Efficacy and Safety of Enstilar Foam in Combination With Apremilast (Otezla) in Patients With Moderate Plaque Psoriasis

Study Overview
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Brief Summary
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This study seeks to show whether there is a benefit of prescribing Enstilar with Otezla in the treatment of patients with moderate plaque type psoriasis. Subjects will be randomized to study treatment at a 1:1 ratio of Otezla plus Enstilar foam versus Otezla plus vehicle foam.

Detailed Description
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Approximately 50 subjects from 4 sites will be enrolled in this investigator-blind study. Subjects will be randomized 1:1 to Otezla plus Enstilar foam or Otezla plus vehicle foam and all adverse events and concomitant medications will be recorded. Subjects will attend a screening visit/baseline visit and those with plaque-type psoriasis who have been started on commercial Otezla in the last 7 days will be randomized to study treatment as outlined above. Enstilar or the vehicle will be initiated for the first 4 weeks and then Otezla will be continued as monotherapy for the next 8 weeks. Enstilar or the vehicle will be reinitiated for the last 4 weeks of the study. Total study period is 16 weeks and study visits will occur as follows: screening/baseline, week 1, 2, 3, 4, week 12, and week 16. Study assessments at each visit will be PASI, BSA, PGA, Itch VAS, DLQI, and standard medical assessments. There will be standard medication/treatment and washout periods.

Official Title
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Efficacy and Safety of Enstilar Foam in Combination With Apremilast (Otezla) in Patients With Moderate Plaque Psoriasis

Conditions
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Plaque Psoriasis

Intervention / Treatment
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* Drug: Enstilar
* Drug: Vehicle
* Drug: Otezla


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: I. Outpatient, male or female subjects of any race, 18 years of age or higher. Female subjects of childbearing potential must have a (-)UPT (urine pregnancy test) result at within 7 days of the first dose of study drug and practice a reliable method of contraception throughout the study; A female is considered of childbearing potential unless she is: - postmenopausal ≥ 5 years of age, without a uterus and/or both ovaries; or has been surgically sterile for ≥ 6 moths. Reliable methods of contraception are: - hormonal methods or IUD (intrauterine device) in use ≥ 90 days prior to study drug administration, barrier methods plus spermicide in use ≥ 14 days prior, or vasectomized partner. [Exception: Female subjects of CBP (child bearing potential) who are not sexually active are not required to practice a reliable method of contraception and may be enrolled at the Investigator's discretion provided they are counseled to remain sexually inactive for the duration of the study and understand the risks involved in getting pregnant during the study.] ii. Subjects with moderate plaque type psoriasis who have been started on commercial Otezla within the last 10 days. iii. Physician Global Assessment (PGA) score of 3. iv. Able to understand study requirements and sign Informed Consent/HIPAA forms. Exclusion Criteria: I. Female subjects who are pregnant, breast-feeding, or who are of childbearing potential and not practicing a reliable method of birth control, or male subjects planning a pregnancy with their spouse or partner while in the study. ii. History of hypercalcemia or vitamin D toxicity or history of significant renal or hepatic disease iii. Patients with guttate, erythrodermic, or pustular psoriasis iv. Serious skin condition (other than psoriasis) or uncontrolled medical condition (in the opinion of the investigator). v. Skin conditions (e.g.eczema) other than psoriasis that may interfere with evaluations of psoriasis. vi. Known hypersensitivity to Enstilar Foam or any of its components. vii. Current drug or alcohol abuse (Investigator opinion). viii. Subject unable to commit to all the assessments required by the protocol. ix. Current enrollment in another clinical study and treatment with another experimental drug or approved therapy for experimental use within 30 days prior to the Screening Visit.

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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Otezla plus Enstilar foam<br>Subjects randomized to this group will receive Otezla 30mg by mouth twice daily and Enstilar applied to affected areas once daily | Drug: Enstilar<br>* Enstilar foam applied to affected areas daily<br>* Other names: calcipotriene and betamethasone dipropionate;Drug: Otezla<br>* Otezla 30mg<br>|
| Placebo Comparator: Otezla plus vehicle foam<br>Subjects in this group will take Otezla 30mg by mouth twice daily and vehicle foam applied to affected areas once daily | Drug: Vehicle<br>* vehicle foam applied to affected areas once daily<br>Drug: Otezla<br>* Otezla 30mg<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent of Subjects With a Psoriasis Assessment and Severity Index (PASI) 75 at Week 16 | PASI combines the assessment of the severity of lesions and the area affected into a single score ranging from 0(no disease) to 72(maximal disease.) The body is divided into 4 sections: head (10% of total body surface area,) arms (20%,) trunk(30%,) and legs (40%.) Each of these is scored by itself and the 4 scores then combined to obtain thePASI. For each body area, the percent of skin area involved is estimated and graded based on this value (0=0% of area involved, 1=<10%, 2=10-29%, 3=30-49%, 4=50-69%, 5=70-89%, 6=90-100%.) Within each area, the severity of disease is based on 3 clinical signs: erythema or redness, induration or thickness, and desquamation or scaliness. Each is graded on a scale from 0(none) to 4(maximum.) The sum of all 3 parameters is calculated for each body section, multiplied by the area score for that section and then multiplied by the weight of that section (.1for head, .2 arms, .3 trunk and .4 legs) | 16 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent of Subjects With PASI 75 at Week 4 and Week 12 | Psoriasis Area & Severity Index (PASI) is a tool used to measure the severity of psoriasis. It combines the assessment of the severity of lesions and the area affected into a single score ranging from 0(no disease) to 72(maximal disease.) | 4 weeks, 12 weeks | 
| Percent of Subjects With PASI 90 and 100 at Week 16 | Psoriasis Area & Severity Index (PASI) is a tool used to measure the severity of psoriasis. It combines the assessment of the severity of lesions and the area affected into a single score ranging from 0(no disease) to 72(maximal disease.) | 16 weeks | 
| Per Cent of Patients With at Least 1-grade Improvement in Physicians Global Assessment (PGA) at Week 4 and Week 12 and Week 16 | The Investigator will rate the severity of of disease based on the assessment of 3 clinical signs (erythema, induration, desquamation) wherein 0=no signs of psoriasis, 1=almost clear, 2=mild, 3=moderate, 4=severe | 4 weeks, 12 weeks, 16 weeks | 
| Global Improvement in Itch Visual Analogue Scale (VAS) at Week 4,12 and 16 | The Itch VAS (Visual Analog Scale) is completed by subjects wherein they are asked to rate the severity of their itching over the last 48 hours on a scale from 0 (no itching) to 10 (unbearable itching); low scores indicate a better outcome. | 4 weeks, 12 weeks, 16 weeks | 
| Global Percent Improvement in Dermatologic Quality of Life Index (DLQI) at Week 4, 12, and 16 | The DLQI is a 10-question tool completed by subjects to ascertain the severity of disease based on the extent to which disease interferes with daily life. Each question is scored according to the response wherein Very Much =3, A lot=2, A little=1 and Not at all=0. The sum of all responses is then recorded on a scale from 0 to 30, lower scores indicating better quality of life. | 4 weeks, 12, weeks, 16 weeks |