Secukinumab for the Inflammatory Phase of Pyoderma Gangrenosum

Study Overview
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Brief Summary
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The purpose of this research study is to find out what effects (good and bad) secukinumab has on the subject and their pyoderma gangrenosum. Secukinumab is a type of medicine called human monoclonal antibodies. Monoclonal antibodies are proteins that recognize and attach to other specific proteins (in this case, immune system hormones called cytokines) that your body produces. The cytokine (a messenger protein in the body) that secukinumab binds to and reduces the activity of is a naturally occurring cytokine called interleukin-17A (IL-17A). IL-17A is believed to be partly responsible for inflammation (pain, swelling, redness), and researchers believe that IL-17A may cause symptoms PG.

Detailed Description
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This is a prospective, single center, Phase IIa study of secukinumab in the treatment of subjects diagnosed with PG. Subjects will be evaluated at Screening, Baseline (week 0), Week 1, Week 2, Week 3, Week 4, and then every 4 weeks for 24 weeks. The total duration of treatment is up to 20 weeks. Subjects may be treated for shorter durations if the lesions clear prior to week 20. Subjects will have a follow-up visit at 24 weeks, or 4 weeks after the last dose of study drug. Subjects will also have standard of care wound dressings done at each visit. Subjects will be given 300 mg of secukinumab SQ at week 0, 1, 2, 3, and 4, followed by injections every 4 weeks, for up to 20 weeks. Subjects may receive a dose increase at week 16 (if there is not at least a 25% reduction in target lesion size) to 300 mg every 2 weeks. Complete Blood Count (CBC), Comprehensive Metabolic panel (CMP), C- reactive protein (CRP), Erythrocyte sedimentation rate (ESR), Hepatitis panel, HIV test, Pregnancy test, and QuantiFERON gold TB test will be performed at screening. (Appendix 6) CBC, CMP, CRP, ESR will be performed at week 8 and week 20. Pain rating by Likert scale (A 10-point scale to rate the level of pain - Appendix 2), an Investigator Global Assessment (IGA) (Appendix 3), Subject Global Assessment (SGA) (Appendix 3), and Ulcer Lesion Assessment (Appendix 5) will be done at Screening, Baseline, and at Weeks 2, 4, 8, 12, 16, 20, and 24. Lesion photography will be done at Screening and all visits. Infection and adverse event assessments and concomitant medication assessments will be performed at each visit. Quality of life will be measured with the Dermatology Life Quality Index (DLQI) at Baseline and Week 20 (Appendix 4).

Official Title
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The Efficacy and Safety of Secukinumab for the Inflammatory Phase of Pyoderma Gangrenosum

Conditions
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Pyoderma Gangrenosum

Intervention / Treatment
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* Drug: secukinumab 150 mg (2 injections per dose


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 1. Must give written informed consent. 2. Has a diagnosis of pyoderma gangrenosum, as determined by the investigator based on the following diagnostic criteria4: a. Diagnosis requires both major criteria and at least two minor criteria i. Major criteria Rapid progression of a painful, necrolytic cutaneous ulcer with an irregular, violaceous, and undermined border Other causes of cutaneous ulceration have been excluded ii. Minor criteria 1. History suggestive of pathergy or clinical finding of cribriform scarring 2. Systemic diseases associated with PG 3. Histopathologic findings (sterile dermal neutrophilia, ± mixed inflammation, ± lymphocytic vasculitis) 4. Treatment response (rapid response to systemic steroid treatment) 3. PG global assessment of moderate to severe, with at least one ulcer measuring at least 3 cm in diameter. 4. 18 years of age or greater. 5. Must require systemic therapy for their pyoderma gangrenosum, as determined by the investigator prior to Baseline. Currently prescribed low-dose corticosteroids (≤ 10 mg/day), and other medications within one week prior to investigational drug administration, may be continued with no change in dose or frequency during the study. Exclusion Criteria: Female subjects who are not postmenopausal for at least 1 year, surgically sterile, or willing to practice effective contraception during the study. Nursing mothers, pregnant women and women planning to become pregnant while on study are to be excluded. Current enrollment in any investigational study in which the subject is receiving any type of drug, biologic, or non-drug therapy (participation in registry-type studies is allowed). Serious local infection (e.g., cellulitis, abscess) or systemic infection (e.g., pneumonia, septicemia) within the 3 months prior to the first dose of investigational drug. Treatment with another investigational drug or approved therapy for investigational use within 28 days prior to investigational drug administration. Treatment with high dose (>10 mg/day) systemic steroids (prednisone) within one week prior to investigational drug administration. Treatment with cyclosporine, thalidomide, methotrexate, mycophenolate mofetil, azathioprine, or other systemic immunosuppressant agents within the 14 days prior to investigational drug administration (requirement of a 2-week washout). Known HIV+, known viral hepatitis infection, known tuberculosis infection. Any subject with a current or history of a malignancy in the last five years (excluding treated basal cell carcinoma). Clinically significant abnormal laboratory measures at screening. Known Irritable Bowel Disease-associated PG

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental<br>2 s.c. secukinumab 150 mg injections | Drug: secukinumab 150 mg (2 injections per dose<br>* secukinumab 150 mg (2 injections per dose<br>* Other names: secukinumab;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy - Investigator Global Assessment (IGA) | Investigator Global Assessment (IGA) as measured by a 7 point scale anchored by 'Completely Clear and Worse | Screening visit | 
| Efficacy - Investigator Global Assessment (IGA) | Investigator Global Assessment (IGA) as measured by a 7 point scale anchored by 'Completely Clear and Worse | Change from Screening visit to Baseline visit. | 
| Efficacy - Investigator Global Assessment (IGA) | Investigator Global Assessment (IGA) as measured by a 7 point scale anchored by 'Completely Clear and Worse | Change from Baseline visit to Week 2. | 
| Efficacy - Investigator Global Assessment (IGA) | Investigator Global Assessment (IGA) as measured by a 7 point scale anchored by 'Completely Clear and Worse | Change from week 2 to week 4. | 
| Efficacy - Investigator Global Assessment (IGA) | Investigator Global Assessment (IGA) as measured by a 7 point scale anchored by 'Completely Clear and Worse | Change from Week 4 to week 8. | 
| Efficacy - Investigator Global Assessment (IGA) | Investigator Global Assessment (IGA) as measured by a 7 point scale anchored by 'Completely Clear and Worse | Change from Week 8 to week 12. | 
| Efficacy - Investigator Global Assessment (IGA) | Investigator Global Assessment (IGA) as measured by a 7 point scale anchored by 'Completely Clear and Worse | Change from Week 12 to week 16. | 
| Efficacy - Investigator Global Assessment (IGA) | Investigator Global Assessment (IGA) as measured by a 7 point scale anchored by 'Completely Clear and Worse | Change from Week 16 to week 20. | 
| Efficacy - Investigator Global Assessment (IGA) | Investigator Global Assessment (IGA) as measured by a 7 point scale anchored by 'Completely Clear and Worse | Change from Week 20 to week 24. | 
| Efficacy - Subject Global Assessment (SGA) | Subject Global Assessment (SGA) as measured by a 7 point scale anchored by 'Completely Clear and Worse | Baseline. | 
| Efficacy - Subject Global Assessment (SGA) | Subject Global Assessment (SGA) as measured by a 7 point scale anchored by 'Completely Clear and Worse | Change from Baseline to week 2. | 
| Efficacy - Subject Global Assessment (SGA) | Subject Global Assessment (SGA) as measured by a 7 point scale anchored by 'Completely Clear and Worse | Change from Week 2 to Week 4. | 
| Efficacy - Subject Global Assessment (SGA) | Subject Global Assessment (SGA) as measured by a 7 point scale anchored by 'Completely Clear and Worse | Change from Week 4 to Week 8. . | 
| Efficacy - Subject Global Assessment (SGA) | Subject Global Assessment (SGA) as measured by a 7 point scale anchored by 'Completely Clear and Worse | Change from Week 8 to Week 12. | 
| Efficacy - Subject Global Assessment (SGA) | Subject Global Assessment (SGA) as measured by a 7 point scale anchored by 'Completely Clear and Worse | Change from Week 12 to Week 16. | 
| Efficacy - Subject Global Assessment (SGA) | Subject Global Assessment (SGA) as measured by a 7 point scale anchored by 'Completely Clear and Worse | Change from Week 16 to Week 20. | 
| Efficacy - Subject Global Assessment (SGA) | Subject Global Assessment (SGA) as measured by a 7 point scale anchored by 'Completely Clear and Worse | Change from Week 20 to Week 24. | 
| Efficacy - Ulcer Lesion Assessment PG Target Lesion | Number of subjects achieving 50% improvement in PG lesion size | Change from Screening visit, Baseline, and at Weeks 2, 4, 8, 12, 16, 20, and 24. | 
| Efficacy - Ulcer Lesion Assessment PG Target Lesion | Number of subjects achieving resolution of inflammation with an erythema score of 0 and a border elevation of 0 on five point scales of none to very severe | Change from Screening visit, Baseline, and at Weeks 2, 4, 8, 12, 16, 20, and 24. |