Enstilar® Foam in the Treatment of Chronic Plaque Psoriasis in Patients With Skin of Color

Study Overview
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Brief Summary
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This will be a single-center, randomized, double-blinded, vehicle-controlled clinical study to determine the efficacy of Enstilar® foam, a combination of calcipotriene and betamethasone dipropionate 0.005%/0.064%, in the treatment of psoriasis vulgaris in skin of color (FST IV-VI). This study will also evaluate the degree of erythema versus hyperpigmentation in psoriasis plaques in skin of color (and its change with Enstilar ® treatment) as well as the effect of Enstilar ® on post-inflammatory hyperpigmentation and quality of life.

Detailed Description
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Psoriasis is a chronic inflammatory disorder primarily affecting the skin and joints. This condition occurs in different ethnic groups worldwide with varying prevalence. There are notable differences in psoriasis presentation in skin of color groups. Black patients with psoriasis tend to have less erythema, increased risk of pigmentation, thicker plaques, more scaling, and greater body involvement as compared to white patients. The resolution of psoriasis lesions in darker skin types is associated with a higher rate of dyspigmentation (both hyper- and hypo-pigmentation), which may be more bothersome to patients than the psoriasis itself. Further, several studies have shown that psoriasis is associated with greater psychological impact and worse quality of life in non-whites with psoriasis compared to whites. Unique issues in skin of color populations make studies dedicated to darker skin types essential for the treatment of psoriasis in these populations. This study will evaluate the efficacy of Enstilar® foam, a combination of calcipotriene and betamethasone dipropionate 0.005%/0.064%, in the treatment of psoriasis vulgaris in darker skin types. This study will also evaluate the degree of erythema versus hyperpigmentation in psoriasis plaques as well as the effect of Enstilar ® on post-inflammatory hyperpigmentation and quality of life in skin of color.

Official Title
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A Double-blinded, Placebo-controlled Study to Evaluate the Tolerability and Efficacy of Enstilar® (Calcipotriene and Betamethasone Dipropionate) Foam in the Treatment of Chronic Plaque Psoriasis in Patients With Skin of Color

Conditions
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Plaque Psoriasis, Psoriasis

Intervention / Treatment
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* Drug: Enstilar® foam
* Drug: Vehicle foam


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Provide written, signed and dated informed consent prior to initiating any study-related activities. Male or female >18 years of age at the time of screening Fitzpatrick Skin phototype IV-VI, non-white race/ethnicity, including but not limited to - --African Americans, Asians, Pacific Islanders and Hispanics. Clinical diagnosis of chronic plaque-type psoriasis of the body Plaque psoriasis with ≥2% Body Surface Area (BSA) involvement (may include scalp involvement), PASI Score ≥ 2, IGA mod 2011 score of 2 or greater (based on scale of 0-4) Females of childbearing potential (FCBP) must have a negative pregnancy test at Screening and Baseline. While using investigational product and for at least 28 days after last application of investigational product, FCBP who engage in activity in which conception is possible must use one of the approved contraceptive options d Must be in general good health as judged by the Investigator, based on medical history and physical examination. Exclusion Criteria: Form of diagnosed psoriasis other than chronic plaque psoriasis (i.e. guttate, erythrodermic, pustular) Diagnosis of other active, ongoing skin diseases or skin infections that may interfere with examination of psoriasis lesions Ongoing use of other psoriasis treatment including but not limited to topical or systemic corticosteroids, other topical medications (i.e. coal tar), oral or biologic medications for the treatment of psoriasis, and UV therapy. The following washout periods will be required: 2 weeks for topical therapy; 2 weeks for phototherapy; 12 weeks for biologic or targeted therapies; 4 weeks for other systemic therapies Use of oral estrogen therapy, excluding oral contraceptive pills Women who are pregnant, nursing, or of child-bearing potential who are unwilling to use appropriate method(s) of contraception. Patients unwilling to limit exposure to UV light Current significant medical problems that, in the discretion of the investigator, would put the patient at significant risk Patients with disorders of calcium metabolism and/or hypercalcemia Use of any investigational drug within 4 weeks prior to randomization, or 5 pharmacokinetic/pharmacodynamics half-lives, if known (whichever is longer) History of allergy to any component of the IP

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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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: 4:1 Enstilar(R): placebo from baseline to week 4, then open-label Enstilar from weeks 4 to 8.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Enstilar® foam<br>Enstilar® foam - a combination of calcipotriene and betamethasone dipropionate 0.005%/0.064%. | Drug: Enstilar® foam<br>* for 4 weeks<br>* Other names: Enstilar 0.005%-0.064% Topical Foam;|
| Placebo Comparator: Vehicle foam<br>does not contain the active ingredient | Drug: Vehicle foam<br>* for 4 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Patients Who Achieved Treatment Success | Number of patients at week 4 who achieved treatment success according to Investigator's Global Assessment (IGA mod 2011) of the entire body including scalp. IGA ranges from 0 (clear) to 4 (severe). Treatment success is defined as IGA of clear (0) or almost clear (1) for patients with ≥ moderate disease at baseline or IGA of clear (0) for patients with mild disease at baseline. | Week 4 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Achieving Targeted Psoriasis Area and Severity Index (PASI) | Number of patients achieving ≥50% improvement and/or ≥75% improvement in PASI at weeks 4 and 8 . PASI combines the assessment of the severity of lesions and the area affected into a single score in the range of 0 (no disease) to 72 (maximal disease) | 4 weeks, 8 weeks | 
| Number of Patients Achieving Targeted Psoriasis Scalp Severity Index (PSSI) | Number of patients achieving ≥50% improvement and/or ≥75% improvement in PSSI at weeks 2, 4 and 8. The Psoriasis Scalp Severity Index (PSSI) assesses severity of scalp disease along the parameters of erythema, induration, and desquamation. The PSSI uses a 5-point scale to grade the three aforementioned clinical parameters. The parameters scores are summed and multiplied by an integer (0-6) that represents the area of affected scalp. The PSSI score ranges from 0 (no disease) to 72 (maximal disease). | 2 weeks, 4 weeks, 8 weeks | 
| Number of Patients With Treatment Success According to Investigator Global Assessment (IGA Mod 2011) | Number of patients at week 8 who achieved treatment success according to IGA mod 2011 of the entire body including scalp. IGA ranges from 0 (clear) to 4 (severe). Treatment success is defined as IGA of clear (0) or almost clear (1) for patients with ≥ moderate disease at baseline or IGA of clear (0) for patients with mild disease at baseline. | at week 8 | 
| Number of Participants Who Achieved Treatment Success According to Scalp Investigator Global Assessment (ScIGA) | Number of patients at weeks 4 and 8 who achieved treatment success according to ScIGA. ScIGA ranges from 0 (clear) to 4 (severe). Treatment success is defined as ScIGA of clear (0) or almost clear (1) for patients with ≥ moderate disease at baseline or ScIGA of clear (0) for patients with mild disease at baseline. | 4 weeks, 8 weeks | 
| Patient's Global Assessment of Itch | Patient's Global Assessment of Itch as compared to baseline measured by Visual Analog Scale (VAS). The VAS is a numerical scale used to assess patients' perception of pruritus/itch.The evaluation is a 10cm long line on which the subjects indicate the severity of their pruritus from 0 (no pruritus) to 10 (severe pruritus). | Baseline, 2 weeks, 4 weeks, 8 weeks | 
| Number of Participants Who Clear or Almost Clear Disease According to the Patient's Global Assessment of Disease Severity (PaGA) | PaGA have 5 distinct options ranging from (0) Clear to (4) Severe. Number of participants with treatment response defined as clear or almost clear disease (for those with moderate or severe disease at baseline) or clear disease (for those with mild disease at baseline) at 4 weeks and 8 weeks. | 4 weeks, 8 weeks | 
| Erythema Indices of Target Psoriasis Plaque | A skin spectrophotometer (Mexameter) was used to quantify the degree of erythema of lesional skin compared to an index area (of unaffected skin). The mexameter measures from 0-999. The higher the value for erythema index the more red pigmentation in the skin, this is assessed by quantification of hemoglobin in the skin via reflectance spectroscopy. | Baseline, 2 weeks, 4 weeks, 8 weeks | 
| Melanin Indices of Target Psoriasis Plaque | A skin spectrophotometer (Mexameter) was used to quantify the melanin index (degree of hyperpigmentation or hypopigmentation) of lesional skin compared to an index area of unaffected skin. The mexameter measures from 0-999. The higher the value for melanin index, the more brown pigment in the skin, this is assessed by quantification of melanin in the skin via reflectance spectroscopy. | Baseline, 2 weeks, 4 weeks, 8 weeks | 
| Physician Dyspigmentation Visual Analog Scale (VAS) | An investigator performed a visual analog scale (VAS) rating the degree of dyspigmentation of the skin. This VAS ranges from - 5 to 5 as follows: 5 severe dark brown pigmentation (darkest imaginable color), 4 dark brown pigmentation, 3 medium brown pigmentation, 2 light brown pigmentation, 1 slight dark pigmentation (barely perceptible compared to surrounding skin), 0 baseline skin pigmentation, -1 slight hypopigmentation (barely perceptible compared to surrounding skin), -2 mild hypopigmentation (light brown), -3 moderate hypopigmentation (creme-colored skin), -4 severe hypopigmentation (almost complete absence of pigment), -5 depigmentation (complete absence of pigment). | baseline, 4 weeks, 8 weeks | 
| Mean Change in Dermatology Life Quality Index (DLQI) | DLQI full scale ranges from 0 (no effect at all on patient's life) to 30 (extremely large effect on patients' life). Mean change from Baseline in DLQI at 2, 4, and 8 weeks. | Baseline, 2 weeks, 4 weeks, 8 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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skin of color, psoriasis, Enstilar, skin diseases