Open-label, Prospective, Multicenter Study to Evaluate the Cutera enLighten™ Laser and a Micro-Lens Array Handpiece Attachment for the Treatment of Moderate and Severe Acne Scars
Phase: NA
Conditions: Acne Scars - Mixed Atrophic and Hypertrophic
Sponsor: Cutera Inc.



Cutera, Inc. 
Protocol # C-17-ML02 
“Open-label, Prospective, Multicenter Study to Evaluate the Cutera enlighten™ Laser and a Micro-Lens Array Handpiece Attachment for the 
Treatment of Moderate and Severe Acne Scars” 
Confidential and Proprietary 
 Page 2 of 37                                                                      Version 1.0; 17JUL2017 
 
 
 
Protocol Signature Sheet – Principal Investigator 
 
 
PROTOCOL C-17-ML02 
 
 
Study Title:   Open-label, Prospective, Multicenter Study to Evaluate the Cutera enlighten™ Laser and a 
Micro-Lens Array Handpiece Attachment for the Treatment of Moderate and Severe Acne Scars  
 
Protocol Version 1.0, Date: 17JUL2017   
 
I have received and read the protocol dated July 17, 2017and agree to adhere to the requirements. I am 
aware that my adherence to the above protocol is mandatory and that any changes in the protocol or 
informed consent form must first be approved by Cutera, Inc. and the Institutional Review Board, except 
those changes necessary to eliminate apparent immediate hazards to subjects.  I will provide copies of this 
protocol and all pertinent information to the study personnel under my supervision. I will discuss this 
material with them and ensure they are fully informed regarding their role in the study. I will ensure that 
the study is conducted in compliance with the protocol, Good Clinical Practice (GCP), and all applicable 
regulatory requirements, and with the reviewing Institutional Review Board (IRB) requirements. I agree to 
commence this study only after documented IRB approval is obtained. 
 
 
 
 
Principal 
Investigator 
 
 
 
 
 
 
Signature 
 
Date 
 
 
 
 
 
 
 
 
 
Printed Name 
 
Date 
 
 
 
 
 
 
 

Cutera, Inc. 
Protocol # C-17-ML02 
“Open-label, Prospective, Multicenter Study to Evaluate the Cutera enlighten™ Laser and a Micro-Lens Array Handpiece Attachment for the 
Treatment of Moderate and Severe Acne Scars” 
Confidential and Proprietary 
 Page 3 of 37                                                                      Version 1.0; 17JUL2017 
TABLE OF CONTENTS 
Protocol Summary ..............................................................................................................................................................................................6 
1. PURPOSE ..........................................................................................................................................................................................................7 
2. BACKGROUND INFORMATION ....................................................................................................................................................................7 
3. STUDY DEVICE .................................................................................................................................................................................................8 
4. STUDY OBJECTIVES.........................................................................................................................................................................................9 
a. To evaluate the safety of the Cutera enlighten laser with a Micro-Lens Array handpiece attachment to achieve 
improvement of acne scars....................................................................................................................................................................9 
b. To evaluate the efficacy of the Cutera enlighten laser with a Micro-Lens Array handpiece attachment in the 
improvement of acne scars....................................................................................................................................................................9 
5. STUDY DESIGN.................................................................................................................................................................................................9 
5.1 Study Endpoints .................................................................................................................................................................................... 10 
5.1.1 
Primary Efficacy Endpoint ..................................................................................................................................................... 10 
5.1.2 
Secondary Efficacy Endpoints............................................................................................................................................... 10 
5.1.3 
Safety Endpoints ..................................................................................................................................................................... 10 
         5.1.4     Exploratory Analysis…………………………………………………………………………………………………………………………………………10 
5.2 Study Duration ...................................................................................................................................................................................... 10 
5.3 Study Effectiveness Assessments ....................................................................................................................................................... 10 
5.3.1 
Blinded Evaluators and Investigator’s Global Assessment of Improvement ............................................................... 10 
5.3.2 
Investigator Assessments...................................................................................................................................................... 11 
5.3.3 
Subject Satisfaction Assessment.......................................................................................................................................... 12 
5.4 Study Safety Assessments ................................................................................................................................................................... 12 
5.4.1 Incidence and Severity of Adverse Events: ............................................................................................................................ 12 
5.4.2 Treatment-related Discomfort ................................................................................................................................................. 13 
5.4.3 Phone Follow-up......................................................................................................................................................................... 13 
5.5 Photographs .......................................................................................................................................................................................... 13 
5.6 Study Discontinuation .......................................................................................................................................................................... 13 
5.7 Investigator Selection........................................................................................................................................................................... 13 
6. STUDY POPULATION ................................................................................................................................................................................... 13 
6.1 Study Subject Recruitment and Selection ......................................................................................................................................... 13 
6.1.1 Inclusion Criteria ......................................................................................................................................................................... 14 
6.1.2 Exclusion Criteria ........................................................................................................................................................................ 14 
6.2 Subject Numbering ............................................................................................................................................................................... 15 
6.3 Subject Discontinuation Criteria......................................................................................................................................................... 15 
7. STUDY PROCEDURES................................................................................................................................................................................... 16 
7.1 Screening / Enrollment ........................................................................................................................................................................ 16 
7.2 Laser Treatment 1 to 6 – Visit Window and Pre-Treatment Procedures .................................................................................... 16 
7.3 Laser Treatment Procedures............................................................................................................................................................... 17 
7.4 Phone and Follow-Up Visits ................................................................................................................................................................ 18 

Cutera, Inc. 
Protocol # C-17-ML02 
“Open-label, Prospective, Multicenter Study to Evaluate the Cutera enlighten™ Laser and a Micro-Lens Array Handpiece Attachment for the 
Treatment of Moderate and Severe Acne Scars” 
Confidential and Proprietary 
 Page 4 of 37                                                                      Version 1.0; 17JUL2017 
8. ADVERSE EVENTS and ADVERSE DEVICE EFFECTS ................................................................................................................................ 19 
8.1 Definitions .............................................................................................................................................................................................. 19 
8.1.1 
Adverse Event ......................................................................................................................................................................... 19 
8.1.2 
Serious Adverse Event ........................................................................................................................................................... 19 
 
8.1.2.1   Anticipated Serious Adverse Device Event (ASADE)……………………………………………………………………………………..19 
 
8.1.2.2   Unanticipated Serious Adverse Device Event (USADE)…………………………………………………………………………………19 
8.2 Recording AEs, ADEs and SADEs ........................................................................................................................................................ 22 
8.3 Follow-up of subjects after AEs/ADEs and SAEs/SADEs:................................................................................................................ 22 
9. POTENTIAL RISKS / BENIFITS..................................................................................................................................................................... 22 
9.1 Potential Risks ....................................................................................................................................................................................... 22 
9.2 Potential Benefits.................................................................................................................................................................................. 23 
10. RISK MANAGEMENT ................................................................................................................................................................................. 23 
11. DATA ANALYSIS PLAN .............................................................................................................................................................................. 24 
11.1 Sample Size .......................................................................................................................................................................................... 24 
11.2 Demographics and Subject Characteristics at Baseline ............................................................................................................... 24 
11.3 Statistical Analysis Methods............................................................................................................................................................. 24 
11.3.1 Analysis Sets .............................................................................................................................................................................. 24 
11.3.2 Efficacy Analyses ...................................................................................................................................................................... 24 
11.3.3 Analysis of Secondary Endpoints........................................................................................................................................... 24 
          11.3.4 Safety Analysis……………………………………………………………………………………………………………………………………................25 
12. SUBJECT PAYMENT ................................................................................................................................................................................... 25 
13. STUDY MANAGEMENT AND ADMINISTRATIVE PROCEDURES ........................................................................................................ 25 
13.1 Training and Monitoring ................................................................................................................................................................... 25 
13.2 Informed Consent ............................................................................................................................................................................... 25 
13.3 Protocol Compliance .......................................................................................................................................................................... 26 
13.4 Protocol Amendments................................................................................................................................................................ 26 
13.5 Protocol Deviations ..................................................................................................................................................................... 26 
13.6 Study Personnel .................................................................................................................................................................................. 26 
13.7 Disclosure of Financial Interest ........................................................................................................................................................ 26 
13.8 Data Collection, Record Keeping and Storage............................................................................................................................... 27 
14. SUBJECT CONFIDENTIALITY ..................................................................................................................................................................... 27 
15. PUBLICATION POLICY ............................................................................................................................................................................... 28 
Appendix 1: Study Schedule .......................................................................................................................................................................... 30 
Appendix 2: Pain Rating Scale ....................................................................................................................................................................... 31 
Appendix 3:  Follow-Up Subject Questionnaire (page 1 of 2)................................................................................................................. 32 
Appendix 3:  Follow-Up Subject Questionnaire (page 2 of 2)................................................................................................................. 33 

Cutera, Inc. 
Protocol # C-17-ML02 
“Open-label, Prospective, Multicenter Study to Evaluate the Cutera enlighten™ Laser and a Micro-Lens Array Handpiece Attachment for the 
Treatment of Moderate and Severe Acne Scars” 
Confidential and Proprietary 
 Page 5 of 37                                                                      Version 1.0; 17JUL2017 
Appendix 4:  Baseline Subject Questionnaire (page 1 of 1) .................................................................................................................... 34 
Appendix 5:  1 Week Follow-Up Questionnaire ........................................................................................................................................ 35 
Appendix 7:  Before and After Laser Treatment Instructions ................................................................................................................ 37 
 
 
 
 
 
 
 

Cutera, Inc. 
Protocol # C-17-ML02 
“Open-label, Prospective, Multicenter Study to Evaluate the Cutera enlighten™ Laser and a Micro-Lens Array Handpiece Attachment for the 
Treatment of Moderate and Severe Acne Scars” 
Confidential and Proprietary 
 Page 7 of 37                                                                      Version 1.0; 17JUL2017 
1. PURPOSE 
The purpose of this pivotal investigation is to evaluate the efficacy and safety of the Cutera enlighten 
multi-wavelength 532 nm and 1064 nm Nd:YAG picosecond pulse duration laser and an investigational 
micro-lens array (MLA) handpiece attachment for improvement of acne scars. 
2. BACKGROUND INFORMATION 
Affecting nearly 40 to 50 million people annually, acne is the most common skin condition in the United 
States.1 Acne lesions typically begin to appear in puberty and persist throughout adolescence. 
Approximately 85% of people between the ages of 12 and 24 have experienced acne.2 This wide spread 
skin condition predominantly affects teens and young adults, but can occur in older adults as well. 
Countless treatment modalities exist for acne sufferers, however even with effective treatment moderate 
and severe lesions can result in scarring. Post-acne scarring is estimated to occur in 95% of patients and is 
a common cosmetic concern for many patients.3 Furthermore, in some patient groups acne scarring is 
especially devastating and may be a risk factor for suicide.4 
 
Scar formation occurs as a result of damage to the layers and substructures of the skin. Following injury 
to the skin from the acne infection and more severe lesions, a multi-stage healing process begins, which 
includes inflammation, proliferation and maturation. Unsightly scars result from an abnormal healing 
process. While the exact cause of abnormal skin healing is unknown, it is thought that excessive collagen 
and fibrotic tissue forms and a lack of elastic fibers contributes to tough, stiff, nodular scar tissue.5-6 
Certain factors increase the likelihood of an abnormal skin healing process, such as patient age or 
racial/ethnic background, depth of injury and extent of infection.7-8  
 
Acne scars are atrophic scars, with subtypes classified based on scar appearance and skin depth. Ice pick 
scars are narrow in width at the surface (<2mm) and typically taper in width as the scar extends vertically 
deep into the dermis. Box car scars are round or oval indentations in the skin surface, with well-defined 
edges, that may be shallow or deep. Rolling scars are atrophic scars that occur as a result of abnormal 
fibrous anchoring of the dermis to the subcutis and create a rolling or rippling appearance of the skin 
surface.9 
 
Treatment modalities for acne scarring include ablative laser skin resurfacing, dermabrasion, chemical 
peels, or a combination of modalities.10 These traditional, highly effective treatment options are 
accompanied by undesirable side effects such as significant pain and post-procedure downtime. There is 
a demand for effective, noninvasive treatment methods for patients suffering from acne scars such as 
non-ablative laser and light-based therapy to devices that utilize radiofrequency waves.11-13 Treatment 
with non-ablative, non-invasive devices cause heat production and heat-induced wound healing within 
the dermis that over time causes a cascade of cellular events leading to new collagen production.14-15 
Dermal collagen remodeling leads to an improved texture and appearance of the skin, which should also 
improve the appearance of facial acne scars.  
 
Histology of fractionated laser delivery has demonstrated the formation of vacuoles, or areas of laser 
induced optical breakdown (LIOB).16 LIOB occurs when the intensity of the pulse is sufficiently high to 
generate plasma.  Plasma is caused by electrons being stripped from the target material.  The resulting 
electrons continue to absorb the laser heat, creating a vapor plume which forms a cavitation bubble that 
is observed as an LIOB in histological preparations.   

Cutera, Inc. 
Protocol # C-17-ML02 
“Open-label, Prospective, Multicenter Study to Evaluate the Cutera enlighten™ Laser and a Micro-Lens Array Handpiece Attachment for the 
Treatment of Moderate and Severe Acne Scars” 
Confidential and Proprietary 
 Page 11 of 37                                                                      Version 1.0; 17JUL2017 
• Rate the degree of improvement observed from baseline using the Acne Scar Assessment Scale (ASAS) 
 
5.3.2 
Investigator Assessments 
 
At baseline,
, the Investigator will assess the efficacy of the Cutera 
enlighten laser with the MLA handpiece attachment treatment using the ASAS, GAIS, and Skin Quality 
Rating Scale.  Baseline photos of subjects may be used while assessing the ASAS, GAIS, and Skin Quality 
Rating Scale.  
 
 
 
 
 
 
 
 
 
 
 
 

Cutera, Inc. 
Protocol # C-17-ML02 
“Open-label, Prospective, Multicenter Study to Evaluate the Cutera enlighten™ Laser and a Micro-Lens Array Handpiece Attachment for the 
Treatment of Moderate and Severe Acne Scars” 
Confidential and Proprietary 
 Page 14 of 37                                                                      Version 1.0; 17JUL2017 
 
Each subject will be evaluated by the Investigator to assess his/her suitability for entry into the study 
according to the following inclusion and exclusion criteria.  
6.1.1 Inclusion Criteria 
To be included in the study, subjects must meet all of the following Inclusion Criteria: 
 
1.  
Subject must be able to read, understand and sign the Informed Consent Form. 
2.  
Female or Male, 18 to 65 years of age (inclusive). 
3.  
Fitzpatrick Skin Type I – VI (Appendix 6). 
4.  
Subject desires treatment for acne scars and wishes to undergo laser treatments for 
improvement. 
5.  
Subject has bilateral moderate to severe signs of facial acne scarring. 
6.  
Must be willing to have Cutera enlighten laser with the Micro-Lens Array handpiece 
attachment treatments and able to adhere to the treatments, follow-up visit schedule, 
and post-treatment care instructions. 
7.  
Willing to have very limited sun exposure and use sunscreen on the treatment area 
every day for the duration of the study, including the follow-up period. 
8.  
Willing to have digital photographs taken of the treatment area and agree to use of 
photographs for presentation (educational and/or marketing), publications, and any 
additional marketing purposes. 
9.  
Agree to not undergo any other procedure(s) or treatment(s) for acne scars during the 
study and has no intention of having such procedures performed during the course of 
the study. 
10.  
For female subjects: not pregnant or lactating and is either post-menopausal, surgically 
sterilized, or using a medically acceptable form of birth control at least 3 months prior to 
enrollment and during the entire course of the study.,  
6.1.2 Exclusion Criteria 
Subjects will be excluded from the study if they meet any of the following Exclusion Criteria: 
 
1. 
 
Participation in a clinical trial of another drug, or device administered to the 
treatment area, within 6 months prior to enrollment or during the study. 
2. 
Any type of prior cosmetic treatment to the target area within 6 months of study 
participation, such as laser  procedures, facial fillers, i.e. (Bellafill) and those used for 
general aesthetic correction, facial peel, lightening creams, or facial surgery. 
3. 
Use of prescription topicals in the treatment area within one month prior to 
treatment or use of topical agents one week prior to treatment that may cause facial 
sensitivity. 
4. 
Suffering from significant skin conditions in the treated areas or inflammatory skin 
conditions, including but not limited to, open lacerations or abrasions, hidradenitis, 
rash, infection , or dermatitis of the treatment area prior to treatment (duration of 
resolution as per the Investigator’s discretion). 
5. 
Pregnant and/or breastfeeding, or planning to become pregnant. 

Cutera, Inc. 
Protocol # C-17-ML02 
“Open-label, Prospective, Multicenter Study to Evaluate the Cutera enlighten™ Laser and a Micro-Lens Array Handpiece Attachment for the 
Treatment of Moderate and Severe Acne Scars” 
Confidential and Proprietary 
 Page 15 of 37                                                                      Version 1.0; 17JUL2017 
6. 
Significant concurrent illness, such as diabetes mellitus, immunosuppression/immune 
deficiency disorders (including HIV infection or AIDS) or using immunosuppressive 
medication. 
7. 
Hypersensitivity to light exposure.  
8. 
Any use of medication that is known to increase sensitivity to light according to the 
Investigator’s discretion. 
9. 
History of keloid scarring, hypertrophic scarring or abnormal wound healing or prone 
to bruising.  
10. 
Has a history of squamous cell carcinoma or melanoma in the treatment area. 
11. 
History of epidermal or dermal disorders (particularly if involving collagen or 
microvascularity), including collagen vascular disease or vasculitic disorders. 
12. 
A history or active skin condition that in the opinion of the Investigator may 
interfere/confound with the treatment.  
13. 
History of connective tissue disease, such as systemic lupus erythematosus or 
scleroderma.  
14. 
History of disease stimulated by heat, such as recurrent herpes simplex and/or herpes 
zoster (shingles) in the treatment area, unless treatment is conducted following a 
prophylactic regimen. 
15. 
History of pigmentary disorders, particularly tendency for hyper- or hypo-
pigmentation, or any that are considered not acceptable by the study investigator. 
16. 
Has used oral isotretinoin (Accutane or therapeutic vitamin A supplements of ≥ 
10,000 units per day) within 12 months of initial treatment or plans on using during 
the course of the study (note: skin must regain its normal degree of moisture prior to 
treatment, e.g. lack of noticeable skin flaking and peeling).  
17. 
Excessively tanned or active sun tan in facial area to be treated, or unable/unlikely to 
refrain from tanning during the study.  
19.  
Excessive facial hair in the area to be treated (beards, sideburns, and/or moustache,) 
that would interfere with diagnosis, assessment, and treatment. 
20. 
As per the Investigator’s discretion, any physical or mental condition which might make 
it unsafe for the subject to participate in this study, including excessive alcohol or drug 
abuses, or a condition that would compromise the subject’s ability to comply with the 
study requirements. 
6.2 Subject Numbering  
If a subject completes the Informed Consent Form, meets the study eligibility criteria and is willing to 
participate, the subject will be assigned a study subject identification number. This number is comprised 
of a site number (which is provided by the sponsor) and a sequential subject number and the subject 
initials (first and last names). 
6.3 Subject Discontinuation Criteria 
If possible, every subject should remain in the study until completion of the required follow-up period. 
However, participation in this study is completely voluntary and a subject can choose to withdraw from 
the study at any time.  Decision to withdraw will not affect or prejudice the subject’s continued medical 
care in any way. In those instances, the investigator will attempt to obtain a final clinical assessment and 
an adverse device effect evaluation for the subject prior to this withdrawal. A subject will be considered 

Cutera, Inc. 
Protocol # C-17-ML02 
“Open-label, Prospective, Multicenter Study to Evaluate the Cutera enlighten™ Laser and a Micro-Lens Array Handpiece Attachment for the 
Treatment of Moderate and Severe Acne Scars” 
Confidential and Proprietary 
 Page 30 of 37                                                                      Version 1.0; 17JUL2017 
 
 

Cutera, Inc. 
Protocol # C-17-ML02 
“Open-label, Prospective, Multicenter Study to Evaluate the Cutera enlighten™ Laser and a Micro-Lens Array Handpiece Attachment for the 
Treatment of Moderate and Severe Acne Scars” 
Confidential and Proprietary 
 Page 31 of 37                                                                      Version 1.0; 17JUL2017 
 
 
 
 
 
 
 
 
 
 

Cutera, Inc. 
Protocol # C-17-ML02 
“Open-label, Prospective, Multicenter Study to Evaluate the Cutera enlighten™ Laser and a Micro-Lens Array Handpiece Attachment for the 
Treatment of Moderate and Severe Acne Scars” 
Confidential and Proprietary 
 Page 32 of 37                                                                      Version 1.0; 17JUL2017 
 
 
 
 

Cutera, Inc. 
Protocol # C-17-ML02 
“Open-label, Prospective, Multicenter Study to Evaluate the Cutera enlighten™ Laser and a Micro-Lens Array Handpiece Attachment for the 
Treatment of Moderate and Severe Acne Scars” 
Confidential and Proprietary 
 Page 33 of 37                                                                      Version 1.0; 17JUL2017 

Cutera, Inc. 
Protocol # C-17-ML02 
“Open-label, Prospective, Multicenter Study to Evaluate the Cutera enlighten™ Laser and a Micro-Lens Array Handpiece Attachment for the 
Treatment of Moderate and Severe Acne Scars” 
Confidential and Proprietary 
 Page 34 of 37                                                                      Version 1.0; 17JUL2017 
 
 
 
 

Cutera, Inc. 
Protocol # C-17-ML02 
“Open-label, Prospective, Multicenter Study to Evaluate the Cutera enlighten™ Laser and a Micro-Lens Array Handpiece Attachment for the 
Treatment of Moderate and Severe Acne Scars” 
Confidential and Proprietary 
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