An Investigator Initiated Study Evaluating the Efficacy and Tolerability of Enstilar Foam (Calcipotriene and Betamethasone Dipropionate) in Patients With Nail Psoriasis
Phase: PHASE4
Conditions: Nail Psoriasis
Sponsor: University of Alabama at Birmingham

 
 
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An investigator initiated study evaluating the efficacy and tolerability 
of Enstilar Foam (calcipotriene and betamethasone dipropionate) in 
patients with nail psoriasis  
 
 
 
 
 
Study Protocol  
 
 
 
 
 
NCT04227288  
 
 
 
 
 
August 22, 2017 
 
 
 
 
Boni Elewski, M.D., Principal Investigator 
 
University of Alabama at Birmingham 
 
Birmingham, AL 35233 
 
 

 
 
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An investigator initiated study evaluating the efficacy and tolerability 
of Enstilar Foam (calcipotriene and betamethasone dipropionate) in 
patients with nail psoriasis 
 
PI: Boni Elewski, MD  
 
Sponsor:  Investigator Initiated 
 
 
 
Introduction 
Psoriasis is a chronic, incurable skin disease affecting millions of people worldwide.  Nail 
abnormalities occur concomitantly in 50% of patients with psoriasis, with a lifetime 
incidence of 80% to 90%.(1)  In patients with psoriatic arthritis the incidence of nail 
disease is greater than 80%.(2)  Nail psoriasis significantly impacts quality of life. In a 
survey of 1728 patients, 93% considered it a significant cosmetic handicap, 52% 
reported pain as a symptom and 58% reported difficulty carrying out their job.(3)  
Treatment of nail bed psoriasis poses a challenge to the clinician as there is a lack of 
controlled clinical trials and no gold standard for therapy to date. When nail bed psoriasis 
is not associated with widespread skin disease or psoriatic arthritis, topical treatment 
should be the initial approach. The choice of treatment depends on the type of disease 
present. Many physicians use topical and intralesional corticosteroids or a vitamin D 
analog for treatment of nail bed disease (eg onycholysis and subungual hyperkeratosis) 
(4).  There are published reports demonstrating the increased tolerability of calcitriol 
ointment as compared to calciprotriol cream in the treatment of the sensitive 
intertriginous areas (5, 6) 
 
In a study by Tosti et al. calcipotriol was as effective as a corticosteroid preparation at 
reducing subungual hyperkeratosis. (7)  Adverse events with vitamin D analog therapy 
were limited to erythema and burning irritation. The nail unit is a sensitive area that might 
benefit from a less irritating vitamin D topical medication. In a pilot study by Kole, 
Cantrell, and Elewski, it was demonstrated that calcitriol ointment was as effective as 
betamethasone diproprionate ointment for the treatment of nail thickness in nail 
psoriasis. (8) Furthermore, in a study by Park et al. the fixed combination formulation of 
calcipotriol/betamethasone dipropionate ointment was safe and effective in the treatment 
of trachyonychia, which may be associated with psoriasis. (9) Lind et al demonstrated 
that the fixed combination calcipotriene/betamethasone dipropionate foam had greater 
skin penetration than the ointment formulation. (10) As such we propose that the 
combination product of vitamin D and topical steroids in the foam formulation 
(specifically, Cal/BD Foam), with increased penetration, will be an effective and safe 
option in the topical treatment of nail psoriasis. 
 
The aim of the proposed study is to evaluate the efficacy and safety of Enstilar Foam 
(calcipotriene and betamethasone dipropionate) for the treatment of nail psoriasis.  
 
 
 
 
 
 

 
 
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STUDY OBJECTIVES  
 
Primary Objective 
To compare the efficacy of a 24-week regimen of twice daily Enstilar Foam (calcipotriene 
and betamethasone dipropionate) in the treatment of nail bed psoriasis.  The primary 
efficacy outcome measure is the proportion of subjects achieving clinical 
improvement as measured by the nail thickness (hyperkeratosis) measurement. 
Secondary Objectives 
1. modified NAPSI (mNAPSI) score of target nail at Baseline, wk 12 and wk 
24 
2. NAPSI score of target nail at Baseline, wk 12 and wk 24 
3. Physician global assessment (PGA) of nail disease. 
4. Determine the most optimal method of assessing nail psoriasis (mNAPSI 
or NAPSI). 
 
Additional Objectives 
To assess the safety of a 24-week regimen of twice daily Enstilar Foam (calcipotriene 
and betamethasone dipropionate) in the treatment of nail bed psoriasis. 
 
STUDY DESIGN 
 
Study Outline 
This is open label investigator initiated study to examine the efficacy and safety of twice 
daily Enstilar Foam (calcipotriene and betamethasone dipropionate) in a population of 
nail bed psoriasis subjects who are eligible for topical treatment as deemed by the 
investigator. 
 
Number of Subjects 
Up to 20 eligible subjects will be provided twice daily daily Enstilar Foam (calcipotriene 
and betamethasone dipropionate).  Subjects will be instructed to apply a thin layer on 
the nail plate, around the nail plate and under the nail plate. The patient will be instructed 
to apply one application at night immediately before bed and not wash their hands 
before morning. At week 12, those patients with a mNAPSI50 or less may elect to 
discontinue study treatment. All subjects who completed the 6-month treatment will be 
followed for 1 month after discontinuation.   
 
Visit Schedule 
Screening Period 
Patient eligibility will be determined within 28 days prior to study entry. Subjects who 
meet the entry criteria may proceed to the first dosing visit.  
 
Dosing Visit 
Subjects will report to the investigational site to receive twice daily Enstilar Foam 
(calcipotriene and betamethasone dipropionate)  
 
Study Visit 
Subjects will report monthly to the investigational site for nail assessments.  
 

 
 
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Follow-Up Visits 
Subjects will return to the investigational site for follow-up visit at 4 weeks after the last 
study visit. 
 
Discontinuation of the Study 
The study may be discontinued at the discretion of the investigator at any time. 
 
STUDY ENTRY CRITERIA 
 
Study Inclusion Criteria 
To be eligible to participate in this study, candidates will meet the following eligibility 
criteria at the time of enrollment: 
 
1. Give written informed consent prior to any study procedures being conducted, 
and candidates will authorize the release and use of protected health 
information (PHI) 
2. Between the ages of 18 and 85 years old  
3. Have a diagnosis of nail psoriasis in either fingernails or toenails. 
4. Candidate for topical therapy in the opinion of the investigator. 
5. History of plaque psoriasis or psoriatic arthritis 
6. Target nail will be KOH negative for dermatophyte fungus 
 
Study Exclusion Criteria 
Candidates will be excluded from study entry if any of the following exclusion criteria 
exist at the time of enrollment: 
1. Males and females unable to practice effective contraception throughout 
study treatment  
2. Unable to comply with the protocol (as defined by the Investigator; i.e. drug or 
alcohol abuse or history of noncompliance) 
3. The presence of skin or nail conditions that might interfere with patient status 
assessments, as determined by the study investigator. 
4. Nursing mothers, pregnant women, and women planning to become pregnant 
while in this study. 
5. Patients with erythrodermic or pustular psoriasis. 
6. Other sustained treatment to target fingernail within 6 months prior to 
screening. 
7. History of trauma or surgery to target fingernail. 
8. History of any disease known to affect nails (e.g., lichen planus, 
onychomycosis) 
9. History of systemic psoriasis therapy for less than 6 months 
 
Drug Accountability 
The investigational site will maintain accurate records demonstrating dates and amount 
of study medication received, and accounts of any study medication accidentally or 
deliberately destroyed.   
 
STUDY PROCEDURES & TREATMENT PLAN GUIDELINES 
 
Informed Consent: 

 
 
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A written, signed informed consent form (ICF) and, in the US, written authorization to 
release and use PHI, will be obtained prior to performing any tests or evaluations under 
this protocol.  
 
See Protocol Flowchart (Section 1.0) for detailed timing of tests and evaluations.   
 
 
General Concomitant Therapy: 
For subjects on any prescription medications, every attempt should be made to keep the 
patient on a stable dose of that medication for at least 14 days prior to the first dose of 
study medication and throughout the study 
 
Subjects should advise the investigator if they start taking any new medications, 
including non-prescribed drugs. 
 
Concomitant Psoriasis Therapy 
Patients will be allowed to use the study medication to treat psoriatic skin lesions, if 
present. The study medication will be applied once daily on areas other than nails, 
to remain consistent with the prescribing information  
 
Patients will be allowed to use systemic therapy to treat psoriatic lesions.  The regimen 
should be stable for at least 6 months prior to study entry. 
 
SAFETY PLAN 
 
Clinical Safety Assessments 
The following clinical safety assessments will be performed:  (See study flowchart) 
• 
Physical examinations 
• 
Vital signs (temperature, heart rate, and blood pressure) 
• 
Monitoring for adverse events 
• 
Monitoring for concomitant therapy 
 
Laboratory Safety Assessments 
The following laboratory tests will be performed at screening: 
• 
Urine pregnancy test, if applicable. 
 
 
STUDY FLOWCHART: 
Vectical vs. Betamethasone 
Screening 
Treatment 
Follow 
Up 
Test / Evaluation 
Within 28 
Visit 1 
2 
3 
4 
5 
6 
7 
8 
Days Prior 
W k 1 
Wk 4 
Wk 8 
Wk 12 
Wk 16 
Wk 20 
Wk 24 
Wk 28 
to Day 1 
Day 1 
22 
50 
78 
106 
134 
162 
 
Informed Consent 
X 
 
 
 
 
 
 
 
 
Medical History 
X 
  
  
  
  
  
  
  
 
Physical Exam 
X 
 
  
  
  
  
X  
  
 
Psoriasis Nail Assessment  
(mNapsi, NAPSI) 
X 
X 
X  
X 
X  
 X 
X 
X 
X 
Nail Thickness Measurement 
X 
X 
X 
X 
X 
X 
X 
X 
X 

 
 
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References:  
 
1. Jiaravuthisan M, Sasseville D, Vender R, Murphy F, Muhn C. Psoriasis of the 
nail: anatomy, pathology, clinical presentation, and a review of the literature 
on therapy. J Am Acad Dermatol. 2007 Jul;57(1):1-27. 
2. Lawry M. Biological therapy and nail psoriasis. Dermatol Ther.20(1):60-7. 
3. de Jong E, Seegers B, Gulinck M, Boezeman J, van de Kerkhof P. Psoriasis of 
the nails associated with disability in a large number of patients: results of a 
recent interview with 1,728 patients. Dermatology. 1996;193(4):300-3. 
4. Usmani, N., Wilson, C. A case of nail psoriasis threated with topical calcitriol. 
Clinical and Experimental Dermatology. 2006 31: 712-3. 
5. Ortonne, J.P., Humbert, P., Nicolas, J.F., Tsankov, N., Tonev, S.D., Janin, A., 
Czernielewksi, J., Lahfa, M., Dubertret, L. Intra-individual comparision of the 
cutaneious safety and efficacy of calcitriol 3mcg/g ointment and calcipotriol 
50 mcg/g ointment on chronic plaque psoriasis localized in facial, hairline, 
retroauricular or flexural areas. Br J Dermatol. 2002 Sept; 148: 326-33.  
6. Wozel, G. Psoriasis treatment in difficult locations: scalp, nails, and intertriginous 
areas. Clinics in Dermatology. 2008; 26: 448-59. 
7. Tosti A, Piraccini B, Cameli N, Kokely F, Plozzer C, Cannata G, et al. Calcipotriol 
ointment in nail psoriasis: a controlled double-blind comparison with 
betamethasone dipropionate and salicylic acid. Br J Dermatol. 1998 
Oct;139(4):655-9. 
8. Kole L, Cantrell W, Elewski B. A Randomized, Double-Blinded Trial Evaluating 
the Efficacy and Tolerability of Vectical Ointment (Calcitriol 3 mcg/g 
Ointment) When Compared to Betamethasone Diproprionate Ointment (64 
mg/g) in Patients With Nail Psoriasis. J Drugs Dermatol. 2014; 13(8): 611-14. 
9.  Park JM, Cho HH, Kim WJ, et al. Efficacy and safety of 
calcipotriol/betamethasone dipropionate ointment for the treatment of 
trachyonychia: an open-label study. Ann Dermatol . 2015:27(4):371-
375. 
10.  Lind M, Nielsen KT, Schefe LH, et al. Supersaturation of calcipotriene and 
betamethasone dipropionate in a novel aerosol foam formulation for 
topical treatment of psoriasis provides enhanced bioavailability of the 
active ingredients. Dermatol Ther. 2016;6:413–425. 
 
 
 
 
 
Vital Signs 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Urine Pregnancy Test, 
 
X 
  
 
  
  
 
X 
 
Photography 
  
X 
X 
 X 
X  
X  
X 
X  
X 
Adverse Events 
 
X 
X 
X 
X 
X 
X 
X 
X 
Concomitant Medications 
X 
X 
X 
X 
X 
X 
X 
X 
X