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

FRX19005 Revision Date 18 Oct 2019 
Page 1 of 24 
 
 
 
 
Protocol Title: 
Clinical Evaluation of a Nonablative Fractional 1940 nm Diode 
Laser for Treatment of Pigmented Lesions 
 
Protocol Number: 
FRX19005 
 
NCT: 
 
 
NCT04202419 
 
Revision Date: 
 
18 October 2019 
 
Sponsor:  
 
Candela Corporation 
 
 
 
 
 
530 Boston Post Road 
 
 
 
 
Wayland, MA  01778 
and 
251 Locke Dr 
Marlborough, MA 01752 
 
 
 
 
Phone: 508-358-7400 or 800-733-8550 
 
 
Study Contact:   
Nguyet T. Labenski 
Clinical Research Manager 
Candela Corporation 
Phone: +1.508.916.2829 
Email: nguyetl@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. 
 

FRX19005 Revision Date 18 Oct 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 
7. 
Compliance ............................................................................................................... 8 
8. 
Materials and Equipment ........................................................................................... 8 
9. 
Regulatory Status .................................................................................................... 10 
10. 
Non-Significant Risk Determination ......................................................................... 11 
11. 
Institutional Review Board (IRB) .............................................................................. 11 
12. 
Study Visits ............................................................................................................. 11 
13. 
Study Endpoints ...................................................................................................... 16 
14. 
Study Data Analysis Methods .................................................................................. 16 
15. 
Risks and Benefits ................................................................................................... 16 
16. 
Adverse Events ....................................................................................................... 17 
17. 
Investigational Sites ................................................................................................ 18 
18. 
Study Monitoring ..................................................................................................... 18 
19. 
Protocol Deviation Reporting ................................................................................... 19 
20. 
Record Maintenance ............................................................................................... 19 
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 
 
 
 

FRX19005 Revision Date 18 Oct 2019 
Page 3 of 24 
 
Study Synopsis 
 
 
Protocol Number FRX19005 
Protocol Title Clinical Evaluation of a Nonablative Fractional 1940nm Diode Laser 
for Treatment of Pigmented Lesions 
Short Title FRAX 1940 Pigment 
Device Description 
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 
Primary Objective Evaluate the safety and efficacy of the FRAX 1940 nm fractional 
diode laser handpiece for treatment of pigmented lesions such as, but 
not limited to lentigos (age spots), solar lentigos (sunspots) and 
ephelides (freckles) 
Study Population Up to 60 enrolled subjects  
Investigative Sites Up to five 5) investigational sites 
Study Treatment Areas Face, hands, arms, back, chest or legs 
Study Treatment Visits • 
One (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 (Phase II may begin, pending 
subject’s skin response) 
• 
28 ± 7 days after test spots (if required) 
 
Phase II – Following Treatments 
• 
7 ± 3 days after each treatment 
• 
Optional interim visits if required to assess adverse events 
• 
1 months (4 ± 1 week) after final treatment 
• 
3 months (12 ± 1 weeks) after final treatment 
• 
Additional visits beyond 12 weeks if required to assess adverse 
events 
Measurement 
Instruments 
• 
Pigment Improvement Score  
• 
Subject Numerical Pain Scale 
• 
Global Assessment Improvement Scale (GAIS) 
• 
Subject Satisfaction Questionnaire  
Primary Efficacy 
Endpoint 
Blinded assessment of improvement in clearance of pigmented 
lesions such as, but not limited to lentigos (age spots), solar lentigos 
(sunspots) and ephelides (freckles) 
Secondary Efficacy 
Endpoint 
• 
Blinded assessment of textural improvement using a 5-point 
Global Aesthetic Improvement Scale (GAIS)  
• 
Subject assessment of improvement using a 5-point Global 
Aesthetic Improvement Scale (GAIS)  
• 
Subject satisfaction with treatment results will be characterized 
using a 5-point scale 
Primary Safety 
Endpoint Incidence, severity and relatedness of adverse events 

FRX19005 Revision Date 18 Oct 2019 
Page 4 of 24 
 
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 
 
 
 

FRX19005 Revision Date 18 Oct 2019 
Page 5 of 24 
 
Objective 
This study is intended to evaluate the efficacy and safety of a 1940 nm diode fractional 
laser handpiece for treatment of pigmented lesions such as, but not limited to lentigos (age 
spots), solar lentigos (sunspots) 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 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 (NAF) 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 treatment of pigmented lesions.  
Secondarily, textural improvement of the treated area (s) will be assessed.  
Up to 60 enrolled subjects who agree to have treatment of pigmented lesions will be 
enrolled at up to five 5) 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 the face, hands, arms, back, chest 
or legs using the FRAX 1940 laser to help the Investigator or study staff determine 
appropriate treatment settings for each individual subject.  The test spots are performed to 
check for safety of the parameter settings.  Each test spot area will 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 (Follow-Up Visit #1) and 14 ± 7 
days (Follow-Up Visit #2) after the test spots.  Based on the observed skin responses and 
healing seen at Follow-Up Visit #2, the Investigator or study staff will determine if a subject 
is an appropriate candidate to proceed with the full treatment of the pigmented lesions.  
The full treatment will be performed immediately following Follow-Up Visit #2 or will be 
scheduled at a future time point during a 14 to 21-day period following the test spots.   
 
 

FRX19005 Revision Date 18 Oct 2019 
Page 6 of 24 
 
If it is determined by the Investigator or study staff at the 14 ± 7 day visit following test 
spots that the skin response seen exhibits adverse events such that full treatment 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 Treatment #1, subjects will be scheduled for a follow-up visit 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 to monitor the 
treated area(s), and possibly 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 (usually after Treatment #3). 
 
A final follow-up visit will be scheduled approximately 12 ± 1 weeks (3 months) after the 
final treatment (usually after Treatment #3).  
 
Note: Subjects may undergo fewer than three treatments, as decided by the Investigator or 
study staff. 
 
 

FRX19005 Revision Date 18 Oct 2019 
Page 7 of 24 
1. 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 VI 
4. Willingness to have test spots and up to three (3) treatments for pigmented lesions 
on or off the face which are rated at baseline as moderate or higher per Investigator 
or study staff  
5. Provide signed informed consent to participate in the study 
6. Adhere to study treatment and follow-up schedules 
7. Willing to have hair removed from the intended treatment area prior to treatment 
and/or photography 
8. 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 
9. Adhere to post-treatment care instructions   
10. 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 
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 disorder 
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  
17. Prior treatment, such as surgery, light, laser or radiofrequency (RF) procedures in 
the intended treatment area during the past three (3) months 
18. Prior injectable dermal fillers (e.g. collagen, hyaluronic acid) in the intended 
treatment area within the past 12 months 

FRX19005 Revision Date 18 Oct 2019 
Page 8 of 24 
19. Prior injectable toxins (e.g. Botox) in the intended treatment area 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 
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 xxxxxxxx xxxxxxxx xxxxxxxx xxxxxxxx xxxxxxxx 
xxxxxxxx xxxxxxxx xxxxxxxx xxxxxxxx xxxxxxxx xxxxxxxx xxxxxxxx xxxxxxxx xxxxxxxx 
xxxxxxxx xxxxxxxx xxxxxxxx xxxxxxxx xxxxxxxx xxxxxxxx xxxxxxxx x 
 
xxxxxxxx xxxxxxxx xxxxxxxx xxxxxxxx xxxxxxxx xxxxxxxx xxxxxxxx xxxxxxxx xxxxxxxx 
xxxxxxxx xxxxxxxx xxxxxxxx xxxxxxxx xxxxxxxx 
 
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. 
 
 
 

FRX19005 Revision Date 18 Oct 2019 
Page 9 of 24 
 
Figure 2:  NORDLYS and Ydun Base Systems (left) and FRAX 1940 Handpiece (right) 
 
 
   
                   
  
 
Figure 3:  Fractional Beam Patterns Selectable from xxxxxxxx micro thermal zones (MTZ) per line 
 
  
[redacted due to confidential information] 
 
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. 
 
Table 2:  Technical Specifications – FRAX 1940 Handpiece 
Parameter 
Specifications 
Wavelength (nm) 
xxxxxxxx  
Energy per MTZ (mJ) 
xxxxxxxx  
MTZ Diameter (microns) 
xxxxxxxx  
Scan Width 
xxxxxxxx  
MTZ per scan line 
xxxxxxxx  
Pulse Duration (ms) 
xxxxxxxx  
Pulse Repetition Rate (Hz) 
xxxxxxxx  
Aiming Beam 
xxxxxxxx  
Treatment Cooling8 
xxxxxxxx  
Delivery System 
xxxxxxxx  
 
[redacted due to confidential information] 

FRX19005 Revision Date 18 Oct 2019 
Page 10 of 24 
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: 
 
• 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 (eg 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): 
CAUTION – Investigational Device. 
Limited by Federal (or United States) law to 
i
ti
ti
l

FRX19005 Revision Date 18 Oct 2019 
Page 11 of 24 
• 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: 
o Matrixectomy 
o Periungal and subungal warts 
o 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 
d) Otherwise, use of the device does not present a potential for serious risk to the 
health, safety, or welfare of a subject. 
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 
 A Study Visit Schedule of Events is provided in Table 1.   
 

FRX19005 Revision Date 18 Oct 2019 
Page 12 of 24 
 
 
Table 1:  Study Visit Schedule of Events 
 
Phase I 
Phase II 
Activity 
Screening 
Baseline/ 
Test 
Spots* 
Follow Up 
Visit #1 
Follow Up 
Visit #2 
Treatment 
#1** 
Follow Up 
Visits  
Treatments 
#2 & #3 
Follow Up 
Visits*** 
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 
 
1 Month  
(4 ± 1 Weeks) 
and 
3 months  
(12 ± 1 Weeks) 
after 
final Treatment  
 
Eligibility Criteria 
X 
 
 
 
 
 
 
 
Informed Consent 
X 
 
 
 
 
 
 
 
Assign Study ID, 
Identify Treatment 
Location 
 
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 to monitor resolution of adverse events 
 
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. 
 

FRX19005 Revision Date 18 Oct 2019 
Page 13 of 24 
 
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 approximately 60 to 90 minutes.   
 
Clinical photography will be taken of treatment areas at baseline before treatment, at all 
treatment and follow-up visits using a non-contact digital camera.  Flash photography is not 
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. 
 
Test Spot and Treatment Procedures 
Prior to receiving 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 not exceed approximately 5 cm X 5 cm 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 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 treatments will be performed in accordance with general guidelines and 
parameters provided by the manufacturer for the FRAX 1940 handpiece.  Specific laser 

FRX19005 Revision Date 18 Oct 2019 
Page 14 of 24 
parameters will be determined by the Investigator through the skin response and healing 
response of test spots. 
The test spots and 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. 
If an appropriate clinical response is seen at 14 ± 7 days after test spots (Follow-Up #2), 
then subjects will be scheduled to receive up to three (3) treatments of pigmented lesions 
on the hands, arms, back, chest, or legs.  Pigmented lesions will include, but not be limited 
to, lentigos (age spots), solar lentigos (sunspots) and ephelides (freckles). 
 
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. 
 
The 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 study treatment at this subsequent visit will be exited from the study. 
Treatment will be avoided in the periorbital region, or directly on the lips.  Total treatment 
times will be noted on the appropriate CRF. 
Following test spots and each 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 treatments, 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. 
 
 
 

FRX19005 Revision Date 18 Oct 2019 
Page 15 of 24 
 
Table 4:  Suggested Treatment Parameters FRAX 1940 Handpiece 
 
Treatment Area 
 Minimum 
Energy 
Maximum 
Energy 
Line Width 
Coverage 
Test Spots 
xxxxxxxx  
xxxxxxxx  
xxxxxxxx  
xxxxxxxx  
Pigmented Lesion 
Treatment 
xxxxxxxx  
xxxxxxxx  
xxxxxxxx  
xxxxxxxx  
 
 
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. 
 
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 of 
the skin and possibly clearance of the pigmented lesions treated.  If an appropriate clinical 
response is seen from the test spots at this visit, then subjects may proceed to receive up 
to three (3) treatments of their pigmented lesions. 
 
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: Pigmented Lesion Treatment  
 
Subjects will be scheduled to return for a follow-up visit 7 ± 3 days after each treatment in 
order to evaluate 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 visits will be scheduled approximately 4 ± 1 weeks (1 month) and 12 ± 1 weeks 
(3 months) after the final treatment.  Note:  Fewer than three treatments may be performed 
at the discretion of the Investigator or study staff due to adverse events or complete 
clearance of the pigmented lesion(s). 
 
 

FRX19005 Revision Date 18 Oct 2019 
Page 16 of 24 
 
Study Endpoints 
 
Primary Effectiveness Endpoint 
Improvement in the clearance of pigmented lesions as determined by three (3) blinded 
evaluators comparing photographs taken at Baseline and 1 Month Follow-Up (post final 
treatment) using a validated 5-Point Pigment Improvement Score:   
0 = 0% (No Improvement) to 4 = 75-100% (Excellent Response).10 (Appendix D) 
 
Primary Safety Endpoint 
The primary safety endpoint will be an analysis of the incidence and severity of the reported 
Adverse Events. 
 
Secondary Effectiveness Endpoints 
1. Blinded assessment of textural improvement using a 5-point Global Aesthetic 
Improvement Scale (GAIS) (1 = Very Much Improved, 5 = Worse) at the 1 month and 3-
month follow-up visit (Appendix B). 
2. Subject assessment of improvement using a 5-point Global Aesthetic Improvement 
Scale (GAIS) (1 = Very Much Improved, 5 = Worse) at the 1 month and 3-month follow-
up visit (Appendix B). 
3. Subject satisfaction with treatment results will be characterized using a 5-point scale  
(1 = Not Satisfied, 5 = Very Satisfied) at the 1 month and 3-month follow-up visit 
(Appendix C).   
 
Subject reported pain during treatment as scored on an 11-point scale (0=None, 10=  
Extreme) will be recorded after Test Spots and after each Treatment. (Appendix A) 
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 type of anticipated local skin response unique to nonablative fractional laser 
treatment is the formation of micro epidermal necrotic debris (MENDs) which appear as 

FRX19005 Revision Date 18 Oct 2019 
Page 17 of 24 
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. 
 
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 may experience improvement in the appearance of pigmented lesions.   
 
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 5 and 6) 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 

FRX19005 Revision Date 18 Oct 2019 
Page 18 of 24 
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 
 
 
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 four to five (4-5) Investigational Sites may be included in this study after signed 
Clinical Trial Agreements are in place with the Sponsor, and IRB/EC 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 
required monitoring 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. 
 

FRX19005 Revision Date 18 Oct 2019 
Page 19 of 24 
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 
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. 
 
 

FRX19005 Revision Date 18 Oct 2019 
Page 20 of 24 
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. 
 
 
 
 
 

FRX19005 Revision Date 18 Oct 2019 
Page 21 of 24 
 
Appendix A - Numerical Pain Rating Scale 
 
 

FRX19005 Revision Date 18 Oct 2019 
Page 22 of 24 
 
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 
 
 
 

FRX19005 Revision Date 18 Oct 2019 
Page 23 of 24 
 
 
Appendix C - Subject Satisfaction Questionnaire 
 
 
Score 
 
Rating 
❑ 1 
Not Satisfied 
❑ 2 
Little Satisfied 
❑ 3 
Somewhat Satisfied 
❑ 4 
Satisfied 
❑ 5 
Very Satisfied 
 
 
 

FRX19005 Revision Date 18 Oct 2019 
Page 24 of 24 
 
 
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:  Most lesions 
much lighter 
 
 
❑ 4 
 
75 - 100% 
Excellent response:  Most or all 
lesions much lighter or gone