Study to Evaluate the Efficacy and Safety of P-3073 Nail Solution in the Treatment of Mild to Moderate Psoriatic Fingernail/s

Study Overview
=================
Brief Summary
-----------------
The objective of this phase III study is to evaluate the efficacy, systemic safety and local tolerability of P-3073 (calcipotriene 0.005%) nail solution in patients with mild to moderate psoriatic fingernail/s.

Detailed Description
-----------------
This phase III study versus vehicle will be conducted to confirm the clinical efficacy and safety of P-3073 in patients affected by isolated psoriatic nail(s) and/or those with psoriatic nails and concomitant mild-to-moderate plaque psoriasis. The evaluation of the primary endpoint will be made using the Nail Psoriasis Severity Index (NAPSI). The secondary objectives will be: To assess if the topical treatment with P-3073 is able to improve the quality of life and discomfort in patients with psoriatic fingernail. To assess the safety and tolerability of topical P-3073 in the treatment of psoriatic fingernail. The study consists of two arms comparing P-3073 (calcipotriene 0.005%) and vehicle. Eligible patients will be randomized to either P-3073 or placebo in a 1:1 ratio, stratified by their target nail NAPSI severity at screening. The study population will include at least 470 patients (235 for each group) with nail psoriasis (fingernails) of the matrix and/or of the nail bed in at least one fingernail. The total duration of the trial for each patient will be approximately 29 weeks (from Screening to Follow-up). During the 24 weeks of the treatment period, patients will apply the assigned treatment to all affected psoriatic fingernails once daily.

Official Title
-----------------
A Randomized, Doubleblind, Vehicle-controlled, Parallel-group Trial to Assess the Efficacy, Safety and Tolerability of P-3073 for Topical Treatment of Nail Psoriasis

Conditions
-----------------
Nail Psoriasis

Intervention / Treatment
-----------------
* Drug: P-3073 (calcipotriene 0.005%)
* Drug: Vehicle of P-3073


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Written informed consent before starting any study related procedure. Patients ages ≥ 18 and ≤ 80 years old. Men or women. Outpatients. Patients with mild to moderate psoriatic fingernail/s, defined as fingernail/s with matrix psoriasis NAPSI score and/or bed psoriasis NAPSI score ≥ 1 and ≤ 3 at baseline. The sum of the scores for each nail should range between 1 and 6. In case of skin involvement, patients with established clinical diagnosis of mild to moderate psoriasis (BSA involvement ≤ 8% or Psoriasis Area Severity Index (PASI) ≤ 10). Exclusion Criteria: Use of any systemic treatment for psoriasis and/or nail psoriasis during the last six months before the screening visit. Use of any topical treatment for nail psoriasis on fingernails during the last six months before the screening visit. Use of photochemotherapy (phototherapy is allowed) or other forms of radiotherapy during the last four weeks before the screening visit. Positive mycology findings (KOH evaluation or culture) obtained in the three months before the screening visit or positive KOH evaluated at the screening visit. Patients using nail polish or other nail cosmetic products during last 72 hours prior to study drug application. Systemic use of the following therapies for any reason during last three months before the screening visit: immunosuppressives, chemotherapy and corticosteroids (topical use for plaque psoriasis is allowed). Consumption of oral Vitamin D or its analogues for any reason during the last three months before the screening visit (Calcipotriene topical use for plaque psoriasis is allowed). Patients with a clinically significant history of cardiovascular, renal, neurologic, liver, immunologic or endocrine dysfunction. A clinically significant disease is defined as one that in the opinion of the investigator may either put the patient at risk because of participation in the study or a disease that may influence the results of the study or the patient's ability to participate in the study. Patients with a recent history (< 1 year) of myocardial infarction and/or (< 3 years) of heart failure or patients with any cardiac arrhythmia requiring drug therapy. History of hypercalcaemia or hypercalciuria. History of previous or current malignancy in particular lymphoma, melanoma and/or basal cell carcinoma. History of allergic reactions to Calcipotriene or P-3073 excipients. Patients unable to understand the procedures and purposes of the study. Patients unable or unwilling to accept and meet study requirements. Use of an investigational drug or participation in an investigational study within 30 days, or 6 half lives whichever is longer, prior to application of study medication. Alcohol or substance abuse. AIDS symptoms or any other immunodeficiency. Additional exclusion criteria for females only: Breast-feeding patients. Positive urine pregnancy test at screening (performed for all females of child bearing potential or for those in non-surgical post-menopause for less than 1 year). Female of childbearing potential having unprotected sexual intercourse with any non-sterile male partner (i.e., a male who has not been sterilized by vasectomy at least 6 months prior to drug application) within 14 days prior to study drug application. Acceptable methods of contraception are the following: condom, diaphragm, intrauterine contraceptive device (placed at least 4 weeks prior to study drug application), pill + condom.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 80 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: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: P-3073<br> | Drug: P-3073 (calcipotriene 0.005%)<br>* Topical solution P-3073 (calcipotriene 0.005%) once daily for 24 weeks.<br>|
| Placebo Comparator: Vehicle<br> | Drug: Vehicle of P-3073<br>* Once daily for 24 weeks.<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients with clear target nail at Week 24 | Defined as Nail Psoriasis Severity Index (NAPSI) =0 | Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of affected nails at baseline with NAPSI=0 at Week 24 | Defined as affected nails with NAPSI=0 | Baseline - Week 24 | 
| Proportion of patients with clear target nail bed at Week 24 | Defined as nail bed in NAPSI=0 | Baseline - Week 24 | 
| Proportion of patients with clear target nail matrix at Week 24 | Defined as nail matrix in NAPSI=0 | Baseline - Week 24 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Calcipotriene