Immunologic Response to Secukinumab in Plaque Psoriasis

Psoriasis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02592018
• Other study ID #: CAIN457AUS04T
• Status: Completed
• Phase: Phase 4
• Start date: October 2016
• Est. completion date: December 2018

Study information

• Verified date: August 2020
• Source: University of California, San Francisco
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 15
• Est. completion date: December 2018
• Est. primary completion date: December 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Psoriasis

Intervention

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.

Locations

Country	Name	City	State
United States	UCSF Psoriasis and Skin Treatment Center	San Francisco	California

Sponsors (2)

Lead Sponsor	Collaborator
University of California, San Francisco	Novartis Pharmaceuticals

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Percentage of CD4+ T Effector Cells Expressing IL17 Compared to Baseline		Baseline to Week 2
Primary	Change in Percentage of CD4+ T Effector Cells Expressing IL17 Compared to Baseline		Baseline to Week 4
Primary	Change in Percentage of CD4+ T Effector Cells Expressing IL17 Compared to Baseline		Baseline to Week 12
Secondary	Change in Number of Differentially Expressed Genes in CD4+ Effectors Compared to Baseline Across All Participants	by RNA-seq	Baseline to Week 2
Secondary	Change in Number of Differentially Expressed Genes in CD4+ Effectors Compared to Baseline	by RNA-seq	Baseline to Week 4
Secondary	Change in Number of Differentially Expressed Genes in CD4+ Effectors Compared to Baseline	by RNA-seq	Baseline to Week 12
Secondary	Change in Number of Differentially Expressed Genes in CD4+ T Regs Compared to Baseline	by RNA-seq	Baseline to Week 2
Secondary	Change in Number of Differentially Expressed Genes in CD4+ T Regs Compared to Baseline	by RNA-seq	Baseline to Week 4
Secondary	Change in Number of Differentially Expressed Genes in CD4+ T Regs Compared to Baseline	by RNA-seq	Baseline to Week 12
Secondary	Change in Number of Differentially Expressed Genes in CD8+ T Effectors Compared to Baseline	by RNA-seq	Baseline to Week 2
Secondary	Change in Number of Differentially Expressed Genes in CD8+ T Effectors Compared to Baseline	by RNA-seq	Baseline to Week 4
Secondary	Change in Number of Differentially Expressed Genes in CD8+ T Effectors Compared to Baseline	by RNA-seq	Baseline to Week 12