A Single-Center, Open-Label Pilot Study of a Novel Microlens Array Device for Skin Rejuvenation
Phase: NA
Conditions: Wrinkles, Scars
Sponsor: Cutera Inc.



Cutera, Inc. 
Protocol # C-16-ML01 
“A Single-Center, Open-Label Pilot Study of a Novel Microlens Array Device for Skin Rejuvenation” 
 
Confidential and Proprietary 
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Version 1.0, 16 Jun 2016 
Protocol Signature Sheet – Principal Investigator 
 
 
PROTOCOL C-16-ML01 
 
 
Study Title:   A Single-Center, Open-Label Pilot Study of a Novel Microlens Array Device for Skin 
Rejuvenation 
 
 
Protocol Version 1.0, June 16, 2016 
 
I have received and read the protocol dated June 16, 2016 and 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 
 
 
 
 
 
 
 
 
 

Cutera, Inc. 
Protocol # C-16-ML01 
“A Single-Center, Open-Label Pilot Study of a Novel Microlens Array Device for Skin Rejuvenation” 
 
Confidential and Proprietary 
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TABLE OF CONTENTS 
Protocol Summary 
5 
 
PURPOSE 
6 
 
BACKGROUND INFORMATION 
6 
2.1 
PHOTO-REJUVENATION 
6 
2.2 
STUDY DEVICE 
7 
2.3 
ONGOING CLINICAL STUDIES USING THE CUTERA PICOSECOND Q-SWITCHED ND:YAG 
8 
 
STUDY OBJECTIVES 
9 
 
STUDY DESIGN 
9 
4.1 
STUDY ENDPOINTS 
10 
4.1.1 
Efficacy Endpoints 
10 
4.1.2 
Safety Endpoints 
10 
4.2 
STUDY DURATION 
10 
4.3 
STUDY EFFECTIVENESS ASSESSMENTS 
10 
4.3.1 
Investigator Assessments 
10 
4.3.2 
Subject Assessments 
11 
4.3.3 
Exploratory Assessments 
11 
4.4 
Study Safety Assessments 
11 
4.4.1 
Incidence and Severity of Adverse Events: 
11 
4.4.2 
Treatment-related Discomfort 
11 
4.4.3 
Phone Follow-up 
11 
4.5 
PHOTOGRAPHS 
12 
4.6 
STUDY DISCONTINUATION 
12 
4.7 
INVESTIGATOR SELECTION 
12 
 
Study Population 
12 
5.1 
STUDY SUBJECT RECRUITMENT AND SELECTION 
12 
5.1.1 
Inclusion Criteria 
12 
5.1.2 
Exclusion Criteria 
13 
5.2 
SUBJECT NUMBERING 
14 
5.3 
SUBJECT DISCONTINUATION CRITERIA 
14 
 
Study Procedures 
14 
6.1 
SCREENING / ENROLLMENT 
14 
6.2 
LASER TREATMENT 1 TO 7 – VISIT WINDOW AND PRE-TREATMENT PROCEDURES 
15 
6.3 
LASER TREATMENT PROCEDURES 
15 
6.4 
FOLLOW-UP VISITS 
17 
6.5 
BIOPSY PROCEDURE (OPTIONAL) 
17 
 
ADVERSE DEVICE EFFECTS 
17 
7.1. DEFINITIONS 
17 
7.1.1 
Adverse Device Effect 
17 
7.1.2 
Serious Adverse Device Effect 
18 
7.2 
RECORDING ADES AND SADES 
20 
7.3 
FOLLOW-UP OF SUBJECTS AFTER ADES AND SADES: 
20 
 
Potential Risks / Benefits 
20 
8.1 
POTENTIAL RISKS 
20 
8.2 
POTENTIAL BENEFITS 
21 

Cutera, Inc. 
Protocol # C-16-ML01 
“A Single-Center, Open-Label Pilot Study of a Novel Microlens Array Device for Skin Rejuvenation” 
 
Confidential and Proprietary 
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Risk Management 
21 
 
DATA ANALYSIS PLAN 
22 
10.1 
SAMPLE SIZE 
22 
10.2 
DEMOGRAPHICS AND SUBJECT CHARACTERISTICS AT BASELINE 
22 
10.3 
STATISTICAL ANALYSIS METHODS 
22 
10.3.1 
Analysis Sets 
22 
10.3.1.3 
Exploratory Analyses 
23 
 
SUBJECT PAYMENT 
23 
12 
STUDY MANAGEMENT AND ADMINISTRATIVE PROCEDURES 
23 
12.1 
TRAINING AND MONITORING 
23 
12.2. 
INFORMED CONSENT 
23 
12.3 
PROTOCOL COMPLIANCE 
24 
12.3.1  
Protocol Amendments 
24 
12.3.2 
 Protocol Deviations 
24 
12.4 
STUDY PERSONNEL 
24 
12.5 
DISCLOSURE OF FINANCIAL INTEREST 
24 
12.6 
DATA COLLECTION, RECORD KEEPING AND STORAGE 
25 
13  
Subject Confidentiality 
26 
 
Publication Policy 
26 
Appendix 1: Study Schedule 
30 
Appendix 2: Fitzpatrick Wrinkle Classification System 
31 
Appendix 3: Fitzpatrick Skin Type Classification 
32 
Appendix 4: Visual Analog Scale (VAS) 
33 
Appendix 5:  Immediate Post-Treatment Subject Questionnaire 
34 
Appendix 6:  Before and After Laser Treatment Instructions 
35 
Appendix 7:  Post-Treatment Subject Questionnaire 
36 
Appendix 8: Subject Questionnaire – Photo-Rejuvenation 
38 
Appendix 9:  Phone Follow-Up Questionnaire 
40 
Appendix 10:  Post-Biopsy Care Instructions 
41 
 
 
 
 
 
 
 
 
 
 
 
 
 

Cutera, Inc. 
Protocol # C-16-ML01 
“A Single-Center, Open-Label Pilot Study of a Novel Microlens Array Device for Skin Rejuvenation” 
 
Confidential and Proprietary 
Page 5 of 41                                                       
Version 1.0, 16 Jun 2016 
 
Protocol Summary 
 
Title 
A Single-Center, Open-Label Pilot Study of a Novel Microlens Array Device 
for Skin Rejuvenation 
Objective 
 
1. To evaluate the safety of the Cutera Microlens Array Device 
when used with the enlighten™ 532nm /1064nm/670nm laser 
for photo-rejuvenation. 
 
2. To evaluate the efficacy of the Cutera Microlens Array Device 
for skin rejuvenation, including improvement in acne scars, fine 
rhytides, lentigines or pigmentation, erythema and skin 
texture. 
Study Design 
A single-center prospective, open-label uncontrolled pilot study. 
Subjects will receive 
laser treatments, 
 
 and will be followed at 2
 
 12 weeks (±2 weeks) post-final treatment. 
 
 
 
 
Enrollment 
A maximum of 50 subjects 
 
 
 
Study Endpoints 
 
 
• 
 
 
 
• Degree of improvement at 12 weeks post-final treatment as 
assessed by the Investigator (Physician’s Global Assessment of 
Improvement). 
• 
. 
Subject Population 
Female or male subjects, age 20 to 75 years, Fitzpatrick skin types I-VI 
Planned Schedule 
First subject enrolled:  July 2016 
Last subject last visit:  July 2018 
 
 

Cutera, Inc. 
Protocol # C-16-ML01 
“A Single-Center, Open-Label Pilot Study of a Novel Microlens Array Device for Skin Rejuvenation” 
 
Confidential and Proprietary 
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 PURPOSE 
The purpose of this pilot investigation is to evaluate the safety and efficacy of an investigational microlens 
array (MLA) handpiece attachment used with the Cutera enlighten™ laser for skin rejuvenation, 
specifically improvement of acne scars, fine rhytides, lentigines, pigmentation, erythema and skin texture. 
 
 BACKGROUND INFORMATION 
2.1 
Photo-Rejuvenation 
Non-invasive treatment options are in high demand by patients wanting to improve their appearance 
without surgical intervention. As a result, patients now have a variety of options for non-invasive skin 
rejuvenation, from laser and light-based treatments to devices that utilize ultrasound and radiofrequency, 
however this was not always the case. Initial skin rejuvenation procedures utilized ablative lasers, such as 
the carbon dioxide (CO2) and erbium:yttrium-aluminum-garnet (Er:YAG), and resulted in substantial 
improvement in skin appearance, texture, rhytides and laxity[1-3]. Since ablative treatments destroy the 
epidermal layer of the skin in order to penetrate and heat the deeper dermal layers, ample post-procedure 
recovery time is required and patients may experience side effects lasting for a few weeks. Furthermore, 
hypo- or hyperpigmentation, prolonged wound healing and even scarring can occur following ablative 
procedures [4-6]. Treatment methods with less risk of side effects and post-treatment down time are in 
high demand. As such, the choices are vast and varied, ranging from fractional non-ablative laser devices 
to those that use radiofrequency [7-15]. Fractional lasers inflict microscopic zones of thermal damage in 
the dermal layers of the skin without destruction of the epidermis, thereby reducing recovery time 
significantly as compared to ablative procedures [16]. Non-fractional, non-ablative laser devices of various 
wavelengths are effective for skin rejuvenation based on the principle of selective photothermolysis, 
whereby laser light is absorbed by hemoglobin in blood vessels and melanin in pigment-producing skin 
cells [17]. Absorption of laser light by these molecular chromophores results in the production of heat, 
leading to destruction of unwanted blood vessels and pigment cells. Heat production within the dermis 
by the laser light also results in immediate collagen contraction and heat-induced wound healing that, 
over time, causes a cascade of cellular events leading to new collagen production and improved skin 
appearance [8, 10].  
 
Full face and fractional ablative resurfacing have been used successfully to treat fine lines, wrinkles, 
scarring and dyschromia; however, ablative techniques, while effective, require downtime and are 
associated with higher risks such as scarring.  Fractional ablative resurfacing, a technique where only a 
fraction of the skin is ablated and the other fraction remains intact, is used more frequently than full field 
due to a higher safety profile and less downtime.  The results from fractional ablative are usually less 
dramatic than full field and the patient still has to care for their skin and cannot return to normal activities 
until fully re-epithelized.   
 
Non-ablative resurfacing techniques have become highly popular as they can achieve effective facial 
rejuvenation without the downtime associated with ablative resurfacing.  Current non-ablative skin 
rejuvenation procedures utilize various energy sources from radio-frequency, to ultrasound to lasers.  The 
concept involves the delivery of energy to tissue to treat dyschromia or to stimulate the wound healing 
cascade promoting collagenesis and elastogenesis leading to improvements in dyspigmentation,  fine 
lines, wrinkles and acne scars.   
 

Cutera, Inc. 
Protocol # C-16-ML01 
“A Single-Center, Open-Label Pilot Study of a Novel Microlens Array Device for Skin Rejuvenation” 
 
Confidential and Proprietary 
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Histologies of fractionated laser delivery has demonstrated the formation of vacuoles, or areas of laser 
induced optical breakdown (LIOB) [18].  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.   
 
In 2012, Habbema et al., demonstrated that highly focused, fractionated 1064 nm picosecond pulses could 
create subsurface LIOBs in the upper dermis and 30 days post treatment, they showed new collagen in 
the areas of the LIOBs, a natural wound healing process as a response to this type of injury [19].   
 
Subsequently, picosecond lasers utilizing 755nm wavelength and a fractionated delivery system have been 
shown to improve the appearance of facial acne scars [20] and facial wrinkles [21].  Histological samples 
taken from the acne scar patients demonstrated improvements in the dermal elastic fibers, collagen and 
mucin.  For both studies, no severe side effects were observed and the patients tolerated the procedures 
without complications.  The LIOBs observed in both the acne and facial wrinkle studies were located in 
the epidermis due to the higher absorption characteristics of 755nm in melanin as compared to 1064nm 
used in Habbema’s study.   
 
Fractionated delivery of picosecond lasers on humans has been demonstrated to be safe.  A similar device 
to MLA, utilizing 755nm wavelength and a fractionated delivery system, has obtained FDA 510K clearance 
(K143105) and has been shown to improve the appearance of facial acne scars [20] and facial wrinkles 
[21]. For both studies, no severe side effects were observed and the patients tolerated the procedures 
without complications.   
 
Recently, a holographic diffractive beam-splitter technology delivering fractionated picosecond 532nm 
and 1064nm wavelengths has also been described and is available commercially outside of the US 
(Syneron Candela), but to date, no FDA clearance exists for this device.  The company reports the device 
is able to focus the LIOBs in the epidermis with the 532nm wavelength and in the upper papillary dermis 
with the 1064nm wavelength safely [22]. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Cutera, Inc. 
Protocol # C-16-ML01 
“A Single-Center, Open-Label Pilot Study of a Novel Microlens Array Device for Skin Rejuvenation” 
 
Confidential and Proprietary 
Page 9 of 41                                                       
Version 1.0, 16 Jun 2016 
 
 
    
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
  
 
 
STUDY OBJECTIVES 
The objectives of this pilot study are: 
 
1) To evaluate the safety of the Microlens Array device when used with the enlighten 
532nm/670nm//1064nm  laser for photo-rejuvenation; 
 
2) To evaluate the efficacy of Microlens Array device for efficacious skin rejuvenation, including 
improvement in fine acne scars, rhytides, lentigines, pigmentation, erythema and skin texture. 
 
 
STUDY DESIGN 
This is a single-center prospective, open-label, uncontrolled feasibility study in up to 50 male or female 
subjects, age 20 to 75 years who desire laser treatment for photo-rejuvenation, specifically improvement 
of acne scars, fine rhytides, lentigines or pigmentation, erythema and skin texture. Subjects may be 
treated on the face and/or body (such as, but not limited to, hand, forearm, chest or décolleté).  
 
Subjects will receive 
 laser treatments, 
 and will be followed at 
 
 12 weeks post final treatment 
). The number of treatments 
as well as the interval between treatments will be determined at the Investigator’s discretion. 
 
 
 
 

Cutera, Inc. 
Protocol # C-16-ML01 
“A Single-Center, Open-Label Pilot Study of a Novel Microlens Array Device for Skin Rejuvenation” 
 
Confidential and Proprietary 
Page 10 of 41                                                       
Version 1.0, 16 Jun 2016 
 
 
    
4.1 
Study Endpoints 
4.1.1 Efficacy Endpoints 
4.1.1.1 Primary Efficacy Endpoint 
• Degree of improvement at 12 weeks post-final treatment as assessed by the Investigator 
(Physician’s Global Assessment of Improvement). 
 
 
 
 
4.1.2 Safety Endpoints 
• 
 
• Incidence and severity of adverse device effects during the study period, including subject pain 
level during laser treatment. 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
4.3 Study Effectiveness Assessments 
4.3.1 
Investigator Assessments 
4.3.1.1 Investigator’s Global Assessment of Improvement 
At 12 weeks post-final treatment, the Investigator will be asked to rate the degree of improvement 
observed in the subject’s treated area using the Physician’s Global Assessment Scale:  
 
3 = Very Significant Improvement 
 
2 = Significant Improvement 
 
1 = Moderate Improvement 
 

Cutera, Inc. 
Protocol # C-16-ML01 
“A Single-Center, Open-Label Pilot Study of a Novel Microlens Array Device for Skin Rejuvenation” 
 
Confidential and Proprietary 
Page 11 of 41                                                       
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0 = Mild or No Improvement 
 
4.3.2 Subject Assessments 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
  
 4.4 
Study Safety Assessments 
 
4.4.1 Incidence and Severity of Adverse Events: 
 
Following the first laser treatment, adverse device effects (ADEs) will be assessed post-treatment and 
at each subsequent subject visit using the following scale: 
1= mild: requires minimal or no treatment and does not interfere with the Subject’s daily activities. 
2= moderate: may cause some interference with functioning.  
3= severe: interrupts Subject’s usual daily activity and may require treatment. 
4.4.2 Treatment-related Discomfort 
After each laser treatment, subjects will be asked to rate the average amount of discomfort experienced 
during treatment and immediately after laser treatment using the Pain Rating Scale found in the Subject 
Questionnaire located in Appendix 5.   
4.4.3 Phone Follow-up 
 
 
 
 

Cutera, Inc. 
Protocol # C-16-ML01 
“A Single-Center, Open-Label Pilot Study of a Novel Microlens Array Device for Skin Rejuvenation” 
 
Confidential and Proprietary 
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4.5 
Photographs 
Standardized digital photographs will be taken of each subject’s treatment area at baseline, prior to all 
laser treatments and at each follow-up. Any jewelry will be removed from the area being photographed. 
For facial photographs, hair will be pulled away from the face with a headband and subject will have 
recently cleansed skin. Photographs will be taken prior to all laser treatments and at each follow-up visit. 
Facial photographs will be obtained from 3 angles: with the subject facing forward, 45° to the right and 
45° to the left. Photographs will be taken in the same windowless room equipped with adequate lighting. 
The room lighting, camera positioning and subject positioning should be consistent for all study visit 
photographs. Digital camera settings should remain the same for all photographs and the highest 
resolution settings should be utilized.  
4.6 
Study Discontinuation 
Cutera, Inc. (the sponsor) has the right to terminate this study at any time.  Reasons for terminating the 
study may include, but are not limited to, the following: incidence or severity of adverse events in this or 
other studies indicates a potential health hazard to subjects; subject enrollment is unsatisfactory; number 
of protocol deviations is unacceptable; data recording is inaccurate or incomplete; or questionable study 
site compliance with ICH-E6, Good Clinical Practice. 
4.7 
Investigator Selection 
The Investigator will be invited to participate in the study based on his or her medical specialty, experience 
conducting clinical research studies and experience in the use of light-based devices for aesthetic 
indications. Access to potential study subjects and the Investigator’s sincere interest in this study along 
with expressed willingness to cooperate with the study process and requirements was also considered.  
 
Study Population 
5.1 
Study Subject Recruitment and Selection 
Up to 50 male or female subjects, ages 20 to 75, with Fitzpatrick Skin Type I-VI who desire laser treatment 
for skin rejuvenation on the face. Subjects will be recruited to participate from the local population. 
Subjects may also be recruited from the Investigator’s existing patient database or from patients who 
present themselves to the study site requesting treatment. Only subjects who meet all eligibility criteria 
and who provide written informed consent will be enrolled into the study. 
 
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.  
5.1.1 
Inclusion Criteria 
To be included in the study, subjects must meet all of the following Inclusion Criteria: 
1.  
Female or Male, 20 to 75 years of age (inclusive). 
2.  
Fitzpatrick Skin Type I – VI (Appendix 3). 
3.  
Desires photo-rejuvenation of the skin or improvement in the appearance of acne 
scarring. 
4.  
Subject has visible signs of acne scarring or moderate sun-damaged and/or aging skin in 
the treatment area with visible areas of fine rhytides, pigmentation, erythema or 
telangiectasia. 

Cutera, Inc. 
Protocol # C-16-ML01 
“A Single-Center, Open-Label Pilot Study of a Novel Microlens Array Device for Skin Rejuvenation” 
 
Confidential and Proprietary 
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5.  
Subject must be able to read, understand and sign the Informed Consent Form. 
6.  
Must be willing and able to adhere to the treatment and follow-up schedule and post-
treatment care instructions. 
7.  
Willing to have very limited sun exposure and use an approved sunscreen of SPF 50 or 
higher 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 or marketing purposes. 
9.  
Agree to not undergo any other procedure(s), including injectable agents, for skin 
rejuvenation during the study and has no intention of having such procedures 
performed during the course of the study. 
10.  
Post-menopausal or 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, 
and no plans to become pregnant. 
5.1.2 
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 target 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 or light-based procedures or surgery. 
3.  
Prior injection of botulinum toxin, collagen, hyaluronic acid filler or other dermal filler 
within 6 months of study participation. 
4.  
History of malignant tumors in the target area. 
5.  
Skin abnormalities in the target area, e.g., cuts, scrapes, wounds, scars, large moles. 
6.  
Pregnant and/or breastfeeding.  
7.  
Having an infection, dermatitis or a rash in the treatment area. 
8.  
Significant concurrent illness, such as diabetes mellitus or cardiovascular disease, e.g., 
uncontrolled hypertension. 
9.  
Suffering from coagulation disorders or taking prescription anticoagulation medications.  
10.  
History of keloid scarring, hypertrophic scarring or of abnormal wound healing.  
11.  
History of immunosuppression/immune deficiency disorders or currently using 
immunosuppressive medications.  
12.  
History of vitiligo, eczema, or psoriasis. 
13.  
History of connective tissue disease, such as systemic lupus erythematosus or 
scleroderma.  
14.  
History of seizure disorders due to light. 
15.  
Any use of medication that is known to increase sensitivity to light according to 
Investigator’s discretion. 
16.  
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 
17.  
History of radiation to the treatment area or undergoing systemic chemotherapy for the 
treatment of cancer.  

Cutera, Inc. 
Protocol # C-16-ML01 
“A Single-Center, Open-Label Pilot Study of a Novel Microlens Array Device for Skin Rejuvenation” 
 
Confidential and Proprietary 
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18.  
History of pigmentary disorders, particularly tendency for hyper- or hypo-pigmentation. 
19.  
Systemic use of retinoid, such as isotretinoin, or corticosteroid, as applicable, within 6 
months of study participation.  
20.  
Topical use of retinoid, such as isotretinoin, corticosteroid or hydroquinone, as 
applicable, on the treatment area within 1 month of participation. 
21.  
Anytime in life, having have used gold therapy (gold salts) for disorders such as 
rheumatologic disease or lupus. 
22.  
Excessively tanned in areas to be treated or unable/unlikely to refrain from tanning during 
the study.  
23.  
Current smoker or history of smoking within 6 months of study participation. 
24.  
As per the Investigator’s discretion, any physical or mental condition which might make 
it unsafe for the subject to participate in this study. 
5.2 
Subject Numbering  
If a subject 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 sequential subject number and the 
subject initials (first and last names). 
5.3 
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 
lost to follow-up only after three unsuccessful, documented attempts to contact the subject have been 
made.   
 
In addition, a subject can be discontinued for any of the following reasons: the Principal Investigator 
decides that continuing in the study would not be in the subject’s best interest, a subject is noncompliant 
with the protocol, a subject has a serious reaction to the treatment, a subject develops any of the exclusion 
criteria during the study period or the study is stopped by the study sponsor.  
 
Study Procedures 
 
 
 
 
 
 
 
 
 
 
 
 
. 

Cutera, Inc. 
Protocol # C-16-ML01 
“A Single-Center, Open-Label Pilot Study of a Novel Microlens Array Device for Skin Rejuvenation” 
 
Confidential and Proprietary 
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Cutera, Inc. 
Protocol # C-16-ML01 
“A Single-Center, Open-Label Pilot Study of a Novel Microlens Array Device for Skin Rejuvenation” 
 
Confidential and Proprietary 
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 ADVERSE DEVICE EFFECTS  
7.1. Definitions 
 
 
 
 
 
 
 
 
 

Cutera, Inc. 
Protocol # C-16-ML01 
“A Single-Center, Open-Label Pilot Study of a Novel Microlens Array Device for Skin Rejuvenation” 
 
Confidential and Proprietary 
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7.1.2 Serious Adverse Device Effect 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 

Cutera, Inc. 
Protocol # C-16-ML01 
“A Single-Center, Open-Label Pilot Study of a Novel Microlens Array Device for Skin Rejuvenation” 
 
Confidential and Proprietary 
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Figure 1. Flowchart for classification of adverse device effects [27]. 

Cutera, Inc. 
Protocol # C-16-ML01 
“A Single-Center, Open-Label Pilot Study of a Novel Microlens Array Device for Skin Rejuvenation” 
 
Confidential and Proprietary 
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8.2 
Potential Benefits 
The subjects may or may not benefit from the treatment with the study device. Potential benefit of laser 
treatment for photo-rejuvenation is improved appearance of treated area. There is no guarantee of 
success.  
 Risk Management 
The investigator participating in this study was chosen based on extensive and safe experience with the 
use of lasers in dermatology applications. This is the most critical element in managing subject risk. In 
addition, study investigators will be trained on the use of the Cutera Enlighten laser system by a 
representative of Cutera. 

Cutera, Inc. 
Protocol # C-16-ML01 
“A Single-Center, Open-Label Pilot Study of a Novel Microlens Array Device for Skin Rejuvenation” 
 
Confidential and Proprietary 
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 DATA ANALYSIS PLAN  
10.1 Sample Size 
Up to 50 subjects will be enrolled in this pilot study. 
10.2 
Demographics and Subject Characteristics at Baseline 
Subject demographics, medical history, concomitant medications will be tabulated and summarized 
descriptively. 
10.3 
Statistical Analysis Methods 
This is a pilot study to evaluate safety and efficacy of the MLA device, therefore, formal statistical 
analyses are not planned.   
 
Outcome measures will be assessed around multiple endpoints.  These measures will be: degree of 
improvement as assessed by the Investigator, 
and safety. Additional assessments 
may also be performed but are not considered part of the analysis 
 
).  The specific assessment tools, collection method and time points are listed herein.   
10.3.1 Analysis Sets 
The efficacy analysis set will include all subjects who received at least one laser treatment session and 
complete at least one follow-up visit. The safety analysis set will include all subjects enrolled in the study 
who had at least one laser treatment session. 
 
Missing data will not be imputed for efficacy or safety endpoints. 
10.3.1.1  
 Efficacy Analyses 
Descriptive statistics such as mean, standard deviation, median and range will be performed for: 
 
• The degree of improvement at 12 weeks post-final treatment as assessed by the Investigator, using 
the Physician’s Global Assessment tool. 
• 
 
 
10.3.1.2   
Safety Analyses 
The safety variables for this study are: 
 
• Incidence and severity of adverse effects during study duration (to be displayed descriptively as 
counts and frequency distributions)  
• Subject discomfort (pain) during treatment (to be descriptively displayed). 
 
Enrolled subjects who received at least one treatment will be included in the safety analyses. Device-
related and procedure-related adverse effects (AEs) and subjects who prematurely terminate from the 
study due to an adverse device effect, including the treatment-related pain ratings, as reported on case 
report forms will be tabulated and analyzed. For a given AE term, counting will be done by subject, not by 
event, i.e. for a subject reporting the same AE more than once, the event will be counted only once, at the 
most severe and most-related occurrence.  The number and percentage of subjects experiencing each AE 
Term will be descriptively summarized. Statistical hypothesis testing will not be performed for safety data. 

Cutera, Inc. 
Protocol # C-16-ML01 
“A Single-Center, Open-Label Pilot Study of a Novel Microlens Array Device for Skin Rejuvenation” 
 
Confidential and Proprietary 
Page 23 of 41                                                       
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Interim analyses of adverse events and adverse device effect incidence and severity will be performed 
when all treated subjects have completed the 12 week post-final treatment visit.  At the conclusion of 
the study, complete analyses of the safety variables will be displayed descriptively.   
 
 
 
 
  
 
 
 
   
 
 
  SUBJECT PAYMENT 
 
 
 
 
12 
STUDY MANAGEMENT AND ADMINISTRATIVE PROCEDURES  
 
 
 
 
 
  
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 

Cutera, Inc. 
Protocol # C-16-ML01 
“A Single-Center, Open-Label Pilot Study of a Novel Microlens Array Device for Skin Rejuvenation” 
 
Confidential and Proprietary 
Page 24 of 41                                                       
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12.3 
Protocol Compliance 
The principal investigator must comply with all terms of the protocol. 
12.3.1  Protocol Amendments 
Neither the principal investigator nor the sponsor will modify or alter this protocol without first obtaining 
the concurrence of the other party (with the exception of amendments which involves mitigating a 
medical emergency or immediate health risk to the subject). The party initiating an amendment must 
confirm it clearly in writing and it must be signed and dated by the sponsor and the principal investigator. 
IRB approval must be obtained before implementation of an amendment. 
12.3.2  Protocol Deviations 
All protocol deviations must be clearly described on the case report form (i.e., Cutera Protocol Deviation 
Form). Deviations from the protocol may include but are not limited to subject’s failure to attend 
scheduled visit during a visit window, use of out of range treatment parameters and incomplete or 
incorrect study procedures. Any medical emergency or immediate health risk to the subject which results 
in a protocol deviation and must be reported to the sponsor within 5 working days 
 
Significant protocol deviations must be reported to IRB according to their policies. 
12.4 
Study Personnel 
Prior to the start of the study, the investigator must supply the sponsor with a list of the names and 
curricula vitae that describe the professional backgrounds of the clinically responsible study investigators 
(principal, sub-investigators), research nurses, and other possible participants (e.g. medical doctor, nurse, 
etc.). 
12.5 
Disclosure of Financial Interest 
Each investigator [principal and sub-investigator(s)] is required to disclose sufficient accurate financial 
information to the sponsor, to allow sponsor to submit complete and accurate certification or disclosure 
statements. 

Cutera, Inc. 
Protocol # C-16-ML01 
“A Single-Center, Open-Label Pilot Study of a Novel Microlens Array Device for Skin Rejuvenation” 
 
Confidential and Proprietary 
Page 25 of 41                                                       
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12.6 
Data Collection, Record Keeping and Storage 
 
 
  
 
 
 
 
 
 
  
 
 
  
  
  
 
 
  
 
 
 
 
 
 
 
 
 
 
  
  
 
 
 
 
 
 
  
 
  
 
 
 
 
 
 
  
 
 
 

Cutera, Inc. 
Protocol # C-16-ML01 
“A Single-Center, Open-Label Pilot Study of a Novel Microlens Array Device for Skin Rejuvenation” 
 
Confidential and Proprietary 
Page 26 of 41                                                       
Version 1.0, 16 Jun 2016 
 
 
  
13  Subject Confidentiality 
This study preserves the confidentiality of all subjects under the Health Insurance Portability and 
Accountability Act of 1996 (HIPAA) Privacy Rule. The following safeguards will be in place to protect the 
privacy of the individuals who are the subjects of the health information to be used in the research and 
the confidentiality of that information:   
 
 
 
 
  
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
  
 
 Publication Policy 
The investigator shall have the right to publish the results of the study. Unless mutually agreed upon in 
writing, prior to submission for publication of any manuscript, poster, presentation, abstract or other 
written or oral material describing the results of the study, the investigator shall allow sponsor to review 
manuscript, poster presentation, abstract or other written or oral material which describes the results of 
the study for the purpose only of determining if any patentable information is disclosed. At the sponsor’s 
request, the investigator shall withhold any publication or presentation to permit sponsor to seek patent 
protection and to remove any confidential information from all publications.  
 
The International Committee of Medical Journal Editors (ICMJE) member journals have adopted a trials 
registration policy as a condition for publication. This policy requires that all clinical trials be registered in 
a public trials registry such as ClinicalTrials.gov, which is sponsored by the National Library of Medicine. It 

Cutera, Inc. 
Protocol # C-16-ML01 
“A Single-Center, Open-Label Pilot Study of a Novel Microlens Array Device for Skin Rejuvenation” 
 
Confidential and Proprietary 
Page 27 of 41                                                       
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is the responsibility of the sponsor to register this trial in ClinicalTrials.gov. Any clinical trial starting 
enrollment after September 27, 2007 must be registered either on or before the onset of patient 
enrollment. 
 
 
 
 
 
 
 
 

Cutera, Inc. 
Protocol # C-16-ML01 
“A Single-Center, Open-Label Pilot Study of a Novel Microlens Array Device for Skin Rejuvenation” 
 
Confidential and Proprietary 
Page 28 of 41                                                       
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Cutera, Inc. 
Protocol # C-16-ML01 
“A Single-Center, Open-Label Pilot Study of a Novel Microlens Array Device for Skin Rejuvenation” 
 
Confidential and Proprietary 
Page 29 of 41                                                       
Version 1.0, 16 Jun 2016 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Cutera, Inc. 
Protocol # C-16-ML01 
“A Single-Center, Open-Label Pilot Study of a Novel Microlens Array Device for Skin Rejuvenation” 
 
Confidential and Proprietary 
Page 30 of 41                                                       
Version 1.0, 16 Jun 2016 
 
 
 
  
 
 

Cutera, Inc. 
Protocol # C-16-ML01 
“A Single-Center, Open-Label Pilot Study of a Novel Microlens Array Device for Skin Rejuvenation” 
 
Confidential and Proprietary 
Page 31 of 41                                                       
Version 1.0, 16 Jun 2016 
 
 
 
 
 
 
 

Cutera, Inc. 
Protocol # C-16-ML01 
“A Single-Center, Open-Label Pilot Study of a Novel Microlens Array Device for Skin Rejuvenation” 
 
Confidential and Proprietary 
Page 32 of 41                                                       
Version 1.0, 16 Jun 2016 
 
 
 
 
 
 
 

Cutera, Inc. 
Protocol # C-16-ML01 
“A Single-Center, Open-Label Pilot Study of a Novel Microlens Array Device for Skin Rejuvenation” 
 
Confidential and Proprietary 
Page 33 of 41                                                       
Version 1.0, 16 Jun 2016 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Cutera, Inc. 
Protocol # C-16-ML01 
“A Single-Center, Open-Label Pilot Study of a Novel Microlens Array Device for Skin Rejuvenation” 
 
Confidential and Proprietary 
Page 34 of 41                                                       
Version 1.0, 16 Jun 2016 

Cutera, Inc. 
Protocol # C-16-ML01 
“A Single-Center, Open-Label Pilot Study of a Novel Microlens Array Device for Skin Rejuvenation” 
 
Confidential and Proprietary 
Page 35 of 41                                                       
Version 1.0, 16 Jun 2016 
 
 
  
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Cutera, Inc. 
Protocol # C-16-ML01 
“A Single-Center, Open-Label Pilot Study of a Novel Microlens Array Device for Skin Rejuvenation” 
 
Confidential and Proprietary 
Page 40 of 41                                                       
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