A Phase II Open Label Clinical Trial of Etanercept for the Treatment of Hidradenitis Suppurativa

Trial Information

A Phase II Open Label Clinical Trial of Etanercept for the Treatment of Hidradenitis Suppurativa

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.