Etanercept for Treatment of Hidradenitis
Etanercept for Treatment of Hidradenitis
This study is being done to test a drug called etanercept (Enbrel®). Etanercept has been
 approved by the U.S. Food and Drug Administration (FDA) for the treatment of chronic moderate
 to severe plaque psoriasis (PsO), for use in reducing the signs and symptoms of moderately to
 severely active rheumatoid arthritis (RA) in adults and children, and psoriatic arthritis
 (PsA) and ankylosing spondylitis (AS) in adults. It is available by prescription for the
 treatment of PsO, RA, PsA, and AS. Etanercept is approved for injection under the skin at a
 dose of 50 mg per week in patients with psoriasis.

 The purpose of this study is to determine whether etanercept is safe and effective for the
 treatment of hidradenitis. Another purpose of this study is to determine the impact of
 etanercept treatment of hidradenitis on skin related to quality of life.

 The skin lesions typically associated with hidradenitis are thought to be partly due to a
 blockage that occurs in sweat glands, called apocrine ducts, which become inflamed and
 eventually destroyed. A protein found in the body called tumor necrosis factor alpha, or TNF-
 α, is a hormone that causes this inflammation or swelling. The study drug, etanercept, blocks
 the action of TNF- α. By blocking the action of TNF-α, etanercept may provide a reduction in
 the signs and symptoms of hidradenitis.

 This study will take place at the University of Pennsylvania and will involve up to 21
 participants ages 18 and up. Approximately 21 subjects will participate at the University of
 Pennsylvania.

 Each patient will participate in this study for a maximum of 6 months. The study consists of
 a screening visit, baseline assessment visit (Day 1), a treatment period (Week 2 - Week 14),
 and a one month follow-up visit (Week 18 visit). The total duration of the study will be
 approximately 2 years.
Purpose: The primary objective of this study is to determine the safety and estimate the
 efficacy of etanercept for the treatment of hidradenitis suppurativa. The secondary objective
 of this study is to determine the impact of etanercept treatment of hidradenitis suppurativa
 on skin related quality of life.

 Duration:

 Each patient will participate in this study for a maximum of 6 months. The study consists of
 a screening visit, baseline assessment visit (Day 1), a treatment period (Week 2 - Week 14),
 and a one month follow-up visit (Week 18 visit). The total duration of the study will be
 approximately 2 years.

 Subject Recruitment and Selection:

 It is planned that enrollment will be 12-21 patients.

 Background:

 Hidradenitis suppurativa is a physically, psychologically, and socially disabling disease
 characterized by inflammatory, cystic papules and nodules affecting the underarms, groin,
 perineum, and breasts. Lesions can become erosive and often develop deep abscesses and sinus
 tracts and drain foul smelling pus. Left untreated, hidradenitis can result in permanent
 scarring. In the most severe cases, characterized by chronic ulceration and granulation,
 there may be an increased risk of aggressive squamous cell carcinoma.

 Current treatment of hidradenitis consists of intra-lesional injections of steroids, topical
 and/or systemic antibiotics, hormonal therapy, and isotretinoin. For many patients with
 severe hidradenitis (stage II and III), these therapies are often ineffective. Patients with
 stage II and III hidradenitis often require surgical excision of the affected area (a highly
 morbid procedure) to control the disease. Unfortunately, for most patients with hidradenitis,
 existing therapies are ineffective and there is an unmet medical need for therapies that
 control this disabling and destructive disease.

 The pathophysiology of hidradenitis is unknown. The leading hypothesis is that occlusion of
 apocrine ducts leads to severe dilatation, apocrine gland inflammation, with ensuing
 bacterial growth and neutrophilic infiltration and destruction of the duct. The importance of
 the immune dysregulation in hidradenitis is further demonstrated by its association in many
 individuals with inflammatory bowel disease.

 The pathologic immune reaction to follicular occlusion in hidradenitis suggests a strong
 rationale for the use of treatments that may neutralize this inflammatory reaction. In fact,
 the existing standard treatment of hidradenitis is intra-lesional injections of steroids, in
 the effort to minimize the destructive nature of the immune response. Medications that are
 broadly immuno-suppressive, such as cyclosporine, have also been used to successfully treat
 hidradenitis, but are limited by organ toxicity. This rationale is further supported by case
 reports of dramatic and rapid (e.g. within days) improvement in hidradenitis treated with
 infliximab, a monoclonal antibody that blocks TNF-alpha.

 Etanercept is a TNF-alpha inhibitor currently FDA approved to treat various inflammatory
 disorders including rheumatoid arthritis, psoriatic arthritis and psoriasis. By inhibiting
 TNF-alpha, etanercept stops the inflammatory cascade by binding directly to circulating
 TNF-alpha and inhibiting its binding to cell surface receptors.

 Etanercept has been used in over 200,000 patients world wide for more than 5 years and has a
 well established safety record. The most common adverse effect of etanercept is injection
 site reaction which is typically mild and self-limited. Currently, laboratory monitoring for
 patients being treated with etanercept is not recommended according to its label since the
 drug has not been associated with a significant incidence of laboratory abnormalities.

 The well established safety profile of etanercept and its potent role in suppressing
 pathologic immune responses through TNF-inhibition make it a promising agent for the
 treatment of hidradenitis suppurativa. In this phase II clinical trial, we will determine
 preliminary evidence of safety and estimate the efficacy of etanercept in the treatment of
 hidradenitis. This study will provide critical preliminary data for planning larger pivotal
 trials.

 Research Design:

 This is a phase II, open label, two-stage clinical trial of etanercept for the treatment of
 hidradenitis. This design is a widely accepted method for early investigations of safety and
 efficacy of medications for new indications. Etanercept 50 mg will be administered
 subcutaneously once a week for 12 weeks in an open label manner. At week 12, the etanercept
 dose will be tapered to 25 mg subcutaneously once a week for 2 weeks.

 This is an 18 week study. Subjects will be screened to determine eligibility. Day -95 to -3
 will be a screening period which will allow washout of concurrent therapies if necessary.

 Potential Risks:

 Etanercept was generally well tolerated in patients with rheumatoid arthritis, psoriatic
 arthritis, and ankylosing spondylitis. Adverse events that were reported in at least 3% of
 all patients with higher incidence in patients treated with etanercept than placebo are:

 -  Injection site reaction;

 -  Infection;

 -  Headache;

 -  Nausea;

 -  Rhinitis;

 -  Dizziness;

 -  Pharyngitis;

 -  Cough;

 -  Asthenia;

 -  Abdominal pain;

 -  Rash;

 -  Peripheral edema;

 -  Respiratory disorder;

 -  Dyspepsia;

 -  Sinusitis;

 -  Vomiting;

 -  Mouth ulcer;

 -  Alopecia

 Potential Benefits:

 No direct benefits from participation in the study can be guaranteed. The study medication
 will be provided by the Financial Sponsor at no charge.
Inclusion Criteria:

 -  Subjects must be able to give informed consent.

 -  Severe hidradenitis suppurativa clinically confirmed by the investigator and defined
 as recurrent abscesses, with 4 or more lesions (e.g. nodules or abscesses) with sinus
 track and scar formation (e.g. Stage II or III disease) that has not responded to
 previous standard therapies such as topical or oral antibiotics, or intralesional
 injections of steroids.

 -  Age 18 or older.

 -  Willingness to use at least one form of effective contraception during the study
 period and for one month after discontinuation of etanercept if female and of child
 bearing capacity or if male. If the patient elects to use a hormonal form of
 contraception then the patient must be on the same form of hormonal contraception for
 90 days prior to the start of Etanercept and must plan to continue using the same form
 of hormonal contraception for the duration of the study (e.g. until week 18).

 Exclusion Criteria:

 -  Use of oral or topical antibiotics, isotretinoin, or intralesional steroids within 30
 days prior to day 0 or at any time during the study treatment period.

 -  Use of systemic immunosuppressants within 90 days prior to day 0 of this study.

 -  Use of an investigational medication 90 days prior to day 0 of this study.

 -  Use of a live vaccine 90 days prior to day 0 of this study.

 -  Any previous use of TNF- α inhibitors.

 -  If using a hormonal form of contraception, the patient will be excluded if they have
 not used the same form of hormonal contraception for 90 days prior to the start of the
 etanercept (e.g. day 0) or are not willing to continue the use of the same form of
 hormonal contraception for the duration of the study.

 -  Active infection within 30 days of day 0 of the study that is moderate (discomfort
 sufficient to reduce or affect normal daily activity) or severe (incapacitating with
 inability to work or perform normal daily activities) or requires treatment with
 antibiotics.

 -  History of tuberculosis or other mycobacterial disease or positive screening visit
 purified protein derivative (PPD) (≥ 5 mm).

 -  Known history of an immuno-suppressing disease (e.g. HIV)

 -  Clinically significant abnormality in liver function, renal function, chemistry panel
 or complete blood count (CBC) (aspartate aminotransferase (AST) or alanine
 aminotransferase (ALT) ≥ 2 times the laboratory's upper limit of normal, hemoglobin <
 10.0 g/dL, platelet count <125,000/cm3, white blood count <3,500 cells/cm3 or > 15,000
 cells/cm3, or serum creatinine ≥ 2.0 mg/dL) or severe co-morbidities defined as
 diabetes mellitus requiring insulin, congestive heart failure, history of myocardial
 infarction, unstable angina, uncontrolled hypertension (systolic blood pressure > 180
 mmHg or diastolic blood pressure >110 mmHg), severe pulmonary disease (requiring
 oxygen therapy), history of cancer within 5 years (other than resected basal cell or
 squamous cell carcinoma and in situ cervical cancer), known history of active
 hepatitis B or C or HIV infection, history of demyelinating diseases or lupus.

 -  Pregnancy or lactation

 -  History of alcohol or drug abuse within 12 months of screening visit