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

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

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.

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.

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.