An Investigator Initiated Open Label Study Evaluating the Efficacy and Tolerability of Oral Apremilast for the Treatment of Nail Psoriasis

Study Overview
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Brief Summary
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Psoriasis vulgaris is a common inflammatory condition of the skin that results in scaly red itchy plaques. In addition to affecting the skin, psoriasis can also cause disease in the finger and toe nails. The most characteristic nail findings associated with nail psoriasis are nail pitting, onycholysis with a rim of erythema, and oil spots. Because nail psoriasis causes a substantial disease burden for patients, it is critical that safe and effective treatments are found for this specific type of psoriasis. Unfortunately, nail psoriasis is often difficult to treat. Apremilast is an orally available small molecule inhibitor of phosphodiesterase 4 (PDE4) that is FDA approved for the treatment of psoriasis and psoriatic arthritis. Apremilast has shown promising results for treating psoriatic arthritis and nail disease; however more data is needed regarding its effect on nail psoriasis (Kavanaugh, et al). We hypothesize that apremilast will prove to be highly effective in treating nail psoriasis. We propose to conduct an open label clinical trial to investigate the efficacy and tolerability of apremilast in treating nail psoriasis, where we will follow the package insert guidelines for treating patients with apremilast.

Detailed Description
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Psoriasis vulgaris is a common inflammatory condition of the skin that results in scaly red itchy plaques. In addition to affecting the skin, psoriasis can also cause disease in the finger and toe nails. Nail psoriasis is a chronic disease and can present with the following clinical findings: splinter hemorrhage, leukonychia, red spots in the lunula, nail pitting, nail plate crumbling, hyperkeratosis, and/or nail plate separation from the nail bed. The most characteristic nail findings associated with nail psoriasis are nail pitting, onycholysis with a rim of erythema, and oil spots. Special interest will be paid to identifying these particular nail findings in patients, however all potential nail psoriasis symptoms will be assessed in patients in this study. Due to the highly visible nature of disease in the fingernails, nail psoriasis often results in a substantial deleterious effect on a patient's quality of life. Patients also can have significant pain and disability due to nail psoriasis. Psoriasis patients who have nail involvement are known to have more severe psoriasis disease and diminished quality of life when compared to psoriasis patients without nail disease. Patients with nail psoriasis often also have psoriatic arthritis, and untreated psoriatic arthritis is known to lead to joint destruction with potentially severe morbidity. Nail psoriasis has a reported incidence of 80 to 90% (Jiaravuthiasan, et al). Because nail psoriasis causes a substantial disease burden for patients, it is critical that safe and effective treatments are found for this specific type of psoriasis. Unfortunately, nail psoriasis is often difficult to treat. Apremilast is an orally available small molecule inhibitor of phosphodiesterase 4 (PDE4) that is FDA approved for the treatment of psoriasis and psoriatic arthritis. PDE4 is one of the main phosphodiesterases expressed in immune cells, and its inhibition by apremilast is thought to increase cyclic adenosine monophosphate and thereby decrease the inflammatory response. Specifically, apremilast is believed to down regulate pro-inflammatory cytokines including TNF-α, (Tumor necrosis Factor) IL-23 (Interleukin), IL-17, and others. Apremilast has shown promising results for treating psoriatic arthritis and nail disease; however more data is needed regarding its effect on nail psoriasis (Kavanaugh, et al). We hypothesize that apremilast will prove to be highly effective in treating nail psoriasis. We propose to conduct an open label clinical trial to investigate the efficacy and tolerability of apremilast in treating nail psoriasis, where we will follow the package insert guidelines for treating patients with apremilast.

Conditions
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Psoriatic Nail, Psoriasis Vulgaris, Psoriasis

Intervention / Treatment
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* Drug: Apremilast


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: - Patients older than 18 Give written informed consent prior to any study procedures being conducted, and candidates will authorize the release and use of protected health information (PHI) Be willing and consent to having photos taken of their fingernails Diagnosis of chronic plaque psoriasis that has been present for at least 6 months prior to baseline Plaque psoriasis involving at least 5% of the patient's body surface area Nail psoriasis in at least one finger nail with a mNAPSI of 5 or greater A Nail Pain VAS score of 4 or higher. The Nail Pain VAS will assess the severity of pain linked to the nail disease. Must have discontinued all systemic therapies for the treatment of psoriasis or psoriatic arthritis at least 4 weeks or 5 half-lives, and biologics 2 months or 5 half-lives (whichever is longer) prior to baseline visit Must have discontinued all topical therapies for the treatment of psoriasis at least 2 weeks prior to baseline visit Subjects must have discontinued UV therapy at least 2 weeks prior to baseline and PUVA (psoralen ultraviolet light therapy) at least 4 weeks prior to baseline. Subjects must be in good general health without significant uncontrolled comorbidities, other than psoriasis, as determined by the investigator based on exam findings, medical history, and clinical laboratories. Patients with stable mild renal insufficiency are eligible for enrolling in this trial. Females of childbearing potential must use an approved birth control method while receiving treatment and for 28 days following the last dose of apremilast, and there must be a documented negative pregnancy tests prior to initiating treatment. Approved birth control methods include hormonal contraception (oral, injection, implant, transdermal patch, vaginal ring), intrauterine device, partners vasectomy, or male or female condoms that are not made of natural materials plus a diaphragm with spermicide, cervical cap with spermicide, or a contraceptive sponge with spermicide. Females not of child bearing potential are defined as being at least 1 year postmenopausal or surgically sterile (bilateral tubal ligation, bilateral oophorectomy and/or hysterectomy). Male subjects, including those who have had a vasectomy, must use condoms not made of natural materials for the duration of the trial and for at least 28 days after the last dose of apremilast if conception is possible. Exclusion Criteria: - Unable to comply with the protocol (as defined by the Investigator; i.e. drug or alcohol abuse or history of noncompliance) Pregnancy or breastfeeding Female patients of childbearing potential and male patients who engage in activity where contraception is possible who are unable to use the approved methods of contraception throughout the length of the study and 28 days following the last dose Patients who have or have had thoughts of suicide or hurting themselves. Patients with prior exposure to apremilast Subject has been treated with an investigational drug within 30 days or 5 half-lives (whichever is longer) prior to baseline visit. Patients with severe, progressive, or uncontrolled medical or psychiatric disease. Concomitant therapy with medications that are strong cytochrome P450 inducers, including rifampin, phenobarbital, carbamazepine, or phenytoin Any other dermatologic conditions that prohibit or confound the ability of the investigator to interpret skin and/or nail exam findings. Patients who will be unable to avoid the use of systemic steroids, excluding intranasal or inhaled steroids that will be permitted, for the duration of the trial Any known hypersensitivity to apremilast Any subject who, in the opinion of the investigator, will be uncooperative or unable to comply with duty procedures

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Study Group<br>Open-label drug administration group. No comparator. | Drug: Apremilast<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Percent Change of mNAPSI (Modified Nail Area Psoriasis Severity Index) at Week 36 Compared to Baseline for All Nails. | mNAPSI is an objective scoring system administered by trained health care providers. Scores range from 0 (no nail disease) to 130 (complete nail involvement in all ten nails.) | 36 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Percent Change in mNAPSI of Target Nail at Weeks 12, 24, 36, 48, and 52 Compared to Baseline. | The target nail will be defined as the nail that has the highest mNAPSI singe nail score at baseline. This nail will remain the target nail for the remainder of the study. mNAPSI is an objective scoring system administered by trained health care providers. Scores range from 0 (no nail disease) to 130 (complete nail involvement in all ten nails.) | 12, 24, 36, 48, and 52 weeks | 
| Proportion of Patients Achieving mNAPSI of 0 in All Fingernails at Weeks 36 and 52. | mNAPSI is an objective scoring system administered by trained health care providers. Scores range from 0 (no nail disease) to 130 (complete nail involvement in all ten nails.) | 36 and 52 weeks | 
| Change in Patient Reported Nail Pain, as Based on the Nail Pain VAS Score, at Week 52 Compared to Baseline Score. | Nail pain VAS is a subjective survey completed by patients. Scores range from 0 to 10. | 52 weeks | 
| Pain Change in Psoriatic Arthritis Symptoms at Week 52 Compared to Baseline, in Patients Who Self-identify as Having Psoriatic Arthritis at Baseline. | Symptoms will be assessed using a visual analogue scale (VAS) for reporting psoriatic arthritis pain, which is a subjective survey that patients will complete on a scale of 1 to 10. | 52 weeks | 
| Safety Adverse Effects Will be Assessed at Each Visit | Patients will be asked about illnesses and other health related events while taking part in the study. | 52 weeks | 
| Proportion of Patients Achieving a mNAPSI 75 Response, as Defined by 75% or Greater Reduction Over Baseline in mNAPSI Score at Weeks 12, 24, 36, 48, and 52 for the Target Fingernail. | The target nail will be defined as the nail that has the highest mNAPSI singe nail score at baseline. This nail will remain the target nail for the remainder of the study. mNAPSI is an objective scoring system administered by trained health care providers. Scores range from 0 (no nail disease) to 130 (complete nail involvement in all ten nails.) | 12, 24, 36, 48, and 52 weeks | 
| Mean Change in the Total Number of Nails Involved Assessed at Weeks 36 and 52 Compared to Baseline. | Health care providers to assess number of nails involved. | 36 and 52 weeks |