Clinical trial NCT03506477
Conditions: Plaque Psoriasis Psoriasis
Keywords: skin of color psoriasis Enstilar skin diseases
Sponsor: Icahn School of Medicine at Mount Sinai
Start date: 2018-05-21; Completion date: 2019-09-25
Enrollment: 25 participants; Allocation: RANDOMIZED; Intervention model: CROSSOVER

Brief summary:
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:
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.

Arms: arm 1: Enstilar® foam - a combination of calcipotriene and betamethasone dipropionate 0.005%/0.064%. arm 2: does not contain the active ingredient
Interventions: intervention 1: Enstilar® foam intervention 2: Vehicle foam
Intervention descriptions: intervention 1: for 4 weeks intervention 2: for 4 weeks

Protocol documents:
Prot_000.pdf: 
NCT03506477 
Document Date: 8/10/2017
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 (Fitzpatrick skin phototypes IV-VI). 
PI: Andrew Alexis, MD, MPH 


 
Protocol Name: 
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 (Fitzpatrick skin 
phototypes IV-VI). 
Principal Investigator:  
Andrew Alexis, MD, MPH 
Primary Contact 
Name/Contact Info: 
Andrew Alexis, MD, MPH 
212-523-3888 
Date Revised: 
08/10/2017 
Study Number: 
IF2166478 
 
1 
Revised 9/2/14 
HRP-503 PROTOCOL TEMPLATE  
• Note that, depending on the nature of your research, certain questions, directions, or entire sections 
below may not be applicable. Provide information if and when applicable, and in cases where an 
entire section is not applicable, indicate this by marking the section “N/A”.  Do not delete any 
sections. 
• For any items below that are already described in the sponsor’s protocol, the investigator’s 
protocol,  the grant application, or other source documents, you may simply reference the title and 
page numbers of these documents in the sections below, rather than cutting and pasting into this 
document. Do not refer to the Sample Consent document, or information on the application form 
in this document. 
• Keep an electronic copy of this version of the document. You will need to modify this copy when 
making changes. 
 
Brief Summary of Research:  
Psoriasis is a chronic inflammatory disorder primarily affecting the skin and joints that occurs in diverse 
ethnic groups worldwide.  There is paucity of data on the use of topical medications in dark-skinned 
individuals. Unique issues in skin of color (SOC) populations, including increased risk of 
dyspigmentation (hyperpigmentation and hypopigmentation), make studies dedicated to darker skin types 
essential for treatment of psoriasis in these populations. 
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 SOC (FST IV-VI).  A total of 25 subjects (ages 
18+, male and female, BSA ≥2%, PASI Score ≥ 2, IGA mod 2011 score ≥ 2) are expected to complete 
this study, which will run for a total of up to 12 weeks.  
The study consists of three periods: Screening (from 0 to 4 weeks); Double-blind, vehicle-controlled 
treatment period (4 weeks), and open-label treatment period (4 weeks). During the second period (double-
blind, vehicle-controlled), a total of 20 subjects will be randomized to Enstilar ® and a total of 5 subjects 
will be randomized to vehicle. Those who meet all of the inclusion/exclusion criteria and are enrolled in 
the study will receive study drug (either Enstilar® or vehicle) for the entire treatment period. 
 
1) Objectives 
The purpose of this study is to evaluate the efficacy and safety of combination calcipotriene and 
betamethasone dipropionate 0.005%/0.064% foam in the treatment of psoriasis vulgaris in males and 
females with skin of color (SOC).  
 


 
Protocol Name: 
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 (Fitzpatrick skin 
phototypes IV-VI). 
Principal Investigator:  
Andrew Alexis, MD, MPH 
Primary Contact 
Name/Contact Info: 
Andrew Alexis, MD, MPH 
212-523-3888 
Date Revised: 
08/10/2017 
Study Number: 
IF2166478 
 
2 
Revised 9/2/14 
2) Background 
 
Psoriasis is a chronic inflammatory disorder primarily affecting the skin and joints. This condition occurs 
in different ethnic groups worldwide with varying prevalence. In the United States, the Health and 
Nutrition Examination Survey estimated the prevalence of psoriasis to be 3.2% in adults; a significant 
number of affected were of darker phototypes, including African Americans (1.9%) and Hispanics 
(1.6%).1,2 The true prevalence of psoriasis in black and Hispanic populations may actually be higher, 
given that non-whites are more likely to have undiagnosed psoriasis than whites (in part due to barriers to 
care and decreased health care utilization in these groups).3,4  
 
Chronic plaque psoriasis classically presents as sharply demarcated erythematous plaques with micaceous 
scale. Nonetheless, 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.5,6,7 Several studies suggest that 
erythema is more challenging to detect in skin of color, and inflammation that typically manifests as pink 
or red lesions in lighter skin may appear violaceous or hyperpigmented in darker skin types.8 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.7,8  
 
Further, several studies have shown that psoriasis is associated with greater psychological impact and 
worse QOL in non-whites with psoriasis compared to whites.5,8,9,10 Dermatology Life Quality Index 
(DLQI) scores are consistently lower in blacks and Hispanics compared to whites, even when controlling 
for body surface area affected and severity of disease.10  
 
Despite differences in psoriasis between whites and non-whites, there is paucity of data on the use of 
topical medications in dark-skinned individuals.11,12 Unique issues in SOC populations, including 
masking of erythema and high risk of post-inflammatory pigmentary sequelae, make studies dedicated to 
darker skin types essential for treatment of psoriasis in these populations.  
 
Combination of calcipotriene and betamethasone dipropionate 0.005%/0.064% aerosol foam (Enstilar®) 
has been shown to be effective in the treatment of mild or greater plaque psoriasis when used once daily 
for 4 weeks.13,14,15 Use of Enstilar ® has also been associated with significant improvement in health-
related quality of life.16 Nonetheless, pivotal phase II and III trials of Enstilar ® included a predominately 
white population; 87.1% of subjects in three pooled US phase II and III pivotal trials were white.17 Given 
the small number of non-white subjects, it is difficult to make meaningful comparisons between different 
race/ethnicity subgroups.17 
 


 
Protocol Name: 
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 (Fitzpatrick skin 
phototypes IV-VI). 
Principal Investigator:  
Andrew Alexis, MD, MPH 
Primary Contact 
Name/Contact Info: 
Andrew Alexis, MD, MPH 
212-523-3888 
Date Revised: 
08/10/2017 
Study Number: 
IF2166478 
 
3 
Revised 9/2/14 
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 SOC (FST IV-VI). This study 
will also evaluate the degree of erythema versus hyperpigmentation in psoriasis plaques in SOC (and 
its change with Enstilar ® treatment) as well as the effect of Enstilar ® on post-inflammatory 
hyperpigmentation and quality of life in SOC. 18   
 
3) Setting of the Human Research 
All research activity will take place at Mount Sinai West Department of Dermatology, located at 
2109 Broadway, 2nd Floor, New York, NY 10023. 
 
4) Resources Available to Conduct the Human Research 
 
The research team consists of the Principal Investigator, Sub-Investigator, and Research Coordinator(s). 
Dr. Alexis, Principal Investigator of this study and director of Mount Sinai St. Luke’s and West Skin of 
Color Center, cares for a large number of SOC patients with psoriasis vulgaris. We therefore do not 
foresee any difficulties in recruiting the suggested number of patients for this research study. All members 
of the study team have several years of research experience and have all completed the required trainings 
and certifications mandated by our IRB. All research team members have read and understand the 
protocol and all study related procedures. 
 
 
5) Study Design 
 
a) Recruitment Methods 
 
Subjects will be recruited from the dermatology faculty practices and the dermatology 
resident clinics in the Mount Sinai Health System. Once approved by the Sponsor, we will 
use IRB approved flyers, online advertisements (including social media postings and 
clinical trials listing services) as well as questionnaires and phone scripts. 
 
b) Inclusion and Exclusion Criteria 
Inclusion: 


 
Protocol Name: 
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 (Fitzpatrick skin 
phototypes IV-VI). 
Principal Investigator:  
Andrew Alexis, MD, MPH 
Primary Contact 
Name/Contact Info: 
Andrew Alexis, MD, MPH 
212-523-3888 
Date Revised: 
08/10/2017 
Study Number: 
IF2166478 
 
4 
Revised 9/2/14 
1. Provide written, signed and dated informed consent prior to initiating any study-
related activities. 
2. Male or female >18 years of age at the time of screening 
3. Fitzpatrick Skin phototype IV-VI, non-white race/ethnicity, including but not limited 
to African Americans, Asians, Pacific Islanders and Hispanics. 
4. Clinical diagnosis of chronic plaque-type psoriasis of the body 
5. 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) 
6. 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 
described below:  
Option 1:  Any one of the following highly effective methods:  hormonal 
contraception (oral, injection, implant, transdermal patch, vaginal ring); intrauterine 
device (IUD); tubal ligation; or partner’s vasectomy; 
OR  
Option 2:  Male or female condom (latex condom or nonlatex condom NOT made 
out of natural [animal] membrane [for example, polyurethane]; PLUS one 
additional barrier method: (a) diaphragm with spermicide; (b) cervical cap with 
spermicide; or (c) contraceptive sponge with spermicide. 
 
7. Must be in general good health as judged by the Investigator, based on medical history and 
physical examination. (NOTE: The definition of good health means a subject does not have 
uncontrolled significant co-morbid conditions).   
 
Exclusion: 
1. Form of diagnosed psoriasis other than chronic plaque psoriasis (i.e. guttate, 
erythrodermic, pustular) 
2. Diagnosis of other active, ongoing skin diseases or skin infections that may interfere 
with examination of psoriasis lesions 


 
Protocol Name: 
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 (Fitzpatrick skin 
phototypes IV-VI). 
Principal Investigator:  
Andrew Alexis, MD, MPH 
Primary Contact 
Name/Contact Info: 
Andrew Alexis, MD, MPH 
212-523-3888 
Date Revised: 
08/10/2017 
Study Number: 
IF2166478 
 
5 
Revised 9/2/14 
3. 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 
4. Use of oral estrogen therapy, excluding oral contraceptive pills 
5. Women who are pregnant, nursing, or of child-bearing potential who are unwilling to 
use appropriate method(s) of contraception.  
6. Patients unwilling to limit exposure to UV light 
7. Current significant medical problems that, in the discretion of the investigator, would 
put the patient at significant risk 
8. Patients with disorders of calcium metabolism and/or hypercalcemia. 
9. Use of any investigational drug within 4 weeks prior to randomization, or 
5 pharmacokinetic/pharmacodynamics half-lives, if known (whichever is longer). 
10. History of allergy to any component of the IP 
 
c) Number of Subjects 
Patients with skin types IV-VI with chronic plaque-type psoriasis will be screened with a 
goal of 25 total subjects randomized. All 25 randomized subjects are expected to complete 
all study procedures. Individuals who provide informed consent and fail to meet all of the 
inclusion and exclusion criteria during the initial evaluation will be considered a 
“screening failure.” 
 
d) Study Timelines 
The study will consist of 6 visits over up to 12 weeks (up to 4 week screening period plus 8 
weeks enrolled in study). Study visits will be conducted at Screening (Visit 1), Baseline 
(Visit 2, Week 0), Week 1 (Visit 3), Week 2 (Visit 4), Week 4 (Visit 5), and Week 
8/discontinuation (Visit 6).  


 
Protocol Name: 
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 (Fitzpatrick skin 
phototypes IV-VI). 
Principal Investigator:  
Andrew Alexis, MD, MPH 
Primary Contact 
Name/Contact Info: 
Andrew Alexis, MD, MPH 
212-523-3888 
Date Revised: 
08/10/2017 
Study Number: 
IF2166478 
 
6 
Revised 9/2/14 
Enrollment will occur over a 6 month period from November 2017 to May 2018.  
 
e) Endpoints 
 
Primary Endpoint:  
 
1. Investigator Global Assessment (IGA mod 2011) at week 4 
Proportion of patients at week 4 who achieved treatment success according to investigator 
global assessment (IGA mod 2011) of the entire body including scalp. IGA will range 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. 
 
 
 
Secondary Endpoints: 
1. Psoriasis Area and Severity Index 50 and 75 (PASI50 and PASI75) at weeks 2, 4, and 8. 
Proportion of patients achieving ≥50% improvement and/or  ≥75% improvement in Psoriasis 
Area and Severity Index (PASI) at weeks 4 and 8 compared to baseline (PASI 50 and PASI 
75, respectively). PASI will be completed by the investigator or trained qualified designee at 
screening and weeks 0, 2, 4, and 8.  
 
2. Psoriasis Scalp Severity Index 50 and 75 (PSSI50 and PSSI75) at weeks 2, 4 and 8, if 
applicable 
Proportion of patients achieving ≥50% improvement and/or  ≥75% improvement in Psoriasis 
Scalp Severity Index (PSSI) at weeks 4 and 8 compared to baseline (PSSI 50 and PSSI 75, 
respectively), if applicable. PSSI will be completed by the investigator or trained qualified 
designee at screening and weeks 0, 2, 4, and 8 if the subject has/had scalp involvement at the 
baseline visit. 
 
3. Investigator Global Assessment (IGA mod 2011) at weeks 2 and 8 
Proportion of patients at week 8 who achieved treatment success according to investigator 
global assessment (IGA mod 2011) of the entire body including scalp. IGA will range 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. 
 
4. Scalp Investigator Global Assessment (ScIGA) at weeks 4 and 8, if applicable 


 
Protocol Name: 
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 (Fitzpatrick skin 
phototypes IV-VI). 
Principal Investigator:  
Andrew Alexis, MD, MPH 
Primary Contact 
Name/Contact Info: 
Andrew Alexis, MD, MPH 
212-523-3888 
Date Revised: 
08/10/2017 
Study Number: 
IF2166478 
 
7 
Revised 9/2/14 
Proportion of patients at weeks 4 and 8 who achieved treatment success according to scalp 
investigator global assessment (ScIGA). ScIGA will range 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. 
 
5. Patient’s Global Assessment of Itch at weeks 1, 2, 4, and 8 
 
The VAS is a numerical scale used to assess patients’ perception of pruritus/itch. Subjects will 
be asked to complete the VAS scale at all scheduled visits. 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).  
 
6. Patient’s Global Assessment of disease severity (PaGA) at weeks 4 and 8. 
Treatment success will be defined as clear or almost clear 
 
At weeks 4 and 8, subjects will be asked to assess the severity of their psoriasis on a PaGA 
patient questionnaire. PaGA will have 5 distinct options ranging from “Clear” to “Severe.” 
Treatment response will be 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). 
 
7. Change in erythema index of target psoriasis plaque from baseline to weeks 2, 4, and 8 
 
A skin spectrophotometer (Mexameter) will be used to quantify the degree of erythema of 
lesional skin compared to an index area (of unaffected skin) at baseline, week 2, week 4, and 
week 8. Erythema index will be recorded at these timepoints and compared to baseline 
measurements.  
 
8. Change in melanin indices of target psoriasis plaque from baseline to weeks 2, 4, and 8 
 
A skin spectrophotometer (Mexameter) will be used to quantify the melanin index (degree of 
hyperpigmentation or hypopigmentation) of lesional skin compared to an index area  of 
unaffected skin)at baseline, week 2, week 4, and week 8. Melanin index will be recorded at 
these timepoints and compared to baseline measurements.  
 
 
9. Change in physician dyspigmentation visual analog scale (VAS) at weeks 4 and 8. 
 
An investigator will perform a visual analog scale (VAS) rating the degree of 
dyspigmentation of the skin. This VAS will range from - 5 to 5 as follows: 5 severe dark 


 
Protocol Name: 
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 (Fitzpatrick skin 
phototypes IV-VI). 
Principal Investigator:  
Andrew Alexis, MD, MPH 
Primary Contact 
Name/Contact Info: 
Andrew Alexis, MD, MPH 
212-523-3888 
Date Revised: 
08/10/2017 
Study Number: 
IF2166478 
 
8 
Revised 9/2/14 
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). This VAS will be performed at baseline and weeks 4 and 8.  
 
10.  Change from baseline in Dermatology Life Quality Index (DLQI) total score at weeks 
2, 4 and 8. 
Subjects will complete a DLQI at baseline, week 2, week 4 and week 8. Change in DLQI total 
score between baseline and week 4 will be assessed. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


 
Protocol Name: 
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 (Fitzpatrick skin 
phototypes IV-VI). 
Principal Investigator:  
Andrew Alexis, MD, MPH 
Primary Contact 
Name/Contact Info: 
Andrew Alexis, MD, MPH 
212-523-3888 
Date Revised: 
08/10/2017 
Study Number: 
IF2166478 
 
9 
Revised 9/2/14 
 
 
a) Procedures Involved in the Human Research 
Table 1: Assessment Schedule 
Visit 1 
2 
3 
4 
5 
6 
Week -4 to BL 
 
0 (BL) 
1 
2 
4 
8 
ET/E
OT 
Visit Window (days)  
 
±2 
±2 
±5 
±5 
Assessment 
 
 
 
 
 
 
Informed Consent 
X 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
Inclusion/Exclusion 
X 
X 
 
 
 
 
Medical History 
X 
 
 
 
 
 
Psoriasis treatment history 
X 
 
 
 
 
 
AE/SAE assessment 
X 
X 
X 
X 
X 
X 
Concomitant medications 
X 
X 
X 
X 
X 
X 
Vital Signs 
X 
 
 
 
 
 
Height and Weight 
X 
 
 
 
 
 
Physical Examination 
X 
 
 
 
 
 
Fitzpatrick Skin Type assessment 
X 
 
 
 
 
 
Photography 
 
X 
 
 
X 
X 
Urine Pregnancy Test 
X 
X 
 
 
 
 
BSA 
X 
X 
 
X 
X 
X 
Investigator IGA mod 2011 score (and ScIGA 
if applicable) 
X 
X 
 
X 
X 
X 
PASI score (PSSI if applicable) 
X 
X 
 
X 
X 
X 
Mexameter measurement of erythema and 
melanin indices 
 
X 
 
X 
X 
X 
Investigator dyspigmentation VAS 
 
X 
 
 
X 
X 
Patient Global Assessment of severity (PaGA) 
 
X 
 
X 
X 
X 
Patient pruritus VAS  
 
X 
X 
X 
X 
X 
Patient dyspigmentation VAS 
 
X 
 
 
X 
X 
Dermatology Life Quality Index (DLQI)  
 
X 
 
X 
X 
X 
Local Tolerability Assessment 
 
X 
X 
X 
X 
X 
Treatment satisfaction evaluation 
 
 
 
X 
X 
X 
Study Drug Training 
 
X 
 
 
 
 
Study Drug Dispensation and Return 
 
X 
 
 
X 
X 


 
Protocol Name: 
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 (Fitzpatrick skin 
phototypes IV-VI). 
Principal Investigator:  
Andrew Alexis, MD, MPH 
Primary Contact 
Name/Contact Info: 
Andrew Alexis, MD, MPH 
212-523-3888 
Date Revised: 
08/10/2017 
Study Number: 
IF2166478 
 
10 
Revised 9/2/14 
 
This is a single-center study and will consist of 3 phases. Phase 1 - screening phase, Phase 2 - Double-
blinded, vehicle-controlled phase, and Phase 3 - Open-label and maintenance phase  
Phase 1 - The screening phase will last up to 28 days. Screening and baseline may occur on the same day 
if subject does not require a wash-out period. 
Phase 2 - double-blinded, placebo-controlled phase to evaluate the tolerability and efficacy of Enstilar® 
(calcipotriene and betamethasone dipropionate) Foam versus placebo in the treatment of chronic plaque 
psoriasis in patients with skin of color (Fitzpatrick skin phototypes IV-VI). This phase will last 4 weeks 
(baseline to week 4). Subjects will be randomized in a 4:1ratio to Enstilar® or placebo, respectively. The 
study product will be applied once daily for 4 weeks.  
Phase 3 - Open-label and maintenance phase. Subjects who were randomized to placebo during 
phase 2 will receive Enstilar daily x 4 weeks. Subjects who were randomized to Enstilar during 
phase 2 will switch to Enstilar twice weekly x 4 weeks as maintenance treatment. 
Prior to the start of the study, potential subjects will be given an IRB-approved Informed Consent 
Document (ICD) containing a Health Insurance Portability and Accountability Act (HIPAA) disclosure 
agreement to read, understand, and sign. After providing informed consent, subjects will be assessed for 
study eligibility at the Screening visit. The PI or a medically qualified designee must review this 
information (i.e. medical history, concomitant medication, and eligibility review) for each subject to 
confirm their eligibility before enrollment. 
 
A total of 25 subjects who meet eligibility criteria will undergo Baseline / Day 0 assessments. At this 
Baseline visit, subjects will undergo randomization to either active drug or vehicle. All subjects will 
receive study drug training. Study drug will be dispensed at baseline and week 4. Un-used drug will be 
returned to the site at each visit. 
 
Subjects will return for visits at weeks 1, 2, 4, and 8 so that a review of concomitant medications and 
adverse events can be assessed. The PI or designee will interview the subjects to collect and record any 
adverse events (AEs) or changes to health/concomitant medications that may have occurred since the 
previous visit. Additional procedures and assessments will be performed as outlined in table 1. 
 
If a subject terminates early or chooses to discontinue the study, he/she will be asked to return for a final 
visit, at which time the procedures for visit 6 will be performed.  
 
Enstilar ® foam is a combination of calcipotriene 0.005%, a vitamin D analog, and betamethasone 
diproprionate 0.064%, a corticosteroid. Enstilar ® foam is indicated the treatment of plaque psoriasis in 
patients 18 years of age and older. 


 
Protocol Name: 
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 (Fitzpatrick skin 
phototypes IV-VI). 
Principal Investigator:  
Andrew Alexis, MD, MPH 
Primary Contact 
Name/Contact Info: 
Andrew Alexis, MD, MPH 
212-523-3888 
Date Revised: 
08/10/2017 
Study Number: 
IF2166478 
 
11 
Revised 9/2/14 
 
During phase 2 of the study, the study product (Enstilar ® foam or vehicle) should be applied topically to 
affected areas of the skin once daily. During phase 3, frequency of Enstilar ® is dependent on treatment 
group. Those randomized to Enstilar ® during phase 2 will start a maintenance regimen: twice weekly 
application of Enstilar ® for 4 weeks. Those randomized to vehicle during phase 2 will start the treatment 
regimen: once daily application of Enstilar ® for 4 weeks. 
 
The procedures and assessment performed during this study are described in detail below: 
 
Informed Consent: Prior to the start of the study, potential subjects will be given an IRB-
approved Informed Consent Document (ICD) containing a Health Insurance Portability and 
Accountability Act (HIPAA) disclosure agreement to read, understand, and sign. All questions 
about the study should be answered to the satisfaction of the candidate subject. They will have all 
of their study-related questions answered by the PI or designee, and if they agree to participate, the 
subject will sign the ICD. The subjects will retain one original copy and one photocopy will be 
kept in the study file. The subjects who sign an ICD will be assigned a screening number. 
 
Demographics: Subjects will be asked to complete a questionnaire about their demographics at 
the screening visit. This will include date of birth, sex, race, and ethnicity. 
 
Eligibility Assessment (Inclusion/Exclusion): After providing informed consent, subjects will be 
assessed for study eligibility at the Screening visit, which includes limited physical examination, 
skin type assessment, vital signs, height and weight, investigator severity ratings (PASI, PGA, 
PSSI and PScIGA if applicable), review of medical history and concomitant medications as well 
as prior medications/treatments, and urine pregnancy test (if applicable). These assessments will 
be described below. The PI or a medically qualified designee must review this information (i.e. 
medical history, concomitant medication, and eligibility review) for each subject to confirm their 
eligibility before enrollment. Eligibility will be assessed at Screening and Baseline visits. 
 
Medical History and Concomitant Medications: At the screening visit, subjects will be asked 
about current medical conditions or history of any medical conditions. Subjects will also be asked 
about current medication use and use of medications for 1 month prior to screening. Concomitant 
medications will be reviewed and recorded at every scheduled visit. 
 
Psoriasis Treatment History: At the screening visit, subjects will be asked about their current 
and all past treatments for psoriasis, including over-the-counter and prescription therapies.  
 
Vital Signs: Vital signs will be assessed at the screening visit. Whether action needs to be taken 
regarding abnormal vital signs (as defined below) will be at the investigator’s discretion. After the 


 
Protocol Name: 
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 (Fitzpatrick skin 
phototypes IV-VI). 
Principal Investigator:  
Andrew Alexis, MD, MPH 
Primary Contact 
Name/Contact Info: 
Andrew Alexis, MD, MPH 
212-523-3888 
Date Revised: 
08/10/2017 
Study Number: 
IF2166478 
 
12 
Revised 9/2/14 
subject has been sitting for at least five minutes with back supported and both feet on the ground, 
systolic and diastolic blood pressure (BP) will be measured using an appropriately sized cuff. 
Pulse will also be measured using either an automated machine or manually. Normal Blood 
pressure will be defined as systolic 90 to <120mmHg and diastolic 60 to <80mm Hg. Notable 
blood pressure will be hypertension (systolic ≥140 mmHg and/or diastolic ≥100 mmHg). A 
normal pulse rate will be defined as 60 to 100 beats per minute. Notable pulse rates will be defined 
as bradycardia (<50bpm) and tachycardia (>100bpm).  
 
Height and Weight: Height and weight will be measured by a designated site individual at the 
screening visit. 
 
Physical examination: Physical examination will be performed by the investigator, sub-
investigator, or other qualified individuals at screening. This will include examination of the heart, 
lungs, abdomen, extremities, and skin, as well as any additional body systems as deemed 
necessary by the investigator.  
 
Photography: Standardized photographs will be taken of the entire body (front and back). The 
photograph will be taken with the patient standing up in front of a neutral background; 
photographs will be taken at a standardized distance with the patient facing towards and away 
from the camera such that the entire body included in the picture. Photographs will be taken at 
baseline and weeks 4 and 8. 
 
Body Surface Area (BSA): The total body involvement of psoriasis will be recorded as a 
percentage of the totally BSA at screening, baseline, and weeks 2, 4, and 8. 
 
 
Investigator’s Global Assessment (IGA mod 2011): The IGA mod 2011 is a standardized rating 
scale for assessment of overall psoriatic disease severity. IGA mod 2011 (entire body including 
scalp) will be performed by the investigator or designated qualified site staff at screening, 
baseline, and weeks 2, 4, and 8. If the subject has scalp involvement at the baseline visit, Scalp 
IGA (ScIGA) will be performed.  For ScIGA, the IGA mod 2011 scale will be used to evaluate the 
severity of psoriasis on the scalp only. 
 
 
 
 
 
 
 


 
Protocol Name: 
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 (Fitzpatrick skin 
phototypes IV-VI). 
Principal Investigator:  
Andrew Alexis, MD, MPH 
Primary Contact 
Name/Contact Info: 
Andrew Alexis, MD, MPH 
212-523-3888 
Date Revised: 
08/10/2017 
Study Number: 
IF2166478 
 
13 
Revised 9/2/14 
The scale is as follows: 
 
Score 
Short Description 
Detailed Description 
0 
Clear 
No signs of psoriasis. Post-inflammatory hyperpigmentation may be 
present 
1 
Almost clear 
Normal to pink coloration of lesions; no thickening; no to minimal 
focal scaling 
2 
Mild 
Pink to light red coloration; just detectable to mild thickening; 
predominantly fine scaling 
3 
Moderate 
Dull bright red, clearly distinguishable erythema; clearly 
distinguishable to moderate thickening; moderate scaling 
4 
Severe  
Bright to deep dark red coloration; severe thickening with hard 
edges; severe / coarse scaling covering almost all or all lesions 
 
 
Psoriasis Area and Severity Index (PASI) (and Psoriasis Scalp Severity Index (PSSI) if 
applicable) 
 
The investigator or trained qualified site staff will complete the PASI (and PSSI assessment) at 
screening, baseline, and weeks 2, 4, and 8.  
When calculating the PASI score, four separate body regions are evaluated: the head (including 
face, scalp, and neck), upper limbs, trunk (including axillae and groin area), and lower extremities 
(including the buttocks). These body regions correspond to 10%, 20%, 30%, and 40% of the total 
body surface area (BSA), respectively. Therefore, the score for each body region will be 
multiplied by its relative proportion of the body surface area (0.1, 0.2, 0.3, or 0.4) when 
calculating the PASI score. 
Three different parameters will be evaluated: erythema (E), desquamation (D), and induration (I). 
These will be graded on a scale of 0 (none) to 4 (very severe). Desquamation refers to the scaling 
of a lesion. Induration refers to the thickening and plaque elevation. 
 
PASI is calculated based on the following formula: 
PASI = 0.1(EH+IH+DH)AH + 0.2(EU+IU+DU)AU + 0.3(ET+IT+DT)AT + 0.4(EL+IL+DL)AL 
 
 
 
 
 
 
 
 


 
Protocol Name: 
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 (Fitzpatrick skin 
phototypes IV-VI). 
Principal Investigator:  
Andrew Alexis, MD, MPH 
Primary Contact 
Name/Contact Info: 
Andrew Alexis, MD, MPH 
212-523-3888 
Date Revised: 
08/10/2017 
Study Number: 
IF2166478 
 
14 
Revised 9/2/14 
PASI Scoring System: 
 
 
Body Region 
Erythema (E) 
Induration (I) 
Desquamation(D) 
Area Score (A) 
Head (H) 
0 – none 
1– slight 
2 – moderate 
3– severe 
4 – very severe 
0 – none 
1– slight 
2 – moderate 
3– severe 
4 – very severe 
0 – none 
1– slight 
2 – moderate 
3– severe 
4 – very severe 
0– no involvement 
1– >0 to <10% 
2– 10 to <30% 
3– 30 to <50% 
4– 50 to <70% 
5– 70 to <90% 
6– 90 to 100% 
Trunk (T) 
0 – none 
1– slight 
2 – moderate 
3– severe 
4 – very severe 
0 – none 
1– slight 
2 – moderate 
3– severe 
4 – very severe 
0 – none 
1– slight 
2 – moderate 
3– severe 
4 – very severe 
0– no involvement 
1– >0 to <10% 
2– 10 to <30% 
3– 30 to <50% 
4– 50 to <70% 
5– 70 to <90% 
6– 90 to 100% 
Upper Extremities 
(U) 
0 – none 
1– slight 
2 – moderate 
3– severe 
4 – very severe 
0 – none 
1– slight 
2 – moderate 
3– severe 
4 – very severe 
0 – none 
1– slight 
2 – moderate 
3– severe 
4 – very severe 
0– no involvement 
1– >0 to <10% 
2– 10 to <30% 
3– 30 to <50% 
4– 50 to <70% 
5– 70 to <90% 
6– 90 to 100% 
Lower Extremities 
(L) 
0 – none 
1– slight 
2 – moderate 
3– severe 
4 – very severe 
0 – none 
1– slight 
2 – moderate 
3– severe 
4 – very severe 
0 – none 
1– slight 
2 – moderate 
3– severe 
4 – very severe 
0– no involvement 
1– >0 to <10% 
2– 10 to <30% 
3– 30 to <50% 
4– 50 to <70% 
5– 70 to <90% 
6– 90 to 100% 
 
When calculating PSSI, similar grading of erythema (E), induration (I), and desquamation (D) will 
be performed with a scale of 0 (none) to very severe (4). In addition, the extent of scalp 
involvement (0 to 100%) will be assessed. The area score will graded in the same manner as the 
PASI score (1– >0 to <10%, 2– 10 to <30%, 3– 30 to <50%, 4– 50 to <70%, 5– 70 to <90%, 6– 90 
to 100%). For those with no scalp involvement (0) at baseline, PSSI will not be performed.  
 
PSSI score = (Es+Is+Ds)As 
 
 
 


 
Protocol Name: 
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 (Fitzpatrick skin 
phototypes IV-VI). 
Principal Investigator:  
Andrew Alexis, MD, MPH 
Primary Contact 
Name/Contact Info: 
Andrew Alexis, MD, MPH 
212-523-3888 
Date Revised: 
08/10/2017 
Study Number: 
IF2166478 
 
15 
Revised 9/2/14 
Patient Global Assessment of severity (PaGA): 
Patient will complete a PaGA questionnaire at baseline, week 2, week 4, and week 8 to ask about 
severity of their overall clinical condition. The scale will include 5 categorical options – clear, 
very mild, mild, moderate, and severe.  
 
Short Description 
Detailed Description 
Clear 
No signs of psoriasis at all 
Very Mild 
Very slight psoriasis symptoms that do not interfere with daily life at all  
Mild 
Slight psoriasis symptoms that only occasionally interfere with daily life  
Moderate 
Definite psoriasis symptoms that frequently interfere with daily life 
Severe  
Intense psoriasis symptoms that very often interfere with or restrict 
daily life  
 
 
Subject VAS of pruritus: The VAS is a numerical scale used to assess patients’ perception of 
pruritus/itch. Subjects will be asked to complete the VAS scale at baseline and weeks 1, 2, 4, and 
8. The evaluation is scored from 0 (no pruritus) to 10 (severe pruritus).  
 
 
Dermatology Life Quality Index (DLQI): DLQI is a validated 10-question questionnaire 
developed to address quality of life in patients with dermatological disorders. It has previously 
been used with success to assess the impact of psoriasis on quality of life. Patients will be asked to 
fill out a DLQI at baseline, week 2, week 4, and week 8. 
 
Patient Satisfaction Questionnaire: Subjects will be asked to complete a questionnaire asking 
about satisfaction with the study product, including satisfaction with the product vehicle, ease of 
application, and overall satisfaction with the treatment product. 
 
Local Tolerability Assessment: Assessment of local safety and tolerability will be completed at 
baseline and weeks 1, 2, 4, and 8. The investigator or designated site staff will assess for: 
perilesional erythema, edema, dryness, and erosion. These parameters will be graded on a scale of 
0 (absent) to 3 (severe). The subjects will also be asked about application site burning and pain 
after application of the study drug. Subjects will be asked to grade their burning/stinging from 0 
(absent) to 3 (severe). Only severe site reactions or reactions that require discontinuation of the 
study product will be recorded as AEs.  
 


 
Protocol Name: 
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 (Fitzpatrick skin 
phototypes IV-VI). 
Principal Investigator:  
Andrew Alexis, MD, MPH 
Primary Contact 
Name/Contact Info: 
Andrew Alexis, MD, MPH 
212-523-3888 
Date Revised: 
08/10/2017 
Study Number: 
IF2166478 
 
16 
Revised 9/2/14 
 
Urine Pregnancy test:  Urine pregnancy test will be performed at screening and baseline visits 
for women of child-bearing potential. A woman is considered post-menopausal if she has not had 
a menstrual period in >12 months. 
 
Adverse Events and Serious Adverse Events: An adverse event (AE) is any noxious, 
unintended, or untoward medical occurrence occurring at any dose that may appear or worsen in a 
subject during the course of a study. It may be a new intercurrent illness, a worsening concomitant 
illness, an injury, or any concomitant impairment of the subject’s health, including laboratory test 
values (as specified by the criteria below), regardless of etiology. Any medical condition that was 
present prior to study treatment and that remains unchanged or improved should not be recorded 
as an AE. If there is a worsening of that medical condition this should be considered an AE. All 
AEs will be recorded by the Investigator(s) from the time of signing the informed consent through 
the end of the designated follow-up period. 
 
 
b) Specimen Banking 
 
N/A 
 
c) Data Management and Confidentiality 
 
As used in this protocol, the term case report form (CRF) should be understood to refer to either a 
paper form or an electronic data record or both, depending on the data collection method used in 
this trial. All subject source documents are the site’s subject records and are to be maintained at 
the study site. These source documents must be attributable, legible, contemporaneous, original, 
and accurate.  
 
A CRF/source document is required and should be completed for each included subject. It is the 
PI's responsibility to ensure completion and to review and approve all CRFs/source documents. 
These must be signed by the PI or by an authorized staff member. These signatures serve to attest 
that the information contained on the CRFs/source documents is true. At all times, the PI has final 
personal responsibility for the accuracy and authenticity of all clinical and laboratory data entered 
on the CRFs/source documents.  SAE forms and pregnancy notification forms will be provided by 
the Sponsor.  
 


 
Protocol Name: 
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 (Fitzpatrick skin 
phototypes IV-VI). 
Principal Investigator:  
Andrew Alexis, MD, MPH 
Primary Contact 
Name/Contact Info: 
Andrew Alexis, MD, MPH 
212-523-3888 
Date Revised: 
08/10/2017 
Study Number: 
IF2166478 
 
17 
Revised 9/2/14 
Good documentation practices should be used on all study documentation. The clinical study will 
be performed in accordance with the protocol, applicable standard operating procedures (SOPs), 
the International Conference on Harmonization Good Clinical Practice (ICH GCP) guidelines, and 
applicable local regulatory requirements and laws. 
 
The Sponsor requires that all records (e.g., ICFs, source documents, test article dispensing record, 
etc.) which support CRFs/source documentation of this study must be retained in the files of the 
responsible investigator for a period of 2 years from the time the final report is issued. 
If the investigator relocates, retires, or for any reason withdraws from the trial, the Sponsor should 
be prospectively notified. The study records must be transferred to an acceptable designee, such as 
another investigator, another institution, or to the Sponsor.  The investigator must obtain Sponsor's 
written permission before disposing of any records, even if retention requirements have been met.  
The Sponsor must be notified in writing of the name and address of the new custodian prior to re-
assignment/transfer. 
All records identifying the subject will be kept confidential and, to the extent permitted by 
the applicable laws and/or regulations, will not be made publicly available. Only the 
subject number will be recorded in the CRF. The code that links the subject to the subject’s 
ID# is stored on paper in a locked cabinet, accessible only by Department of Dermatology 
research personnel. Photographs will be stored on the camera for approximately one week 
before being transferred to the computer database. Study findings stored on a password- 
protected computer will be encrypted and stored in accordance with local data protection 
laws. As part of the informed consent process, the subjects will be informed in writing that 
representatives of the IRB, or regulatory authorities may inspect their medical records to 
verify the information collected, and that all personal information made available for 
inspection will be handled in strictest confidence and in accordance with local data 
protection laws. If the results of the study are published, the subject’s identity will remain 
confidential. Only the investigator will maintain a list to enable subjects to be identified. 
The data will be stored indefinitely.  
 
d) Provisions to Monitor the Data to Ensure the Safety of Subjects 
 
Part I: Elements of a Data and Safety Monitoring Plan 
 
MSSM Principal Monitor: 
Indicate whether this person is the PI, a Team Member, or is Independent: 
Last Name: Alexis (PI) 


 
Protocol Name: 
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 (Fitzpatrick skin 
phototypes IV-VI). 
Principal Investigator:  
Andrew Alexis, MD, MPH 
Primary Contact 
Name/Contact Info: 
Andrew Alexis, MD, MPH 
212-523-3888 
Date Revised: 
08/10/2017 
Study Number: 
IF2166478 
 
18 
Revised 9/2/14 
First Name: Andrew 
Academic Title: MD, MPH 
Department: Dermatology 
Mailing Address: 
, New York NY 10025 
Phone: 212-523-3888 
Fax: 212-523-3808 
E-mail: aalexis@chpnet.org 
 
 
2. The principal monitor is the Principal Investigator. Please refer to curriculum vitae for further 
information. 
3.  The specific items that will be monitored for safety are pregnancy, adverse events, subject 
compliance with the protocol and drop outs. 
4. Subjects will be monitored for adverse events the day of their participation in the study. Should 
subjects experience any adverse effects after their participation in the study, they will be 
instructed to contact the investigator(s) and make an appointment immediately.  
5. The investigator(s) will not change the Clinical Study Protocol without written approval of the 
IRB. 
6. N/A  
7. Adverse events will be graded using the Common Terminology Criteria for Adverse Events 
(CTCAE).    
8.  The study will be conducted in compliance with regulatory requirements and Good Clinical 
Practice. Quality control will be applied to each stage of data handling to ensure that data are 
accurate, reliable and processed correctly.  
9.   Should a temporary or permanent suspension of our study occur, the occurrence will be 
reported to the PPHS, sponsor, and IRB.  
 
Part II. Data Monitoring Committee/Data Safety Monitoring Board (DMC/DSMB) 
 
 
N/A 
 
e) Withdrawal of Subjects 
When an individual who has signed the ICF is not enrolled in the study or withdraws/is withdrawn 
prior to completing the study, the reason is to be documented on the Discontinuation/Completion 
Form (or equivalent) and in the final study report.  Reasons for subject withdrawal may include:  


 
Protocol Name: 
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 (Fitzpatrick skin 
phototypes IV-VI). 
Principal Investigator:  
Andrew Alexis, MD, MPH 
Primary Contact 
Name/Contact Info: 
Andrew Alexis, MD, MPH 
212-523-3888 
Date Revised: 
08/10/2017 
Study Number: 
IF2166478 
 
19 
Revised 9/2/14 
• Not enrolled (e.g. fails to meet inclusion/exclusion criteria, chooses not to enroll, etc.) 
• Participant is determined to be ineligible after enrollment 
• Subject’s choice to withdraw 
• Investigator terminated (e.g. noncompliance, etc.) 
• Adverse Event 
• Lost to follow-up 
• Other 
 
Subjects may withdraw from the trial at any time at their request, or they may be withdrawn at any 
time at the discretion of the Sponsor, PI, or designee for safety, behavioral, or administrative 
reasons. Subjects may be withdrawn from this study without their consent if the research study is 
being stopped; or if the instructions of the study team have not been followed. 
 If a subject does not return for a scheduled visit, three documented attempts will be made to 
contact the subject in order to establish the reason for withdrawal, and the outcome will be 
documented.  The PI or designee should inquire about the reason for withdrawal, request that the 
subject return for a final visit, if applicable, and follow-up with the subject regarding any 
unresolved adverse events.   
 
Should a subject withdraw from the trial and also withdraw consent for disclosure of future 
information, no further evaluations should be performed and no additional data should be 
collected.  The PI and staff may retain and continue to use any data collected before such 
withdrawal of consent.  Removed or withdrawn subjects will not be replaced. 
 
If a subject fails to report to the test facility for a scheduled visit and cannot be rescheduled within 
the permitted window of time (as applicable), the Site should consult with the Sponsor to 
determine if the subject should be documented as having withdrawn/dropped from the study. 
 
2) Risks to Subjects 
 
The following list of side effects is the ones that may be associated with the use of Enstilar ® 
foam: 
 
 
Observed in less than 1% of subjects (based on clinical trials): 
• Application site reactions: 
o Irritation 
o Pruritus 
• Folliculitis 
• Skin hypopigmentation 


 
Protocol Name: 
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 (Fitzpatrick skin 
phototypes IV-VI). 
Principal Investigator:  
Andrew Alexis, MD, MPH 
Primary Contact 
Name/Contact Info: 
Andrew Alexis, MD, MPH 
212-523-3888 
Date Revised: 
08/10/2017 
Study Number: 
IF2166478 
 
20 
Revised 9/2/14 
• Hypercalcemia 
• Urticaria 
• Exacerbation of psoriasis 
 
Observed uncommon adverse reactions (based on post-marketing data): 
• Atrophy of thin skin 
• Telangiectasia of the skin 
• Dryness of the skin 
• Perioral dermatitis 
• Secondary infections of the skin 
• Miliaria 
 
Other warnings: 
• Hypercalcemia and hypercalciuria – Hypercalcemia and hypercalciuria have been 
observed with the use of Enstilar ® foam. If either of these conditions develop, Enstilar ® 
should be discontinued until calcium levels normalize in the blood and/or urine. 
• Endocrine system effects – The systemic absorption of topical corticosteroids may lead to 
reversible suppression of the hypothalamic-pituitary-adrenal (HPA) axis, which may result 
in clinical glucocorticoid insufficiency either during treatment or upon withdrawal of the 
topical steroid. The risk of HPA axis suppression is higher with use of high-potency 
steroids, treatment of a large surface area, prolonged use, use of occlusive dressings, 
altered skin barrier, liver failure, and young age.  
• Allergic contact dermatitis – Topical calcipotriene and topical corticosteroids have both 
been associated with allergic contact dermatitis.  
• Risk of ultraviolet light exposure – patients would have using Enstilar ® foam should 
avoid excessive exposure to natural and artificial sunlight (i.e. tanning booths, sun lamps) 
• Flammability – The propellants in Enstilar ® foam are flammable. Subjects should avoid 
smoking, flames, and fire during and immediately following Enstilar ® application. 
 
 
 
Enstilar ® foam is designated as pregnancy category C, meaning that there are no adequate and well 
controlled studies in pregnant women. Studies of calcipotriene administered orally in rats and rabbits 
have demonstrated increased maternal and fetal toxicity at doses above 144 mcg/m2/day (rabbits) and 
skeletal abnormalities at dosages above 432 mcg/m2/day in rabbits and 324 mcg/m2 /day in rats. 
These are lower than the estimated maximum topical dose of calcipotriene in humans 
(460mcg/m2/day). 


 
Protocol Name: 
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 (Fitzpatrick skin 
phototypes IV-VI). 
Principal Investigator:  
Andrew Alexis, MD, MPH 
Primary Contact 
Name/Contact Info: 
Andrew Alexis, MD, MPH 
212-523-3888 
Date Revised: 
08/10/2017 
Study Number: 
IF2166478 
 
21 
Revised 9/2/14 
Betamethasone propionate has been shown to be teratogenic in mice and rabbits when given 
subcutaneously at dosages of 468 mcg/m2 /day (mice) and 30 mcg/m2 /day (rabbits). Again, these 
levels are lower than the estimated maximum topical dose in humans (~5,950mcg/m2/day). 
 
When administered systemically, corticosteroids have been shown to enter human milk and can have 
negative effects on infant health. Possible risks of systemic corticosteroids on infants include growth 
suppression and altered production of endogenous steroids. It is not known whether topically 
administered calcipotriene and/or corticosteroids results in sufficient systemic absorption to produce 
detectable quantities of these medications in human milk. Enstilar ®, therefore, should not be used by 
women while breastfeeding. 
 
 
3) Provisions for Research Related Harm/Injury 
 
If a subject experiences a research injury, Mount Sinai St. Luke’s will provide or arrange for 
medical treatment at no cost. If the subject chooses to see their own personal doctor we will not 
offer to pay for the expenses. A research injury is any physical injury or illness caused by 
participation in the study. If a subject is injured by a medical treatment or procedure that would 
have been received even if the subject weren't in the study; that is not a research injury.  Payment 
for things such as lost wages, expenses other than medical care, or pain and suffering is not 
offered. To help avoid injury, it is very important to follow all study directions. 
 
Please be aware that some insurance plans may not pay for research-related injuries.  Subjects 
should contact their insurance company for more information. 
 
 
4) Potential Benefits to Subjects 
The potential benefits to participating subjects are improvement of their psoriasis. 
 
5) Provisions to Protect the Privacy Interests of Subjects 
 
Only subjects who have given us permission to contact them for studies will be contacted. 
All conversations with subjects and potential subjects will be conducted in a private 
examination room with the subject. Subjects’ privacy will be protected by performing any 
study-related procedures in a private examination room. Family members will be allowed 
to remain in the room only if the subject allows this. No information regarding the 
subject’s disease, treatment or the fact that he/she is involved in a study will be conveyed. 


 
Protocol Name: 
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 (Fitzpatrick skin 
phototypes IV-VI). 
Principal Investigator:  
Andrew Alexis, MD, MPH 
Primary Contact 
Name/Contact Info: 
Andrew Alexis, MD, MPH 
212-523-3888 
Date Revised: 
08/10/2017 
Study Number: 
IF2166478 
 
22 
Revised 9/2/14 
Subjects will be made to feel at ease, by allowing them sufficient time to discuss the study 
and any potential queries. 
All parties will ensure protection of subject personal data and will not include subject names on 
any Sponsor forms, reports, publications, or in any other disclosures. In case of data transfer, 
Sponsor will maintain high standards of confidentiality and protection of subject personal data.   
The ICD (containing the HIPAA disclosure agreement) must be agreed to by the IRB and be in 
compliance and consistent with ICH GCP, local regulatory requirements, and legal requirements. 
The investigator must ensure that each study subject is fully informed about the nature and 
objectives of the trial, possible risks associated with participation. The investigator, or a trained 
person designated by the investigator, will obtain written informed consent on two copies from 
each subject before any trial-specific activity is performed.  The subject will retain one copy, and 
one will be kept in the study file. The ICD used in this trial, and any changes made during the 
course of the trial, must be prospectively approved by both the IRB and Sponsor before use.  
 
6) Economic Impact on Subjects 
Leo Pharma, the manufacturer of the study drug, will provide the study drug. Leo Pharma also 
provided a grant toward study-related tests and procedures. While in the study, the subject will 
still need to get regular medical care. The subject will still have to pay for the costs of regular 
medical care that is not a part of this study. 
 
Taking part in this research study may lead to added costs to the subject. If the physical 
examinations reveal information about his/her health, additional tests, treatments and doctors’ 
appointments may be required which could present additional costs to him/her or his/her insurance 
company. 
 
7) Payments to Subjects 
Subjects will be compensated 
upon 
completion of the study. Subjects who complete only the screening visit will not be eligible 
for compensation. If the subject withdraws or is withdrawn before completing the study, 
he/she will receive an amount of money for the visits which have been completed.  They 
will not have to submit receipts to receive this reimbursement. This payment will come in 
the form of a check at the end of the subject’s participation in the study.  
 
. 


 
Protocol Name: 
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 (Fitzpatrick skin 
phototypes IV-VI). 
Principal Investigator:  
Andrew Alexis, MD, MPH 
Primary Contact 
Name/Contact Info: 
Andrew Alexis, MD, MPH 
212-523-3888 
Date Revised: 
08/10/2017 
Study Number: 
IF2166478 
 
23 
Revised 9/2/14 
8) Consent Process 
We will be obtaining written consent as a part of this study. No subject will be evaluated without a 
signed Informed Consent Document (ICD). The consent process will take place in a private exam 
room where the subject will have ample time to review and read the consent form. Subjects will be 
given time to ask questions and may take additional time to consider their options. Subjects will be 
informed that they do not have to participate and may withdraw consent at any time. After 
understanding and agreeing, the subject will express her consent to participate in the study by signing 
two original copies of the ICD. We will follow the SOP HRP-090 Informed Consent Process for 
Research 
 
9) Process to Document Consent in Writing 
We will be using the standard IRB Informed Consent template. The ICD must be agreed to by 
the Sponsor and the IRB and must be in compliance with ICH GCP, local regulatory 
requirements, and legal requirements. The consent process and date that the consent is signed 
is documented in our source notes. Study personnel will adhere to “SOP HRP-091 Written 
Documentation of Consent”. 
 
10) Vulnerable Populations 
Indicate specifically whether you will include (target) or exclude each of the following 
populations: 
Include 
Exclude 
Vulnerable Population Type 
 
x 
Adults unable to consent 
 
x 
Individuals who are not yet adults (e.g. infants, children, teenagers) 
 
x 
Wards of the State (e.g. foster children) 
 
x 
Pregnant women 
 
x 
Prisoners 
 
11) Multi-Site Human Research (Coordinating Center) 
N/A 
12) Community-Based Participatory Research 


 
Protocol Name: 
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 (Fitzpatrick skin 
phototypes IV-VI). 
Principal Investigator:  
Andrew Alexis, MD, MPH 
Primary Contact 
Name/Contact Info: 
Andrew Alexis, MD, MPH 
212-523-3888 
Date Revised: 
08/10/2017 
Study Number: 
IF2166478 
 
24 
Revised 9/2/14 
N/A 
 
13) Sharing of Results with Subjects 
At the completion of the study, subjects will have the right to access their protected health information 
that is created during this research study that relates to their treatment or to payment, provided such 
information is not exempted under certain laws and regulations.  To request this information, subjects 
should contact the study doctor at the address listed above. 
 
Subject to certain exceptions prescribed by law, subjects have a right to request access to the health 
information that we hold about and to request changes if the health information is incorrect or 
incomplete. Any request for access or corrections should be made to the principal doctor conducting 
this study. 
 
14) External IRB Review History 
N/A 
15) Control of Drugs, Biologics, or Devices 
 
Study drug is stored in a combination-locked room accessible only by clinical trials personnel. All 
study materials should be stored at room temperature (59°-77°F), and the Site is responsible for 
maintaining temperature logs. All study products received and dispensed will be inventoried and 
accounted for throughout the study. The investigator must maintain adequate records documenting the 
receipt, use, loss, or other disposition of the products on the Product Accountability Log. The log must 
identify the investigational product and account for its disposition by subject, including specific dates 
and quantities dispensed and returned. The log must be signed by the individual who 
dispensed/retrieved the study product and copies must be provided to the sponsor for inclusion in the 
Trial Master File. 
 
At the completion of the study, all units of product dispensed (whether empty or containing unused 
product) must be collected by the Site and returned, along with un-dispensed product, to the Sponsor.  
Any container not returned by the Site must be accounted for in writing.    
 
 
 
 
 
 
 


 
Protocol Name: 
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 (Fitzpatrick skin 
phototypes IV-VI). 
Principal Investigator:  
Andrew Alexis, MD, MPH 
Primary Contact 
Name/Contact Info: 
Andrew Alexis, MD, MPH 
212-523-3888 
Date Revised: 
08/10/2017 
Study Number: 
IF2166478 
 
25 
Revised 9/2/14 
References: 
 
 
 
1Helmick CG, Lee-Han H, Hirsch SC, Baird TL, Bartlett CL. Prevalence of psoriasis among adults in the U.S.: 2003-2006 and 
2009-2010 National Health and Nutrition Examination Surveys. Am J Prev Med. 2014;47(1):37-45. 
doi:10.1016/j.amepre.2014.02.012. 
2 Rachakonda TD, Schupp CW, Armstrong AW. Psoriasis prevalence among adults in the United States. J Am Acad Dermatol. 
2014;70(3):512-6. doi:10.1016/j.jaad.2013.11.013. 
3 McMichael AJ, Jackson S. Issues in dermatologic health care delivery in minority populations. Dermatol Clin. 
2000;18(2):229-33, viii. 
4 Kurd SK, Gelfand JM. The prevalence of previously diagnosed and undiagnosed psoriasis in US adults: Results from 
NHANES 2003-2004. J Am Acad Dermatol. 2009;60(2):218-24. doi:10.1016/j.jaad.2008.09.022. 
5 McMichael AJ, Vachiramon V, Guzman-Sanchez DA, Camacho F. Psoriasis in African-Americans: a caregivers' survey. J 
Drugs Dermatol. 2012;11(4):478-82. 
6 Child FJ, Fuller LC, Higgins EM, Du Vivier AW. A study of the spectrum of skin disease occurring in a black population in 
south-east London. Br J Dermatol. 1999;141(3):512-7. 
7 Alexis AF, Sergay AB, Taylor SC. Common dermatologic disorders in skin of color: a comparative practice survey. Cutis. 
2007;80(5):387-94.  
8 Alexis AF, Blackcloud P. Psoriasis in skin of color: epidemiology, genetics, clinical presentation, and treatment nuances. J 
Clin Aesthet Dermatol. 2014;7(11):16-24. 
9 Kerr GS, Qaiyumi S, Richards J, Vahabzadeh-Monshie H, Kindred C, Whelton S et al. Psoriasis and psoriatic arthritis in 
African-American patients--the need to measure disease burden. Clin Rheumatol. 2015;34(10):1753-9. doi:10.1007/s10067-
014-2763-3. 
10 Shah SK, Arthur A, Yang YC, Stevens S, Alexis AF. A retrospective study to investigate racial and ethnic variations in the 
treatment of psoriasis with etanercept. J Drugs Dermatol. 2011;10(8):866-72. 
11 Ma L, Yang Q, Yang H, Wang G, Zheng M, Hao F et al. Calcipotriol plus betamethasone dipropionate gel compared with 
calcipotriol scalp solution in the treatment of scalp psoriasis: a randomized, controlled trial investigating efficacy and safety in 
a Chinese population. Int J Dermatol. 2016;55(1):106-13. doi:10.1111/ijd.12788 
12 Tyring S, Mendoza N, Appell M, Bibby A, Foster R, Hamilton T et al. A calcipotriene/betamethasone dipropionate two-
compound scalp formulation in the treatment of scalp psoriasis in Hispanic/Latino and Black/African American patients: 
results of the randomized, 8-week, double-blind phase of a clinical trial. Int J Dermatol. 2010;49(11):1328-33. 
doi:10.1111/j.1365-4632.2010.04598.x. 
 


 
Protocol Name: 
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 (Fitzpatrick skin 
phototypes IV-VI). 
Principal Investigator:  
Andrew Alexis, MD, MPH 
Primary Contact 
Name/Contact Info: 
Andrew Alexis, MD, MPH 
212-523-3888 
Date Revised: 
08/10/2017 
Study Number: 
IF2166478 
 
26 
Revised 9/2/14 
 
13 Leonardi C, Bagel J, Yamauchi P, et al. Efficacy and Safety of Calcipotriene Plus Betamethasone Dipropionate Aerosol 
Foam in Patients With Psoriasis Vulgaris--a Randomized Phase III Study (PSO-FAST). J Drugs Dermatol. 2015;14(12):1468-
77. 
14 Lebwohl M, Tyring S, Bukhalo M, et al. Fixed Combination Aerosol Foam Calcipotriene 0.005% (Cal) Plus Betamethasone 
Dipropionate 0.064% (BD) is More Efficacious than Cal or BD Aerosol Foam Alone for Psoriasis Vulgaris: A Randomized, 
Double-blind, Multicenter, Three-arm, Phase 2 Study. J Clin Aesthet Dermatol. 2016;9(2):34-41. 
15 Stein Gold L, Lebowohl M, Menter A, et al. Aerosol Foam Formulation of Fixed Combination Calcipotriene Plus 
Betamethasone Dipropionate is Highly Efficacious in Patients With Psoriasis Vulgaris: Pooled Data From Three Randomized 
Controlled Studies. J Drugs Dermatol. 2016;15(8):951-7. 
16 Leonardi C, Bagel J, Yamauchi P, et al. The Aerosol Foam Formulation of the Fixed Combination Calcipotriene Plus 
Betamethasone Dipropionate Improves the Health-Related Quality of Life in Patients With Psoriasis Vulgaris: Results from the 
Randomized PSO-FAST Study. J Drugs Dermatol. 2016;15(8):981-7. 
17 Kaufman BP, Gahlawat N, Tiu L, Alexis AF (2016) Efficacy of calcipotriene 0.005%/betamethasone dipropionate 0.064% in 
skin of color: preliminary data from 3 pooled multi-center, randomized, 4-week, parallel-group studies in the United States. 
Skin of Color Society Annual Scientific Symposium; Orlando, FL. 
18 Ahmad Fadzil MH, Ihtatho D, Mohd Affandi A, Hussein SH. Objective assessment of psoriasis erythema for PASI scoring. J 
Med Eng Technol. 2009;33(7):516-24. 

SAP_001.pdf: 
 
Title: 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 (Fitzpatrick skin phototypes IV-VI). 
PI: Andrew Alexis, M.D., MPH 
NCT03506477 
August 10, 2017 
 
Statistical Analysis Plan 
 
• 
Categorical outcomes were compared between treatment groups using a 0.05 level Fisher’s 
exact test.  
 
• 
Continuous outcomes were compared using Wilcoxon signed-rank tests.