who have a reduction of 100% from baseline in the Psoriasis Area and Severity Index (PASI) score (PASI100) at week 12. 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)	week 12
Secondary	Frequency of Adverse Events	Frequency of all Adverse Events (AEs) including Serious Adverse Events (SAEs) that occur during the whole trial including the observational period (AEs and SAEs include but not limited to comorbidities, such as hypertension, diabetes, and cardiovascular diseases).	week 0 through week 72
Secondary	Frequency of Serious Adverse Events	Frequency of Serious Adverse Events (SAEs) that occur during the whole trial including the observational period.	week 0 through week 72