Clinical Evaluation of a Nonablative Fractional 1940 nm Diode Laser for Skin Resurfacing and Treatment of Pigmented Lesions
Phase: NA
Conditions: Skin Texture, Pigmented Lesions
Sponsor: Candela Corporation

 
 
 
 
 
Protocol Title: 
Clinical Evaluation of a Nonablative Fractional 1940 nm Diode 
Laser for Skin Resurfacing and Treatment of Pigmented Lesions 
 
Protocol Number: 
FRX19004 
 
NCT: 
 
 
NCT04203745 
 
Revision:  
 
2.0 
 
Date: 
 
 
30 August 2019 
 
Sponsor:  
 
Candela Corporation 
 
 
 
 
 
530 Boston Post Road 
 
 
 
 
Wayland, MA  01778 
 
 
Sponsor Contact: 
Kristen Howell 
 
 
 
 
Senior Clinical Research Associate 
 
 
 
 
Phone:  508.358.7400 
 
 
 
 
KristenH@candelamedical.com   
 
 
 
 
 
 
 
 
 
 
 
 
STATEMENT OF CONFIDENTIALITY 
The information contained herein is Confidential Information that remains the sole and exclusive 
property of Candela Corporation (the Sponsor).  The conduct of this investigational study protocol is 
expressly subject to the terms and conditions of the Clinical Trial Agreement signed by the 
Investigator and the Sponsor. 
 

FRX19004 Revision 2.0 30 Aug 2019 
Page 2 of 24 
 
Table of Contents 
 
 
1. 
Study Synopsis.......................................................................................................... 3 
2. 
Abbreviations ............................................................................................................ 4 
3. 
Objective ................................................................................................................... 5 
4. 
Background and Rationale ........................................................................................ 5 
5. 
Study Design ............................................................................................................. 5 
6. 
Compliance ............................................................................................................... 7 
7. 
Materials and Equipment ........................................................................................... 7 
8. 
Regulatory Status ...................................................................................................... 9 
9. 
Non-Significant Risk Determination ......................................................................... 10 
10. 
Inclusion and Exclusion Criteria ............................................................................... 11 
11. 
Institutional Review Board (IRB) .............................................................................. 12 
12. 
Study Visits ............................................................................................................. 12 
13. 
Study Endpoints ...................................................................................................... 15 
14. 
Study Data Analysis Methods and Statistical Analysis Plan ..................................... 16 
15. 
Risks and Benefits ................................................................................................... 16 
16. 
Adverse Events ....................................................................................................... 17 
17. 
Investigational Sites ................................................................................................ 18 
18. 
Study Monitoring ..................................................................................................... 18 
19. 
Protocol Deviation Reporting ................................................................................... 18 
20. 
Record Maintenance ............................................................................................... 18 
21. 
Publication Policy .................................................................................................... 19 
22. 
References .............................................................................................................. 20 
Appendix A - Numerical Pain Rating Scale ...................................................................... 21 
Appendix B – Global Aesthetic Improvement Scale (GAIS) ................................................ 22 
Appendix C - Subject Satisfaction Questionnaire ............................................................... 23 
Appendix D - Pigment Improvement Score ........................................................................ 24 
 
 
 

FRX19004 Revision 2.0 30 Aug 2019 
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Study Synopsis 
Protocol 
Number 
FRX19004 v 2.0 
Protocol Title 
Clinical Evaluation of a Nonablative Fractional 1940nm Diode Laser for 
Skin Resurfacing and Treatment of  Pigmented Lesions 
Short Title 
FRAX 1940 Skin Resurfacing and Pigment 
Device 
Description 
The FRAX 1940 is a fractional 1940 nm solid-state diode laser that 
delivers linear arrays of microbeams to create nonablative microscopic 
treatment zones (MTZs) in the skin 
Study Design 
Prospective, open-label, clinical trial  
Objective 
Evaluate the safety and efficacy of the FRAX 1940 nm fractional diode 
laser handpiece for skin resurfacing and treatment of  pigmented lesions 
such as, but not limited to lentigos (age spots), solar lentigos (sun spots) 
and ephelides (freckles) 
Study 
Population 
Up to 60 enrolled subjects  
Investigative 
Sites 
Up to three (3) investigational sites 
Study Treatment 
Visits 
• 
1 test spot visit (Phase I) 
• 
Up to three (3) treatment visits 4 ± 1 weeks apart (Phase II) 
Follow-Up 
Visits 
 
Phase I – Following Test Spots 
• 
4 ± 2 days after test spots 
• 
14 ± 7 days after test spots 
• 
28 ± 7 days after test spots (if required) 
 
Phase II – Following Treatments 
• 
7 ± 3 days after each resurfacing treatment 
• 
Optional interim visits if required to assess adverse events 
• 
4 weeks after final treatment  
• 
12 weeks after final treatment  
• 
Additional visits beyond 12 weeks if required to assess adverse events 
Measurement 
Instruments 
• 
Subject Numerical Pain Scale 
• 
Global Assessment Improvement Scale (GAIS) 
• 
Subject Satisfaction Questionnaire  
• 
Pigment Improvement Score 
Primary 
Efficacy 
Endpoint 
• 
Formation and healing times of micro epidermal necrotic debris (MENDs) 
as measured in days 
Secondary 
Efficacy 
Endpoint 
• 
Improvement in clearance of  pigmented lesions, such as, but not limited to 
lentigos (age spots), solar lentigos (sun spots), and ephelides (freckles). 
Primary Safety 
Endpoint • 
Incidence, severity and relatedness of adverse events 

FRX19004 Revision 2.0 30 Aug 2019 
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Abbreviations  
 
AE 
Adverse Event 
cm, cm2 
Centimeter, Square Centimeters 
CFR 
Code of Federal Regulations 
Ø 
Diameter 
FDA 
Food and Drug Administration 
FST 
Fitzpatrick Skin Type 
GCP 
Good Clinical Practice 
GUI 
Graphic User Interface 
Hz 
Hertz 
IRB 
Institutional Review Board 
J 
Joule 
MEND 
Micro Epidermal Necrotic Debris 
µbeam 
Microbeam 
µm 
Micron 
MTZ 
Microscopic Treatment Zone 
mJ 
Millijoule 
mm 
Millimeter 
ms 
Millisecond 
NAF 
Nonablative Fractional 
nm 
Nanometer 
NSR 
Non-Significant Risk 
UADE 
Unanticipated Adverse Device Effect 
SOP 
Standard Operating Procedure 
SPF 
Sun Protection Factor 
Tx 
Treatment 
 
 
 

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Objective 
This study is intended to evaluate the efficacy and safety of a 1940 nm diode fractional 
laser handpiece for skin resurfacing and treatment of  pigmented lesions. In addition to 
demonstrating skin resurfacing, a secondary goal of this study is to generate data with the 
1940 nm diode fractional laser handpiece to support a regulatory submission for treatment 
of pigmented lesions, such as, but not limited to lentigos (age spots), solar lentigos (sun 
spots), and ephelides (freckles). 
Background and Rationale 
The use of lasers to selectively target chromophores in the skin was first described by 
Anderson and Parrish in 1983.1  Since then several lasers have been developed with 
wavelengths in the near to mid-infrared spectrum that are selectively absorbed by water 
contained in the skin which raise the temperature of the skin enough in a nonablative 
manner to coagulate structures of the epidermis and dermis and promote new collagen 
formation.  Initially these nonablative lasers were used with a flat beam profile for skin 
resurfacing2.  Starting in 2004, these technologies were followed by the introduction of 
nonablative fractional lasers that deliver the energy to the skin as arrays of microscopic 
treatment zones (MTZs) for indications ranging from skin resurfacing, to treatment of 
wrinkles and fine lines, pigmented lesions, scars, and other dermatological 
indications.3,4,5,6,7,8  The microscopic arrays allow the laser energy to leave discrete 
microscopic zones of thermal epidermal and dermal injury separated by areas of untreated 
skin.  This energy delivery technique allows for less healing time compared to traditional flat 
beam laser treatments.   
Study Design 
This study is a prospective, open-label, clinical trial to study the effects of the FRAX 1940 
nonablative, fractional 1940 nm wavelength diode laser for skin resurfacing. 
 
Up to 60 enrolled subjects who agree to have skin resurfacing will be enrolled at up to three 
(3) investigational sites.   After meeting all inclusion criteria and not meeting any of the 
exclusion criteria as well as providing signed informed consent, a subject will be considered 
enrolled in the study, and assigned a unique study identification number. 
 
Subjects will initially receive up to four (4) test spots on their face and up to four (4) test 
spots on other anatomical locations (e.g., hands, arm, back, chest) using the FRAX 1940 
laser to help the study clinicians determine appropriate treatment settings for each 
individual subject.  The test spots are administered to check for safety of the parameter 
settings.  Each test spot area will typically not be larger than approximately 2 inches by 2 
inches (5 cm X 5 cm).     
 
Subjects will be scheduled for a follow-up visit at 4 ± 2 days and 14 ± 7 days (Follow-Up 
Visit #1) after the test spots.  Based on the observed skin responses and healing seen at 
Follow-Up Visit #1, the Investigator or study staff will determine if a subject is an 
appropriate candidate to proceed with the skin resurfacing treatment on the face which will 
be administered either at this same visit, or scheduled at a future time point during a 14 to 
21 day period following administering the test spots.  Additional skin resurfacing treatment 

FRX19004 Revision 2.0 30 Aug 2019 
Page 6 of 24 
may be also administered in other locations that contain  pigmented lesions on the face, 
hands, arms, legs, back, and/or chest. 
 
If it is determined by the Investigator or study staff at the 14 ± 7 day visit after test spots 
that the skin response seen exhibits adverse events such that treatment of the entire face 
is not prudent, then the subject will either be exited from the study, or be asked to return 
approximately two weeks later for further evaluation.  A study flow chart for subject intake 
through final follow-up is shown in Figure 1. 
 
Figure 1:  Study Flow Chart 
 
 
After receiving skin resurfacing Treatment #1, subjects will be scheduled for a follow-up 
visits for clinical evaluation and photography at 7 ± 3 days.  Treatment #2 will be scheduled 
4 ± 1 weeks after Treatment #1 if skin assessment is acceptable; and Treatment #3 will be 
scheduled 4 ± 1 weeks after Treatment #2.  Additional interim follow-up visits may be 
required between treatment visits at the discretion of the Investigator or study staff if 
required to monitor the treated area(s), and possibly 2 and/or 3 months after final treatment 
if lingering adverse events need to be monitored to resolution.  
 
A follow-up visit will be scheduled approximately 4 ± 1 weeks (1 month) after the final 
treatment, typically Treatment #3.   
 
A final follow-up visit will be scheduled approximately 12 ± 1 weeks (3 months) after the 
final treatment, typically Treatment #3.  Note:  Fewer than three treatments may be 
required at the discretion of the Investigator or study staff. 
 
A Study Schedule of Events is provided in Table 1.   
 
 

FRX19004 Revision 2.0 30 Aug 2019 
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Table 1:  Study Visit Schedule of Events 
 
Phase 1 
Phase 2 
Activity 
Screening 
Baseline/ 
Test 
Spots* 
Follow 
Up Visit 
#1 
Follow 
Up Visit 
#2 
Treatment 
#1** 
Follow Up 
Visits  
Treatments 
#2 & #3 
Follow Up 
Visits*** 
#1 & #2 
Day  
-14 to 0 
Day 0 
4 ± 2 
 Days after 
test spots 
  
14 ± 7 
Days after 
test spots 
  
14 ± 7 Days 
or 
28 ± 7 Days 
after test 
spots 
7 ± 3 Days 
after  
each 
Treatment 
 
4 ± 1 Weeks 
after 
prior 
Treatment 
 
4 ± 1 Weeks 
And  
12 ± 1 Weeks 
after 
final 
Treatment  
 
Exclusion 
Criteria 
X 
 
 
 
 
 
 
 
Informed 
Consent 
X 
 
 
 
 
 
 
 
Assign Study 
ID 
 
X 
 
 
 
 
 
 
Photography 
 
X 
X 
X 
X 
X 
X 
X 
Test Spots 
 
X 
 
 
 
 
 
 
Treatment 
 
 
 
X** 
X 
 
X 
 
Subject Pain 
Score 
 
X 
 
 
X 
 
X 
 
Subject 
Satisfaction 
Questionnaire 
 
 
 
 
 
 
 
 
X 
GAIS Subject 
 
 
 
 
 
 
 
X 
Skin Response 
Adverse Event 
Documentation 
 
X 
X 
X 
X 
X 
X 
X 
*Screening, Baseline/Test Spots may occur at the same visit 
**Treatment #1 may occur at same visit as Follow-Up Visit #2 if acceptable clinical endpoint is seen from Test Spots 
***Additional follow-up visits may be required beyond 12 weeks to monitor resolution of adverse events 
Compliance 
This study will be conducted in compliance with this protocol, the manufacturer guidelines 
as provided in the FRAX 1940 User Manual, and other guidelines as required by Good 
Clinical Practices (GCP), IRB, or other local regulatory authorities. Confidentiality and 
privacy of subjects’ medical information will be maintained in compliance with the Health 
Insurance Portability and Accountability Act (HIPAA). 
Materials and Equipment 
The FRAX 1940 handpiece is one of several that can be connected to a main base system 
such as the NORDLYS or Ydun manufactured by Ellipse a subsidiary of Candela 
Corporation, Wayland, MA.  The NORDLYS and Ydun base systems and FRAX 1940 non-
ablative handpiece are shown in Figure 2.  The FRAX 1940 handpiece consists of a 1940 
nm solid-state, diode laser xxxxxxx xxxxxxx xxxxxxx xxxxxxxhelps xxxxxxx xxxxxxx 

FRX19004 Revision 2.0 30 Aug 2019 
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xxxxxxx xxxxxxx xxxxxxx xxxxxxx xxxxxxx xxxxxxx xxxxxxx xxxxxxx xxxxxxx xxxxxxx 
xxxxxxx xxxxxxx xxxxxxx xxxxxxx xxxxxxx xxxxxxx xxxxxxx xxxxxxx xxxxxxx xxxxxxx 
xxxxxxx xxxxxxx xxxxxxx xxxxxxx xxxxxxx xxxxxxx xxxxxxx xxxxxxx xxxxxxx xxxxxxx 
xxxxxxx xxxxxxx xxxxxxx xxxxxxx xxxxxxx xxxxxxx xxxxxxx xxxxxxx xxxxxxx xxxxxxx 
xxxxxxx xxxxxxx xxxxxxx xxxxxxx xxxxxxx xxxxxxx xxxxxxx xxxxxxx xxxxxxx xxxxxxx 
xxxxxxx xxxxxxx xxxxxxx xxxxxxx 
 
xxxxxxx xxxxxxx xxxxxxx xxxxxxx xxxxxxx xxxxxxx xxxxxxx xxxxxxx xxxxxxx xxxxxxx 
xxxxxxx xxxxxxx xxxxxxx xxxxxxx xxxxxxx xxxxxxx xxxxxxx xxxxxxx 
 
The FRAX 1940 is also equipped with an integrated cold air delivery system contained in 
the base system that blows cold air onto the treatment area to provide patient comfort. 
 
Safety Eyewear designed for use with the FRAX 1940 is provided with each laser system 
and must be worn by all personnel in the treatment room while the laser is being used, 
including the patient. 
 
 
Figure 2:  NORDLYS and Ydun Base Systems (left) and FRAX 1940 Handpiece (right) 
 
 
   
  
 
 
 
Figure 3:  Fractional Beam Patterns Selectable from xxxxxxx micro thermal zones (MTZ) per line 
 
 [redacted image, confidential] 
 
 
 
Technical specifications for the FRAX 1940 laser are identical whether it is connected to 
the NORDLYS or Ydun base system and are provided in Table 2. 
 

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Table 2:  Technical Specifications – FRAX 1940 Handpiece 
Parameter 
Specifications 
Wavelength (nm) 
xxxxxxx  
Energy per MTZ (mJ) 
xxxxxxx  
MTZ Diameter (microns) 
xxxxxxx  
Scan Width 
xxxxxxx  
MTZ per scan line 
xxxxxxx  
Pulse Duration (ms) 
xxxxxxx  
Pulse Repetition Rate (Hz) 
xxxxxxx  
Aiming Beam 
xxxxxxx  
Treatment Cooling8 
xxxxxxx  
Delivery System 
xxxxxxx  
 
 
 
[redacted information above due to confidential information] 
Regulatory Status 
Use of the FRAX 1940 nm wavelength handpiece is considered an investigational device 
by FDA.  As a result, to meet the criteria for an Investigational Device it will be labeled with 
the following statement: 
 
 
 
 
 
 
The NORDLYS and Ydun base systems and a family of handpieces that includes intense 
pulsed light (IPL), Nd:YAG 1064nm laser, and a nonablative fractional 1550 nm laser have 
received prior 510(k) market clearances by the U.S. Food and Drug Administration (FDA) 
as shown in Table 3.  Specific cleared indications for use are also listed below. 
 
Table 3:  FDA 510(k) Market Clearances for NORDLYS Base System 
510(k) Number 
Device Name 
K180406 
Ellipse Ydun 
K161162 
Frax 1550 for Ellipse Nordlys/Ellipse Nordlys+, Ellipse 
Sirius, Ellipse Infinity, Ellipse Mjolner, Ellipse Nordlys Ultra 
K150907 
Ellipse Nordlys 
 
510(k) Cleared Indications for Use: NORDLYS and Ydun Base Systems and Family of 
Handpieces 
 
Ellipse Ydun system is intended to be used in dermatology, as tabled below: 
• Ydun is indicated for use in dermatological procedures requiring the coagulation of soft 
tissue, as well as for skin resurfacing procedures 
 
Ellipse NORDLYS system is intended to be used in dermatology, as tabled below: 
CAUTION – Investigational Device. 
Limited by Federal (or United States) law to 
i
ti
ti
l

FRX19004 Revision 2.0 30 Aug 2019 
Page 10 of 24 
 
• Permanent Hair Reduction (defined as the long-term, stable reduction in the number of 
hairs re-growing when measured at 6, 9, and 12 months after the completion of a treatment 
regime) (overall 600-950nm). 
• Treatment of Telangiectasias (530-750nm or 555-950nm). 
• Treatment of Port Wine Stains (530-750nm or 555-950nm). 
• Treatment of Benign Pigmented Lesions (e.g. Mottled Pigmentation, Ephilides [sic]) and 
Benign Vascular Lesions (e.g. Diffuse Redness) (530-750nm or 555-950nm). 
• Treatment of Rosacea (530-750nm or 555-950nm). 
• Treatment of Poikiloderma of Civatte (530-750nm or 555-950nm). 
• Treatment of Benign Epidermal Pigmented Lesions (e.g. Lentigo Solaris) (400-720nm). 
• Treatment of Inflammatory Acne Vulgaris (530-750nm). 
 
Using Nd:YAG Laser, (1064 nm): 
• Treatment of Leg vessels (0.1 -3.0 mm diameter). 
• Treatment of Benign Vascular Lesions. 
• Treatment of Venous Lakes. 
• Treatment of Port Wine Stains. 
• Treatment for Clear Nail defined as: Temporary increase of clear nail in patients with 
onychomycosis (e.g., dermatophytes Trichophyton rubrum and T. mentagrophytes, and/or 
yeasts Candida albicans, etc.). 
• Treatment of benign cutaneous lesions, such as warts. 
• Podiatry (ablation, vaporization, incision, excision, and coagulation of soft tissue), 
including: 
 - Matrixectomy. 
 - Periungal and subungal warts 
 - Plantar warts. 
 
Using Frax 1550 Laser, (1550 nm): 
• The Frax 1550 nm laser is indicated for use in dermatological procedures requiring the 
coagulation of soft tissue, as well as for skin resurfacing procedures. 
Non-Significant Risk Determination 
The Sponsor believes the 1940 FRAX laser handpiece does not meet the criteria of a 
significant risk device. In accordance with the definition of “Significant Risk Device” 
provided in the U.S. Code of Federal Regulation 21 CFR 812.3, the 1940 FRAX laser 
handpiece has been determined to be a Non-Significant Risk (NSR) device based on the 
following: 
 
a) It is not an implant 
b) It is not purported or represented to be for use in supporting or sustaining human life 
and do not present a potential for serious risk to the health, safety or welfare of a 
subject 
c) It is not for a use of substantial importance in diagnosing, curing, mitigating, or 
treating disease or otherwise preventing impairment of human health and does not 
present a potential for serious risk to the health, safety, or welfare of a subject; or 

FRX19004 Revision 2.0 30 Aug 2019 
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d) Otherwise, use of the device does not present a potential for serious risk to the 
health, safety, or welfare of a subject. 
Inclusion and Exclusion Criteria 
Subjects will be enrolled at the discretion of the Investigator after determining that each 
potential subject (1) meets all inclusion criteria, (2) does not meet any exclusion criteria, 
and (3) provides signed informed consent. 
Inclusion Criteria 
1. Male or Female 
2. Age 21 to 70 
3. Fitzpatrick Skin Type I to V 
4. Willingness to have test spots and up to three (3) skin resurfacing treatments on the 
face 
5. Presence of  pigmented lesions to be treated off the face must be rated at baseline 
as moderate or higher per Investigator or study staff  
6. Provide signed informed consent to participate in the study 
7. Adhere to study treatment and follow-up schedules 
8. Willing to have hair removed from the intended treatment area prior to treatment 
and/or photography 
9. Avoid sun exposure to all treated areas and use of sunscreen with sun protection 
factor (SPF) 30 or greater throughout the duration of the study 
10. Adhere to post-treatment care instructions   
11. Allow photography of treated areas and to release their use for scientific and/or 
promotional purposes 
 
Exclusion Criteria 
1. Pregnant, planning to become pregnant, or breast feeding during the study 
2. Allergy to lidocaine or similar medications 
3. Excessively tanned skin in the intended treatment area 
4. Open wound or infection in the intended treatment area 
5. Tattoo(s) or permanent make-up in the intended treatment area 
6. Skin condition in the intended treatment area that could interfere with treatment or 
evaluation of safety or efficacy 
7. Presence or history of melasma 
8. Presence or history of skin cancer within the treatment area(s) 
9. History of keloid or hypertrophic scar formation 
10. History of herpes simplex virus (HSV) or similar condition in the intended treatment 
area unless treated with prophylactic medication 
11. Diagnosed coagulation disorder 
12. Immunosuppression  
13. Presence of any medical condition that in the opinion of the Investigator could 
impair healing or outcome as a result of treatment 
14. Use of systemic retinoid therapy (e.g. Accutane) during the past six (6) months 
15. Use of topical retinoid therapy in the intended treatment area during the past two (2) 
weeks 
16. Use of oral corticosteroid therapy during the past four (4) weeks  

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17. Prior skin resurfacing treatment, such as surgery, light, laser or radiofrequency (RF) 
procedures in the intended treatment area during the past six (6) months 
18. Prior injectable dermal fillers in the intended treatment areas within the past twelve 
(12) months 
19. Prior injectable toxins (Botox) in the treated areas within the past three (3) months 
20. Subjects who in the opinion of the Investigator are unwilling or unable to adhere to 
the study requirements, or who are otherwise not a good candidate for the study 
Institutional Review Board (IRB) 
This study will begin enrollment of subjects at each investigational site only after receiving 
written approval from the appropriate Institutional Review Board (IRB) or other regulatory 
authorities deemed necessary depending on specific country or local requirements.   
Study Visits 
Subject Enrollment 
Once a qualifying subject is enrolled into the study, their visits will be scheduled as 
illustrated in the Study Flow Chart (Figure 1) and study activities as described below.   
 
Screening and Baseline Visits 
Subjects will be evaluated against the inclusion and exclusion criteria at the Screening Visit 
for eligibility to participate in the study. 
 
Eligible subject will be scheduled for a baseline visit during which they will be asked to read 
and sign the Informed Consent Form, receive a unique study identification number, and 
receive their baseline photography.  The baseline visit may occur on the same visit as 
screening. 
 
Enrolled subjects may also receive the study test spots during the same combined 
screening and baseline visit.  The total duration of a combined screening and baseline visit 
with test spots is typically 60 to 90 minutes.   
 
Clinical photography will be taken of treated areas at baseline and all treatment and follow-
up visits using a non-contact digital camera.  Flash photography is not typically required.  
As the treatment areas may be directly on or near the face, photography may contain 
identifying features.   However, efforts will be made to de-identify images if used for 
scientific/research or promotional purposes. 
 
All subjects must agree to have photography performed and released for research 
purposes since the photographs are used to assess the primary endpoint of the study.  
Additionally, subjects will be asked if their photographs can be released for commercial 
marketing purposes. 
Subject Enrollment 
Once a qualifying subject is enrolled into the study, their visits will be scheduled as 
illustrated in the Subject Intake Flow Chart (Figure 1) and study activities as described 
below.   
Test Spot and Skin Resurfacing Treatment Procedures 

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Prior to receiving skin resurfacing treatments subjects will receive up to four (4) test spots 
at the Test Spot Visit.  The Investigator or study staff will deliver FRAX 1940 laser energy in 
or near the intended treatment area(s) as test spots to evaluate the reaction of the skin.  
This helps the Investigator or study staff determine that the laser is set to a safe setting, or 
whether more or less energy should be used to achieve clinical endpoint, typically slight 
edema or erythema.   
Each test spot area size will typically not exceed approximately 2 inches X 2 inches (50 mm 
X 50 mm) and will be treated beginning with low energy and low coverage settings.  One or 
both of these settings may be increased as needed in order to achieve a desired clinical 
endpoint. 
 
Before receiving test spots or skin resurfacing treatment, the areas of the skin intended to 
be exposed to the laser energy may need to be shaved to avoid any influence of hairs 
absorbing the treatment laser energy. 
 
Some subjects may be offered anesthesia to minimize discomfort during treatment in the 
form of a topical cream containing lidocaine/prilocaine (EMLA), 
benzocaine/lidocaine/tetracaine (BLT), or similar product that would be applied 30 to 60 
minutes in advance and removed before laser treatment.    
 
Both the NORDLYS and Ydun base systems incorporate a design feature to blow cool air 
on the skin during treatment to increase patient comfort that subjects may choose to use 
this during their treatments.  Subjects may also choose the use of no anesthesia. 
Subjects and clinical staff will always be required to wear safety eyewear during study 
treatment to protect the structures of the eye from possible injury due to the laser beam 
energy.   
Test spots and skin resurfacing treatments will be administered in accordance with general 
guidelines and parameters provided by the manufacturer for the FRAX 1940 handpiece.  
Specific laser parameters will be determined by the Investigator through the skin response 
and healing response of test spots. 
The test spots and skin resurfacing treatments will be performed by passing the handpiece 
of the FRAX 1940 laser along the skin using a rolling mechanism in the handpiece which 
activates the fractional laser pulses.   Exact treatment parameters are also guided by 
factors such as Fitzpatrick Skin Type (FST), location on the body, or other factors. 
Subjects with presence of benign pigmented lesions off the face may also receive 
treatment on the hands, arms, chest, back, or legs.  Off-face treatment areas will be limited 
in size per the Investigator or study staff decision depending on factors including but not 
limited to practical treatment times, amount of topical anesthetic required, expected 
duration of anesthesia effect. 
 
If an appropriate clinical response is seen from the test spots at 14 ± 7 days after test spots 
(Follow-Up #2), then subjects will be scheduled to receive up to three (3) skin resurfacing 
treatments.  All subjects will receive resurfacing treatment performed on the face. 
 

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Additionally, subjects with presence of  pigmented lesions of at least moderate severity off 
the face on the hands, arms, back, chest, or legs may also receive up to three (3) 
treatments in these areas. 
 
The skin resurfacing treatment(s) may occur during the same visit as the test spot Follow-
Up #2 visit if appropriate skin responses and healing are observed by the Investigator or 
study staff.  If further observation of the test spot healing is deemed necessary, the subject 
may be scheduled for a subsequent follow-up visit after another 14 ± 7 days for re-
evaluation (a total of 28 ± 7 days after initial test spots).   Subjects who are still not 
exhibiting good candidacy for full face treatment at this subsequent visit will be exited from 
the study. 
Facial skin resurfacing treatment will be avoided very close to the eyes, or directly on the 
lips.  Total treatment times will be noted on the appropriate CRF. 
Following each test spot and each skin resurfacing treatment, the study subjects will be 
asked to rate the amount of pain they may have experienced during their test spots or 
treatment on an 11-point pain scale (0=No Pain to 10=Extreme Pain) which will be 
recorded on the appropriate case report form (CRF) by the Investigator or study staff.  A 
sample of the Subject Reported Numerical Pain Scale to be used is provided in Appendix 
A. 
Following all test spots and each treatment, the treated area will be examined and 
photographed, and immediate skin responses (Adverse Events) will be recorded on the 
appropriate CRF. 
 
Appropriate post-treatment care instructions will be provided as deemed appropriate by the 
Investigator or study staff.   
 
Suggested treatment parameter ranges are provided in Table 4. 
 
 
Table 4:  Suggested Treatment Parameters FRAX 1940 Handpiece 
 
Treatment Area 
 Minimum Energy 
Maximum Energy 
Line Width 
Coverage 
Test Spots 
xxxxxxx  
xxxxxxx  
xxxxxxx  
xxxxxxx  
Facial Skin Resurfacing/ 
Off Face Pigmented Lesions 
xxxxxxx  
xxxxxxx  
xxxxxxx  
xxxxxxx  
 
 
Follow-up Visits: Test Spot  
  
Subjects will be scheduled to return for a follow-up visit 4 ± 2 days (Follow Up #1) after 
receiving their test spots in order to evaluate the skin response and have photography 
performed of the test spot areas.  It is anticipated that test spot areas will exhibit the 
formation of MENDs at this visit. 
 

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Subjects will also be scheduled to return for a follow-up visit 14 ± 7 days (Follow Up #2) 
after receiving their test spots in order to evaluate the skin response and have photography 
performed of the test spot areas.  It is anticipated that any MENDs observed at the prior 
visit will have begun to show resolution or disappearance at this visit, indicating healing and 
resurfacing of the skin.  If an appropriate clinical response is seen from the test spots at this 
visit, then subjects may proceed to receive up to three (3) skin resurfacing treatments on 
the face. 
 
Subjects not showing adequate healing or adverse events at Follow Up #2 may be 
scheduled to return for a subsequent follow-up visit after an additional 14 ± 7 days (a total 
of 28 ± 7 days after initial test spots).  After again evaluating the skin response and having 
photography performed of the test spot areas, the Investigator or study staff at this time 
point may decide that a subject exit the study. 
     
Follow-up Visits: Treatments  
 
Subjects will be scheduled to return for a follow-up visit 7 ± 3 days after each skin 
resurfacing treatment in order to evaluate the skin response and perform photography of 
the treated area(s).  
 
Treated areas will also be evaluated just before receiving Treatment #2 and Treatment #3. 
 
Follow-up visit will be scheduled approximately 4 ± 1 weeks (1 month) and 12 ± 1 weeks (3 
months) after the final treatment, typically Treatment #3.  NOTE: Fewer than three 
treatments may be administered at the discretion of the Investigator or study staff due to 
adverse events or complete clearance of the pigmented lesion(s). 
Study Endpoints 
 
Primary Effectiveness Endpoint 
The primary efficacy endpoint for the skin resurfacing treatment will be based on the 
formation of MENDs and the skin’s healing response as measured in days.   
 
Following test spots digital photography and clinical evaluation will be performed at a 
minimum approximately 4 and 14 days after test spots (Test Spot Follow-up Visits #1 and 
#2). 
 
Following skin resurfacing treatments digital photography and clinical evaluation will be 
performed at a minimum approximately 7 days after treatment, and just prior to any 
subsequent treatment which occurs at an approximate 4 week interval.   
 
Primary Safety Endpoint 
The primary safety endpoint will be an analysis of the incidence and severity of the reported 
Adverse Events. 
 
 
 

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Secondary Effectiveness Endpoints 
 
1. Subject reported pain during treatment as scored on an 11-point scale (0=None, 10= 
Extreme) will be recorded after Test Spots and each Treatment . (Appendix A) 
2. Subject assessment of improvement using a 5-point Global Aesthetic Improvement Scale 
(GAIS) at each follow-up visit. (Appendix B) 
3. Subject satisfaction with treatment results will be characterized using a 5-point scale (1 = 
Not Satisfied to 5 = Very Satisfied) at each follow-up period.  (Appendix C) 
4. Improvement in the clearance of  pigmented lesions (if treated) as determined by three (3) 
blinded evaluators comparing photographs taken at Baseline and Final Follow-Up using a 
validated 5-Point Pigment Improvement Score:  0 = 0% No Improvement) to 4 = 75 - 100% 
(Excellent Response). 10 (Appendix D) 
 
Study Data Analysis Methods and Statistical Analysis Plan 
Safety will be evaluated on the Intent to Treat (ITT) population, defined as all subjects 
enrolled, and will include a summary of the incidence, severity, and resolution of all 
reported adverse events. Clinical assessments will be performed at each treatment and 
follow-up visit. 
 
Safety data analyses will be performed using Microsoft Office Excel (Microsoft, Redmond, 
WA) or similar statistical software. 
 
Risks and Benefits 
Potential Risks 
The study treatments to be administered in this trial carry risks of skin reactions that are 
anticipated or in some cases desired endpoints.  These skin responses are typically trace 
to mild in severity, and transient in nature, resolving within a few days to a few weeks after 
treatment, and localized to the treated area(s).  Examples include edema, erythema, 
blanching, sloughing, and bronzing (transient darkening).   
 
An additional special type anticipated local skin response unique to nonablative fractional 
laser treatment is the formation of micro epidermal necrotic debris (MENDs) which appear 
as patterns of small brown dots on the skin surface about the size of the MTZ diameter.  
These are not only common but represent a desired clinical endpoint.  MENDs typically 
resolve within 7 to 14 days after laser exposure3 though in some cases may last a few 
weeks. 
 
Examples of less common but potentially more severe or lingering adverse events may 
include blistering, burning, scarring, herpes simplex virus (HSV) activation, acne eruptions, 
telangiectasia formation, or pigmentary changes such as hypopigmentation or post-
inflammatory hyperpigmentation (PIH) that persist beyond one month. 
 

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There is a risk of eye injury associated with the use of the FRAX1940 laser.  This risk will 
be eliminated by the subject wearing the appropriate protective eyewear during laser 
treatment.   
 
Potential Benefits 
There is no guarantee of a positive clinical result or any other benefit by participating in this 
study.  No significant clinical benefit is expected from receiving test spots.  However, 
subjects treated for skin resurfacing may experience improvement in the appearance of fine 
lines, wrinkles, or general tone, texture or appearance of the skin; or clearance of  
pigmented lesions (if included).   
Adverse Events 
To evaluate safety of the FRAX1940 laser treatments, all adverse events, whether 
expected or less common, will be recorded and scored (see Tables 4 and 5) throughout the 
duration of the study.  Skin assessments will be performed at baseline, immediately before 
and after each treatment, and at each follow‐up visit.  All Adverse Events (AE) that occur in 
the study will be documented on the appropriate CRF.   
 
Anticipated adverse events as a result of laser treatment include: edema, erythema, 
blanching, MENDs, sloughing, and bronzing (transient darkening).  Less common adverse 
events include:  blistering, burning, scarring, herpes simplex virus (HSV) activation, acne 
eruptions, telangiectasia formation, or pigmentary changes such as hypopigmentation or 
post-inflammatory hyperpigmentation (PIH). 
 
All local skin responses and adverse events (AE) will be documented as required on the 
appropriate case report form.  The severity of AE will be scored using a numerical scale 
from 0 (none) to 4 (severe) as shown in Table 5.  The relatedness of AE to study treatment 
will be scored using the relatedness scale as shown in Table 6 from 0 (unrelated) to 3 
(related), including a choice of U (unable to determine if related).  
 
Any Unanticipated Adverse Device Effect (UADE) occurring during this study will be 
reported as soon as possible to the sponsor and IRB, but no later than 10 working days 
after the Investigator first learns of the event as outlined in 21 CFR part 812.150(a)(1). 
However, the Sponsor requests that all Investigators notify the sponsor within 48 hours of 
first learning of the event. UADE is defined as any serious adverse event affecting the 
health or safety, any life-threatening problem or death caused by, or associated with a 
device, if that effect, problem, or death was not previously identified in nature, severity, or 
degree of incidence in the application; or any other unanticipated serious problem 
associated with a device that relates to the rights, safety, or welfare of subjects. 
 
A serious adverse event (SAE) is any adverse event that: 
a) 
led to death, 
b) 
resulted in life-threatening illness or injury 
c) 
resulted in permanent impairment of a body structure or body function 
d) 
resulted in int hospitalization or prolongation of existing hospitalization, 
e) 
resulted in medical or surgical intervention to prevent permanent impairment to 
body structure or body function, or 
f) 
led to fetal distress, fetal death, congenital abnormality or birth defect 
 

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Table 5:  Severity Rating System for AE 
 
Numerical Score 
Severity 
0 
None 
1 
Trace 
2 
Mild 
3 
Moderate 
4 
Severe 
 
 
Table 6:  Relatedness Rating System for AE 
 
Numerical Score 
Relatedness to Treatment 
0 
Not Related 
1 
Possibly Related 
2 
Probably Related 
3 
Related 
U 
Unable to Determine if Related 
 
Investigational Sites 
Up to three (3) Investigational Sites may be included in this study after signed Clinical Trial 
Agreements are in place with the Sponsor, and IRB approval for the study has been 
received. 
 
Investigational sites for this study will be identified by the Sponsor and pre-qualified for 
participation prior to enrolling subjects in this study.  In-service training on all devices will be 
provided to delegated study personnel at each site prior to or at the time of study initiation. 
Study Monitoring  
It will be the responsibility of the Sponsor to develop and execute an adequate Monitoring 
Plan for this study.   Qualified personnel will be identified by the Sponsor to perform 
monitoring required visits.  It is anticipated that three (3) monitoring visits per site should be 
adequate to ensure site compliance for this study, though additional visits may be 
scheduled at the discretion of the Sponsor. 
Protocol Deviation Reporting 
Subjects enrolled without meeting inclusion/exclusion criteria, enrolled without providing 
informed consent and all other deviations from the protocol should be reported immediately 
to the Sponsor.  The Investigator, Study Monitor, or study staff are responsible for 
deviations to the Sponsor.  Each protocol deviation will be investigated by the Sponsor. 
Record Maintenance 
All completed case report forms including the Subject Satisfaction Questionnaire will be 
sent by the clinical site to the Sponsor throughout the duration of the study.   
The Investigator will retain a copy of all study records in accordance with applicable 
regulations for a period of two (2) years following completion or discontinuation of the 

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study.  It is the responsibility of the Investigator to retain study records in a secure location 
within the investigational site. 
Publication Policy 
Study Investigators agree not to publish the results from, or disclose confidential 
information related to, this study as described in the Clinical Trial Agreement without prior 
written agreement from the study Sponsor, Candela Corporation.  If the Sponsor agrees to 
publish the results from this study, the Investigators will provide the Sponsor publication 
manuscript(s) for review at least thirty (30) days before submission for publication.  
Investigators will also provide the Sponsor advance at least (30) days’ notice of any 
planned presentation of study results. 
 
 
 

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References 
1) Anderson RR, Parrish JA.  Selective photothermolysis:  Precise microsurgery by selective 
absorption of pulsed radiation.  Science 1983; 220(4596):524-527. 
2) Lupton JR, Williams CM, Alster TS.  Nonablative Laser Skin Resurfacing using a 1540 nm 
Erbium Glass Laser:  A Clinical and Histological Analysis.  Dermatol Surg 2002; 28:833-
835. 
3) Manstein D, Herron GC, Sink RK, et al. Fractional photothermolysis: a new concept for 
cutaneous remodeling using microscopic patterns of thermal injury. Lasers Surg Med 
2004; 34:426–38. 
4) Laubach HJ, Tannous Z, Anderson RR, Manstein D. Skin responses to fractional 
photothermolysis. Lasers Surg Med  2006; 38:142–9. 
5) Hantash BM, Mahmood MB. Fractional photothermolysis: a novel aesthetic laser surgery 
modality. Dermatol Surg. 2007 May;33(5):525-34. 
6) Hantash BM, Bedi VP, Sudireddy V, et al. Laser-induced transepidermal elimination of 
dermal content by fractional photothermolysis. J Biomed Opt 2006; 11:041115 
7) Geronemus RG. Fractional photothermolysis: current and future applications. Lasers Surg 
Med 2006; 38:169–76. 
8) Waibel J, Wulkan AJ, Lupo M, Beer K, Anderson RR.  Treatment of Burn Scars with the 
1550nm Nonablative Fractional Erbium Laser.  Lasers Surg Med 2012; 44:441-46. 
9) Raulin C, Greve B, Hammes S.  Cold Air in Laser Therapy:  First Experiences With a New 
Cooling System.  Lasers Surg Med 2000; 27:404-410. 
10) Chan CS, Saedi N, Mickle C, Dover JS.  Combined Treatment for Facial Rejuvenation 
Using an Optimized Pulsed Light Source Followed by a Fractional Non-Ablative Laser.  
Lasers Surg Med 2013; 45:405-409 
 
 
 
 
 
 

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Appendix A - Numerical Pain Rating Scale 
 
 
 
 
 

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Appendix B – Global Aesthetic Improvement Scale (GAIS) 
 
 
GAIS 
 
Rating 
Description 
❑ 1 
Very Much Improved  
Optimal cosmetic result in this subject 
❑ 2 
Much Improved  
Marked improvement in appearance form 
the initial condition, but not completely 
optimal for this subject 
❑ 3 
Improved  
Obvious improvement in appearance from 
initial condition, but a re-treatment is 
indicated 
❑ 4 
No Change  
The appearance is essentially the same as 
the original condition 
❑ 5 
Worse  
The appearance is worse than the original 
condition 
 
 
 

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Appendix C - Subject Satisfaction Questionnaire 
 
 
Score 
 
Rating 
❑ 1 
Not Satisfied  
❑ 2 
Little Satisfied  
❑ 3 
Somewhat Satisfied  
❑ 4 
Satisfied  
❑ 5 
Very Satisfied 
 
 
 

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Appendix D - Pigment Improvement Score 
 
 
Score 
Clearance 
Description 
 
❑ 0 
 
0% 
 
No Improvement 
❑ 1 
1% - 24% 
 
Trace to mild improvement of 
some lesions 
❑ 2 
25 - 49% 
 
Moderate Response: Some 
lesions lighter 
❑ 3 
50 - 74% 
 
Good response: Some lesions 
much lighter 
❑ 4 
75 - 100% 
Excellent response: Most or all 
lesions much lighter or gone