Immunologic Response to Secukinumab in Plaque Psoriasis

Characterization of the Response to Secukinumab in Plaque Psoriasis Using Novel Immunologic and Genetic Profiling

This is a single-arm, open-label study, which will examine the effect of secukinumab on the immunologic and genetic environment within psoriatic lesions.

Study Overview

• Status: Completed
• Conditions: Psoriasis
• Intervention / Treatment: Drug: Secukinumab

Detailed Description

Quantitative analysis of the immunologic changes in immune cell populations will be performed after secukinumab treatment in 15 patients at weeks 2, 4, and 12 compared to baseline week 0. The immunologic profiles in psoriasis patients will also be compared to healthy control skin surgical discard specimens (n=10). The number of differentially expressed genes in each cell population will be quantified by RNA-seq at weeks 2, 4, 12 after secukinumab compared to baseline.

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • California
    • San Francisco, California, United States, 94118
      • UCSF Psoriasis and Skin Treatment Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Ability to provide written informed consent and comply with the protocol.
2. At least 18 years of age.
3. Diagnosis of predominately plaque psoriasis for at least 6 months prior to enrollment.
4. Subject is considered a candidate for phototherapy or systemic therapy
5. PASI ≥ 12
6. PGA ≥ 3
7. Subject has a negative Quantiferon Gold, or if positive undergoes CXR. If CXR negative, subject initiated prophylactic therapy with isoniazid for a course of 9 months with one month of therapy completed prior to first dose of secukinumab.
8. Subject is unlikely to conceive (male, post-menopausal, or using adequate oral contraceptive therapy or IUD).
9. Physical exam within clinically acceptable limits.

Exclusion Criteria:

1. Subject is unable to provide written informed consent or comply with the protocol.
2. Subject is younger than 18 years of age.
3. Subject has predominately non-plaque form of psoriasis.
4. Subject with mild psoriasis (PASI<12 and PGA<3) or is not a candidate for phototherapy or systemic treatments.
5. Subject has drug-induced psoriasis.
6. Subject with current, or a history of, severe psoriatic arthritis well controlled on current therapy.
7. Subjects with a serum creatinine level exceeding 176.8 μmol/L (2.0 mg/dl).
8. Screening total white blood cell (WBC count) < 2,500/μl, platelets < 100,000/μl, neutrophils < 1,500/μl, or hemoglobin <8.5 g/dl.
9. Evidence of active tuberculosis infection as defined by a positive QuantiFERON TB-Gold test (QFT) with a positive chest X-ray at screening, or untreated latent tuberculosis defined by positive QFT with a negative chest X-ray without prophylactic therapy with isoniazid for a course of 9 months with one month of therapy completed prior to first dose of secukinumab.
10. History of an ongoing, chronic or recurrent infectious disease including past medical history record of HIV, hepatitis B or hepatitis C.
11. Subjects possess other diagnoses that, in the investigator's opinion, preclude him/her from safely participating in this study or interfere with the evaluation of the subject's psoriasis.
12. History of known or suspected intolerance to any of the ingredients of the investigational study product.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Secukinumab; All subjects will receive Secukinumab 300mg SQ at weeks 0, 1, 2, 3, 4, and every 4 weeks thereafter until week 48.	Drug: Secukinumab; Secukinumab 300mg SQ at weeks 0, 1, 2, 3, 4, and every 4 weeks thereafter until week 48. Skin biopsy procedures will be performed at weeks 0, 2, 4, and 12.; Other Names: Cosentyx

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change in Percentage of CD4+ T Effector Cells Expressing IL17 Compared to Baseline	Baseline to Week 2
Change in Percentage of CD4+ T Effector Cells Expressing IL17 Compared to Baseline	Baseline to Week 4
Change in Percentage of CD4+ T Effector Cells Expressing IL17 Compared to Baseline	Baseline to Week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Number of Differentially Expressed Genes in CD4+ Effectors Compared to Baseline Across All Participants	by RNA-seq	Baseline to Week 2
Change in Number of Differentially Expressed Genes in CD4+ Effectors Compared to Baseline	by RNA-seq	Baseline to Week 4
Change in Number of Differentially Expressed Genes in CD4+ Effectors Compared to Baseline	by RNA-seq	Baseline to Week 12
Change in Number of Differentially Expressed Genes in CD4+ T Regs Compared to Baseline	by RNA-seq	Baseline to Week 2
Change in Number of Differentially Expressed Genes in CD4+ T Regs Compared to Baseline	by RNA-seq	Baseline to Week 4
Change in Number of Differentially Expressed Genes in CD4+ T Regs Compared to Baseline	by RNA-seq	Baseline to Week 12
Change in Number of Differentially Expressed Genes in CD8+ T Effectors Compared to Baseline	by RNA-seq	Baseline to Week 2
Change in Number of Differentially Expressed Genes in CD8+ T Effectors Compared to Baseline	by RNA-seq	Baseline to Week 4
Change in Number of Differentially Expressed Genes in CD8+ T Effectors Compared to Baseline	by RNA-seq	Baseline to Week 12

Collaborators and Investigators

• Sponsor: University of California, San Francisco
• Collaborators: Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2016
• Primary Completion (Actual): December 1, 2018
• Study Completion (Actual): December 1, 2018

Study Registration Dates

• First Submitted: October 16, 2015
• First Submitted That Met QC Criteria: October 28, 2015
• First Posted (Estimate): October 30, 2015

Study Record Updates

• Last Update Posted (Actual): September 16, 2020
• Last Update Submitted That Met QC Criteria: August 31, 2020
• Last Verified: August 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Skin Diseases, Papulosquamous; Psoriasis
• Other Study ID Numbers: CAIN457AUS04T

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO