Clinical trial NCT03511326
Conditions: Actinic Keratoses
Keywords: field-treatment
Sponsor: Galderma R&D
Start date: 2017-06-07; Completion date: 2017-11-28
Enrollment: 50 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
Interventional open label prospective and multicentre study conducted in Germany in subjects with thin or non-hyperkeratotic and non-pigmented multiple AKs in one anatomical area on the face (e.g., forehead or cheek or chin), excluding nose eyelids, lips and mucosa or balding scalp, using Luxerm® DL-PDT treatment.

Detailed description:

Arms: arm 1: None
Interventions: intervention 1: Methyl Aminolaevulinate 16% Cream
Intervention descriptions: intervention 1: Subject will received one session of methyl aminolevulinate Daylight Photodynamic therapy

Protocol documents:
Prot_SAP_000.pdf: 
GALDERMA RESEARCH & DEVELOPMENT 
Protocol N° RD.03.SPR.114384  
Final version - dated on 22 February -2017 
Page 1 of 69 CONFIDENTIAL 
 
CLINICAL TRIAL PROTOCOL 
PROTOCOL NUMBER: N° RD.03.SPR.114384 
 
 
 


GALDERMA RESEARCH & DEVELOPMENT 
Protocol N° RD.03.SPR.114384  
Final version - dated on 22 February -2017 
Page 2 of 69 CONFIDENTIAL 
 
CLINICAL TRIAL PROTOCOL 
PROTOCOL NUMBER: RD.03.SPR.114384 
CONFIDENTIAL 
This document contains confidential, proprietary information 
All the information provided to the Investigator and his/her staff and all data obtained through 
this GALDERMA R&D clinical trial protocol are confidential.  The Sponsor reserves all 
proprietary rights. No information may be disclosed to any third party without prior written 
consent from GALDERMA R&D. 
 


GALDERMA RESEARCH & DEVELOPMENT 
Protocol N° RD.03.SPR.114384  
Final version - dated on 22 February -2017 
Page 3 of 69 CONFIDENTIAL 
TITLE PAGE 
Title: 
Subject reported outcomes on satisfaction, safety and efficacy with Luxerm® in the field-directed treatment of thin or 
non-hyperkeratotic and non-pigmented Actinic Keratosis of the face or the scalp 
Project Name:  
Project Number: 
Clinical Trial Phase: 
834 
RD.03.SPR.114384 
Phase IV 
EUDRACT NUMBER 2017-000066-29  
Version Number: 01  
Sponsor Contact details:  
Name 
GALDERMA R&D 
Address 
Les Templiers 
2400, Route des Colles 
06410 Biot - France 
Tel 
+ 33 4 92 38 67 06 
Fax 
+ 33 4 93 95 71 64 


GALDERMA RESEARCH & DEVELOPMENT 
Protocol N° RD.03.SPR.114384  
Final version - dated on 22 February -2017 
Page 4 of 69 CONFIDENTIAL 
For any urgent medical questions, including safety reasons, please use the contact details 
provided in Section 8.2.2 
 
 
 
 
 
 
 
 
This clinical trial will be performed in compliance with applicable regulations, Good Clinical 
Practice (GCP) and the ethical principles that have their origin in the Declaration of Helsinki. 
This clinical trial Protocol follows guidelines outlined by the International Conference on 
Harmonization (ICH) and the GALDERMA R&D Phase IV department template 


GALDERMA RESEARCH & DEVELOPMENT 
Protocol N° RD.03.SPR.114384  
Final version - dated on 22 February -2017 
Page 5 of 69 CONFIDENTIAL 
CLINICAL TRIAL ADMINISTRATIVE STRUCTURE  
The following table contains the details of GALDERMA R&D employees involved in the 
conduct of the trial.  
SPONSOR PERSONNEL 
Name/Title 
Affiliation/Address/Tel./Fax 
Responsibilities 
Stéphanie Leclerc 
Clinical Project Manager 
GALDERMA R&D SNC, 
Global Phase IV – GBU Rx 
Les Templiers, 2400, Route des Colles 
06410 Biot - France 
Tel: + 33 4 92 38 67 06 
Fax: + 33 93 95 71 64 
Responsible for clinical management 
and monitoring of clinical trial and for 
overall coordination of clinical project 
Chantal Lebas 
Clinical Trial Administrator 
GALDERMA R&D SNC, 
Same as above 
Tel: + 33 4 93 47 66 
Fax: + 33 92 95 21 42 
Responsible for 
administrative follow-up and 
management of Trial Master File 
Rajeev CHAVDA 
Medical Expert  
GALDERMA R&D SNC,  
Tel: + 33 4 92 95 29 28 
Fax: + 33 4 93 95 71 64 
Responsible for medical 
management and safety surveillance 
Philippe Martel 
Phase IV Manager 
GALDERMA R&D SNC, 
Same as above 
Tel: + 33 92 38 67 35 
Fax: + 33 93 95 71 64 
Responsible for the Phase IV group 
Stéphane Cambiaggio 
Data Manager 
GALDERMA R&D SNC, 
Same as above 
Tel: + 33 4 92 38 68 33 
Fax: + 33 493 95 71 64 
Responsible for the coordination of all 
data management activities 
Nabil Kerrouche 
Statistician / Clinical Expert 
GALDERMA R&D SNC, 
Same as above 
Tel: + 33 93 95 71 86 
Fax: + 33 4 92 95 21 56 
Responsible for the management of 
all statistical activities 
Denis MOULIN 
Global Quality Assurance 
Manager 
GALDERMA R&D SNC, 
Same as above 
Tel: + 334 92 38 30 53 
Fax: + 33 4 93 95 70 71 
Responsible for quality assurance 
and audits  
Myriam HELLY 
Clinical supplies Coordinator 
GALDERMA R&D SNC, 
Same as above 
Tel: + 33 4 92 38 67 75 
Fax: + 33 4 93 95 70 71 
Responsible for the management of 
all clinical supplies activities 
Palma Seljan 
Clinical Safety Physician 
GALDERMA  
14501 North Freeway 
Fort Worth TX 76177 
United States 
Tel: + 1 817-961-5339  
Fax: + 1 610 504-2661 
Responsible for safety surveillance 
 


GALDERMA RESEARCH & DEVELOPMENT 
Protocol N° RD.03.SPR.114384  
Final version - dated on 22 February -2017 
Page 6 of 69 CONFIDENTIAL 
SIGNATURE PAGE 
Investigator’s Agreement 
I agree to: 
 Implement and conduct this clinical trial diligently and in strict compliance with the 
protocol, Good Clinical Practices and all applicable laws and regulations. 
 Accurately record all required data on each patient’s electronic Case Report Forms (eCRFs) 
in a timely manner on an ongoing basis. 
 Use the investigational product(s) for this clinical trial only. Maintain a complete and 
accurate inventory during and at the completion of the clinical trial. Maintain records of all 
investigational product units received, dispensed, returned by the subjects, and the number 
of product units returned to GALDERMA R&D. 
 Allow authorized representatives of GALDERMA R&D or regulatory authorities to conduct 
on-site visits to review, audit, and copy clinical trial documents. I will personally meet 
these representatives at mutually convenient times to answer any clinical trial-related 
questions. 
 Comply strictly with the agreement signed for the carrying out of my services within the 
scope of this protocol, especially with the provisions regarding confidentiality and 
intellectual property (results and publications). 
I have read this protocol in its entirety, including the above statement, and I agree to all aspects. 
PRINCIPAL INVESTIGATOR   
 
SIGNATURE 
 
 
 
DATE 
PRINTED NAME: 
 
 
 
 
 
 
 
 
GALDERMA R&D  
 
 
SIGNATURE 
 
 
 
DATE 
PHASE IV MEDICAL EXPERT 
PRINTED NAME: 
RAJEEV CHAVDA 
 
SPONSOR REPRESENTATIVE 
PRINTED NAME: 
PHILIPPE MARTEL 
RETURN THE ORIGINAL SIGNED COPY TO GALDERMA R&D AND KEEP A COPY AT YOUR SITE 


GALDERMA RESEARCH & DEVELOPMENT 
Protocol N° RD.03.SPR.114384  
Final version - dated on 22 February -2017 
Page 7 of 69 CONFIDENTIAL 
DISTRIBUTION 
Copy of the Protocol: All signatories and, 
Stéphanie LECLERC 
Global Phase IV Clinical Project Manager, GALDERMA R&D 
Nabil KERROUCHE 
Global Phase IV Senior Statistician, GALDERMA R&D 
Sabine HOMATTER 
Global Phase IV Operational Manager, GALDERMA R&D 
Stephane CAMBIAGGIO 
Global Phase IV Data Manager, GALDERMA R&D 
Chantal LEBAS 
Global Phase IV Clinical Trial Administrator, GALDERMA R&D 
Myriam HELLY 
Pharmaceutical Unit, GALDERMA R&D, SNC 
Laurence SALIN 
HEAD OF CLINICAL SAFETY GROUP, GALDERMA R&D 
Orla DUFFY-ROGER 
Regulatory Affairs, GALDERMA R&D. 
Denis MOULIN 
Site Quality Assurance Manager, GALDERMA R&D SNC 
Delphine KEROB 
Medical Affairs Director, GALDERMA International 
Isabelle DRACACCI 
Head of Global Stategic Franchise, Dermato-Oncology, Galderma 
International 
Thomas KNAPPE 
Regulatory affairs manager, GALDERMA Germany. 
Bernd FRIEDGEN 
Local Safety Officer of the involved countries, GALDERMA 
Germany 
Géraldine LANCELOT 
Industrial Property, GALDERMA R&D 
 
Copy of the Synopsis: 
 
Andreas JAECKEL 
Head of Medical Department, Medical Department, GALDERMA 
Germany 
Birgit JANNING 
Medical Marketing Manager, Prescription 
Harold DUMONT 
Global Brand Manager, GALDERMA Global Marketing 
Paul Antoine HAMON 
Market Access Manager, GALDERMA R&D  Global Marketing 
 
 
Original Protocol: Archives (GALDERMA R&D Sophia Antipolis) 


GALDERMA RESEARCH & DEVELOPMENT 
Protocol N° RD.03.SPR.114384  
Final version - dated on 22 February -2017 
Page 8 of 69 CONFIDENTIAL 
TABLE OF CONTENTS 
TITLE PAGE ............................................................................................................................................... 3 
CLINICAL TRIAL ADMINISTRATIVE STRUCTURE ........................................................................ 5 
SIGNATURE PAGE .................................................................................................................................... 6 
DISTRIBUTION .......................................................................................................................................... 7 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS ......................................................... 12 
1 
SYNOPSIS ........................................................................................................................................ 14 
2 
BACKGROUND AND RATIONALE ........................................................................................... 18 
2.1 
Medical background and short rationale for the clinical trial................................................ 18 
2.2 
Investigational product profile .................................................................................................. 20 
2.3 
Risk/Benefit assessment .............................................................................................................. 20 
3 
CLINICAL TRIAL OBJECTIVES AND CLINICAL HYPOTHESIS ...................................... 21 
3.1 
Clinical trials objectives ............................................................................................................. 21 
3.2 
Clinical hypothesis ...................................................................................................................... 21 
4 
SELECTION AND DISPOSITION OF CLINICAL TRIAL POPULATION ........................... 21 
4.1 
Number of subjects ..................................................................................................................... 21 
4.2 
Clinical trial population ............................................................................................................. 21 
4.2.1 
Inclusion criteria .................................................................................................................... 22 
4.2.2 
Exclusion criteria ................................................................................................................... 22 
4.3 
Prior and concomitant therapies ............................................................................................... 24 
4.3.1 
Definition ................................................................................................................................ 24 
4.3.2 
Categories ............................................................................................................................... 24 
4.3.3 
Recording ............................................................................................................................... 25 
4.3.4 
Authorised therapies during the clinical trial. .................................................................... 25 
4.3.5 
Prohibited therapies during the clinical trial ...................................................................... 25 
4.4 
Procedures / reasons for discontinuation .................................................................................. 26 
5 
INVESTIGATIONAL PLAN.......................................................................................................... 27 
5.1 
Overall clinical trial design ........................................................................................................ 27 


GALDERMA RESEARCH & DEVELOPMENT 
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Final version - dated on 22 February -2017 
Page 9 of 69 CONFIDENTIAL 
5.2 
Discussion of clinical trial design ............................................................................................... 28 
5.3 
Clinical trial duration and termination .................................................................................... 28 
5.4 
Clinical trial flow chart .............................................................................................................. 29 
5.5 
Clinical trial visit description and procedures ......................................................................... 30 
5.5.1 
Visit 1 - Baseline visit ............................................................................................................. 30 
5.5.2 
Visit 2 (day 1 after treatment ±2 days) ................................................................................ 32 
5.5.3 
Week 12 / Last clinical trial visit or Early trial termination visit ..................................... 32 
5.6 
Subject instructions .................................................................................................................... 33 
6 
CLINICAL SUPPLIES ................................................................................................................... 34 
6.1 
Investigational product identification and use ......................................................................... 34 
6.1.1 
Product identity ..................................................................................................................... 34 
6.1.2 
Method of treatment assignment .......................................................................................... 34 
6.1.3 
Subject Identification Number (SIN) ................................................................................... 35 
6.1.4 
Instructions for use and administration .............................................................................. 35 
6.2 
Other supplies ............................................................................................................................. 37 
6.3 
Investigational product packaging and labeling ...................................................................... 37 
6.4 
Investigational product management ........................................................................................ 38 
6.4.1 
Accountability ........................................................................................................................ 38 
6.4.2 
Dispensing ............................................................................................................................... 38 
6.4.3 
Investigational product compliance management and record ........................................... 38 
6.4.4 
Storage of investigational product ....................................................................................... 39 
6.4.5 
Return of investigational product ........................................................................................ 39 
6.5 
Blinding ........................................................................................................................................ 39 
7 
STUDY ASSESSMENTS ................................................................................................................ 39 
7.1 
Subject Reported Outcomes (PRO): ......................................................................................... 40 
7.2 
Efficacy assessments ................................................................................................................... 40 
7.2.1 
AK lesion assessment ............................................................................................................. 40 
7.2.2 
Clinical assessment of the subject’s skin aspect .................................................................. 41 


GALDERMA RESEARCH & DEVELOPMENT 
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Final version - dated on 22 February -2017 
Page 10 of 69 CONFIDENTIAL 
7.3 
Safety assessments ...................................................................................................................... 41 
7.3.1 
Adverse Events ....................................................................................................................... 41 
7.3.2 
Subject’s self-assessment of pain .......................................................................................... 41 
7.4 
Other assessments ....................................................................................................................... 42 
7.4.1 
Photodamage assessment by Dovers Scale .......................................................................... 42 
7.4.2 
Photographs (for selected sites) ............................................................................................ 42 
7.4.3 
Investigator questionnaire .................................................................................................... 42 
7.5 
Appropriateness of measurements ............................................................................................ 42 
8 
ADVERSE EVENT .......................................................................................................................... 43 
8.1 
Definitions .................................................................................................................................... 43 
8.1.1 
Adverse Events (AE).............................................................................................................. 43 
8.1.2 
Serious Adverse Events (SAE) .............................................................................................. 44 
8.1.3 
Unexpected adverse drug reaction ....................................................................................... 45 
8.1.4 
Adverse event reporting period ............................................................................................ 45 
8.1.5 
Severity ................................................................................................................................... 45 
8.1.6 
Relationship to the study drug(s) and/or clinical trial procedure ..................................... 46 
8.2 
Reporting procedures ................................................................................................................. 47 
8.2.1 
Procedures for reporting adverse events ............................................................................. 47 
8.2.2 
Procedure for reporting a serious adverse event ................................................................ 48 
8.3 
Procedure for suspected allergic contact reaction ................................................................... 49 
8.4 
Procedures for reporting pregnancies ...................................................................................... 51 
9 
STATISTICAL METHODS PLANNED ....................................................................................... 52 
9.1 
Statistical and analytical plans .................................................................................................. 52 
9.1.1 
Analysed Variables ................................................................................................................ 52 
9.1.2 
Populations analysed, evaluability and limitations / evaluation of Bias ........................... 54 
9.1.3 
Data presentation and graphics ............................................................................................ 54 
9.1.4 
Statistical analyses ................................................................................................................. 55 
9.2 
Sample size determination ......................................................................................................... 55 


GALDERMA RESEARCH & DEVELOPMENT 
Protocol N° RD.03.SPR.114384  
Final version - dated on 22 February -2017 
Page 11 of 69 CONFIDENTIAL 
9.2.1 
Historical data and assumptions .......................................................................................... 55 
9.2.2 
Sample size calculation .......................................................................................................... 55 
10 
TRAINING / MONITORING / DATA MANAGEMENT / QUALITY ASSURANCE ............ 55 
10.1 
Personnel training ....................................................................................................................... 55 
10.2 
Clinical monitoring ..................................................................................................................... 56 
10.3 
Data management ....................................................................................................................... 56 
10.4 
Quality assurance / audit / inspection ....................................................................................... 57 
11 
ETHICS AND GENERAL CLINICAL TRIAL CONDUCT CONSIDERATIONS ................. 57 
11.1 
Institutional review board (IRB) or ethics committee (EC) .................................................... 57 
11.2 
Ethical conduct of the clinical trial ........................................................................................... 57 
11.3 
Subject information sheet / informed consent .......................................................................... 58 
11.4 
Contractual requirements .......................................................................................................... 58 
11.5 
Data collection and archiving .................................................................................................... 58 
11.5.1 
Data Collection ....................................................................................................................... 58 
11.5.2 
Source documentation ........................................................................................................... 59 
11.5.3 
Archives .................................................................................................................................. 59 
11.6 
Insurance ..................................................................................................................................... 59 
12 
REFERENCE LIST ......................................................................................................................... 60 
13 
ATTACHMENTS ............................................................................................................................ 63 
Appendix 1: Subject questionnaire – Treatment day after daylight exposure ..................................... 63 
Appendix 2: Subject questionnaire–Week 12 / early termination ......................................................... 66 
Appendix 3: physician satisfaction questionnaire when all subjects have completed the 
study .................................................................................................................................................. 68 
 
 
 


GALDERMA RESEARCH & DEVELOPMENT 
Protocol N° RD.03.SPR.114384  
Final version - dated on 22 February -2017 
Page 12 of 69 CONFIDENTIAL 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS 
Abbreviation 
Term 
AE 
Adverse Event 
AK 
Actinic Keratosis 
APT 
All Subjects Treated (Safety Population) 
CDMS 
Clinical Data Management System 
c-PDT 
Conventional Photodynamic Therapy 
CPM 
Clinical Project Manager 
CRA 
Clinical Research Associate 
CRF 
Case Report Form 
CRO 
Contract Research Organization 
DL 
Daylight 
DMP 
Data Management Plan 
EC 
Ethics Committee 
FSI 
First Subject In (first subject who signs the Informed Consent Form) 
FU 
Follow-Up 
GCP 
Good Clinical Practice 
GMP 
Good Manufacturing Practice 
ICH 
International Conference on Harmonization 
i.e. 
That is (Latin: id est) 
IB 
Investigator Brochure 
IRB 
Institutional Review Board 
ISF 
Investigator Site File 
IUD 
Intra Uterine Device 
ITT 
Intent-To-Treat 
LSI 
Last Subject In (Last subject randomised/assigned to treatment) 
LSO 
Last Subject Out ( Last subject who completed its last clinical trial visit) 
MAL 
Methyl Aminolevulinate 
MedDRA 
Medical Dictionary for Regulatory Activities 
NMSC 
Non Melanoma Skin Cancer 
NRS 
Numeric rating scale 


GALDERMA RESEARCH & DEVELOPMENT 
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Final version - dated on 22 February -2017 
Page 13 of 69 CONFIDENTIAL 
Abbreviation 
Term 
OTC 
Over-The-Counter 
PDT 
Photodynamic Therapy 
PP 
Per Protocol 
SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
SAS 
Statistical Analysis  System (SAS Institute Inc., Cary, NC) 
SIN 
Subject Identification Number 
SCC 
Squamous cell carcinoma 
SOC 
System Organ Class 
SOP 
Standard Operating Procedure 
SmPC 
Summary Product Characteristics 
UPT 
Urine Pregnancy Test 
UV 
Ultraviolet 


GALDERMA RESEARCH & DEVELOPMENT 
Protocol N° RD.03.SPR.114384  
Final version - dated on 22 February -2017 
Page 14 of 69 CONFIDENTIAL 
1 
SYNOPSIS 
Clinical trial title: 
Subject reported outcomes on satisfaction, efficacy and safety with Luxerm® in the field-directed treatment of thin or 
non-hyperkeratotic and non-pigmented Actinic Keratosis of the face or the scalp 
Short title (± acronym): SESAME 2 
 
Project number: 
834 
Clinical trial phase: 
Phase IV 
Clinical trial period 
Planned  First Subject In: May 2017 
Planned Last Subject Out: Nov. 2017 
Objective(s): 
Luxerm® with daylight photodynamic therapy has been approved in 
Germany, for the treatment of thin or non-hyperkeratotic and non-
pigmented Actinic Keratosis (AK) on face and scalp.  
 
The main objective of this trial is to evaluate the subject reported outcome 
of Luxerm® Daylight field-directed treatment of thin or non-hyperkeratotic 
and non-pigmented AK lesions on the face or scalp after one session.  
 
Also the efficacy and safety of Luxerm® in terms of subject complete 
response rate will be assessed. 
 
Methodology: 
It is an interventional open label prospective and multicentre study 
conducted in Germany in subjects with thin or non-hyperkeratotic and non-
pigmented multiple AKs in one anatomical  area on the face (e.g., forehead 
or cheek or chin), excluding nose eyelids, lips and mucosa or balding 
scalp, using Luxerm® DL-PDT treatment. 
 
The study will collect the subject’s characteristics and medical history, how 
Luxerm® treatment has been performed, concomitant treatments, safety 
information, investigator and subject‘s satisfaction with the efficacy and 
safety of Luxerm® DL-PDT in the field-directed treatment of thin or non-
hyperkeratotic and non-pigmented AK. 
Total number of planned subjects:  
50 subjects will be enrolled 
 
Total number of planned sites: 
Approximately 8 sites 
Approximate number of 
subjects/site: 
5 to 10 subjects per site 
Country(ies) involved: 
Germany 
Population and main inclusion 
criteria: 
Subjects over 18 years old with thin or non-hyperkeratotic and non-
pigmented AKs in one anatomical area on the face (e.g., forehead or cheek 
or chin) excluding nose, eyelids, lips and mucosa, or balding scalp 
requiring field treatment with Luxerm® DL-PDT. 
Clinical trial duration per subject  
maximum 15 weeks 
Number of visits: 
3 study visits (baseline, day 1 post-treatment, week 12 post-treatment).   


GALDERMA RESEARCH & DEVELOPMENT 
Protocol N° RD.03.SPR.114384  
Final version - dated on 22 February -2017 
Page 15 of 69 CONFIDENTIAL 
Clinical trial title: 
Subject reported outcomes on satisfaction, efficacy and safety with Luxerm® in the field-directed treatment of thin or 
non-hyperkeratotic and non-pigmented Actinic Keratosis of the face or the scalp 
Short title (± acronym): SESAME 2 
 
Project number: 
834 
Clinical trial phase: 
Phase IV 
Clinical trial period 
Planned  First Subject In: May 2017 
Planned Last Subject Out: Nov. 2017 
Investigational product: 
 
Name: 
Luxerm® 
Pharmaceutical form: 
Cream 
Dose/concentration: 
160mg/g of methyl aminolevulinate 
Total daily dose: 
One application 
Mode and frequency of administration: 
One session of Luxerm® daylight photodynamic therapy: a sunscreen with 
chemical filters will be applied to all sun exposed areas including the 
treatment area to prevent subsequent UVA and UVB exposure (as 
provided for the study). After the sunscreen has dried, the selected 
anatomical area should be prepared to facilitate access of the cream and 
light to all lesions. An abrasive pad should be used to roughen the affected 
area. Following skin preparation, a thin layer of Luxerm cream should be 
applied on the anatomical area (field application), without occlusion. 
 
After Luxerm® application, subject will go outdoor under direct daylight no 
later than 30 minutes. On sunny days, should the subject feel 
uncomfortable in direct sunlight, shelter in the shade may be taken. 
 
After 2-hour of daylight exposure, subjects will return indoors and Luxerm® 
will be removed.  
 
Subjects will be instructed to avoid sun exposure and use sunscreen for 
the next 48 hours. 
 
The subject will be assessed at baseline and day 1 post-treatment as well 
as at week 12 post-treatment.   
Location of treated area: 
Face or scalp 
Duration of treatment: 
One day 
Comparator product: 
Not applicable 
Non-investigational product to be 
provided for the clinical trial: 
 
Urine Pregnancy Test 
 
Actinica sunscreen SPF 50+ on all exposed areas.   
 
Cetaphil moisturizer cream at night for 8 days on the treated area after 
Luxerm DL-PDT 
 
Skin abrasive pad for skin preparation on the anatomical area 


GALDERMA RESEARCH & DEVELOPMENT 
Protocol N° RD.03.SPR.114384  
Final version - dated on 22 February -2017 
Page 16 of 69 CONFIDENTIAL 
Clinical trial title: 
Subject reported outcomes on satisfaction, efficacy and safety with Luxerm® in the field-directed treatment of thin or 
non-hyperkeratotic and non-pigmented Actinic Keratosis of the face or the scalp 
Short title (± acronym): SESAME 2 
 
Project number: 
834 
Clinical trial phase: 
Phase IV 
Clinical trial period 
Planned  First Subject In: May 2017 
Planned Last Subject Out: Nov. 2017 
Measurement criteria 
Subject-reported outcomes 
 
Subject questionnaire the day of treatment after the daylight 
photodynamic session and at last visit (Week 12/Early 
termination) (appendices 1-2) 
 
Efficacy:  
 
Count of AK lesions at baseline in the anatomical area 
 
Lesion response at week 12 of treated AK lesions in the 
anatomical area 
 
Subject’s skin aspect assessed at week 12 for lesion complete 
response using a 4-point scale 
 
Count of new AK Lesions at week 12 in the anatomical area 
 
Safety  
 
Subject’s self-assessment of pain post daylight PDT procedure 
using a 11-point Numeric Rating Scale (NRS) (appendix 1); 
 
Incidence and severity of adverse events throughout the study  
 
Other variables 
 
Photodamage score (Dover scale) assessment at baseline and 
week 12 
 
Physician questionnaire once all subjects from a site have 
completed the study (appendix 3) 
 
Photographs at baseline and week 12 at selected sites 
 


GALDERMA RESEARCH & DEVELOPMENT 
Protocol N° RD.03.SPR.114384  
Final version - dated on 22 February -2017 
Page 17 of 69 CONFIDENTIAL 
Clinical trial title: 
Subject reported outcomes on satisfaction, efficacy and safety with Luxerm® in the field-directed treatment of thin or 
non-hyperkeratotic and non-pigmented Actinic Keratosis of the face or the scalp 
Short title (± acronym): SESAME 2 
 
Project number: 
834 
Clinical trial phase: 
Phase IV 
Clinical trial period 
Planned  First Subject In: May 2017 
Planned Last Subject Out: Nov. 2017 
Analysed variables 
Subject-reported outcomes  
 
Subject questionnaire the day of treatment after daylight session and 
at last visit (week 12 or early termination)  
 
Efficacy endpoints: 
 
Lesion complete response rate, defined as the percentage of 
preexisting and treated lesions in the anatomical area at baseline 
assessed as clear at week 12 
 
Subject complete response rate defined as the percentage of subjects 
with all treated lesions clear in the anatomical area at Week 12. 
 
Subject partially clear defined as the percentage of subjects with at 
least 75% lesion complete response in the anatomical area at week 12 
 
Number of new AK lesions in the anatomical area at week 12 
 
Clinical assessment of subject’s skin aspect at week12: mean score 
on anatomical area at week12  
 
Safety variable 
 
Subject’s self-assessment of maximal pain using a 11-point Numeric 
Rating Scale (NRS) from 0 (no pain) to 10 (extreme pain) after the 
treatment session 
 
Incidence and severity of adverse events 
 
Other variables 
 
Photodamage score with Dover’s scale at baseline visit and week 12  
 
Physician questionnaire once all subjects from a site have completed 
the study. 
 
Principal statistical methods and 
sample size calculation: 
The objective of this trial is to evaluate the subject reported outcome with 
Luxerm® Daylight field treatment after one session. Also the efficacy and 
safety of Luxerm® in terms of subject complete response rate will be 
assessed. 
 
The Intent-to-Treat (ITT) population consists of all enrolled subjects. The 
safety population (APT) consists of the ITT population, after exclusion of 
subjects who never took the treatment.  
The efficacy endpoint will be analysed on the intent to treat (ITT) 
population, using a worst case approach, in which the lesions with missing 
lesion response assessment will be considered as having not responded. 
 
No inferential statistics will be performed. All variables will be descriptively 
summarized on ITT population and on APT population for the safety 
variables.  
 


GALDERMA RESEARCH & DEVELOPMENT 
Protocol N° RD.03.SPR.114384  
Final version - dated on 22 February -2017 
Page 18 of 69 CONFIDENTIAL 
2 
BACKGROUND AND RATIONALE 
2.1 
Medical background and short rationale for the clinical trial 
AK is a common epithelial non-infiltrative lesion caused by chronic exposure to ultraviolet (UV) 
radiation damaging cell cycle regulators and leading to proliferation of cytologically abnormal 
epidermal keratinocytes. They are characteristically found on sun-exposed areas such as the face, 
bald scalp, neck, chest, back of the hands and forearms. The etiology of AK is multifactorial, 
common in elderly, fair-skinned men with a history of extensive outdoor activities (Goldberg et 
al 2010). A review of epidemiological studies showed that the prevalence and incidence of AK 
are highly variable depending on the population studied, location, age, and gender (Frost et al 
1994). For example, estimated rates of nearly 1.7 million AK cases have been reported in 
Germany, with standardized prevalence of 1.8%. Age-specific rates were below 1.5% for up to 60 
years and rose to 8.2% in the group of 80-89 years old with as high as 13.2% in men in this sub-
population of elderly patients (Schaefer et al 2014). In particular, no robust data on the German 
prevalence are available. Investigations from Australia reveal a rate about 60% (Frost et al 1994; 
Frost et al 2000). In Europe, prevalence rates of 1.4%–6% (women) and 15% (men) have been 
reported in selected regions (Schaefer et al 2014). AKs themselves are deemed not serious but 
they are very common, highly widespread and recurrent.  Many authors suggest that AKs should 
be classified as early in situ SCCs. It is, however, not possible to predict which lesions will 
progress into SCC (Ferrandiz et al 2017; Fernandez et al 2015). 
Various treatment options are available for the treatment of AK lesions, including destructive 
lesion directed therapies (e.g. cryosurgery, laser or excisional surgery) and topical field directed 
therapies (e.g. 5-fluorouracil [5-FU], imiquimod, diclofenac, ingenol mebutate) (Gold et al 2006; 
Fenske et al 2010). However, patient satisfaction with many of these treatments, especially 
cryotherapy, can be affected by considerable discomfort and residual scarring while with topical 
treatments the longer duration of treatment (imiquimod, diclofenac, 5FU) and/or frequent and 
unpredictable  local skin reaction ( ingenol mebutate, imiquimod, 5FU)  and/or low efficacy 
(diclofenac cream) may be a contributing factor. Photodynamic therapy (PDT) is a highly 
effective treatment for AK, offering the advantage of excellent cosmesis (Sidoroff et al 2010). 
However, issue with conventional PDT (cPDT) was pain. More recently daylight (DL) PDT has 
been approved based on its non-inferiority vs cPDT for efficacy and superiority in terms of pain 
intensity (Rubel et al 2014; Lacour et al 2015). As with DL-PDT large and/or multiple AKs can 
be treated at the same time, it is recommended as a first-line treatment for individual with 
multiple and/or confluent AKs (Wiegell et al 2012; Morton et al 2013). 
Metvix, a cream formulation containing Methyl Aminolevulinate (MAL), has been approved 
with a red LED light via a suitable lamp (conventional PDT) for the treatment of AK, Bowen’s 
Disease and Basal Cell Carcinoma in several countries worldwide (for further details on Metvix 
use, known benefits and risks, please refer to the Product label). Topical application of MAL 
results in the formation of photoactive protoporphyrin IX (PpIX) which leads to a photochemical 


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reaction and thereby phototoxicity to the exposed target cells. The effectiveness and safety of 
MAL conventional and Daylight PDT have been demonstrated in several clinical trials for the 
treatment of AK (Wiegell et al 2008; Fargnoli et al 2015; Lacour JP et al 2015). Several clinical 
studies have shown that Metvix can be activated by natural daylight (Genovese et al 2016; 
Fargnoli et al 2015; Lacour et al 2015; Rubel et al 2014, Wiegell SR et al 2008). Most recently, 
clinical studies performed in Australia and Europe have confirmed that Metvix with Daylight 
Photodynamic Therapy (DL-PDT) treatment regimen was non-inferior to cPDT in terms of 
efficacy, with the advantage of being almost painless and leading to less treatment-related 
adverse events (Rubel et al 2014;  Lacour et al 2015). Metvix DL-PDT treatment regimen is 
currently approved for the treatment of AK in Europe, Australia and Latin American countries. 
Metvix DL-PDT is an effective, safe and alternative treatment for thin or non-hyperkeratotic 
and non-pigmented AK lesions and is associated with high subject satisfaction (See et al 2015). . 
Patients with AKs usually suffer from multiple and coalescent lesions. Clinical markers relate it 
to an increased risk of developing malignant epithelial cancers. This can occur even on seemingly 
unimpaired skin areas surrounding AK. Such pathological condition is described as “field 
cancerization” reflecting the field actinic damage, raising the basis of ‘field cancerization’ 
concept (Samrao et al 2013). This concept suggests that subclinical pre-neoplastic changes exist 
in the apparently normal skin surrounding AKs. Studies confirm the presence of neoplastic 
changes involving the entire field and not only areas of clinically evident NMSCs. The 
management of AK and field cancerization with field-directed treatments as photodynamic 
therapy (PDT) is recommended by international guidelines (Rossi et al 2009; Stockfleth et al 
2008; Dreno et al 2014). AKs have been described to be a field disease and not limited to single 
clinically apparent lesions. In the definition of field cancerization, clinically normal appearing 
skin surrounding AKs contains subclinical features of genetically damaged cells which may 
develop into new AKs and NMSCs (Sotiriou et al 2015). Treatment should therefore target an 
area of field change especially when patients present with multiple AK which may reduce the risk 
of development of further AKs, secondary tumors and local recurrence (Wiegell et al 2012; 
Szeimies et al 2012; Bagazgoita et al 2011).  
 
Metvix DL-PDT is an attractive treatment for treating AKs and different ways of simplification 
of the procedure have been investigated. More recently researchers/physicians’ attention has been 
focused not only on how to activate the photosensitizer but also on how to prepare the skin prior 
to its application. Daylight -PDT is a novel and simplified modality, less expensive and less time-
consuming and has been shown to be more tolerated. Besides, recent trials have demonstrated 
that DL-PDT has a similar effectiveness compared with cPDT for the treatment of AK using field 
treatment (Rubel et al 2014; Wiegell et al 2008). These studies showed similar AK clearance with 
tolerability profile superior for DL-PDT in terms of local skin responses and pain. DL-PDT was 
more cosmetically acceptable but skin preparation technique was not precised (Wiegell et al 
2012). Pre-treatment of the skin is essential for adequate penetration of topical photosensitizing 
agents and subsequent PpIX accumulation. For skin preparation procedure, microneedling, 
curettage, fractional lasers or ablative fractionated laser systems (AFXL) or abrasive skin 
preparation pads or microdermabrasion are the most popular ways to prepare the skin as an 
effective, acceptable and relatively inexpensive but also for cosmetic purposes. A recent study 


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showed microdermabrasion with skin pad led to attain same levels of PPIX and erythema as with 
curettage (Bay et al 2017). Other keratolytic therapy in patients with AK prior to MAL-PDT with 
10% salicylic acid or 40% urea cream are also effective in respect of higher lesion response rates 
but are associated with a higher rate of localised side effects such as pain and local skin reactions 
(Gholam et al 2016).  
2.2 
Investigational product profile 
In Germany MAL Daylight PDT has been approved with the brand name Luxerm® and is 
indicated for thin or non-hyperkeratotic and non-pigmented AKs. 
In the proposed study, we aim to evaluate the patient reported outcomes on satisfaction and 
efficacy and safety of MAL with Daylight Photodynamic Therapy (DL-PDT) in the treatment of 
AK lesions in one anatomical area on the face (e.g., forehead or cheek or chin), excluding nose, 
eyelids, lips and mucosa or balding scalp.  
Table 1 - Investigational study Product profile 
 
Investigational product 
Trade Name or Equivalent 
Luxerm®  
Name of Drug Substance   
methyl aminolevulinate hydrochloride 
Pharmaceutical Form 
Cream 
Strength 
160 mg/g 
Packaging (type and size) 
2g collapsible aluminium white tubes 
Storage Conditions 
Between 2 to 8 °Celsius 
Dosage (total daily dose) 
Thin layer on selected anatomical area of either face or scalp 
Route 
Topical 
Dose Regimen  
Single dose 
Duration of administration 
2 hours and 30 minutes 
Location of Treated Area 
Face or scalp 
2.3 
Risk/Benefit assessment 
Based on the previous studies (Rubel et al 2014; Wiegell et al 2008), the use of natural daylight 
PDT is expected to improve the tolerability of the treatment (less pain during illumination) and 
simplify the use of Metvix while maintaining a similar efficacy compared to the previous 
studies with conventional PDT. 
The use of red LED light can result in discomfort for patients due to large amounts of PpIX 
which is photobleached in a short period of time.  The continuous activation of PpIX associated 
with the use of natural daylight would result in a corresponding reduction in pain. 


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Overall, the cumulative post-marketing experience as well as the information from clinical 
studies and literature confirm that the benefit-risk ratio remains positive for the use of methyl 
aminolevulinate in the approved indications. 
MAL Daylight PDT (marketed under the name Luxerm® in Germany) is a commercial product 
that will be used according to the approved indications and usage.  Warnings and precautions 
with MAL Daylight PDT are well known and documented in the product monograph. For more 
details regarding the clinical adverse reactions and/or the post-marketing experience, please refer 
to the product monograph. 
 
3 
CLINICAL TRIAL OBJECTIVES AND CLINICAL HYPOTHESIS 
3.1 
Clinical trials objectives 
The objective of this multi-centre study is to evaluate the subject reported outcomes on 
satisfaction with Luxerm® DL-PDT in the field-directed treatment of thin or non-hyperkeratotic 
and non-pigmented multiple AKs in one anatomical  area on the face (e.g., forehead or cheek or 
chin) excluding nose, eyelids, lips and mucosa, or balding scalp at 12 weeks.  
The other objectives are to assess the efficacy of Luxerm® DL-PDT in subjects with actinic 
keratosis, safety assessments including adverse events and assessment of skin appearance. 
3.2 
Clinical hypothesis 
Based on previous results available, the efficacy of MAL DL-PDT is non-inferior to cPDT and 
Ingenol mebutate in treatment of AKs (Wiegell et al 2008; Fargnoli et al 2015; Genovese et al 
2016). The assumption is also to have similar efficacy in terms of field treatment with better 
tolerability in terms of pain. 
4 
SELECTION AND DISPOSITION OF CLINICAL TRIAL POPULATION 
4.1 
Number of subjects 
A total of 50 subjects presenting with thin or non-hyperkeratotic and non-pigmented actinic 
keratosis on the face or scalp will be enrolled in approximately 8 sites located in Germany. 
4.2 
Clinical trial population  
Subjects who meet all of the following criteria will be eligible for the clinical trial.  


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4.2.1 
Inclusion criteria 
In order to be eligible for the clinical trial, the subject must meet all of the following inclusion 
criteria:  
1. Male or female age  18 years old.  
2. Subject with at least 5 clinically confirmed thin or non-hyperkeratotic and non-pigmented 
actinic keratoses in an anatomical area on the face (e.g., forehead or cheek or chin) excluding 
nose, eyelids, lips and mucosa, or balding scalp, at baseline visit. 
3. Subject or caregiver capable of performing the skin preparation and Luxerm treatment 
application as per the investigator instructions. 
4. Female subject of childbearing potential must have a negative UPT at baseline (UPT should 
have a sensitivity of 25 IU/L or less) and agree to be strictly abstinent or use a highly 
effective method of birth control during the study (i.e. progestogen-only oral hormonal 
contraception; male or female condom; cap, diaphragm or sponge with spermicide; bilateral 
tubal ligation; combined (estrogen and progestogen-containing) oral hormonal contraception, 
or injectable or implants hormonal contraception (at a stable dose for at least 1 month prior to 
baseline); intra-uterine devices inserted at least 1 month prior to baseline; vasectomized 
partner for at least 3 months prior to baseline). 
5. Female subject of non-childbearing potential, e.g.: post-menopausal (absence of menstrual 
bleeding for 1 year without any other medical reason), hysterectomy or bilateral ovariectomy. 
6. Subject has read and signed the approved informed consent form (ICF) prior to any 
participation in the study. 
7. Subject has read and signed a Photograph Release Consent Form if he/she is willing to be 
photographed. 
8. Subject (or caregiver) willing and able to comply with all of the time commitments and 
procedural requirements of the clinical trial protocol. 
4.2.2 
Exclusion criteria 
Any subject who meets one or more of the following exclusion criteria will not be included in 
this clinical trial.  
1. Subject with a clinical diagnosis of a skin disease other than AK (including non-melanoma 
skin cancer) on the target anatomical area. 
2. Subject with severe AK (thick, hyperkeratotic AK) per anatomical area (face or scalp).  


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3. Subject with clinical diagnosis of other skin disease on the target anatomical area.  
4. Subject with pigmented AK on the target anatomical area. 
5. Subject with melanoma at any location. 
6. Immunocompromised subject or requiring immunosuppressive therapies. 
7. Subject with porphyria; photosensitivity- related disorders, active infectious disease. 
8. Subject with known or suspected hypersensitivity to the active substance or to any excipients 
of Luxerm® (see Summary of Product Characteristics).  
9. Female subject who is pregnant, nursing or planning a pregnancy during the study.  
10. Subject who has used any of the following topical preparations on the area to be treated: 
keratolytics including urea (greater than 5%), alpha hydroxyacids [e.g. glycolic acid, lactic 
acid, etc. greater than 5%], salicylic acid (greater than 2%) within 2 days of initiation of 
treatment. 
11. Subject with a wash-out period from baseline for topical or systemic treatment or 
medical/surgical procedure in the anatomical area (for AKs) less than the following: 
 
Retinoids, including tazarotene, adapalene, tretinoin, retinol 
4 weeks 
 
Cryotherapy, diclofenac, corticosteroids or other treatments for AK 
8 weeks 
 
Microdermabrasion, laser ablative treatments or chemical peels 
8 weeks 
 
5-FU, imiquimod  
24 weeks  
 
Surgical: excision and reconstructive surgery, chemosurgery,  
12 weeks 
 
Any Photodynamic Therapy, ingenol mebutate (Pep-005), Radiotherapy and UV radiation 
therapy 
12 weeks 
 
Investigational therapies  for Actinic Keratoses 
12 weeks 
 
Immunosuppressive drugs (such as glucocorticoids, cytostatic, antibodies, drugs acting on 
interferon, opioids, TNF binding proteins, Mycophenolate, small biologics agents) 
12 weeks 
 
12. Subject who is currently participating to/ or who has participated in another investigational 
treatment or device research study within 4 weeks of baseline visit.  
13. Subject may be unreliable for the study including subjects who engage in excessive alcohol 
intake or drug abuse, or subjects who are unable to return for scheduled follow-up visits. 
14. Subject who is unable to communicate or cooperate with the investigator due to language 
problems, poor mental development, or impaired cerebral function. 
15. Subject who is unwilling to refrain from use of prohibited medication during the clinical trial 
(see section 4.3.5). 


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16. Subject who is vulnerable (such as deprived of freedom) as defined in Section 1.61 of the 
International Conference on Harmonisation (ICH) Guideline for Good Clinical Practice 
(GCP). 
17. Subject with clinically significant abnormal laboratory finding (if any available report) at the 
baseline visit or medical/surgical condition (other than for actinic keratoses), which might, in 
the Investigator’s opinion, interfere with study evaluations or pose a risk to subject safety 
during the study. 
18. The subject is a study site staff member (investigator, study nurse, etc.) or a relative of one. 
19. Subjects with any condition that may be associated with a risk of poor protocol compliance 
4.3 
Prior and concomitant therapies 
4.3.1 
Definition 
Previous therapies (drugs and/or procedures) are defined as therapies that have been stopped 
within 12 weeks prior to the investigational product application.  
Concomitant therapies are defined as follows: 
 any existing therapies ongoing at the time of the baseline visit , or 
 any changes to existing therapies (such as changes in dose or formulation) during the 
course of the clinical trial, or 
 any new therapies received by the subject since the baseline visit 
4.3.2 
Categories 
The following two categories will be considered for previous and concomitant therapies:  
 Drugs/therapies including, but not limited to, prescription, over-the-counter (OTC), birth 
control pills/patches/hormonal devices, vitamins, moisturizers, sunscreens, herbal 
medicines/supplements, and homeopathic preparations. 
 Medical and surgical procedures including, but not limited to, laser/radiation procedures, 
dermal fillers, X-rays, etc. 


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4.3.3 
Recording 
Previous and concomitant therapies will be recorded on the Drugs/Therapies Form (for 
drugs/therapies) and/or on the Medical and Surgical Procedures form (for medical/surgical 
procedures) in the case report form (CRF). 
Concomitant therapies will be recorded, reviewed, and updated at each trial visit. 
Every attempt should be made to keep concomitant therapy dosing and regimen constant during 
the study. Any change to the concomitant therapy should be noted on the CRF. Any new 
concomitant therapy or modification of an existing therapy may be linked to an adverse event 
(AE). A corresponding Adverse Event Form must be completed to account for the change in 
therapy, except in some cases such as therapy used for prophylaxis, dose modification for a 
chronic condition, etc. 
4.3.4 
Authorised therapies during the clinical trial. 
Unless listed in the exclusion criteria above or in the prohibited therapies (see sections 4.2.2 and 
4.3.5), all therapies are authorised. 
Subject may use the sunscreen and moisturizer provided for the trial as required for the 
symptomatic relief of skin dryness or irritation (use of moisturizer other than the provided one 
will be captured in the CRF as concomitant therapy).  
Note: It is preferred that a moisturizer (provided one or a one not containing alpha hydroxy acid) 
be added to the treatment regimen as opposed to implementing an altered dosage regimen. 
4.3.5 
Prohibited therapies during the clinical trial  
The following therapies are prohibited because they may interfere with the efficacy and/or safety 
assessment of the investigational product, or because they may interact with the metabolism of 
the investigational product: 
 On the anatomical area, all topical treatment, medical/surgical procedures listed as exclusion 
criteria (section 4.2.2). 
 All systemic therapies listed in exclusion criteria (section 4.2.2). 
 Any other drugs/procedures which in the investigator’s judgment are liable to interfere or 
interact with the efficacy or safety of Luxerm®. 
 Any UV-therapy should be discontinued before treatment.  


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 As a general precaution, sun exposure of the treated anatomical area should be avoided for 
about 2 days following treatment 
 If any outdoor sun exposure the subject will be recommended to apply the provided sunscreen. 
 Any treatment including cryotherapy is prohibited except at the end of the study to treat AK 
lesions at last visit after study clinical assessments.  
 If subject presents mild/moderate/severe AKs outside anatomical area and investigator wishes 
not to wait the end of study before treating them, he/she can do so but in this case only 
cryotherapy can be used. In order to avoid interference with subject pain assessment, it should 
be done once all study assessments, including subject questionnaire completion, have been 
performed at the baseline visit. 
If prohibited therapies become a necessary treatment for the safety or best interest of the subject, 
GALDERMA R&D will be notified to discuss possible alternatives prior to administration of a 
prohibited therapy and to discuss the pertinence and the modalities for the subject to continue in 
the clinical trial. 
4.4 
Procedures / reasons for discontinuation 
An Investigator may decide to discontinue a subject from the clinical trial for safety reasons. 
Although the importance of completing the entire clinical trial should be explained to the subject 
by the clinical trial personnel, any subject is free to discontinue his/her participation in this 
clinical trial at any time and for whatever reason, specified or unspecified, and without prejudice.  
Subjects who discontinue the clinical trial prematurely should be fully evaluated, whenever 
possible. The procedures designated for the week 12 post-treatment visit will be performed for all 
premature discontinuation subjects. The appropriate CRF pages should be completed. 
For all subjects who prematurely discontinue the clinical trial, the reason must be carefully 
documented by the investigator on the Exit Form, and, if applicable, on the Adverse Event Form 
if discontinuation is due to an AE.  
At 1 week post-baseline the investigator will call the subject if he has not heard from the 
subject since baseline visit, to check if the study treatment has been performed: 
- 
If the subject was not able to perform the study treatment during the week post-
baseline due to bad weather conditions, another additional period of maximum 7 days 
is offered to perform the study treatment.  
- 
For an additional period greater than 7 days the decision to maintain the subject in 
the study will be based on discussion between investigator and sponsor. 


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- 
If the subject decides to stop his participation for whatever reason, he/she will be 
asked to return the study product to the site. The study product must not be 
reallocated to another subject and should be discarded from the study product stock.  
Investigator has the possibility to replace the subject. 
In the case of early termination, the investigator should ensure that the subject receives 
appropriate therapy for his/her condition. 
GALDERMA R&D may also decide to prematurely terminate or suspend the clinical trial or the 
participation of a subject in the clinical trial. 
All data gathered on the subject prior to termination will be made available to GALDERMA R&D. 
Reasons for clinical trial completion/discontinuation, as listed on the Exit Form of the CRF are 
described below: 
Normal study Completion 
Subject completes the clinical trial as planned in protocol. 
Pregnancy 
Withdraw the subject from the clinical trial following the procedure described in the 
protocol section 8.3 
Adverse Event 
Complete CRF Adverse Event Form. 
Withdrawal by subject  
Includes consent withdrawal, subject relocation, schedule conflicts, etc… Does not 
include AE. Explain the reason for withdrawal in the comments section of the CRF 
Exit Form. 
Protocol Violation 
Explain the violation in the comments section of the CRF Exit Form 
Lost to Follow-up 
Confirm with 2 documented phone calls and a certified letter (delivery receipt 
requested) without response. Explain in the comments section of the CRF Exit Form. 
Other 
This category is to be used for a subject who discontinues for a reason other than 
those specified in the predefined categories above. Explain the reason for 
discontinuation in the comments section of CRF Exit Form. 
If reason for discontinuation is “withdrawal by subject” or “other”, the subject must be 
questioned to rule out the possibility of an AE; this should be documented in the CRF. 
5 
INVESTIGATIONAL PLAN 
5.1 
Overall clinical trial design 
This clinical trial will be conducted as a multicentre, open label clinical trial involving male or 
female subjects of any race, aged  18 years with clinically confirmed thin or non-hyperkeratotic 
and non-pigmented multiple AKs in an anatomical area on the face or scalp , and meeting other 
specific eligibility criteria. 
A total of 50 subjects will be enrolled in approximately 8 sites in Germany. Approximately 5 to 
10 subjects are planned for each site. 


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At baseline subject eligibility will be validated and the anatomical area to be treated on the face 
(e.g., forehead or cheek or chin) excluding nose, eyelids, lips and mucosa, or balding scalp, will 
be selected by the investigator.  
Subjects will receive from the investigator adequate training and detailed instructions about 
Luxerm treatment. Eligible subjects will apply the Luxerm treatment with daylight PDT within 
1 week (± 7 days) to the baseline visit depending on appropriate weather conditions to allow 
daylight exposure. 
Subjects will be evaluated up to three times during the study; at baseline, Day 1 post-treatment 
(±2 days) and week 12 post treatment (±7 days). 
5.2 
Discussion of clinical trial design 
Luxerm is registered in Germany; this study is therefore considered as Phase IV. Luxerm® 
cream is a topical therapy currently approved for treatment of thin or non-hyperkeratotic and non-
pigmented actinic keratoses (AKs) on the face and scalp. In several clinical trials it has been 
shown to be highly effective, safe, well-tolerated and to give excellent cosmetic outcomes with 
minimal risk of scaring. 
An interventional design is applied in this study because it allows assessment of patient reported 
outcomes to Luxerm treatment satisfaction in addition to safety and efficacy evaluations of 
Luxerm daylight photodynamic therapy as per local SmPC. Information on the treatment 
application will be recorded by the subject in a questionnaire and reported in an electronic Case 
Report Form (eCRF).   
Although several studies have already been conducted with MAL DL-PDT to treat different skin 
conditions, it is felt that a clinical trial is required to confirm the subject reported outcomes with 
DL-PDT to assess the level of satisfaction. 
5.3 
Clinical trial duration and termination 
The average planned period for the clinical trial from First Subject In (FSI) to Last Subject Out 
(LSO) is 6 months. The end date of the clinical trial will be the date of the last visit of the last 
subject who participates in the clinical trial. 
The planned duration of recruitment (i.e. From FSI to Last Subject In (LSI)) is approximately 3 
months. 
The clinical trial may be terminated by the investigator at his/her clinical trial site at any time 
with appropriate notification to GALDERMA R&D. Likewise, GALDERMA R&D may terminate 
the clinical trial and/or the participation of the clinical trial site(s) with appropriate notification. 
The expected duration of subject participation is approximately 15 weeks. 


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5.4 
Clinical trial flow chart 
STUDY PROCEDURES 
Baseline 
Visit 1 
D0 
Treatment 
Dayg 
(at patient’s 
home) 
Day 1 post-
treatment 
Visit 2 
(± 2 days) 
Week 12 post-
treatment 
Visit 3 
(± 7 day) 
Informed consent 
X 
 
 
 
Inclusion/Exclusion criteria 
X 
 
 
 
Demography/Medical history 
X 
 
 
 
Previous therapies a 
X 
 
 
 
Urine pregnancy test d 
X 
 
 
X e 
Concomitant therapies  
X 
 
X 
X e 
Lesion mapping and counting c 
X 
 
 
X e 
Sunscreen application 
 
X 
 
 
Skin preparation  
Xk 
Xi 
 
 
Luxerm® application and DL 
treatment session 
 
X 
 
 
Lesion 
response 
using 
the 
transparent plastic sheet (for 
initial treated AK lesions) 
 
 
 
X e 
Clinical assessment of skin 
aspect for AK lesions in 
complete response 
 
 
 
X e 
Count of new AK lesions using 
the transparent plastic sheet  
 
 
 
X 
Photodamage Dovers assessment  
X 
 
 
X e 
Adverse events b (including local 
skin reaction) 
X 
 
X 
X e 
Subject questionnaire  
 
Xf 
 
X e 
Physician questionnaire j 
 
 
 
X e 
Photographs h 
X 
 
 
X e 
Treatment Dispensed 
X 
 
 
 
Subject Compliance 
 
 
X 
 
Study treatment return 
 
 
X 
 
Exit form 
 
 
 
X e 
a.  Treatment that continues after visit 1 should be recorded on the concomitant therapies form of the CRF. 
b.  Adverse Events have to be collected from the moment the Informed Consent signature is obtained and recorded on the 
AE form of the CRF. 
c.  Actinic keratosis lesions in the treated area will be counted. For accurate counting, lesion localization and follow-up, a 
clear plastic sheet will be placed over the anatomical area of the face or scalp being treated and other anatomical 
landmarks will also be marked on this sheet 
d.  For subject of childbearing potential: The determination of UPT is mandatory at baseline and at week 12 or before if 
there is early termination. UPT must have a sensitivity of less than at least 25IU/L. In case of positive UPT during the 
study the investigator will withdraw the subject from the clinical trial according to the procedure for reporting pregnancy 
details in the protocol.  
e.  To be performed at week 12 or before in case of early termination.  


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f.  After the 2 hours daylight exposure. 
g.  Subject advised to ensure the treatment as close as possible to the baseline visit (within 1 week (± 7 days)) and with 
appropriate weather conditions, to ensure the treatment instructions are followed. At 1 week post-baseline, if the 
investigator has not heard from subject, he will call the subject to check if the study treatment has been performed (see 
section 4.4). Subject instructs to call the investigator to confirm the treatment has been well completed and to schedule 
the day 1 post-treatment visit. 
h.  At selected sites and for subjects who have signed a photograph release informed consent form. 
i.  
Using the skin pad as per investigator instructions. 
j.  
To be completed once all subjects from the site have completed the study 
k.  Removal of any scales and crusts in the anatomical area by the investigator if deemed necessary 
5.5 
Clinical trial visit description and procedures 
5.5.1 
Visit 1 - Baseline visit 
1. 
Explain the nature and the constraints of the clinical trial to the subject particularly the 
study treatment instructions.   
2. 
Have the subject read, understand, date and sign an approved informed consent form (ICF). 
Give a dated and signed copy to the subject. 
3. 
Perform a urine pregnancy test (UPT) for female subjects of childbearing potential. 
4. 
If subject female of childbearing potential agrees to participate to the clinical trial, make 
sure she is using the requiring method(s) of contraception (see inclusion criteria 4.2.1). 
Make sure that the urine pregnancy test is done and the result is negative before subject 
inclusion in the trial 
5. 
Check inclusion/exclusion criteria (see sections 4.2.1 and 4.2.2). 
6. 
Log into the electronic case report form (eCRF) to get a Subject Identification Number. 
7. 
Question the subject about demography, relevant medical history, prior and concomitant 
therapies. 
8. 
Inform the subject about authorized and prohibited concomitant therapies. If the subject 
requires a medication washout period, the subject’s baseline evaluation must be conducted 
after the washout period has been completed. 
9. 
Select the subject‘s anatomical  area on the face (e.g., forehead or cheek or chin) excluding 
nose, eyelids, lips and mucosa, or balding scalp to be treated according to inclusion criteria 
2 (see 4.2.1) 
10. 
Map the selected anatomical area on the transparent plastic sheet and mark and count the 
AK lesions  
a) Delimit clearly the anatomical area on a transparent plastic sheet using a permanent 
marker to ensure clinical assessments are always done on the exact same area (indicate 
some reference to “landscape markers” such as: eyebrows, nose, ears, joints, nevus, 
etc.) and draw the clinical margins of each AK lesion. 


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b) Circle and mark each AK lesion of the anatomical area on the transparent plastic sheet. 
c) Record the total number of AK lesions presents in the anatomical area in the CRF. 
d) If necessary, scales and crusts should be carefully removed on the treated areas of the face 
and/or balding scalp.  
11. 
If the subject is eligible, dispense the study treatment (see specific section 6.1.2): 
a) Fill in a prescription form.  
b) Dispense to the subject the investigational product according to the prescription form  
c) Affix the tear-off portion of the label on the product dispensation log and report the 
required information on the labels if applicable. 
d) Provide appropriate verbal and written instructions on how to properly use the 
investigational product(s) and how to perform the treatment procedure (see instruction 
in section 6.1.4) 
e) Emphasize the importance of complying with the given instructions and treatment; 
instruct the subject to bring back the dispensed investigational product(s) at the next 
visit. 
12. 
Dispense to the subject any associated non-investigational product(s).  
13. 
Give and provide instruction to the subject how to use the provided Moisturizer in case 
some tolerability reactions occur (see 0). 
14. 
Remind the Subject to avoid sun exposure of the treated anatomical area and the use of 
sunscreen for about 2 days following treatment procedures. 
15. 
Assess the skin photodamage of the selected anatomical area using the Dover’s modified 
global photodamage score (see 7.4.1).  
16. 
Provide guidance on the satisfaction questionnaire (see appendix 1) and ask the subject to 
fill it out the day of treatment after the daylight exposure. Remind the subject to return it at 
the next study visit (Day 1 post-treatment). 
17. 
For selected sites only, take photographs of the target anatomical area according to the 
provided procedure only if subject has agreed on the approved photo release consent form.  
18. 
For all female subjects of childbearing potential, emphasize the guidelines about 
contraception and risks in case of pregnancy.  
19. 
Instruct the subject to call you the day of treatment to confirm the treatment has been well 
completed and to schedule the next study visit (Day 1 post-treatment). If you have not 
heard of subject one week after the baseline, contact him/her to get news and refer to 
section 4.4. 
At a minimum, tasks numbered 9, 10 and 15 have to be performed by a Dermatologist. 
 


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5.5.2 
Visit 2 (day 1 after treatment ±2 days) 
1. 
Question the Subject about AEs by asking an open-ended question taking care not to 
influence the Subject’s answer, such as “Have you noticed any change in your health since 
the last visit, including any potential skin reaction in the treated anatomical area?”. Record 
all events (including Local Skin Reaction), as appropriate on the corresponding CRF pages. 
2. 
Enquire whether any concomitant therapies have been added, stopped, or changed since the 
subject’s last visit. Document all changes in the CRF. 
3. 
Collect the first subject questionnaire and ensure it is fully completed including the SIN and 
the treatment date. Report the subject’s questionnaire in the eCRF. 
4. 
Assess subject’s compliance with regard to the study treatment. Based on the subject’s 
questionnaire and discussion with the subject. Check the study treatment has been 
performed according to the provided instructions. Report the results in the eCRF. 
5. 
Ensure that the subject has returned all used/unused investigational product.  
a) Missing investigational product must be documented in the product dispensation log 
comments section and on other accountability form.  
b) For all female subjects, reiterate the guidelines about contraception and risks in case of 
pregnancy. 
6. 
Schedule the next follow up visit, week 12 (7 days). 
In case of early termination of the Clinical Trial for whatever reason: 
a) The subject will be fully evaluated. 
b) The procedures designated for the week 12 visit should be performed. 
5.5.3 
Week 12 / Last clinical trial visit or Early trial termination visit 
1. 
Question the Subject about AEs by asking an open-ended question taking care not to 
influence the Subject’s answer, such as “Have you noticed any change in your health since 
the last visit, including any potential skin reaction in the treated anatomical area?”. Record 
all events (including Local Skin Reaction), as appropriate on the corresponding CRF pages. 
2. 
Enquire whether any concomitant therapies have been added, stopped, or changed since the 
subject’s last visit. Document all changes in the CRF. 
3. 
Using the transparent sheet which was completed at Baseline, relocate the anatomical area 
defined at baseline and each treated AK lesion.  Assess the lesion response for each treated 
AK mapped at Baseline (see Sections 7.2.1 and 7.2.1.2). Identify new lesions. 
Note: Any lesion in the anatomical area identified at Week 12 but not at Baseline is defined 
as a new lesion. Total number of new lesions should be recorded in the eCRF. 


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4. 
On each AK lesion that has completely responded, perform Investigator Clinical 
Assessment of the subject’s Skin Aspect (see 7.2.2). 
5. 
Assess the skin photodamage of the selected anatomical area using the Dover’s modified 
global photodamage score (see 7.4.1).  
6. 
Conduct a pregnancy test on any female of childbearing potential.  In case of positive 
result, please refer to Section 8.3. 
7. 
For selected sites only, take photographs of anatomical area according to the provided 
procedure only if subject has agreed on the approved Photo release consent form.  
8. 
Ask the subject to fill out the subject week 12 questionnaire and collect it. Ensure it is fully 
completed and with SIN number. Report the week 12 questionnaire in the eCRF. 
9. 
Complete CRF Exit form and discharge Subject from the study. 
10. 
Physician questionnaire should be completed once all subjects from the site have completed 
the study 
 
At a minimum, the tasks numbered 3, 4, 5, and 9 have to be performed by a Dermatologist. 
5.6 
Subject instructions 
At baseline, subject will be requested to comply with the treatment procedure instructions. After 
having trained the subject, the investigator will provide him/her with the written study treatment 
instruction sheet including storage conditions. 
Throughout the study, Subject will be requested to comply with the following: 
1. 
To avoid the use of antalgics the day of treatment and the day before treatment until the 
subject self-assessment of pain is complete. 
2. 
To avoid Sun exposure of treated anatomical area and use sunscreen during the 2 days 
following the treatment. 
3. 
To apply a moisturizer in case signs of local skin irritation such as dryness or erythema are 
observed after the PDT procedure.  The subject will be instructed that the use of a 
moisturizer should be considered only after the study treatment and when self-assessment 
of pain is performed. 
4. 
To respect the visit timeframe. 
5. 
In case the subject is using forbidden topical therapy listed in exclusion criterion 
(Section 4.2.2) or any other treatment on an area other than the anatomical area, the 
Investigator will remind him/her to pay a strict attention to not apply any of these therapies 
on the anatomical area.  


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Please refer to Section 4.2.1 and Section 4.2.2 for other items linked to eligibility criteria. 
 
6 
CLINICAL SUPPLIES 
Investigational product and supplies will be provided by the sponsor and shipped by the clinical 
supply unit to each investigator site. The investigational product used during this clinical trial is 
marketed product.  
6.1 
Investigational product identification and use 
6.1.1 
Product identity 
 
Investigational Product 
Trade Name 
Luxerm® 
Name of Active Ingredient 
methyl aminolevulinate hydrochloride 
Pharmaceutical Form 
Cream 
Dose or Concentration 
160 mg/g 
Formula number 
0401 
Total Daily dose 
Thin layer on field area of either face or scalp 
Mode and frequency of administration 
Topical, single dose 
Duration of administration 
2 hours and 30 minutes 
Location of treated area 
Face or scalp 
Manufacturer 
(Name and address) 
Laboratoires Galderma  
Zone Industrielle de Montdésir 
74540 ALBY SUR CHERAN 
Packaging type and size (primary) 
2g collapsible aluminium white tubes 
Storage Conditions 
Between 2 to 8 °Celsius 
6.1.2 
Method of treatment assignment  
This study is an open study without randomization. Indeed there is no treatment assignment, the 
investigational product will be provided in bulk.  
A tracking of the investigational products used will be done by recording the dispensation in the 
investigational product dispensation log. 


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6.1.3 
Subject Identification Number (SIN) 
Upon signature of the informed consent, a subject meeting all inclusion/exclusion criteria will be 
allocated a unique Subject Identification Number at baseline automatically generated by the 
eCRF.  
During the whole clinical trial, the subject will only be identified using the SIN for all 
documentation and discussion. 
6.1.4 
Instructions for use and administration 
At baseline visit the investigator or designee will give each subject verbal and written instructions 
on how to use the investigational and non-investigational products. It will be confirmed to treat 
the selected AKs anatomical area on the face excluding nose (e.g., forehead or cheek or chin), or 
balding scalp (excluding eyelids, lips and mucosa) with field therapy by providing the subject 
with the study treatment and by explaining in details the procedure. 
 
 


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Table 2: Procedures for Luxerm DL-PDT treatment 
Baseline Visit 
1 
Anatomical area and lesion mapping by the investigator using a transparent plastic sheet (after 
confirmation that all inclusion criteria and none of the exclusion criteria are met). Removal of any 
scales and crusts in the anatomical area by the investigator if deemed necessary. 
 
Subject provided with oral and written instructions on the treatment procedure of the anatomical area 
(lesions and field). The patient should undergo treatment at home in the following week (± 7 days), 
with appropriate weather conditions, as follow: 
Treatment 
day*  
t -15 min 
The subject applies Actinica sunscreen on the selected anatomical area and all other 
sun exposed skin.  The quantity of sunscreen will be sufficient to cover all areas 
exposed during the DL exposure step. 
t=0 min 
After approximately 15 min once the sunscreen (Actinica sunscreen) has dried, the 
subject prepares the anatomical area to be treated with an abrasive pad to remove 
scales and crusts and roughen the surface of the lesions  
 
Then, the subject applies a thin layer of Luxerm® on the entire anatomical area using 
the provided finger glove and avoiding contact with eyes, lips and mucous 
membranes. 
t=30 min 
The subject goes outdoors no later than 30mins of application of Luxerm® for 2 hours 
daylight exposure. 
On sunny days, should the subject feel uncomfortable in direct sunlight, shelter in the 
shade may be taken. 
t=2h30 
The subject returns indoors and Luxerm® is removed by washing 
* Subject will be advised to follow the instructions as close to the baseline visit (within 1 week ± 7 days) with 
appropriate weather condition to ensure the instructions are well followed.  
As a general precaution, sun exposure of the treated anatomical area should be avoided for about 
2 days following treatment. Subjects are advised to use a sunscreen in all exposed areas, 
including the treated area, during this period 
At 1 week post-baseline the investigator will call the subject to check if the study treatment 
has been performed: 
If the subject was not able to perform the study treatment during the week post-baseline 
due to bad weather conditions, another additional period of maximum 7 days is offered to 
perform the study treatment.  
For an additional period greater than 7 days the decision to maintain the subject in the 
study will be based on discussion between PI and sponsor. 
If the subject decides to stop his participation for whatever reason, he/she will be asked to 
return the study product to the site. Appropriate treatment will be decided at investigator 
discretion. The study product must not be reallocated to another subject and should be 
discarded from the study product stock.  Investigator has the possibility to replace the 
subject. 


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6.2 
Other supplies 
Galderma will provide the sites with: 
- 
The Urinary Pregnancy Tests (UPT) that may detect urinary Human Chorionic Gonadotropin 
concentrations equal to or greater than 25 international unit)  
- 
Cetaphil moisturizer cream  
- 
Actinica Sunscreen SPF 50+ 
- 
Nitril finger gloves for Luxerm cream application 
- 
An abrasive pad for skin preparation 
- 
Cool bag for Luxerm cream transportation 
No specific labels will be used. 
No accountability will be conducted on these products. 
The provided sunscreen has been selected so as not to prevent the transmission of light 
wavelengths required for activation of PpIX and to offer an adequate sun protection for the 2-
hour duration of the DL exposure. The provided sunscreen will be used only for the treatment 
preparation and will be applied if any sun exposure is expected following the treatment. 
Cetaphil moisturizer cream will be used on the whole anatomical area at night for 8 days after 
treatment. It is provided in case of occurrence of phototoxicity reaction on the anatomical area 
treated (burning sensation, prickling or tingling skin, irritation such as dryness, redness, edema or 
crusts) after the daylight exposure or soon after, requiring the use of moisturizer.  Moisturizer 
application should not be done before the treatment procedure or before the Subject Self-
assessment of Pain is completed.  
6.3 
Investigational product packaging and labeling 
Each Luxerm tube will be supplied with single label. Label on secondary packaging (box) will 
comprise affixed and tear-off portions.  
For treatment documentation, the affixed portion of the label will remain on the appropriate box. 
The tear-off portion of the label is to be removed at the time of dispensation and affixed to the 
product dispensation log. 
The label (including tear-off part) will be printed in German and  will contain information 
required by Good Manufacturing Practice (GMP) and local regulations and will be printed in 
local language. 


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6.4 
Investigational product management 
6.4.1 
Accountability 
Upon receipt of the clinical supplies at the site, the investigational product dispenser will conduct 
a complete inventory of all investigational products and assume responsibility for their storage, 
accountability and dispensation. 
The Investigator or designee will sign the original Acknowledgement of receipt form upon 
receipt and inspection of the supplies, fax the signed copy to GALDERMA R&D and retain the 
receipt in the Investigator Site File (ISF). 
All supplies sent to the investigator site will be accounted for and in no case used in any 
unauthorized situation.  
At the end of the trial, all used and unused investigational product will be appropriately 
inventoried by the monitor and will be returned to GALDERMA R&D for further reconciliation, 
appropriate inventory and destruction. 
6.4.2 
Dispensing 
All investigational products will be prescribed only to subjects enrolled into the clinical trial, at 
no cost and in accordance with the conditions specified in the protocol. 
Dispensation will be appropriately documented on the product dispensation log by the 
investigational product dispenser at each visit. 
Each subject will receive 1 tube of Luxerm® 2g at Baseline. 
6.4.3 
Investigational product compliance management and record 
Each subject will be instructed by the investigator about the importance of being compliant with 
clinical trial treatment as well as the importance of returning their investigational product (used 
and/or not used) at day 1 post-treatment. 
The investigational product will be collected and counted at day 1 post-treatment by the 
investigator or designee. 
Subjects will also be questioned by the investigator regarding the skin preparation, application 
technique of investigational product, the daylight exposure conditions and the use of any other 
additional topical, systemic drug as well as OTC product. 


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A subject’s questionnaire will be given to each subject in order to record the information on 
treatment procedure. The investigator will review the subject’s questionnaire at visit 2. 
The return of used/unused investigational product will be appropriately documented on the 
product dispensation log by the investigator or designee. 
6.4.4 
Storage of investigational product 
The investigator has to agree to keep all investigational products in a safe, temperature controlled 
and secure area with restricted access, in accordance with applicable regulatory requirements 
(e.g., in the site pharmacy, if applicable). 
Investigational products should be stored at appropriate storage conditions specified by 
GALDERMA R&D (see section 6.1.1). 
The investigator will inform each subject about the storage conditions until treatment application. 
6.4.5 
Return of investigational product 
The investigator will inform each subject about the importance of returning their investigational 
products (used and/or not used) at the visit 2. 
In the event of early termination/suspension of the clinical trial for safety reasons, a rapid recall 
of the trial product(s) will be initiated.  The investigator or designee must immediately instruct all 
subjects to not perform the clinical trial treatment procedure and return the investigational 
product to the clinical trial site. 
As a general procedure, GALDERMA R&D will provide the investigator with a detailed list of 
units being recalled so that any of the units remaining on site can be put immediately into 
quarantine. 
6.5 
Blinding 
The present study design is considered as an open study and subjects will receive commercially 
packaged study products. 
7 
STUDY ASSESSMENTS 
Clinical evaluations should be performed by the same investigator throughout the clinical trial.  
If it is not possible to use the same investigator to follow a subject, then evaluations should 
overlap for at least one visit in order to examine the subject together and discuss findings. This 
should be documented in medical source documents. 


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7.1 
Subject Reported Outcomes (PRO):  
The day of treatment after daylight exposure and at Week 12/Early termination, subjects will 
complete a questionnaire regarding the treatment procedure (skin preparation, study product 
application, weather condition daylight exposure, skin discomfort, efficacy, overall satisfaction, 
etc.) (Appendices 1 & 2). 
7.2 
Efficacy assessments 
7.2.1 
AK lesion assessment 
7.2.1.1 
AK lesions mapping and numbering at baseline 
At baseline, the investigator will map the targeted anatomical area and mark each AK lesion 
within the anatomical area using a transparent plastic sheet. The total number of lesions will be 
reported in the eCRF.  
7.2.1.2 
Lesion’s response at week 12 
At last visit the investigator will use the transparent plastic sheet to locate the anatomical area 
defined at baseline and the treated AK lesions.  
For each pre-existing AK treated lesion present at Baseline, the lesion response will be evaluated 
at week 12 as follow and reported in the eCRF: 
Table 3 - Lesion response 
Complete response (CR) 
1 
Complete disappearance of the lesion, visually and by palpation 
Non-complete response (NCR) 
0 
Non-complete disappearance of the lesion 
 
7.2.1.1 
New AK lesions numbering at week 12 
Any AK lesion in the anatomical area identified at Week 12 but not at Baseline is defined as a 
new lesion. The total number of new lesions will be recorded in the eCRF but not taken into 
account in the lesion response assessment. 
At the last visit, lesions in non-complete response or newly appeared lesions will be treated at the 
discretion of the investigator (off study). 


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7.2.2 
Clinical assessment of the subject’s skin aspect 
At last visit, for each lesion that has responded completely (see table 3) the investigator will 
assess the subject’s skin aspect on the following signs or symptoms: scarring, atrophy, induration, 
redness or change in pigmentation. The clinical assessment of skin aspect will be graded for each 
lesion as follow: 
Table 4 – Skin aspect assessment 
Excellent 
3 
No scarring, atrophy or induration, and no or slight occurrence of redness or change in 
pigmentation compared to adjacent skin 
Good 
2 
No scarring, atrophy or induration but moderate redness or change in pigmentation 
compared to adjacent skin 
Fair 
1 
Slight to moderate occurrence of scarring, atrophy or induration 
Poor 
0 
Extensive occurrence of scarring, atrophy or induration 
7.3 
Safety assessments 
A safety assessment will be conducted for all subjects at the baseline visit (after the ICF has been 
signed) and every subsequent visit.  The safety parameters which are adverse events and subject’s 
self-assessment of pain should be recorded as described in the section 7.3.1 and 7.3.2. 
7.3.1 
Adverse Events 
Adverse events (AEs) are to be monitored throughout the course of the clinical trial. 
All AEs including local skin reactions are to be reported on an Adverse Event Form of the eCRF 
with complete information as required. If AEs occur, the main concern will be the safety of the 
subject. At the time of the ICF signature, each subject must be provided with the name and 
telephone number of clinical trial center personnel for reporting AEs and medical emergencies. 
7.3.2 
Subject’s self-assessment of pain 
After the treatment procedure when 2 hours daylight exposure is completed, the subject will be 
requested to assess the maximal pain felt during the duration of the light exposure. The pain 
sensation will be assessed on an 11-point Numeric Rating Scale (NRS), where 0 = no pain at all 
and 10 = extreme pain and will be reported by the subject in the first subject questionnaire. 
Table 5 -  NRS - subject’s self-assessment of pain 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
 
 
 
 
 
 
 
 
 
 
 
No pain 
at all 
 
 
 
 
 
 
 
 
Extreme 
Pain 


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7.4 
Other assessments 
7.4.1 
Photodamage assessment by Dovers Scale 
At baseline visit and last visit, the investigator will assess the skin photodamage of the anatomical 
area using the following scale: 
Table 6 - Dover’s modified global photodamage score  
0 
Skin smooth to the touch without significant fine lines, coarse lines, erythema, telangiectasia, sebaceous 
hyperplasia, or unevenness in pigmentation in any of the scalp/facial areas (cheeks, forehead, and the 
perioral area) 
1 
Scalp/facial skin (on the cheeks, forehead, or the perioral area) shows 1 area of significant roughness, 
coarse lines, erythema, telangiectasia, sebaceous hyperplasia, dyspigmentation (hypopigmentation or 
hyperpigmentation), or fine lines 
2 
Scalp/facial skin (on the cheeks, forehead, or the perioral area) shows 2 areas of significant roughness, 
coarse lines, erythema, telangiectasia, sebaceous hyperplasia, dyspigmentation, or fine lines; or shows 
roughness, coarse lines, erythema, telangiectasia, sebaceous hyperplasia, dyspigmentation, and fine lines 
in 1 area 
3 
Scalp/facial skin (on the cheeks, forehead, or the perioral area) shows 3 areas with significant roughness, 
coarse lines, erythema, telangiectasia, sebaceous hyperplasia, dyspigmentation, or fine lines; or shows 
roughness, coarse lines, erythema, telangiectasia, sebaceous hyperplasia, dyspigmentation, and fine lines 
in 2 areas  
4 
Scalp/facial skin shows any degrees of photodamage greater than level 3 
7.4.2 
Photographs (for selected sites) 
At selected sites only, standardized digital photographs of the anatomical area will be taken at 
baseline and week 12 using a digital camera. Detailed procedures will be provided separately.  
Only subjects who have signed a Photography Release Consent Form will be photographed at 
baseline and last visit.  
7.4.3 
Investigator questionnaire 
 
The investigator will be asked to fill out a questionnaire (appendix 3) once all subjects from his 
site have completed the study.  
7.5 
Appropriateness of measurements 
All measurements planned in this study are non-invasive. 
PRO will be evaluated using a questionnaire after treatment and at the end of the study. 
Treatment compliance will be evaluated based on the recording of treatment information on the 
subject questionnaire. The questionnaire will collect specifically information on the treatment 


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procedure, the subject’s opinion on the treatments and on the associated cosmetics products used 
in the trial. 
Efficacy will be evaluated by assessing the lesion response which is a sensitive endpoint widely 
used in clinical practice to assess cure of AKs.  At the Week 12 visit, the Investigator will 
identify all AK lesions (new or initial) on the anatomical area and will define, for each lesion pre-
existing at Baseline, the lesion response as CR or non-CR (see 7.2.1.2).  This will allow 
determining the number and percentage of cured lesions.     
The safety of investigational product will be assessed through the reported AEs.  To complete 
safety assessment, the Subject’s pain assessment after treatment and Subject’s skin aspect at 
Week 12 will also be measured. 
The same investigator will evaluate the same subject at each visit throughout the clinical trial. 
8 
ADVERSE EVENT 
8.1 
Definitions 
8.1.1 
Adverse Events (AE) 
According to ICH E2A, an AE is any untoward medical occurrence in a subject or clinical 
investigation subject administered a pharmaceutical product and which does not necessarily have 
a causal relationship with this treatment.  An AE can therefore be any unfavorable and 
unintended sign (including an abnormal laboratory value), symptom, or disease temporally 
associated with the use of a medicinal (investigational) product, whether or not related to the 
medicinal (investigational) product. 
Thus any new sign, symptom or disease, or clinically significant increase in the intensity of an 
existing sign, symptom or disease since the first visit (including the disease being treated), should 
be considered as an adverse event. Lack of efficacy should not be considered as an AE. 
Each new episode of a chronic disease (e.g., hay fever, allergy, etc.) from the screening visit 
should be reported as a new AE. 


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Notes: 
 Any new sign or symptom reported by the subject that appears after accidental or intentional 
overdose or misuse should also be reported as an AE. 
 There should be an attempt to report a diagnosis rather than the signs, symptoms or abnormal 
laboratory values associated with the report of an AE.  However, a diagnosis should be 
reported only if, in the Investigator’s judgment, it is relatively certain.  Otherwise, symptoms, 
signs, or laboratory values should be used to describe the AE. 
 Pregnancy should not be considered as an adverse event but must be followed up as described 
in section 8.3 
 For an AE of irritation, the “date of onset” should be the date that the first symptom occurred. 
8.1.2 
Serious Adverse Events (SAE) 
A serious adverse event is any untoward medical occurrence that at any dose:  
 results in death, 
 is life-threatening, 
 requires hospitalization or prolongation of existing hospitalization, 
 results in persistent or significant disability/incapacity, or 
 is a congenital anomaly/birth defect. 
Important medical events that may not result in death, be life-threatening, or require 
hospitalization may be considered as an SAE when, based upon appropriate medical judgment, 
they may jeopardize the safety of the subject, and may require medical or surgical intervention to 
prevent one of the outcomes listed in this definition. Examples of such events are intensive 
treatment in an emergency room or at home for allergic bronchospasm, blood dyscrasia, or 
convulsions that do not result in hospitalization. 


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Note: 
 The term “life-threatening” refers to an event in which the subject was at risk of death at the 
time of the event; it does not refer to an event which hypothetically might have caused death if 
it was more severe. 
 Inpatient hospitalization is considered to have occurred if the subject has had to stay in 
hospital overnight. The criterion for the prolongation of hospitalization is also defined as an 
extra night at the hospital. Hospitalization may not constitute sufficient grounds to be 
considered as an hospitalization if it is solely for the purpose of diagnostic tests, (even if 
related to an AE), elective hospitalization for an intervention which was already planned 
before subject enrolment in the clinical trial, admission to a day-care facility, social admission 
(e.g., if the subject has no place to sleep), or administrative admission (e.g., for a yearly 
examination). 
8.1.3 
Unexpected adverse drug reaction 
According to ICH E6, an unexpected adverse drug reaction is defined as an adverse reaction, the 
nature or severity of which is not consistent with the applicable study drug information (in this 
clinical trial: the summary of product characteristics for an approved product at the time of AE 
occurence). 
8.1.4 
Adverse event reporting period 
The clinical trial period during which AEs must be reported is the period from when the subject 
signs the Informed Consent Form to the end of the subject’s participation. 
The sponsor should be informed if the investigator becomes aware of any unusual safety 
information or any safety information that appears to be drug-related involving a subject who has 
participated in a clinical trial, even after a subject has completed the clinical trial. The 
investigator should be diligent in looking for possible latent safety effects that do not appear until 
a medication has been discontinued. 
8.1.5 
Severity 
Severity is a clinical determination of the intensity of an AE and not of a disease. 
The investigator will classify the intensity of AEs using the following definitions as a guideline 
for all AEs occurring during clinical trials conducted or sponsored by GALDERMA. For this 
classification, the investigator will take into account the possible range of the intensity of the 
event and report the grade of intensity which is the most appropriate according  his medical 
judgment. 


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Mild 
Awareness of sign or symptom, but easily tolerated 
Moderate 
Discomfort, enough to cause interference with usual activity 
Severe 
Incapacitating with inability to work or perform usual activity 
8.1.6 
Relationship to the study drug(s) and/or clinical trial procedure 
The investigator is to determine whether there is a reasonable causal relationship between the 
occurrence of the AE and exposure to the study drug and/or clinical trial procedure. Medical 
judgment should be used to determine the relationship, considering all relevant factors, including 
pattern of reaction, temporal relationship, positive dechallenge or rechallenge, relevant medical 
history, and confounding factors such as co-medication or co-concurrent diseases. 
The expression “reasonable causal relationship” is meant to convey in general that there are facts 
or arguments to suggest a causal relationship (International Conference on Harmonization (ICH) 
E2A, section IIIA 1). 
The relationship assessment for an AE is to be completed using the following definitions as a 
guideline for all adverse events occurring during clinical trials conducted or sponsored by 
GALDERMA: 
Reasonable possibility: 
According to the reporting investigator, there is a reasonable possibility (i.e. suggestive evidence 
or arguments) that there is a causal relationship irrespective of the dose administered between: 
 The study drug  (investigational product) and the AE,  
 The clinical trial protocol procedure (e.g., skin preparation, skin pad, daylight exposure, 
such as moisturizers or sunscreen, etc. and the AE. 
The Investigator has to complete these 2 causality assessments on the AE form. 
No Reasonable Possibility: 
No suggestive evidence or arguments can be identified regarding a causal relationship between 
the investigational product or the clinical trial protocol procedure and the AE. 


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8.2 
Reporting procedures  
8.2.1 
Procedures for reporting adverse events 
The collection of AEs is from the time that a subject signs the ICF to their final trial visit. 
At each post-baseline visit, the investigator (or sub-investigator) will enquire about adverse 
events using an open question taking care not to influence the subject’s answer (e.g., “Have you 
noticed any change in your health since the last visit?”). Direct questioning and examination will 
then be performed as appropriate. 
Any AE occurring during the AE reporting period, whether it is related to the study drug  or not, 
will be recorded immediately in the source document, and described in the Adverse Event Form 
of the eCRF along with the date of onset, severity, relationship to the study drug, and outcome, 
without omitting any requested and known information.  Additional information will be requested 
under certain circumstances. Adverse Events (AEs) assessed as related to the treatment will be 
monitored until they are completely or satisfactorily resolved. Other AEs will be monitored until 
the last visit if they are not resolved or satisfactorily resolved. 
Adverse events assessed as related to the treatment or study procedure will be monitored until 
they have resolved or reached a stable condition. Other AEs will be monitored until the last visit 
if they have not resolved or reached a stable condition. The investigator will obtain and maintain 
in the subject’s files all pertinent medical records, information and medical judgment from 
colleagues who assisted in the treatment and follow-up of the subject. If necessary, the 
investigator will contact the subject’s personal physician or hospital staff to obtain further details. 
For SAEs (see section 8.2.2) and pregnancies (see section 8.3), the Sponsor is to be informed 
immediately by e-mail/fax.  The event must be reported by fax or sent by e-mail to the Sponsor 
within 24 hours of receipt of the information (contact details in section 8.2.2). 


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8.2.2 
Procedure for reporting a serious adverse event 
For an SAE occurring during the period of the clinical trial, regardless of whether it is related to 
the treatment or not, and of whether it is expected or not, the investigator must do the following: 
11. 
Take prompt and appropriate medical action, if necessary. The safety of subject is the 
first priority. 
12. 
Ensure that the event is classified as an SAE. Immediately (no later than 24 hours) 
inform the Sponsor  of the event by email/ fax/, and discuss further actions  to be taken: 
 
GALDERMA R&D 
Name 
Stéphanie Leclerc 
Title 
Clinical Project Manager (CPM) 
Address 
Les Templiers 
2400, Route des Colles 
06460 BIOT France 
Tel. during office hours 
+33 4 92 38 67 06 (CPM #) 
Tel. Outside office hours 
+33 6 70 40 94 22 (Rajeev CHAVDA, medical expert) 
Fax  
+33 4 97 04 90 67 
Email 
pharmacovigilance@galderma.com 
13. 
 Print and complete the Serious Adverse Event form (available in the EDC system as PDF 
document). Fax or send by email the completed form, accompanied any other relevant 
information or anonymized medical records (e.g., laboratory test results) within 24 hours of 
receipt of this information to the sponsor (see contact details above). The demographics, 
medical history, drugs/therapies forms, and adverse event pages of the eCRF must be 
completed and available for review in the EDC system at the time of the report. 
14. 
Monitor and record the progress of the event until it resolves or reaches a clinically 
stable outcome, with or without sequelae. For all additional follow-up evaluations, fax or 
send by e-mail all additional follow-up information on the SAE to the sponsor (see contact 
details above) within 24 hours of receipt of the updated information.  SAEs will be 
monitored until the Investigator and Sponsor agree that the event is satisfactorily resolved. 
15. 
Obtain and maintain in his/her files all pertinent medical records, information, and medical 
judgments from colleagues who assisted in the treatment and follow-up of the subject.  If 
necessary, contact the subject’s personal physician or hospital staff to obtain further details. 
16. 
Inform the sponsor of the final outcome of the event. Send a revised or updated SAE 
form and AE form, if appropriate. 
17. 
Prompt notification of SAEs by the investigator to GALDERMA is essential so that legal 
obligations and ethical responsibilities towards the safety of subjects are met. GALDERMA 
has a legal responsibility to notify both the local regulatory authority and other regulatory 
agencies about the safety of a product under clinical investigation. GALDERMA will 
comply with country specific regulatory requirements relating to safety reporting to 
regulatory authorities, IRBs/IECs and investigators. Investigator safety reports are prepared 


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for Suspected Unexpected Serious Adverse Reactions (SUSARs) according to local 
regulatory requirements and GALDERMA policy and are forwarded to investigators as 
necessary. An investigator who receives an investigator safety report describing an SAE(s) 
or other specific safety information (e.g., summary or listing of SAEs) from GALDERMA 
will file it with the Investigator’s Brochure (IB) and will notify the IRB/IEC, if appropriate 
according to local requirements. 
18. 
Comply with the applicable regulatory requirements related to the reporting of SAEs to 
your IRB/EC. 
8.3 
Procedure for suspected allergic contact reaction  
This is a general procedure and further details can be discussed with the sponsor. 
 Stop the study product 
 Take a picture of the affected area and the non-affected surrounding skin  
 Document the event as an Adverse Event of Special Interest, email/fax the Sponsor 
immediately, and report the event within 24 hours of receipt of the information as described 
in section ‎8.2.2. 
In case of suspicion of allergic contact dermatitis  
1. 
After all signs and symptoms have resolved and after a minimum of two weeks from last 
dose application, a re-challenge test with the assigned study product will be performed.  
2. 
Ensure the subject has not been under any treatment with corticosteroids or antihistamines, 
regardless of the route of administration, the week before testing. 
3. 
Ensure that the skin on the back has not been exposed to the sun or artificial ultraviolet 
sources the week before testing. 
4. 
Apply an appropriate quantity of the assigned study product to fill the cupule of the test 
chamber on the skin of the upper back on either the right or left side of the centre line (or 
the inner forearm if the back cannot be tested). If no test chamber is available on-site, patch 
test units will be provided. It may be preferable to perform the test under semi-occlusive 
conditions depending on the irritant potential of the study product and the intensity of the 
reaction that was observed. The method to be used will be discussed with the sponsor.  
Choose a skin site that was not previously involved in the inflammatory skin reaction. 
Cover it for 48 hours with a hypoallergenic tape. 
5. 
Patient should be informed about avoiding exercise, showers, application of toiletries 
products, etc. to keep the test system dry 
6. 
After 48 hours, remove the tests and evaluate the site: 


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 at approximately 30 minutes after patch test removal (1st reading) and, 
 24 to 48 hours later (i.e. 72 or 96 hours after application) (2nd reading). 
 A facultative 3rd reading may be performed 96 to 120 hours later (i.e. 6 to 7 days 
after application of the patch) if the overall assessment so far equivocal or if asked 
by the sponsor. 
 Pictures of the tested areas will be taken systematically at each reading and 
properly documented. 
Duration of study product 
application 
1st Reading 
2nd  Reading 
3rd reading  
(optional) 
48 hours 
48 hours after study product 
application (30 minutes 
after patch test removal) 
 72 to 96 hours after study 
product application (24 to 
48  hours after patch test 
removal) 
6 or 7 days after study 
product application (96 to 
120 
hours 
after 
patch 
removal) 
 
7. 
Refer to the scoring system (Spiewak 2008) used by the International Contact Dermatitis 
Research Group (ICDRG) to assign a score at each reading:  
Score 
Morphology 
Interpretation 
- 
No skin changes in the tested area 
Negative 
? 
Faint, non-palpable erythema  
Doubtful reaction 
+ 
Palpable erythema (moderate edema or infiltrate), papules not present or 
scarce, vesicles not present  
Weak positive reaction 
++ 
Strong infiltrate, numerous papules, vesicles present 
Strong positive reaction 
+++ 
Erythema, infiltration, confluent vesicles, bullae or ulceration 
Extreme positive reaction 
ir 
Inflammation sharply limited to the exposed area, lack of infiltrate, small 
petechiae, pustules, and efflorescences other than papules and vesicles 
Irritant reaction 
Nt 
 
Not tested 
 
8. 
At last reading, the investigator will provide an assessment regarding a possible 
sensitization reaction using the following scale: 
Sensitization Reaction 
0 
Negative (absence of reaction or might be irritant reaction) 
1 
Equivocal 
2 
Positive 
 
9. 
Report the results from the re-challenge test as directed by the sponsor and document with 
photographs. 
10. 
In case of absence of reaction, the subject may resume treatment if appropriate 
11. 
If the re-challenge is positive or equivocal, notify the sponsor immediately. Except specific 
situations, a new series of patch test will be initiated as directed by the sponsor (with 
individual ingredients at different concentrations if applicable, and possibly negative and 


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positive controls) after a minimum of additional two weeks (but not later than 6 months) 
and after all signs and symptoms have resolved. The patch tests will be placed on the 
subject’s back (or the inner forearm if the back cannot be tested) distant from the site of the 
re-challenge test (e.g., the left upper back skin if the re-challenge test was done on the right 
side). Follow the same procedure for the patch test as for the re-challenge.  
In case of suspicion of immediate contact skin reaction (such as urticaria) 
A case by case approach will be applied and the procedure to follow will be discussed with the 
sponsor. 
 
8.4 
Procedures for reporting pregnancies 
Any pregnancy occurring during clinical trials, where the foetus could have been exposed to the 
investigational product(s), must be followed-up until outcome in order to ensure the complete 
collection of safety data on GALDERMA  product. 
If a subject becomes pregnant, the Investigator is to do the following: 
1. 
Withdraw the subject from the clinical trial  
2. 
Complete all appropriate visit evaluations and CRF pages. 
3. 
Immediately (no later than 24 hours) contact the Sponsor to inform them of the 
pregnancy occurrence and discuss further steps to be taken. 
4. 
Complete, as fully as possible, the pregnancy surveillance form – Part I: History and 
start of pregnancy - provided by the CRA at the beginning of the clinical trial, as fully as 
possible. Fax or send by email this pregnancy form along with the Exit form within 
24 hours of receipt of the information to the Sponsor. 
 
GALDERMA R&D  
Name 
Title 
Stéphanie Leclerc 
Clinical Project Manager 
Address 
Les Templiers 
2400, Route des Colles 
06460 BIOT France 
Tel. during office hours 
+33 4 92 38 67 06 (CPM #) 
Tel. outside office hours 
+33 6 70 40 94 22 (Rajeev CHAVDA, medical expert) 
Fax 
+33 4 97 04 90 67 
Email 
pharmacovigilance@galderma.com 
 
5. 
Monitor and record the progress of the pregnancy until its outcome.  Contact the subject’s 
regular physician (general practitioner or gynecologist) or hospital staff to obtain further 
details and ask regular follow-up information. 


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6. 
Inform the Sponsor of the progress by tri-monthly updates up to the final outcome of 
the pregnancy. For all the additional follow-up evaluations, fax or send by e-mail the 
additional follow-up information to the sponsor within 24 hours of receipt of the 
information.  If the subject can no longer be reached (lost to follow-up), documentation of 
the non-response/contact with two phone calls and a letter (certified with return receipt) is 
required. 
At outcome of pregnancy, complete as fully as possible the pregnancy surveillance 
form – Part II: Course and outcome of pregnancy, as full as possible. Inform the Sponsor 
by email/ fax, then fax or send by e-mail this pregnancy form to the Sponsor within 
24 hours of receipt of the information. 
7. 
If the pregnancy leads to an abortion (voluntary abortion, spontaneous abortion or 
therapeutic abortion), in utero death or congenital anomaly, follow the procedure for 
declaration of an SAE (see Section 8.2.2). 
9 
STATISTICAL METHODS PLANNED 
9.1 
Statistical and analytical plans 
A Statistical Analysis Plan (SAP) will be developed as a separate document. The SAP will 
contain a more detailed and technical description of specific data conventions, calculations and of 
statistical procedures for executing the analyses that are specified in the sections of the clinical 
trial protocol below.  The SAP will be finalized prior to database lock. 
Any change made to the finalized SAP will be documented in the clinical trial report. 
The purpose of this clinical trial is to evaluate the subject reported outcome with Luxerm® 
Daylight field procedure after one session. Also the efficacy and safety of Luxerm® in terms of 
subject complete response rate will be assessed. 
9.1.1 
Analysed Variables  
The following variables will be analysed: 
9.1.1.1 Efficacy variable 
 Patient Reported Outcomes: subject questionnaire at treatment day after daylight session and 
at last visit (week 12 or early termination).  
 Lesion complete response rate, defined as the percentage of preexisting and treated lesions in 
the anatomical area at baseline assessed as clear at week 12 


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 Subject complete response rate defined as the percentage of subjects with all treated lesions 
clear in the anatomical area at Week 12. 
 Subject partially clear defined as the percentage of subjects with at least 75% lesion complete 
response in the anatomical area at week 12. 
 Number of new AK lesions in the anatomical area. 
 Subject’s skin aspect at week12: mean score on anatomical area at week12. 
9.1.1.2 Safety variables  
 Subject’s self-assessment of maximal pain after daylight exposure. 
 Incidence and severity of adverse events. 
 
9.1.1.3 Other variables 
 Photodamage score with Dover’s scale at baseline visit and week 12.  
 Physician questionnaire at study end once all subjects in the study center have completed the 
study. 


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9.1.2 Populations analysed, evaluability and limitations / evaluation of Bias 
The statistical analyses will be performed based on the following subject populations: 
9.1.2.1 The Intent-to-Treat efficacy population (ITT) 
This population will consist of the entire population enrolled (i.e. treatment dispensed). The ITT 
population will be used for all variables except the safety variables. 
9.1.2.2 The Safety population (All subject treated [APT]) 
This population will consist of the Intent-to-Treat population, after exclusion of subjects who 
never used the treatment with certainty based on monitoring report. The APT population will be 
only used for the safety variables (AEs). 
9.1.2.3 Missing values 
In order to evaluate the effect of major deviations or of data exclusions, lesion response endpoint 
will be analysed using a worst case approach, in which the lesions with missing lesion response 
assessment will be considered as having not responded.  
9.1.3 
Data presentation and graphics 
All continuous data will be summarized using usual statistics: number of values, mean, median, 
standard deviation, minimum and maximum, and by frequency distribution (n, %) for qualitative 
data. For ordinal data, both frequency distribution and usual statistics will be presented. All tables 
will be presented by clinical trial treatment and by visit (when applicable).  
Therapies that have been stopped before the baseline visit will be presented as prior therapies. 
Those reported at screening or starting between screening and baseline visits and still continuing 
after baseline will be classified as concomitant therapies. 
The adverse events will be descriptively summarized (n, %) for the safety population (APT). The 
adverse events will be descriptively summarized (n, %) by relationship to clinical trial treatments 
within System Organ Class (SOC) and preferred term (MedDRA). Subjects will be descriptively 
summarized (n, %) by intensity (i.e. mild, moderate and severe) of adverse events, SOC and 
preferred terms. Deaths and serious adverse events will be reported as well as withdrawals due to 
adverse events. A subject will be counted only once per System Organ Class (SOC) and only 
once per preferred term even if more than one occurrence of an event was reported within a SOC 
or preferred term. In the summary by categories of intensity, the adverse event with the highest 
intensity will be used. The subject will be counted only once per SOC (highest intensity whatever 
the AE within the SOC) and once per preferred term (highest intensity whatever the AE within 
the preferred term).  


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9.1.4 
Statistical analyses 
The objective of this trial is to evaluate the subject reported outcome with Luxerm® Daylight 
field procedure after one treatment session. Also the efficacy and safety of Luxerm® in terms of 
subject complete response rate will be assessed. 
No inferential statistics will be performed. All variables will be descriptively summarized on ITT 
population and on APT population for the safety variables.  
Any changes of the statistical analyses decided after the database lock will be justified and 
documented. 
9.2 
Sample size determination 
9.2.1 
Historical data and assumptions 
As no inferential statistics will be performed and as this study is of exploratory nature, no 
statistical rationale of sample size can be used.  
9.2.2 
Sample size calculation 
However, concerning the satisfaction survey, assuming an overall satisfaction around 85%, with 
total of 50 subjects included in the study, the precision is 10%, which is sufficient. 
10 
TRAINING / MONITORING / DATA MANAGEMENT / QUALITY ASSURANCE 
A contract research organization (CRO) will be responsible for monitoring the clinical trial and 
the sponsor may perform co-monitoring visits at selected sites. 
10.1 
Personnel training 
Clinical Research Associates (CRA) will be trained prior to clinical trial initiation. During this 
training, an overview of the disease of interest and treatment will be presented. Training on safety 
reporting sponsor procedures will be done. Specific monitoring guidelines and procedures to be 
followed during monitoring visits will be discussed. 
Initiation visits will be conducted with all Principal Investigators and site teams. During these 
visits, an extensive review and discussion of the protocol, procedures and CRF will be conducted. 
Evaluation scales will also be reviewed. 
A trial reference monitoring manual will be provided to each CRA as an additional reference tool.  


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An eCRF completion guideline will be provided to each CRA and site. These guidelines will 
contain instructions on how to fill-in the eCRF with some examples in order to standardize the 
eCRF completion as much as possible. 
A trial reference manual will be provided to each site as an additional reference tool. These 
guidelines will contain key CRO and Sponsor contacts and phone numbers and specific 
instructions for site, including specific instruction detailing use of the study treatment, in order to 
standardize as much as possible the assessments performed during the clinical trial.  
During the Investigator meeting this document will be discussed and reviewed thoroughly. 
10.2 
Clinical monitoring  
The conduct of the clinical trial will be closely monitored by representatives of 
CRO/GALDERMA R&D to verify the adherence to the clinical trial protocol, ICH-GCP 
regulations, applicable SOPs, guidelines, and all local regulations.  
The investigator will allow representatives of GALDERMA R&D/CRO to have direct access to all 
clinical trial records, eCRFs, corresponding subject medical records, investigational product 
dispensing records and investigational product storage area, site facilities and any other 
documents considered as source documentation. 
The investigator also agrees to assist the GALDERMA R&D/ CRO representatives, if required. 
10.3 
Data management 
A CRO will be responsible for data management in connection with the sponsor’s data manager. 
All data management procedures will be detailed in the Data Management Plan (DMP).  
The DMP will describe the Clinical Data Management System (CDMS) that will be used to 
collect and validate data. Computerized edit checks and review processes will be performed on an 
ongoing basis as outlined in the DMP until all data discrepancies are resolved. 
After all data discrepancies are resolved, coding is approved, and subject evaluability has been 
determined, the data will be exported to SAS datasets and will be locked. 
The locked SAS database will be used to generate subject listings, tabulations and analyses.  
The data may be audited by the sponsor and/or CRO Quality Assurance department before or 
after the first statistical analysis results on the primary criteria. 


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10.4 
Quality assurance / audit / inspection 
The clinical trial will be conducted under the sponsorship of GALDERMA R&D in compliance 
with all appropriate local and local regulations as well as ICH guidelines and in accordance with 
the SOPs for clinical trial conduct and monitoring from GALDERMA R&D and/or the Contract 
Research Organization (CRO). 
Audits of clinical trial sites may be conducted by the Sponsor/CRO representatives, and 
inspection may be performed by Regulatory Authority inspectorates or IRBs/ECs before, during, 
or after the clinical trial.   
The investigator will allow and assist the CRO/Sponsor’s representatives, IRBs/ECs and any 
regulatory agency to have direct access to all requested clinical trial-related records. 
For the audits performed by, or on behalf of, GALDERMA R&D auditors, audit certificate(s) will 
be provided by Quality Assurance. 
11 
ETHICS AND GENERAL CLINICAL TRIAL CONDUCT CONSIDERATIONS 
11.1 
Institutional review board (IRB) or ethics committee (EC) 
This clinical trial protocol will be reviewed and approved by IRBs/ECs prior to clinical trial 
initiation. 
This protocol may be modified at any time for ethical, medical or scientific reasons. Such 
modifications will be documented by a clinical protocol amendment and, if deemed necessary, an 
amended protocol will be issued. 
Before implementation, the amendment should be submitted and approved by applicable 
IRBs/ECs and, if required by the Regulatory Authority(ies). 
No amendment will be required for modification(s) due to a change in logistical or administrative 
aspects of the clinical trial (e.g., change in monitors, change of telephone numbers). In such a 
case, the appropriate institution(s) and/or person(s) will be directly notified of the changes. 
11.2 
Ethical conduct of the clinical trial 
This clinical trial will be conducted in accordance with the ethical principles originating from the 
Declaration of HELSINKI declaration (1964) and subsequent amendments, the International 
Conference on Harmonization (ICH), Good Clinical Practice (GCP) and in compliance with local 
regulatory requirements. 


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11.3 
Subject information sheet / informed consent 
All subjects who participate in this trial will have to be fully informed about the clinical trial in 
accordance with the applicable regulations and GCP guidelines and in accordance with local legal 
requirements.  
The informed consent form approved by an IRB/EC, will be fully explained to the subject during 
the baseline visit.  
Prior to any clinical trial procedures, the subject will sign and date the informed consent form(s) 
which is written in the local language. A copy of the signed and dated form(s) will be given to the 
subject. The investigator is responsible for maintaining each subject’s consent form(s) in the 
investigator’s site file (ISF) and providing each subject with a copy of the consent form. 
As photographs will be taken during the clinical trial, a specific photograph release consent form 
approved by an IRB/EC will be fully explained to the subject. Subjects willing to be 
photographed will sign and date the photograph release consent form before any to take any 
photograph.  
11.4 
Contractual requirements  
A 
contractual 
agreement 
will 
be 
signed 
between 
the 
CRO/Sponsor 
and 
each 
Investigator/Institution.  This document will contain supplementary information, including 
financial terms, confidentiality, the clinical trial schedule, third party responsibility, and 
publication rights. 
11.5 
Data collection and archiving 
11.5.1 
Data Collection 
The investigator must maintain required records on all clinical trial subjects.  
Data for this clinical trial will be recorded in the subject’s source documents and in the eCRF, the 
product dispensation logs, the subject questionnaires and the investigator questionnaire provided 
by GALDERMA R&D.  
All data recorded in the documents described above should be recorded completely, promptly, 
and legibly using black ink.  
The appropriate pages will be collected upon clinical trial completion or at any other time 
specified by CRO CRA/sponsor.  
A complete set of copies will remain at the investigational site. 


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11.5.2 
Source documentation 
Investigators must keep accurate separate records of all subjects’ visits, and all procedures done, 
being sure to include all pertinent clinical trial related information from which CRF data will be 
recorded.  
A statement should be made on subject’s medical notes indicating that the subject has been 
enrolled in GALDERMA R&D protocol RD.03.SPR.114384 and has provided dated and 
signed informed consent.  
All adverse events with the associated concomitant therapies must be thoroughly documented. 
Results of any diagnostic tests conducted during the clinical trial will be included in the source 
documentation. 
Subject questionnaires completed after the study treatment and at week 12 are considered as 
source documents and must be kept by the investigator with other study records. 
Telephone conversations with the subjects and/or CRO/ GALDERMA R&D concerning the 
clinical trial may be recorded and kept on file. 
11.5.3 
Archives 
All pertinent data, samples, photos, questionnaires, correspondence, original or amended 
protocol, all reports and all other material relating to the clinical trial will be maintained securely 
in GALDERMA R&D / Investigator/Institution archives for the legally-required duration of 
archiving.  
If the investigator retires, relocates, or for any other reason withdraws from the responsibility of 
keeping the clinical trial records, custody must be transferred to a person who will accept the 
responsibility. The sponsor must be notified in writing of the name and address of the new 
custodian. 
11.6 
Insurance 
A certificate attesting third party coverage of CRO/GALDERMA R&D will be provided upon 
request.  


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Protocol N° RD.03.SPR.114384  
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12 
REFERENCE LIST 
 Bagazgoitia L, Cuevas Santos J, Juarranz  A, Jae´n P, Photodynamic therapy reduces the 
histological features of actinic damage and the expression of early oncogenic Markers. British 
Association of Dermatologists 2011. 
 Bay C, Margrethe Lerche C, Ferrick B, Alshede Philipsen P, Togsverd-Bo,K, Haedersdal  M, 
Comparison of Physical Pretreatment Regimens to Enhance Protoporphyrin IX Uptake in 
Photodynamic Therapy A Randomized Clinical Trial, JAMA 2017 
 Dréno B, Amici JM, Basset-Seguin N, et al. Management of actinic keratosis: a practical 
report and treatment algorithm from AKTeam™ expert clinicians. J Eur Acad Dermatol 
Venereol 2014; 28(9): 1141–1149 
 Fenske NA, Spencer J, Adam F. Actinic keratoses: past, present and future. J Drugs 
Dermatol. 2010; 9 (5 Suppl ODAC Conf Pt 1):s45-9. 
 Fernandez MT, Carrato C, Saenz X, Puig L , Musulen E, Ferrandiz C, Ariza A. Actinic 
keratosis with atypical basal cells (AK I) is the most common lesion associated with invasive 
squamous cell carcinoma of the skin. J Eur Acad Dermatol Venereol. 2015;29:991-997. 
 Ferrándiz C, Malvehy J, Guillén C, Ferrándiz-Pulido C, Fernández-Figueras MT. Precáncer 
cutáneo. Actas Dermosifiliogr. 2017;108:31---41. 
 Genovese G, Fai D, Fai C, Mavilia L, Mercuri SR. Daylight methyl-aminolevulinate 
photodynamic therapy versus ingenol mebutate for the treatment of actinic keratoses: an 
intraindividual comparative analysis. Dermatol Ther. 2016 May;29(3):191-6. 
 Gholam P, Fink C, Bosselmann I, Enk A.H., Retrospective analysis evaluating the effect of a 
keratolytic and physical pretreatment with salicylic acid, urea and curettage on the efficacy 
and safety of photodynamic therapy of actinic keratoses with methylaminolaevulinate.  
JEADV 2016 : 30 : 619-623 
 Goldberg LH, Mamelak AJ. Review of actinic keratosis. Part I: etiology, epidemiology and 
clinical presentation. J Drugs Dermatol. 2010;9(9):1125-32. 
 Gold MH, Nestor MS. Current treatments of actinic keratosis. J Drugs Dermatol. 
2006;5(2 Suppl):17-25. Review. 
 Fargnoli MC, Piccioni A, Neri L, Tambone S, Pellegrini C, Peris K. Conventional vs. 
daylight methyl aminolevulinate photodynamic therapy for actinic keratosis of the face and 
scalp: an intra-patient, prospective, comparison study in Italy. J Eur Acad Dermatol Venereol. 
2015 Oct;29(10):1926-32. 
 Frost CA, Green AC. Epidemiology of solar keratoses. Br J Dermatol. 1994;131(4):455-64. 
 Frost C, Williams G, Green A. J Invest Dermatol. High incidence and regression rates of solar 
keratosis in a queensland community. 2000;115:273-7. 


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 Lacour JP, Ulrich C, Gilaberte Y, Von Felbert V, Basset-Seguin N, Dreno B, Girard C, 
Redondo P, Serra-Guillen C, Synnerstad I, Tarstedt M, Tsianakas A, Venema AW, Kelleners-
Smeets N, Adamski H, Perez-Garcia B, Gerritsen MJ, Leclerc S, Kerrouche N, Szeimies RM. 
Daylight photodynamic therapy with methyl aminolevulinate cream is effective and nearly 
painless in treating actinic keratoses: a randomised, investigator-blinded, controlled, phase III 
study throughout Europe. J Eur Acad Dermatol Venereol. 2015 Dec;29(12):2342-8. 
 Morton CA, Szeimies RM, Sidoroff A, Braathen LR. European guidelines for topical 
photodynamic therapy part 1: treatment delivery and current indications - actinic keratoses, 
Bowen's disease, basal cell carcinoma. J Eur Acad Dermatol Venereol. 2013 May; 27(5):536-
44. 
 Rossi R, Calzavara-Pinton PG, Giannetti A, et al. Italian guidelines and therapeutic algorithm 
for actinic keratoses. G Ital Dermatol Venereol 2009; 144 (6): 713–723. 
 Rubel DM, Spelman L, Murrell DF, See JA, Hewitt D, Foley P, Bosc C, Kerob D, Kerrouche 
N, Wulf HC, Shumack S. Daylight photodynamic therapy with methyl aminolevulinate cream 
as a convenient, similarly effective, nearly painless alternative to conventional photodynamic 
therapy in actinic keratosis treatment: a randomized controlled trial. Br J Dermatol. 2014 
Nov;171(5):1164-71. 
 Samrao A, Cockerell CJ. Pharmacotherapeutic management of actinic keratosis: focus on 
newer topical agents. Am J Clin Dermatol 2013; 14 (4): 273–277. 
 Schaefer I, Augustin M, Spehr C, Reusch M, Komek T. Prevalence and risk factors of 
actinick keratosis in Germany analysis of multisource data. J Eur Acad Dermatol Venereol. 
2014;28:309-313  
 See JA, Shumack S, Murrell DF, et al. Consensus recommendations on the use of daylight 
photodynamic therapy with methyl aminolevulinate cream for actinic keratoses in 
Australia. Australas J Dermatol. 2015 
 Sidoroff A, Thaler P. Taking treatment decisions in non-melanoma skin cancer-the place for 
topical photodynamic therapy (PDT). Photodiagnosis Photodyn Ther. 2010;7(1):24-32. 
 Sotiriou E, Apalla Z, Vrani F, Lallas A, Chovarda E, Ioannides D. Photodynamic therapy vs. 
imiquimod 5% cream as skin cancer preventive strategies in patients with field changes: a 
randomized intraindividual comparison study.JEADV.2015 Feb;29(2):325-9.  
 Stockfleth E, Ferrandiz C, Grob JJ, et al. Development of a treatment algorithm for actinic 
keratoses: a European Consensus. Eur J Dermatol 2008; 18 (6): 651–659. 
 Szeimies R.M., Torezan L, Niwa A, Valente N Unger P, Kohl E, Schreml S, Babilas P, 
Karrer S, Festa-Neto C, Clinical, histopathological and immunohistochemical assessment of 
human skin field cancerization before and after photodynamic therapy. British Association of 
Dermatologists 2012 167, pp150–159 
 Wiegell SR, Haedersdal M, Philipsen PA, Eriksen P, Enk CD, Wulf HC. Continuous 
activation of PpIX by daylight is as effective as and less painful than conventional 


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photodynamic therapy for actinic keratoses; a randomized, controlled, single-blinded study. 
Br J Dermatol. 2008;158(4):740-6. 
 Wiegell SR, Wulf HC, Szeimies RM, Basset-Seguin N, Bissonnette R, Gerritsen MJP, et al. 
Daylight photodynamic therapy for actinic keratosis: an international consensus. J Eur Acad 
Dermatol Venereol. 2012;26(6):673-9. 
 
 
 


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13 
ATTACHMENTS 
Appendix 1: Subject questionnaire – Treatment day after daylight exposure 
 
 
This questionnaire aims to collect information on your feelings and opinions regarding the treatments for 
your actinic keratoses. There is no “right” or “wrong” answer. Your feedback will help us to better 
understand your needs and expectations, and they will not affect your future care.  
Thank you for taking the time to complete this questionnaire. 
Instructions: 
 
This questionnaire is to be completed immediately after the 2 hours of daylight exposure  
 
Use a black pen to complete the questionnaire and make sure your answer is legible; 
 
Tick one box only per question unless otherwise indicated; if you need to change your answer, draw a 
line through the previous answer and then record the new answer; 
 
Check for completeness of the questionnaire and give it back to the study doctor at the end of the 
procedure 
 
1. Date of treatment: ____/____ / ____/____ 
 
2. Have you received detailed instructions by your doctor on how to use the study treatment?  
 Yes   No 
 
3. How convenient do you find the study treatment instructions?  
1  
Very convenient 
2  
Convenient 
3  
Inconvenient 
4  
Highly inconvenient  
 
4. Was Actinica applied to protect from sunburn during daylight exposure?  Yes   No 
 
  Time of sunscreen application (hr/hr : min/min- use 24 hour clock): ____/____ : ____/____ 
 
5. Did you use the provided abrasive skin pad to prepare your skin? 
 Yes    No 
 
6. Which anatomical area identified by your doctor did you prepare (check one)? 
a. Scalp 
 
b.  Forehead 
 
c.  Right cheek 
 
d.  Left cheek 
 
e.  Chin 
 
 
 
7. Were the scales and crusts removed on the whole anatomical area? 
 Yes    No 
 


GALDERMA RESEARCH & DEVELOPMENT 
Protocol N° RD.03.SPR.114384  
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8. Did you roughen the surface of the anatomical area with the skin pad?  Yes    No 
 
9. Time of Luxerm® application (hr/hr : min/min- use 24 hour clock): ____/____ : ____/____ 
 
10. At what time did you go outside for 2 hours of daylight exposure (hr/hr : min/min- use 24-hour 
clock): ___/___:___/___  
 
11. At what time did you complete the 2 hours of daylight exposure (hr/hr : min/min- use 24 hour clock): 
___/___:___/___ 
 
12. Did you spend time in the shade during the time you had to stay outdoors?  Yes    No 
 
 If yes, how much time? _______ min 
 
13. Please indicate below how was the overall weather during the daylight exposure? 
 
 
 
  
1 
2  
3 
4 
 
14. What was the overall temperature during the daylight exposure? 
1  10-15°C 
 
 
2  15-20°C 
 
 
3  20-25°C 
 
 
4  25-30°C 
 
 
5  >30°C 
 
15. Was the Luxerm® cream removed after the 2 hours daylight exposure? Yes   No 
 
16. What was the maximal pain you felt during the duration of the daylight exposure? report below 
To be completed after the end of the 2 hours Daylight exposure  
No pain      
 
 
 
 
 
 
 
 
 
 
Extreme pain 
at all 
        
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10  
 
17. How bothered were you by this pain? 
 
1  
Not bothered at all 
 
2  
Bothered somewhat 
 
3 
Bothered a little 
 
4  
Bothered 
 
5  
Bothered a great deal 


GALDERMA RESEARCH & DEVELOPMENT 
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Final version - dated on 22 February -2017 
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18. How convenient do you find Luxerm® daylight illumination (staying outside)? 
1  
Very convenient 
2  
Convenient 
3  
Inconvenient 
4  
Highly inconvenient  
 
19. Globally, how satisfied are you with Luxerm® daylight procedure?  
1 
Very satisfied 
2 
Satisfied 
3 
Somewhat satisfied 
4 
Not satisfied 
 
 
20. If you are dissatisfied with Luxerm® daylight procedure, what are the reasons (more than one answer 
may be chosen)?  
1 
Treatment not effective 
1 
Side effects of the treatment.  
1 
Treatment not easy/convenient to use 
1 
Other. Please specify:________________________________ 
 


GALDERMA RESEARCH & DEVELOPMENT 
Protocol N° RD.03.SPR.114384  
Final version - dated on 22 February -2017 
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Appendix 2: Subject questionnaire–Week 12 / early termination 
 
This questionnaire aims to collect information on your feelings and opinions regarding the treatments for 
your actinic keratosis performed 3 months ago. There is no “right” or “wrong” answer. Your feedback will 
help us to better understand your needs and expectations, and they will not affect your future care.  
Thank you for taking the time to complete this questionnaire. 
Instructions: 
 This questionnaire is to be completed 3 months after the treatment of Actinic Keratosis you have 
received.  
 Use a black pen to complete the questionnaire and make sure your answer is legible; 
 Tick one box only per question unless otherwise indicated; If you need to change your answer, draw a 
line through the previous answer and then record the new answer; 
 Check for completeness of the questionnaire 
 
1. How satisfied are you with the effectiveness of this treatment to clear AKs?  
1 
Very satisfied 
2 
Satisfied 
3 
Somewhat satisfied 
4 
Not satisfied 
 
2. How much have you been bothered by any side effects of this treatment (skin reactions)  
1  
Not bothered at all 
2  
Bothered somewhat 
3 
Bothered a little 
4  
Bothered 
5  
Bothered a great deal 
 
 
3. How satisfied are you with the skin aspect of the treated area?  
1 
Very satisfied 
2 
Satisfied 
3 
4 
Somewhat satisfied 
Not satisfied 
 
4. How long after treatment was the duration of social embarrassment due to skin reactions? 
 
------- (days) 
 
 
5. What was the last treatment you received prior to your treatment with Luxerm® and daylight 
illumination? 
 
1
2 
None 
Cryotherapy 
3 
Efudix, efurix ( 5% cream) 
4 
Aldara, Almiq, Aldiq, Soldara, APO-imiquimod, Terry White Chemist 
Imiquimod, Chemmart Imiquimod, Imiquad, Apotex-imiquimod, Imiquad, Ixium 
5 
Solaraze 


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6 
Picato 
7 
Photodynamic Therapy with a red lamp or a blue lamp (PDT) 
8 
Photodynamic Therapy with daylight 
9 
Peelings 
10 
Laser 
 
6. How did you find Luxerm® with daylight exposure compared to your last treatment ticked in question 
5 (except if it was option 8 “PDT with Daylight”)? 
1  
Better 
2  
Similar 
3  
Worse 
4  
Never treated with previous treatment 
 
7. Would you consider using Luxerm® with daylight illumination again if needed in future?  
0 
No 
1 
Yes 
 
8. Overall, how satisfied are you with this treatment (regarding the procedure, effectiveness, side effects, 
skin aspect)? 
1 
Very satisfied 
2 
Satisfied 
3 
Somewhat satisfied 
4 
Not satisfied 
 
9. If you are dissatisfied with Luxerm® daylight procedure, what are the reasons (more than one answer 
may be chosen)?  
1 
Treatment not effective 
1 
Side effects of the treatment 
1 
1 
Luxerm® daylight procedure not easy/convenient to use 
Skin aspect of the treated area 
1 
Other. Please specify:________________________________ 
 
 


GALDERMA RESEARCH & DEVELOPMENT 
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Final version - dated on 22 February -2017 
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Appendix 3: physician satisfaction questionnaire when all subjects have completed the study 
1. Overall, are you satisfied with Luxerm® DL-PDT? 
1 
Very satisfied 
2 
Satisfied 
3 
Somewhat satisfied (please specify in the comments section below) 
4 
Not satisfied (please specify the reason in question 2) 
 
2. If you are dissatisfied with Luxerm® daylight procedure, what are the reasons (more than one answer 
may be chosen)? 
1 
Treatment not effective 
1 
Side effects of the treatment 
1 
1 
Luxerm® daylight procedure not easy/convenient to use 
Skin aspect of the treated area 
1 
Other. Please specify:________________________________ 
 
3. How satisfied are you with the effectiveness of Luxerm® DL-PDT on clearing AKs? 
1 
Very satisfied 
2 
Satisfied 
3 
Somewhat satisfied (please specify in the comments section below) 
4 
Not satisfied (please specify in the comments section below) 
 
4. How satisfied are you with the tolerability of Luxerm® DL-PDT? 
1 
Very satisfied 
2 
Satisfied 
3 
Somewhat satisfied (please specify in the comments section below) 
4 
Not satisfied (please specify in the comments section below) 
 
5. How satisfied are you with the cosmetic aspect of the treated area? 
1 
Very satisfied 
2 
Satisfied 
3 
Somewhat satisfied (please specify in the comments section below) 
4 
Not satisfied (please specify in the comments section below) 
 
6. Did you think the instructions provided to the patients were adequate to perform the treatment at home 
with Luxerm® DL-PDT? 
1 
Yes 
0 
No 
 If no, please specify _______________________________________ 
 
 
7. Would you consider using Luxerm® again for future patients?  
1 
Yes 
0 
No 
 If no, please check all the reasons that apply 
  Issues on safety  
  Issues on effectiveness 
  Issues on treatment price 


GALDERMA RESEARCH & DEVELOPMENT 
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Final version - dated on 22 February -2017 
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  Other, please specify:___________________________________________ 
 
 
Additional Comments (please write legibly):