Clinical Trial Results:
Multimodal optical imaging for pretreatment evaluation for cutaneous microparticle delivery
Summary
|
|
EudraCT number |
2017-002975-25 |
Trial protocol |
DK |
Global end of trial date |
20 Dec 2019
|
Results information
|
|
Results version number |
v1(current) |
This version publication date |
02 May 2020
|
First version publication date |
02 May 2020
|
Other versions |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
|
|||
Trial identification
|
|||
Sponsor protocol code |
59325
|
||
Additional study identifiers
|
|||
ISRCTN number |
- | ||
US NCT number |
- | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
|
|||
Sponsor organisation name |
Bispebjerg Hospital
|
||
Sponsor organisation address |
Bispebjerg Bakke 23, Kbh N, Denmark,
|
||
Public contact |
Dermatologisk forskningsafdeling, Bispebjerg Hospital, 0045 41184700, merete.haedersdal@regionh.dk
|
||
Scientific contact |
Dermatologisk forskningsafdeling, Bispebjerg Hospital, 0045 41184700, merete.haedersdal@regionh.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 |
30 Mar 2020
|
||
Is this the analysis of the primary completion data? |
Yes
|
||
Primary completion date |
18 Jul 2018
|
||
Global end of trial reached? |
Yes
|
||
Global end of trial date |
20 Dec 2019
|
||
Was the trial ended prematurely? |
No
|
||
General information about the trial
|
|||
Main objective of the trial |
1) To investigate the utility of RCM and OCT to assess micromorphology and gold microparticle delivery in acne skin after 6 weeks of topical treatment with adapalene-benzoyl peroxide (A-BPO).
|
||
Protection of trial subjects |
Before application of didoe laser pulses subjects had to precool the test sites with ice. If participatns experienced erythema and/or pain during A-BPO treatment they were advised to pause the treatment for up to two days.
|
||
Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
01 Nov 2017
|
||
Long term follow-up planned |
No
|
||
Independent data monitoring committee (IDMC) involvement? |
No
|
||
Population of trial subjects
|
|||
Number of subjects enrolled per country |
|||
Country: Number of subjects enrolled |
Denmark: 15
|
||
Worldwide total number of subjects |
15
|
||
EEA total number of subjects |
15
|
||
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) |
15
|
||
From 65 to 84 years |
0
|
||
85 years and over |
0
|
|
|||||||
Recruitment
|
|||||||
Recruitment details |
Patients were recruited from the Department of Dermatology, Bispebjerg Hospital, Copenhagen, Denmark and private dermatological practices in Copenhagen, Denmark. Further, patients were recruited from social media. | ||||||
Pre-assignment
|
|||||||
Screening details |
Patients were screened if they seemed to meet the inclusion criteria. | ||||||
Pre-assignment period milestones
|
|||||||
Number of subjects started |
15 | ||||||
Number of subjects completed |
15 | ||||||
Period 1
|
|||||||
Period 1 title |
overall trial (overall period)
|
||||||
Is this the baseline period? |
Yes | ||||||
Allocation method |
Not applicable
|
||||||
Blinding used |
Not blinded | ||||||
Arms
|
|||||||
Arm title
|
One arm | ||||||
Arm description |
- | ||||||
Arm type |
Experimental | ||||||
Investigational medicinal product name |
Adapalene- Benzoyl Peroxide
|
||||||
Investigational medicinal product code |
|||||||
Other name |
Epiduo
|
||||||
Pharmaceutical forms |
Gel
|
||||||
Routes of administration |
Cutaneous use
|
||||||
Dosage and administration details |
Patients were instructed to apply A-BPO gel once daily in the facial area from baseline (after first imaging session) until 3 days before the week 6 visit.
|
||||||
|
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Baseline characteristics reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
overall trial
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis sets
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set title |
Morphological changes
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set type |
Full analysis | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
Morphological characteristics of hair follicles were evaluated in RCM images.
Median infundibulum diameter, um: Week 0 63um, Week 3 57um, Week 6 54um
Follicle border, dark grey: Week 0: 60.1%, Week 3 91.4%, Week 6: 88.5%
Follicle border, hyperreflective: Week 0: 39.9%, Week 3: 8.6%, Week 6: 11.5%
Follicle content, empty: Week 0 59.8%, Week 3: 72.9%, Week 6: 80.3%
Follicle content, amorphous grey: Week 0: 25.1%, Week 3: 17.4%, Week 6: 11.8%
Follicle content, hyperreflective: Week 0: 15.1%, Week 3: 9.7%, Week 6: 7.9%
Thickened border: Week 0: 46.7%, Week 3: 28.6%, Week 6: 23.4%
OCT characteristics
Epidermal Thickenss, median, um: Week 0: 85.9 um, Week 6: 102.3 um
Blood flow (speckle variance): Week 0: 0.15, Week 6: 0.18
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set title |
Gold microparticle analyses
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set type |
Full analysis | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
RCM: Number of hair follicles with hyperreflective content were evaluated before and after gold microparticle (GMP) application in epidermis, dermoepidermal junction (DEJ) and dermis week 0 and week 6.
Week 0
Epidermis: Before GMP: 6%, after GMP: 89%
DEJ: Before GMP: 7%, after GMP 74%
Dermis: Before GMP 6 follicles, after GMP 13 follicles
Week 6
Epidermis: Before GMP: 9%, after GMP: 85%
DEJ: Before GMP: 5%, after GMP 76%
Dermis: Before GMP 3 follicles, after GMP 14 follicles
OCT
GMP penetration depth week 0: 206 um
GMP penetration depth week 6: 291 um
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|||
End points reporting groups
|
|||
Reporting group title |
One arm
|
||
Reporting group description |
- | ||
Subject analysis set title |
Morphological changes
|
||
Subject analysis set type |
Full analysis | ||
Subject analysis set description |
Morphological characteristics of hair follicles were evaluated in RCM images.
Median infundibulum diameter, um: Week 0 63um, Week 3 57um, Week 6 54um
Follicle border, dark grey: Week 0: 60.1%, Week 3 91.4%, Week 6: 88.5%
Follicle border, hyperreflective: Week 0: 39.9%, Week 3: 8.6%, Week 6: 11.5%
Follicle content, empty: Week 0 59.8%, Week 3: 72.9%, Week 6: 80.3%
Follicle content, amorphous grey: Week 0: 25.1%, Week 3: 17.4%, Week 6: 11.8%
Follicle content, hyperreflective: Week 0: 15.1%, Week 3: 9.7%, Week 6: 7.9%
Thickened border: Week 0: 46.7%, Week 3: 28.6%, Week 6: 23.4%
OCT characteristics
Epidermal Thickenss, median, um: Week 0: 85.9 um, Week 6: 102.3 um
Blood flow (speckle variance): Week 0: 0.15, Week 6: 0.18
|
||
Subject analysis set title |
Gold microparticle analyses
|
||
Subject analysis set type |
Full analysis | ||
Subject analysis set description |
RCM: Number of hair follicles with hyperreflective content were evaluated before and after gold microparticle (GMP) application in epidermis, dermoepidermal junction (DEJ) and dermis week 0 and week 6.
Week 0
Epidermis: Before GMP: 6%, after GMP: 89%
DEJ: Before GMP: 7%, after GMP 74%
Dermis: Before GMP 6 follicles, after GMP 13 follicles
Week 6
Epidermis: Before GMP: 9%, after GMP: 85%
DEJ: Before GMP: 5%, after GMP 76%
Dermis: Before GMP 3 follicles, after GMP 14 follicles
OCT
GMP penetration depth week 0: 206 um
GMP penetration depth week 6: 291 um
|
|
||||||||||
End point title |
Morphological changes | |||||||||
End point description |
The study was designed as an exploratory study with no formal statistical sample size calculation. Fifteen patients with acne and a total of 945 hair follicles were considered sufficient to investigate the effect of A-BPO on hair follicle and skin morphology. Non-parametric statistics were used for morphological changes, and changes in epidermal thickness and blood flow measurements. Descriptive data were presented with medians and interquartile ranges (IQR). Chi square test was applied on hair follicle characteristics. Mann Whitney U was applied to test differences in hair follicle diameters between facial sites at Week 0 and Week 6. Spearman correlation coefficient was calculated to test the association between GMP penetration depth and epidermal thickness in OCT images.
|
|||||||||
End point type |
Primary
|
|||||||||
End point timeframe |
6 weeks
|
|||||||||
|
||||||||||
Attachments |
Table 1 |
|||||||||
Statistical analysis title |
Statistical analyses morphological changes | |||||||||
Comparison groups |
One arm v Morphological changes
|
|||||||||
Number of subjects included in analysis |
30
|
|||||||||
Analysis specification |
Pre-specified
|
|||||||||
Analysis type |
other | |||||||||
P-value |
< 0.05 | |||||||||
Method |
Chi-squared | |||||||||
Parameter type |
Median difference (net) | |||||||||
Confidence interval |
|
||||||||||
End point title |
Gold microaparticle delivery | |||||||||
End point description |
Descriptive statistics is presented as medians and interquartile ranges (IQR). Due to the intra-individual study design, we paired data. Hence, Wilcoxon Signed Rank test of matched pairs was applied on number of follicles and eccrine ducts with hyperreflective content before and after GMP application before and after treatment with A-BPO. P values <0.05 were considered significant and all tests were two-sided.
|
|||||||||
End point type |
Primary
|
|||||||||
End point timeframe |
6 weeks
|
|||||||||
|
||||||||||
Attachments |
Table 2 |
|||||||||
Statistical analysis title |
Gold microparticle delivery | |||||||||
Comparison groups |
One arm v Gold microparticle analyses
|
|||||||||
Number of subjects included in analysis |
30
|
|||||||||
Analysis specification |
Pre-specified
|
|||||||||
Analysis type |
other | |||||||||
P-value |
< 0.05 | |||||||||
Method |
Wilcoxon (Mann-Whitney) | |||||||||
Parameter type |
Median difference (final values) | |||||||||
Confidence interval |
||||||||||
level |
95% | |||||||||
sides |
2-sided
|
|||||||||
lower limit |
- | |||||||||
upper limit |
- | |||||||||
Variability estimate |
Standard deviation
|
|
|||||||||||||||||||||
Adverse events information
|
|||||||||||||||||||||
Timeframe for reporting adverse events |
Adverse events were reported from the participatns during the study period
|
||||||||||||||||||||
Adverse event reporting additional description |
AEs were mostly erythema and scaling. Patients were advised to pause A-BPO for up to two days or apply the gel once every other day for a 4-5 days.
|
||||||||||||||||||||
Assessment type |
Systematic | ||||||||||||||||||||
Dictionary used for adverse event reporting
|
|||||||||||||||||||||
Dictionary name |
MedDRA | ||||||||||||||||||||
Dictionary version |
6
|
||||||||||||||||||||
Reporting groups
|
|||||||||||||||||||||
Reporting group title |
Patients
|
||||||||||||||||||||
Reporting group description |
- | ||||||||||||||||||||
|
|||||||||||||||||||||
Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||
|
|
|||
Substantial protocol amendments (globally) |
|||
Were there any global substantial amendments to the protocol? No | |||
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. | |||
Limitations of the study included the uncontrolled design, the limited sample size, and only 6-weeks treatment with A-BPO. |