Clinical Trial Results:
Assessing the efficacy of image-guided laser-assisted Enstilar® delivery for treatment of psoriatic nails - a proof-of-concept, single-center, prospective, open-label, randomized, clinical trial with an intra-individual comparison of treatments

Trial information Top of page
Trial identification
Sponsor protocol code	79048
Additional study identifiers
ISRCTN number	-
US NCT number	NCT04580537
WHO universal trial number (UTN)	-
Other trial identifiers	Danish Data Protection Agency: P-2020-500, Danish Ethics Committee: 79048/H-19047222
Sponsors
Sponsor organisation name	Copenhagen University Hospital
Sponsor organisation address	Nielsine Nielsens Vej 17, entrance 9, 2nd floor, Copenhagen NV, Denmark, 2200
Public contact	Prof. Merete Hædersdal, MD PhD DMSc, Copenhagen University Hospital, Bispebjerg Department of Dermatology [D92], +45 24 45 43 93, mhaedersdal@dadlnet.dk
Scientific contact	Prof. Merete Hædersdal, MD PhD DMSc, Copenhagen University Hospital, Bispebjerg Department of Dermatology [D92], +45 24 45 43 93, mhaedersdal@dadlnet.dk
Paediatric regulatory details
Is trial part of an agreed paediatric investigation plan (PIP)	No
Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?	No
Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?	No
Results analysis stage
Analysis stage	Final
Date of interim/final analysis	01 Jun 2021
Is this the analysis of the primary completion data?	Yes
Primary completion date	01 Jun 2021
Global end of trial reached?	Yes
Global end of trial date	09 Sep 2021
Was the trial ended prematurely?	No
General information about the trial
Main objective of the trial	Efficacy of Enstilar for treatment of nail psoriasis using laser pretreatment
Protection of trial subjects	Pliapel 70 mg/g + 70 mg/g creme lidocaine + tetracaine, Air chiller device, Image-guided laser-treatment to avoid damage to nail matrix/nail bed
Background therapy	-
Evidence for comparator	-
Actual start date of recruitment	03 Aug 2020
Long term follow-up planned	No
Independent data monitoring committee (IDMC) involvement?	Yes
Population of trial subjects
Number of subjects enrolled per country
Country: Number of subjects enrolled	Denmark: 11
Worldwide total number of subjects	11
EEA total number of subjects	11
Number of subjects enrolled per age group
In utero	0
Preterm newborn - gestational age < 37 wk	0
Newborns (0-27 days)	0
Infants and toddlers (28 days-23 months)	0
Children (2-11 years)	0
Adolescents (12-17 years)	0
Adults (18-64 years)	11
From 65 to 84 years	0
85 years and over	0

Trial information Top of page

Subject disposition Top of page
Recruitment
Recruitment details	Recruitment initiated: 25-September-2020 Last patient last visit: 01-June-2021 End of study: 18-November-2021 Patients were recruited via social media and at the Department of Dermatology at the Copenhagen University Hospital, Bispebjerg, in Denmark.
Pre-assignment
Screening details	We assessed the following during the screening phase: clinical history of psoriasis/psoriatic arthritis, signs of nail psoriasis, no other skin or nail disease that may affect the treatment outcome, willingness to use a smartphone app to collect images for remote assessment throughout the study period
Period 1
Period 1 title	Treatment and follow-up (overall period)
Is this the baseline period?	Yes
Allocation method	Randomised - controlled
Blinding used	Not blinded
Blinding implementation details	Blinding not possible due to intrapatient controlled design and use of an ablative laser
Arms
Are arms mutually exclusive	No
Arm title	AFL + Enstilar
Arm description	Ablative fractional laser pretreatment + topical Enstilar (Calcipotriol/Betamethasone) foam treatment
Arm type	Experimental
Investigational medicinal product name	Enstilar (Calcipotriol/Betamethasone Dipropionate Aerosol Foam)
Investigational medicinal product code
Other name
Pharmaceutical forms	Cutaneous foam
Routes of administration	Cutaneous use
Dosage and administration details	Direct application of Enstilar foam to psoriatic finger and/or toe nails to create a thin even layer; once daily for 24 weeks; no occlusion
Arm title	Enstilar
Arm description	Topical Enstilar (Calcipotriol/Betamethasone) foam treatment
Arm type	Active comparator
Investigational medicinal product name	Enstilar (Calcipotriol/Betamethasone Dipropionate Aerosol Foam)
Investigational medicinal product code
Other name
Pharmaceutical forms	Cutaneous foam
Routes of administration	Cutaneous use
Dosage and administration details	Direct application of Enstilar foam to psoriatic finger and/or toe nails to create a thin even layer; once daily for 24 weeks; no occlusion
Number of subjects in period 1 AFL + Enstilar Enstilar Started 11 11 Completed 10 10 Not completed 1 1      Physician decision 1 1

Subject disposition Top of page

Baseline characteristics Top of page
Baseline characteristics reporting groups
Reporting group title	Treatment and follow-up
Reporting group description	-
Reporting group values Treatment and follow-up Total Number of subjects 11 11 Age categorical Units: Subjects     In utero 0 0     Preterm newborn infants (gestational age < 37 wks) 0 0     Newborns (0-27 days) 0 0     Infants and toddlers (28 days-23 months) 0 0     Children (2-11 years) 0 0     Adolescents (12-17 years) 0 0     Adults (18-64 years) 11 11     From 65-84 years 0 0     85 years and over 0 0 Age continuous Units: years     median (inter-quartile range (Q1-Q3)) 47 (35.5 to 57.5) - Gender categorical Units: Subjects     Female 4 4     Male 7 7
Subject analysis sets
Subject analysis set title	AFL + Enstilar
Subject analysis set type	Intention-to-treat
Subject analysis set description	Half of all psoriatic nails (per patient) received ablative fractional laser pre-treatment and topical treatment
Subject analysis set title	Enstilar
Subject analysis set type	Intention-to-treat
Subject analysis set description	Half of all psoriatic nails (per patient) received only received topical treatment
Subject analysis sets values AFL + Enstilar Enstilar Number of subjects 11 11 Age categorical Units: Subjects     In utero 0 0     Preterm newborn infants (gestational age < 37 wks) 0 0     Newborns (0-27 days) 0 0     Infants and toddlers (28 days-23 months) 0 0     Children (2-11 years) 0 0     Adolescents (12-17 years) 0 0     Adults (18-64 years) 11 11     From 65-84 years 0 0     85 years and over 0 0 Age continuous Units: years     median (inter-quartile range (Q1-Q3)) 47 (35.5 to 57.5) 47 (35.5 to 57.5) Gender categorical Units: Subjects     Female 4 4     Male 7 7

Baseline characteristics Top of page

End points Top of page
End points reporting groups
Reporting group title	AFL + Enstilar
Reporting group description	Ablative fractional laser pretreatment + topical Enstilar (Calcipotriol/Betamethasone) foam treatment
Reporting group title	Enstilar
Reporting group description	Topical Enstilar (Calcipotriol/Betamethasone) foam treatment
Subject analysis set title	AFL + Enstilar
Subject analysis set type	Intention-to-treat
Subject analysis set description	Half of all psoriatic nails (per patient) received ablative fractional laser pre-treatment and topical treatment
Subject analysis set title	Enstilar
Subject analysis set type	Intention-to-treat
Subject analysis set description	Half of all psoriatic nails (per patient) received only received topical treatment

End points Top of page

Primary: Reduction in N-NAIL score Top of page
End point title	Reduction in N-NAIL score
End point description
End point type	Primary
End point timeframe	Baseline vs end of trial (week 24)
End point values AFL + Enstilar Enstilar Number of subjects analysed 11 11 Units: 0-300 28 19
Statistical analysis title	Paired t-test
Statistical analysis description	Tested for normality using Shapiro-Wilk normality test, evaluated using Bonferroni-corrected multiple paired-t tests, p-values less than 0.05 were considered significant
Comparison groups	AFL + Enstilar v Enstilar
Number of subjects included in analysis	22
Analysis specification	Post-hoc
Analysis type	superiority [1]
P-value	= 0.62
Method	t-test, 2-sided
Confidence interval
Notes [1] - No significant difference between groups but significant improvement (p=0.01) at end of trial for both groups compared to baseline

Primary: Reduction in N-NAIL score Top of page

Adverse events Top of page
Adverse events information
Timeframe for reporting adverse events	SAEs are reported within 24 hours to sponsor-investigator Merete Hædersdal. At the end of the trial, a final report with all AEs, ARs, SAEs, and SUSARs was submitted to DKMA and the IRB
Adverse event reporting additional description	The investigators were responsible for routine assessments of AEs and ARs. All clinical complaints, signs or symptoms that meet AE or AR definitions were documented in the study record and the participant’s medical record.
Assessment type	Non-systematic
Dictionary used for adverse event reporting
Dictionary name	MedDRA
Dictionary version	22
Reporting groups
Reporting group title	Adverse events
Reporting group description	All subjects experienced mild local skin reactions to the topical treatment and the laser pretreatment.
Serious adverse events Adverse events Total subjects affected by serious adverse events      subjects affected / exposed 0 / 11 (0.00%)      number of deaths (all causes) 0      number of deaths resulting from adverse events 0
Frequency threshold for reporting non-serious adverse events: 1%
Non-serious adverse events Adverse events Total subjects affected by non serious adverse events      subjects affected / exposed 11 / 11 (100.00%) Injury, poisoning and procedural complications Laser therapy Additional description: Persistent post-laser erythema (fully recovered by end of trial)      subjects affected / exposed 1 / 11 (9.09%)      occurrences all number 1 Skin and subcutaneous tissue disorders Nail disorder Additional description: Onychocryptosis (not treatment-related, fully recovered by end of trial)      subjects affected / exposed 1 / 11 (9.09%)      occurrences all number 1 Pain of skin Additional description: Transient application site pain (fully recovered by end of trial)      subjects affected / exposed 1 / 11 (9.09%)      occurrences all number 1 Paronychia Additional description: Acute nail fold infection affecting two toes due to improper nail care (not treatment related, fully recovered by end of trial)      subjects affected / exposed 1 / 11 (9.09%)      occurrences all number 1 Local reaction Additional description: Mild local and nail reactions related to topical and/or laser treatment including erythema, swelling, crusting, erosion, flaking, skin peeling, onychoschizia, hyperpigmentation (all fully recovered by end of trial)      subjects affected / exposed 11 / 11 (100.00%)      occurrences all number 11 Musculoskeletal and connective tissue disorders Pain in extremity Additional description: Transient proximal interphalangeal joint pain (not treatment-related, fully recovered by end of trial)      subjects affected / exposed 1 / 11 (9.09%)      occurrences all number 1 Muscular weakness Additional description: Transient reduction in grip strength (not treatment-related, fully recovered by end of trial)      subjects affected / exposed 1 / 11 (9.09%)      occurrences all number 1

Adverse events Top of page

More information Top of page
Substantial protocol amendments (globally)
Were there any global substantial amendments to the protocol? Yes
Date	Amendment
07 Jul 2020	Due to Covid-19, an amendment to prevent further delays was necessary. The main changes were: -Request to include social media for recruitment -Extension of the trial period -Healthcare smartphone app (picture collection time point) -Inclusion of finger and toenails to reach recruitment goal
07 Apr 2021	Due to Covid-19, a 2nd amendment was necessary to finalize the study. The main changes were: -Request to extend visit window (+/-3 weeks) -Reduced number of patients from 25 to 11 -Extension of the trial period
Interruptions (globally)
Were there any global interruptions to the trial? No
Limitations and caveats
Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
Small sample size, short follow-up, no rheumatological baseline screening, hybrid trial design with no prior published evidence on remote assessment of AE in a nail psoriasis context

More information Top of page