A Placebo-Controlled Double-Blind Study on the Safety and Efficacy of Etanercept in Palmoplantar Pustulosis

Study Overview
=================
Brief Summary
-----------------
Palmoplantar pustulosis (PPP) is a chronic recurrent skin condition characterized by the presence of pustules, erythema and hyperkeratosis on palms and soles. PPP can be a severe and disabling disease limiting the ability to walk or work. Although studies on the quality of life of patients with PPP are not available, a recent investigation showed that palmoplantar psoriasis (non pustular) has a more important impact on quality of life than plaque psoriasis. This important impact on quality of life is not surprising as palmoplantar psoriasis as well as palmoplantar pustulosis may limit the ability to work or conduct activities with hands or even impair walking. The disease is sometimes associated with psoriasis elsewhere on the body. Current treatments for PPP include topical corticosteroids, cyclosporine, PUVA therapy, methotrexate and acitretin. Response to topical corticosteroids and PUVA therapy is often disappointing presumably because the thickness of the stratum corneum on palms and soles prevents good penetration of topical medications and light. Cyclosporine and methotrexate are sometimes used with success for PPP but there are concerns with long term toxicity of both drugs. Therefore there is a need for new treatments for PPP.

Detailed Description
-----------------
This is a placebo-controlled double blind study. Patients will be randomized to receive etanercept versus placebo in a 2:1 fashion for the first 3 months. All patients will receive etanercept in the last 3 months. Patients with active PPP will be included. A washout of 4 weeks for systemic medications and 2 weeks for Psoralen Ultra Violet A (PUVA) therapy will be required. A washout period of 2 weeks will be required for all other topical medications. The Palmoplantar pustulosis severity index (PPPASI) will be used to evaluate severity. Only patients with a severity score of 8 or more on hands and/or feet will be included. Safety will be assessed by performing physical examinations, evaluation of adverse events and biological parameters (complete blood count (CBC), chemistry, urinalysis). High quality digital medical photographs will be taken at baseline, 3 months and 6 months.

Official Title
-----------------
Phase 3 Study With a Placebo-Controlled, Double-blind, on the Safety and Efficacy of Etanercept in Palmo-Plantar Pustulosis

Conditions
-----------------
Palmoplantaris Pustulosis

Intervention / Treatment
-----------------
* Drug: Placebo comparator
* Drug: Etanercept


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Palmoplantar pustulosis with a severity score of at least 8 on hands and-or feet Age 18 years or older Patient who would benefit from systemic therapy Unless surgically sterile (or at least 1 year post-menopausal for women) patients (heterosexual men and women) must have used a effective method of contraception for at least 30 days before the start of the study drug and until at least 1 month after the last drug administration Informed consent obtained Normal or non clinically significant chest X ray taken within 6 months of screening Negative serum pregnancy test at screening and negative urine pregnancy test at day 0 for women of childbearing potential Negative personal history of tuberculosis Presence of PPP for more than 6 months Subject must be willing to inject themselves subcutaneously. Negative PPD results Exclusion Criteria: Use of topical steroids, topical tar preparations, or other topical anti PPP or anti-psoriatic preparations within the past two weeks Unstable forms of psoriasis (acute guttate psoriasis, psoriatic erythroderma, generalized pustular psoriasis) At the investigator's discretion any significant infection within 30 days of screening or a patient at risk of septicemia Presence of acute forms of tinea pedis and other causes of pustular eruptions of the palms and soles apart from PPP based on clinical evaluation Evidence of any skin condition that would interfere with the evaluation of PPP Use of investigational drugs within the past four weeks Use of systemic anti-PPP or anti-psoriatic drugs such as steroids, retinoids, or methotrexate within the past four weeks Use of parenteral systemic antibiotics within the past four weeks Use of cyclosporine within the past four weeks Use of ultraviolet light therapy (UVB, nbUVB or PUVA) within the past two weeks An unstable or serious medical condition Known sero-positivity for the HIV virus Known hypersensitivity to etanercept or one of its components Receipt of live attenuated vaccines 12 weeks or less before Day 0 and during the course of the study Pregnant or breast feeding female subject Any significant medical condition that might cause this study to be detrimental to the patient At the investigator's discretion current or history of alcohol or drug abuse that would interfere with the ability to comply with the study protocol Presence of congestive heart failure Presence of a demyelinating disorder (optic neuritis, multiple sclerosis or other)

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo then etanercept<br>Patients randomized to initiate the study with placebo for the first 12 weeks - Group 1 then crossed over to etanercept 50mg twice weekly for weeks 12 to 24 | Drug: Placebo comparator<br>* Patients received placebo subcutaneously twice weekly<br>* Other names: Saline;Drug: Etanercept<br>* Patients received etanercept 50 mg subcutaneously twice weekly<br>* Other names: Enbrel;|
| Active Comparator: Etanercept<br>Patients randomized to etanercept - Group 2. Patients received etanercept 50 mg subcutaneously twice weekly for 24 weeks | Drug: Etanercept<br>* Patients received etanercept 50 mg subcutaneously twice weekly<br>* Other names: Enbrel;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage Change in Palmoplantar Pustulosis Severity Index (PPPASI) Before Crossover | Comparison of the percentage change in Palmoplantar pustulosis severity index PPPASI) at 12 weeks in patients treated with placebo or etanercept PPPASI = (E + I + D)Area X 0.2 (R palm) + (E + I + D) Area X 0.2 (L palm) + (E + I + D) Area X 0.3 (R sole) + (E + I + D) Area X 0.3 (L sole). Erythema, pustules and desquamation are evaluated on a scale of 0 to 4 while area is evaluated on a scale of 0 to 6. The PPPASI score can vary from 0 (absence of disease) to 72 (most severe palmoplantar psoriasis possible). | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Adverse Events | Study the safety of etanercept in patients with PPP by collecting adverse events from the screening visit until week 28. For a given AE, a subject will be counted once even if he or she has experienced multiple episodes for that particular AE. An adverse event is any untoward medical occurrence including any clinically significant abnormal laboratory values or variation from the baseline condition to the last visit (week 28) in a patient receiving a pharmaceutical product, without regards to the possibility of a causal relationship with this treatment. | 28 weeks | 
| Percentage Change in Palmoplantar Pustulosis Area and Severity Index (PPPASI) | Evaluate efficacy using palmoplantar pustulosis area and severity index (PPPASI) in patient with palmoplantar pustulosis treated with etanercept for 6 months PPPASI = (E + I + D)Area X 0.2 (R palm) + (E + I + D) Area X 0.2 (L palm) + (E + I + D) Area X 0.3 (R sole) + (E + I + D) Area X 0.3 (L sole). Erythema, pustules and desquamation are evaluated on a scale of 0 to 4 while area is evaluated on a scale of 0 to 6. The PPPASI score can vary from 0 (absence of disease) to 72 (most severe palmoplantar psoriasis possible). | 24 weeks | 
| Percentage Change in Palmoplantar Pustulosis Area and Severity Index (PPPASI) After Crossover | Evaluate efficacy using palmoplantar pustulosis area and severity index (PPPASI) in patient with palmoplantar pustulosis treated with etanercept for 6 months PPPASI = (E + I + D)Area X 0.2 (R palm) + (E + I + D) Area X 0.2 (L palm) + (E + I + D) Area X 0.3 (R sole) + (E + I + D) Area X 0.3 (L sole). Erythema, pustules and desquamation are evaluated on a scale of 0 to 4 while area is evaluated on a scale of 0 to 6. The PPPASI score can vary from 0 (absence of disease) to 72 (most severe palmoplantar psoriasis possible). | 12 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Palmoplantar pustulosis, Psoriasis, Etanercept