Clinical Trial Results:
Title of the publication
Peptidase inhibitor 3 and chemokine ligand 27 may serve as biomarkers for actinic keratoses in organ transplant recipients (Eur J Dermatol. 2019 Jun 1;29(3):259-267. doi: 10.1684/ejd.2019.3559.)
former title:
Topical imiquimod 5% cream therapy versus photodynamic therapy with methyl-aminolaevulinate 16% cream of actinic keratoses in organ transplant recipients
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Summary
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EudraCT number |
2010-024623-24 |
Trial protocol |
AT |
Global end of trial date |
10 Dec 2018
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Results information
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Results version number |
v1(current) |
This version publication date |
29 May 2020
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First version publication date |
29 May 2020
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Other versions |
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Summary report(s) |
Peptidase inhibitor 3 and chemokine ligand 27 may serve as biomarkers for actinic keratoses in organ transplant recipients |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
IPDTAKOTR/V04/24.09.11
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
- | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Medical University of Vienna, Department Dermatology
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Sponsor organisation address |
Waehringer Guertel 18-20, Vienna, Austria, 1090
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Public contact |
Univ. Klinik f. Dermatologie, Medizinische Universität Wien, Univ. Klinik f. Dermatologie, +43 1404007700, stanislava.tzaneva@meduniwien.ac.at
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Scientific contact |
Univ. Klinik f. Dermatologie, Medizinische Universität Wien, Univ. Klinik f. Dermatologie, +43 1404007700, stanislava.tzaneva@meduniwien.ac.at
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
10 Dec 2018
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
10 Dec 2018
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Global end of trial reached? |
Yes
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Global end of trial date |
10 Dec 2018
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
To compare the efficacy of topical imiquimod 5% cream versus photodynamic therapy with methyl-aminolaevulinate 16% cream in the treatment of actinic keratoses in OTR, each pat was his own control
i.e. Molecular profiling of tissue samples in organ transplant recipients (OTR) to assess an early and minimally invasive identification of actinic keratosis (AK). The aim of this study was to compare mRNA expression profiles of genetic markers of AK before and after treatment, employing two different field-therapies, and to correlate the results with histological and clinical parameters.
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Protection of trial subjects |
Ten patients (2 women and 8 men) with multiple AK and field cancerisation were enrolled into the study
each patient was his own control
From the target lesions, 3-mm punch biopsies were obtained from each site initially, then at week 2 (immediately after the second PDT, and 2 weeks after the initiation of IMI, respectively), and 3 months after completion of the active treatment period. The punch biopsies were taken under local anaesthesia, and appropriate wound management was carried out.
For photodynamic therapy (PDT) as well as for photodynamic diagnosis (PDD), methyl-5-aminolevulinate 16% cream (Metvix© Cream, Galderma, France) was employed as photosensitizer, applied in a 1-mm thick layer, covering 50cm2. Before the procedure, local anaesthesia (lidocaine 1%, without vasoconstrictor) was applied, if required. During illumination, cooling was carried out by the integrated air-forced cooling device and/or spray with thermal water (Avene, France).
All patients were evaluated for the intensity of pain during light exposure using a visual analogue scale (VAS), considering 0 as absence of pain and 10 as the most severe pain.
The skin areas were covered after each treatment or PDD and the patients instructed to prevent exposure to direct light for 48 hours and to apply a sunblock in the following days.
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Background therapy |
Prior to initiation of the study, ketoconazole shampoo once daily and commercially available topical steroid foam was prescribed for one week for treatment of the scalp region, in order to reduce scales due to seborrheic eczema. If hyperkeratotic AKs were present at the same time, a local therapy with 10% salicyl vaseline once daily in the evening was given for one week. Afterwards there was a wash out period for a week without any local therapy. All patients received painkillers after PDT, ef necessary | ||
Evidence for comparator |
The reduction of the AKs in the photodynamic therapy (PDT) area vs topical imiquimod had to beassessed clinically, and mRNA expression profiles of various genetic markers before, during and 3 months after therapy were compared for the two treatment modalities. | ||
Actual start date of recruitment |
02 Jan 2012
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Austria: 10
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Worldwide total number of subjects |
10
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EEA total number of subjects |
10
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
5
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From 65 to 84 years |
5
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85 years and over |
0
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Recruitment
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Recruitment details |
The patients were recruited from a dedicated outpatient clinic for organ transplant recipients at the Department of Dermatology, Medical University of Vienna. The requirement was the presence ofwo anatomically separated contralateral areas of AKs on the face or forehead which could be selected, at a minimum distance of 5cm | |||||||||||||||
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Pre-assignment
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Screening details |
At baseline, all patients were clinically evaluated, and two anatomically separated contralateral areas of the face or forehead were selected, at a minimum distance of 5cm, each area of comparable size and extent. A target lesion, a lesion located in the middle of this area was selected, an at least AK grade II with a diameter of at least 8 mm | |||||||||||||||
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Period 1
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Period 1 title |
overall trial (overall period)
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Is this the baseline period? |
Yes | |||||||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | |||||||||||||||
Blinding implementation details |
it was an intraindividual trial; each patient was his own control
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Arms
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Are arms mutually exclusive |
No
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Arm title
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PDT-treatment | |||||||||||||||
Arm description |
a distinct area of field cancerisation (Face) in organ transplant patients (OTP), treated employing PDT with two treatment cycles (two weeks apart) of methyl-aminolevulinate 16% cream-PDT Prior to initiation of the study, ketoconazole shampoo, once daily, and commercially available topical steroid foam was prescribed for one week for treatment of the scalp region, in order to reduce scales due to seborrhoic eczema an at least AK grade II with a diameter of at least 8 mm was chosen as ‘target lesion’ in the treatment area and was biopsied, the 3mm tissue samples subsequently snap frozen in liquid nitrogen From the target lesions, 3-mm punch biopsies were obtained from not only initially, but then at week 2 (immediately after the second PDT, and 3 months after completion of the active treatment period. The treatment areas were also recorded by photodynamic diagnosis (PDD). | |||||||||||||||
Arm type |
Experimental | |||||||||||||||
Investigational medicinal product name |
methyl-5-aminolevulinate hydrochloride (methyl-aminolevulinate 16% cream-PDT
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Cream
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Routes of administration |
Cutaneous use
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Dosage and administration details |
field therapy with PDT with two treatment cycles (2 weeks apart) of methyl-5-aminolaevulinate-PDT
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Arm title
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imiquimod | |||||||||||||||
Arm description |
An area of field cancerisation was treated with Imiquimod 5% cream (three times a week for four weeks, carried out by the patients themselves) Prior to initiation of the study, ketoconazole shampoo and topical steroid foam was prescribed for one week The selected treatment area was recorded by photodynamic diagnosis (PDD). From a target lesions, 3-mm punch biopsies were obtained initially, then at week 2, and 2 weeks after the initiation of Imiquimod 5% cream as well as 3 months after completion of the active treatment period. | |||||||||||||||
Arm type |
Experimental | |||||||||||||||
Investigational medicinal product name |
Imiquimod 5% Cream
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Cream
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Routes of administration |
Cutaneous use
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Dosage and administration details |
Imiquimod 5% cream (three times a week for four weeks, carried out by the patients themselves
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Baseline characteristics reporting groups
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Reporting group title |
PDT-treatment
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Reporting group description |
a distinct area of field cancerisation (Face) in organ transplant patients (OTP), treated employing PDT with two treatment cycles (two weeks apart) of methyl-aminolevulinate 16% cream-PDT Prior to initiation of the study, ketoconazole shampoo, once daily, and commercially available topical steroid foam was prescribed for one week for treatment of the scalp region, in order to reduce scales due to seborrhoic eczema an at least AK grade II with a diameter of at least 8 mm was chosen as ‘target lesion’ in the treatment area and was biopsied, the 3mm tissue samples subsequently snap frozen in liquid nitrogen From the target lesions, 3-mm punch biopsies were obtained from not only initially, but then at week 2 (immediately after the second PDT, and 3 months after completion of the active treatment period. The treatment areas were also recorded by photodynamic diagnosis (PDD). | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
imiquimod
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Reporting group description |
An area of field cancerisation was treated with Imiquimod 5% cream (three times a week for four weeks, carried out by the patients themselves) Prior to initiation of the study, ketoconazole shampoo and topical steroid foam was prescribed for one week The selected treatment area was recorded by photodynamic diagnosis (PDD). From a target lesions, 3-mm punch biopsies were obtained initially, then at week 2, and 2 weeks after the initiation of Imiquimod 5% cream as well as 3 months after completion of the active treatment period. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
PDT-treatment
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Reporting group description |
a distinct area of field cancerisation (Face) in organ transplant patients (OTP), treated employing PDT with two treatment cycles (two weeks apart) of methyl-aminolevulinate 16% cream-PDT Prior to initiation of the study, ketoconazole shampoo, once daily, and commercially available topical steroid foam was prescribed for one week for treatment of the scalp region, in order to reduce scales due to seborrhoic eczema an at least AK grade II with a diameter of at least 8 mm was chosen as ‘target lesion’ in the treatment area and was biopsied, the 3mm tissue samples subsequently snap frozen in liquid nitrogen From the target lesions, 3-mm punch biopsies were obtained from not only initially, but then at week 2 (immediately after the second PDT, and 3 months after completion of the active treatment period. The treatment areas were also recorded by photodynamic diagnosis (PDD). | ||
Reporting group title |
imiquimod
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Reporting group description |
An area of field cancerisation was treated with Imiquimod 5% cream (three times a week for four weeks, carried out by the patients themselves) Prior to initiation of the study, ketoconazole shampoo and topical steroid foam was prescribed for one week The selected treatment area was recorded by photodynamic diagnosis (PDD). From a target lesions, 3-mm punch biopsies were obtained initially, then at week 2, and 2 weeks after the initiation of Imiquimod 5% cream as well as 3 months after completion of the active treatment period. | ||
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End point title |
Reduction of number of lesions after 12 months treatment compared to baseline [1] | ||||||||||||
End point description |
CRR = proportion of healed AKs compared to baseline AKs; assumption: 80% CRR for PDT and 60% CRR for Imiquimod;
alpha: 0.05, beta: 0.80
statistical method: McNemar Test, paired T-Test
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End point type |
Primary
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End point timeframe |
4 weeks after completion of treatment - complete response rate (CRR)
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Statistical analysis was performed within each arm (between different timepoints) but not between the arms. |
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| No statistical analyses for this end point | |||||||||||||
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Adverse events information
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Timeframe for reporting adverse events |
During treatment procedure (either during PDT or self-application of Imiquimod) and the period after - in the healing period
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Adverse event reporting additional description |
There were no serious adverse effects
Tolerance for PDT was very good (local anesthesia), all except 1 pat tolerated the full Tx. Most common side effect erythema (subsided within few days). Imiquimod Th: all patients erythema; 1 pat ulceration, 2 pat flue-like symptoms
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
23
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Reporting groups
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Reporting group title |
PDT-treatment
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Reporting group description |
a distinct area of field cancerisation (Face) in organ transplant patients (OTP), treated employing PDT with two treatment cycles (two weeks apart) of methyl-aminolevulinate 16% cream-PDT Prior to initiation of the study, ketoconazole shampoo, once daily, and commercially available topical steroid foam was prescribed for one week for treatment of the scalp region, in order to reduce scales due to seborrhoic eczema an at least AK grade II with a diameter of at least 8 mm was chosen as ‘target lesion’ in the treatment area and was biopsied, the 3mm tissue samples subsequently snap frozen in liquid nitrogen From the target lesions, 3-mm punch biopsies were obtained from not only initially, but then at week 2 (immediately after the second PDT, and 3 months after completion of the active treatment period. The treatment areas were also recorded by photodynamic diagnosis (PDD). | ||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
imiquimod
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Reporting group description |
An area of field cancerisation was treated with Imiquimod 5% cream (three times a week for four weeks, carried out by the patients themselves) Prior to initiation of the study, ketoconazole shampoo and topical steroid foam was prescribed for one week The selected treatment area was recorded by photodynamic diagnosis (PDD). From a target lesions, 3-mm punch biopsies were obtained initially, then at week 2, and 2 weeks after the initiation of Imiquimod 5% cream as well as 3 months after completion of the active treatment period. | ||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 0% | |||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? No | |||
Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| we were not able to recruit the planned number of patients | |||
