Study of the Effect of Fostamatinib Upon Cutaneous Inflammation in the Setting of Hidradenitis Suppurativa

Study Overview
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Brief Summary
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A 16 week exploratory, Proof of Concept study to evaluate the effect of Fostamatinib (12 weeks of treatment) upon cutaneous inflammation in Hidradenitis Suppurativa.

Detailed Description
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Sample size: 20 patients Study duration: 16 weeks Primary Endpoints: Alterations in Gene Expression Profiling, cell counts (CD3+, CD11c+, Neutrophil Elastase+, CD20+, CD138+) at Week 4 compared to Baseline. Alterations in Gene Expression Profiling, cell counts (CD3+, CD11c+, Neutrophil Elastase+, CD20+, CD138+) at Week 12 compared to Baseline. Secondary Endpoints: Safety and Tolerability (Grade 2/3 Adverse Effects); Changes in Disease Activity (Measures by AN count and IHS4 scoring). Study procedures Clinical Examination, Patient Questionnaires, Skin Biopsy, Blood Draw, medical photography

Official Title
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An Exploratory, Proof-of-Concept Study of the Effect of Fostamatinib Upon Cutaneous Inflammation in the Setting of Hidradenitis Suppurativa

Conditions
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Hidradenitis Suppurativa

Intervention / Treatment
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* Drug: Fostamatinib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Moderate to Severe (Hurley Stage 2 or 3) Hidradenitis Suppurativa as determined by the PI Exclusion Criteria: Uncontrolled hypertension (systolic blood pressure [BP] ≥135 mmHg and/or diastolic BP ≥85 mmHg), unstable angina, congestive heart failure of New York Heart Association classification III or IV, serious cardiac arrhythmia requiring treatment (exceptions: atrial fibrillation, paroxysmal supraventricular tachycardia) at screening. History of myocardial infarction within 3 months prior to screening. Shock or hypotension requiring vasoactive peptides, such as dopamine, norepinephrine, epinephrine, or dobutamine at screening or at randomization. Renal function impairment with creatinine clearance <30 mL/min at screening (estimated glomerular filtration rate will be calculated using the modification of diet in renal disease equation). Liver function impairment with aspartate aminotransferase/alanine aminotransferase >=3x the upper limit of normal or bilirubin >2X the upper limit of normal at screening. Neutrophil count <1000/µL at screening. History of an allergic reaction or hypersensitivity to the study treatment or any component of the study treatment formulation. Has documented HIV infection or documented, active hepatitis B or hepatitis C infection. Women lactating, pregnant or of childbearing potential who are not willing to avoid becoming pregnant during the study. Individuals with concurrent use of systemic antibiotics/ oral retinoids/ systemic immunosuppressants (those with prior use of these medications must have conducted a washout period of 4 weeks or 5 half-lives of the drug, whichever is longer). Any medical, psychological or social condition that, in the opinion of the Investigator, would jeopardize the health or well-being of the participant during any study procedures or the integrity of the data.

Ages Eligible for Study
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Minimum Age: 18 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: Open Label Fostamatinib<br>Open label Fostamatinib 100mg dose adjusted by the Principal Investigator after week 1 | Drug: Fostamatinib<br>* Open label Fostamatinib<br>* Other names: R935788;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Week 4 evaluation | Alterations in Gene Expression Profiling, cell counts (CD3+, CD11c+, Neutrophil Elastase+, CD20+, CD138+) at Week 4 compared to | 4 weeks | 
| Week 12 evaluation | Alterations in Gene Expression Profiling, cell counts (CD3+, CD11c+, Neutrophil Elastase+, CD20+, CD138+) at Week 12 compared to Baseline | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Grade 2/3 Adverse Events | Number of Grade 2/3 Adverse Effects of Fostamatinib over the 12 Week course of treatment. | 12 weeks | 
| Abscess and Nodule Count Week 4 | Changes in Abscess and Nodule count at Week 4 compared to baseline | 4 weeks | 
| International Hidradenitis Suppurativa Severity Score (IHS4) Week 4 | Changes in IHS4 score at Week 4 compared to baseline | 4 weeks | 
| Abscess and Nodule count week 12 | Changes in Abscess and Nodule count at Week 12 compared to baseline | 12 weeks | 
| International Hidradenitis Suppurativa Severity Score (IHS4) Week 12 | Changes in IHS4 score at Week 12 compared to baseline | 12 weeks | 
| Physician Rated Overall Disease Severity | Changes in physician rated overall disease severity by visual analogue scale (0-10) at week 12 compared to baseline | 12 weeks | 
| Dermatology Life Quality Index (DLQI) | Changes in the DLQI (0-30) at week 12 compared to baseline | 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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fostamatinib, HS, Tavalisse