Psoriasis
Conditions
Brief 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.
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.
Interventions
DRUGSecukinumab
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.
Sponsors
Novartis Pharmaceuticals
University of California, San Francisco
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change in Percentage of CD4+ T Effector Cells Expressing IL17 Compared to Baseline | Baseline to Week 2 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Number of Differentially Expressed Genes in CD4+ Effectors Compared to Baseline Across All Participants | Baseline to Week 2 | by RNA-seq |
| Change in Number of Differentially Expressed Genes in CD4+ Effectors Compared to Baseline | Baseline to Week 4 | by RNA-seq |
| Change in Number of Differentially Expressed Genes in CD4+ T Regs Compared to Baseline | Baseline to Week 2 | by RNA-seq |
| Change in Number of Differentially Expressed Genes in CD8+ T Effectors Compared to Baseline | Baseline to Week 2 | by RNA-seq |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Secukinumab All subjects will receive Secukinumab 300mg SQ at weeks 0, 1, 2, 3, 4, and every 4 weeks thereafter until week 48.
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. | 15 |
| Total | 15 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
| Overall Study | Lost to Follow-up | 1 |
Baseline characteristics
| Characteristic | Secukinumab |
|---|---|
| Age, Continuous | 37 years |
| Family history of psoriasis | 5 Participants |
| Race/Ethnicity, Customized Asian/Pacific Islander | 4 Participants |
| Race/Ethnicity, Customized Black/African American | 2 Participants |
| Race/Ethnicity, Customized Caucasian | 5 Participants |
| Race/Ethnicity, Customized Hispanic | 4 Participants |
| Sex: Female, Male Female | 6 Participants |
| Sex: Female, Male Male | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 15 |
| other Total, other adverse events | 13 / 15 |
| serious Total, serious adverse events | 1 / 15 |
Outcome results
Primary
Change in Percentage of CD4+ T Effector Cells Expressing IL17 Compared to Baseline
Time frame: Baseline to Week 2
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Secukinumab | Change in Percentage of CD4+ T Effector Cells Expressing IL17 Compared to Baseline | -1.42 percent change from week 0 | Standard Deviation 4.36 |
Primary
Change in Percentage of CD4+ T Effector Cells Expressing IL17 Compared to Baseline
Time frame: Baseline to Week 4
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Secukinumab | Change in Percentage of CD4+ T Effector Cells Expressing IL17 Compared to Baseline | 0.23 percent change from week 0 | Standard Deviation 8.76 |
Primary
Change in Percentage of CD4+ T Effector Cells Expressing IL17 Compared to Baseline
Time frame: Baseline to Week 12
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Secukinumab | Change in Percentage of CD4+ T Effector Cells Expressing IL17 Compared to Baseline | -0.17 percent change from week 0 | Standard Deviation 8.73 |
Secondary
Change in Number of Differentially Expressed Genes in CD4+ Effectors Compared to Baseline
by RNA-seq
Time frame: Baseline to Week 4
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Secukinumab | Change in Number of Differentially Expressed Genes in CD4+ Effectors Compared to Baseline | 308 number of genes |
Secondary
Change in Number of Differentially Expressed Genes in CD4+ Effectors Compared to Baseline
by RNA-seq
Time frame: Baseline to Week 12
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Secukinumab | Change in Number of Differentially Expressed Genes in CD4+ Effectors Compared to Baseline | 1618 number of genes |
Secondary
Change in Number of Differentially Expressed Genes in CD4+ Effectors Compared to Baseline Across All Participants
by RNA-seq
Time frame: Baseline to Week 2
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Secukinumab | Change in Number of Differentially Expressed Genes in CD4+ Effectors Compared to Baseline Across All Participants | 67 genes |
Secondary
Change in Number of Differentially Expressed Genes in CD4+ T Regs Compared to Baseline
by RNA-seq
Time frame: Baseline to Week 2
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Secukinumab | Change in Number of Differentially Expressed Genes in CD4+ T Regs Compared to Baseline | 453 number of genes |
Secondary
Change in Number of Differentially Expressed Genes in CD4+ T Regs Compared to Baseline
by RNA-seq
Time frame: Baseline to Week 4
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Secukinumab | Change in Number of Differentially Expressed Genes in CD4+ T Regs Compared to Baseline | 240 number of genes |
Secondary
Change in Number of Differentially Expressed Genes in CD4+ T Regs Compared to Baseline
by RNA-seq
Time frame: Baseline to Week 12
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Secukinumab | Change in Number of Differentially Expressed Genes in CD4+ T Regs Compared to Baseline | 127 number of genes |
Secondary
Change in Number of Differentially Expressed Genes in CD8+ T Effectors Compared to Baseline
by RNA-seq
Time frame: Baseline to Week 2
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Secukinumab | Change in Number of Differentially Expressed Genes in CD8+ T Effectors Compared to Baseline | 20 number of genes |
Secondary
Change in Number of Differentially Expressed Genes in CD8+ T Effectors Compared to Baseline
by RNA-seq
Time frame: Baseline to Week 4
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Secukinumab | Change in Number of Differentially Expressed Genes in CD8+ T Effectors Compared to Baseline | 102 number of genes |
Secondary
Change in Number of Differentially Expressed Genes in CD8+ T Effectors Compared to Baseline
by RNA-seq
Time frame: Baseline to Week 12
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Secukinumab | Change in Number of Differentially Expressed Genes in CD8+ T Effectors Compared to Baseline | 104 number of genes |