Clinical Study of the CO2RE® Laser Device for Treatment of Vulvar Lichen Sclerosus
Phase: NA
Conditions: Vulvar Lichen Sclerosus
Sponsor: Candela Corporation

 
Candela Corporation 
Confidential 
Clinical Study of the CO2RE Laser Device for Treatment of Vulvar Lichen 
Sclerosus 
Protocol # 
DHF25211 
Rev. Date 
February 19, 2019 
Page 1 of 39 
 
 
 
 
Study Title: 
Clinical Study of the CO2RE Laser Device for Treatment of Vulvar 
Lichen Sclerosus 
Protocol 
Number: 
DHF25211  
 
IRB Revision 
Date: 
February 19, 2019 
NCT#:  
NCT04148651 
Study Type: 
Prospective Clinical Study 
Device: 
CO2RE Laser  
Sponsored By: 
Candela Corporation 
530 Boston Post Rd  
Wayland, MA 01778 
 
 
 
 
 
 
This document is the property of Candela Corporation No part of this document 
may be reproduced, stored in retrieval system, or transmitted in any form or any 
means, electronic, mechanical, photocopying, recording or otherwise without 
prior written permission from Candela Corporation. 

 
Candela Corporation 
Confidential 
Clinical Study of the CO2RE Laser Device for Treatment of Vulvar Lichen 
Sclerosus 
Protocol # 
DHF25211 
Rev. Date 
February 19, 2019 
Page 2 of 39 
 
 
TABLE 1- STUDY SYNOPSIS 
Short study name 
Vulvar Lichen Sclerosus Treatment with CO2RE 
Proprietary name 
Syneron Candela CO2RE Laser  
Intended Use 
The CO2RE laser system is a fractional CO2 laser that is FDA-cleared under a 510(k) 
K151655 for laser incision, excision, ablation and/or vaporization and of soft tissue in 
gynecology (GYN).  
Design 
Prospective, non-randomized, single group assignment, interventional clinical trial 
Study Population 
Up to 45 female subjects from up to four investigational sites, age 18-80 years  
Sites and 
Investigators 
Up to 4 investigational sites 
Treatment Duration 
Eligible subjects, with a diagnosis of vulvar lichen sclerosus (VLS) supported by 
histologic findings on biopsy and/or clinical signs on physical examination and 
recalcitrant to mid- to high-potency steroid therapy, will undergo up to 5 treatments 
at 4±1-week intervals to the vulva with the CO2RE device and External Intima 
disposable handpiece. Up to 10 subjects will have a biopsy taken at the baseline visit, 
at the 6-week follow-up and at the 6-month follow-up to evaluate histological 
markers compared to pre-treatment biopsy findings. 
A 1 week ± 2 days post first treatment phone call by a study nurse for safety 
evaluation will be performed. 
Subjects will return for 4 follow-up (FU) visits: at 6 weeks, 3 months, 6 months and 12 
months after the final treatment. 
Methodology described in protocol to evaluate efficacy of treatments will be carried 
out at each visit at the clinic. 
Primary Objective 
Evaluate the efficacy of a series of CO2RE treatments to improve the symptoms, 
clinical signs, and architectural changes associated with vulvar lichen sclerosus, at 6 
weeks, 3 months, 6 months and 12 months after the final treatment.  
Secondary Objectives 
• 
Evaluate sexual function at the 3-month and 6-month follow-ups compared to 
baseline. 
• 
Evaluate histological markers at the 6-week and 6-month follow-ups 
compared to baseline. 
• 
Evaluate discomfort following each treatment.  
• 
Evaluate the safety of CO2RE treatments for VLS during the study. 
• 
Evaluate subject satisfaction at the 6-week, 3-month, 6-month and 12-month 
follow-up visits. 
 
 

 
Candela Corporation 
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Clinical Study of the CO2RE Laser Device for Treatment of Vulvar Lichen 
Sclerosus 
Protocol # 
DHF25211 
Rev. Date 
February 19, 2019 
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Primary Endpoint 
Change from baseline in presence and severity of symptoms (5-point severity 
scale), clinical signs (3-point severity scale) and architectural changes (3-point severity 
scale) at the 6-week, 3-month, 6-month and 12-month follow-up visits. (Appendices I 
& II). 
Secondary Efficacy 
Endpoints 
The following parameters will be measured during the study: 
• 
Sexual function, using the Female Sexual Function Index (Appendix III), at 
baseline and at the 3-month and 6-month follow-ups.  
• 
Histological signs (degree of hyperkeratosis, epidermal atrophy and dermal 
inflammation) at baseline and at 6 weeks and 6 months after the final 
treatment. 
• 
Subject satisfaction, using a 5-point Likert scale (-2=very dissatisfied; 2=Very 
satisfied), will be assessed at the 6-week, 3-month and 6-month follow-up 
visits. 
Safety Endpoints 
Evaluate the safety of the CO2RE device for the treatment of VLS in female subjects: 
• 
Pain/discomfort level using a 10-point Numerical Scale Response (NSR) after 
each treatment. 
• 
Number, severity and type of adverse events recorded throughout course of 
the study. 
• 
1 week ± 2 days post first treatment safety phone call to review 1-week 
patient diary. 
INTRODUCTION AND RATIONALE 
Background 
 
Lichen sclerosus (LS) is a chronic, inflammatory skin disorder of genital and extragenital skin.1 It 
most commonly affects the anogenital region of adult women.2 Lichen sclerosus (LS) was 
described for the first time in 1887. Since then, many synonyms have been in use, notably 
'Kraurosis vulvae,' 'vulvar dystrophy,' 'white spot disease,' and 'lichen sclerosus et atrophicus' or 
'guttate scleroderma.1 All of these terms have been abandoned and replaced by ‘lichen 
sclerosus,’ which is now used for genital and extragenital lesions. 1 LS is a chronically relapsing 
disease with a potential for atrophy, destructive scarring, functional impairment, and malignant 
evolution. 1,3,4 Therefore, early diagnosis, prompt treatment, and long-term follow-up of affected 
patients are mandatory. 1 
 

 
Candela Corporation 
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Clinical Study of the CO2RE Laser Device for Treatment of Vulvar Lichen 
Sclerosus 
Protocol # 
DHF25211 
Rev. Date 
February 19, 2019 
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It is estimated that up to 20% of all women will experience significant vulvar symptoms at some 
point in their lifetime.2 Although women’s health is a topic of growing concern in today’s 
society, conditions such as vulvar lichen sclerosus (VLS) are often underdiagnosed and 
undertreated. Most cases are diagnosed in postmenopausal women.5 The involved skin 
becomes thin and white, with frequently present bruises or petechiae and anatomic changes. 
Symptoms include persistent itching and soreness or burning. At advanced stages of lichen 
sclerosus, scarring after inflammation may lead to severe damage by fusion of the labia, 
narrowing of the vaginal opening, burying of the clitoris in women and girls and risk of 
developing squamous cell carcinoma.  
 
The treatment of VLS aims at controlling the symptoms, stopping further scarring and distortion 
and reducing the risk of cancer. Previously, the gold standard in treatment was ultra-potent 
topical steroids (i.e. clobetasol propionate).5 Currently, mid to high-potent topical steroids are a 
first-line therapy. The anti-inflammatory properties of clobetasol and other steroids have been 
most effective in managing associated symptoms, decreasing inflammation, and preventing 
progression of the condition and subsequent scarring.6 Second-line treatments include 
calcineurin inhibitors, retinoids, and immunosuppressors. Surgery is used only for the treatment 
of complications associated with VLS.5 
 
Contemporary VLS treatment modalities suffer from dependence on long-term patient 
compliance and high recurrence rates. The fractional carbon dioxide laser (CO2) has been 
applied to treat skin disorders7 and to induce vaginal rejuvenation8, reconstitute normal vaginal 
flora9 and to drive collagenogenesis tissue remodelling.10 Although topical steroids are the gold 
standard treatment for VLS, fractional CO2 resurfacing was successful in achieving remission for 
severe, hyperkeratotic VLS not responding to super-potent topical corticosteroids. In these 
patients, VLS was subsequently able to be maintained with topical corticosteroid treatment.10  
 
The histological changes and relief of vaginal symptoms, such as itching and dryness, elicited 
with fractional CO2 technology justify testing it as an alternative and/or adjunctive treatment for 
VLS. This clinical research will evaluate treatment efficacy of the CO2RE CO2 laser device with the 
External Intima fractional handpiece for improving the clinical signs of VLS and relieving 
symptoms associated with this condition.  
 
CO2RE Device Description 
The CO2RE laser system (Figure 1) utilizes a sealed-off, metal carbon dioxide gas tube that is 
radiofrequency (RF)-excited and air-cooled, emitting light at a wavelength of 10.6 μm with 

 
Candela Corporation 
Confidential 
Clinical Study of the CO2RE Laser Device for Treatment of Vulvar Lichen 
Sclerosus 
Protocol # 
DHF25211 
Rev. Date 
February 19, 2019 
Page 5 of 39 
 
 
programmable pulse duration and frequency. The system has a programmable 2-axis scanning 
laser beam device that allows the physician to select the skin area coverage from a selection of 
predetermined patterns in different sizes based on the skin area to be treated. The versatility of 
the fractional CO2RE system enables precise, effective and simultaneous treatment of the skin’s 
surface in the middle and deep dermal levels. The CO2RE system consists of a treatment 
component and an internal control component. The treatment component consists of the laser 
delivery handpiece. A computer with a touch screen keyboard also provides controls for the 
fractionated delivery of the 10.6 μm beam. 
 
 
 
Figure 1: CO2RE device 
 
 
In this study, the external fractional handpiece (Figure 2) will be used to perform treatments to 
the vulvar area affected by lichen sclerosus.  
 
 

 
Candela Corporation 
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Clinical Study of the CO2RE Laser Device for Treatment of Vulvar Lichen 
Sclerosus 
Protocol # 
DHF25211 
Rev. Date 
February 19, 2019 
Page 6 of 39 
 
 
 
 
 
Figure 2: CO2RE Intima External Handpiece 
 
INTENDED USE IN GYNECOLOGY 
The CO2RE system device is FDA-cleared under a 510(k) K151655  - intended for laser incision, 
excision, ablation, and/or vaporization of soft tissue in gynecology (GYN) for the treatment of: 
conization of the cervix, including cervical intra-epithelial neoplasia (CIN) and vulvar and vaginal 
intra-epithelial neoplasia (VIN, VAIN); condyloma acuminate, including cervical, genital, vulvar, 
perineal, and Bowen’s disease (Erythroplasia of Queyrat) and Bowenoid papulosa (BP) lesions; 
and leukoplakia (vulvar dystrophies). 
STUDY DESIGN 
Study Duration and Timelines 
This study is a prospective, non-randomized, single group assignment, interventional clinical trial 
to evaluate the CO2RE laser device for safety and efficacy for vulvar lichen sclerosus (vulvar 
dystrophy) treatment.   
 
Up to a total of 45 female candidates, seeking treatment for vulvar lichen sclerosus from the 
participating investigator will be enrolled at a participating study site. Subjects will receive up to 
five (5) CO2RE treatments.  
A 1-week post first treatment safety call will be performed by a study nurse to review the 
patient daily diary. 
Each subject will be followed for 4 additional post treatment visits (FU visits) that will be 
conducted at: 
• 
6 weeks post last treatment – 6wk FU ± 2 weeks (Efficacy & Safety). 
• 
3 months post last treatment – 3m FU ± 2 weeks (Efficacy & Safety). 
• 
6 months post last treatment – 6m FU ± 2 weeks (Efficacy & Safety). 

 
Candela Corporation 
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Clinical Study of the CO2RE Laser Device for Treatment of Vulvar Lichen 
Sclerosus 
Protocol # 
DHF25211 
Rev. Date 
February 19, 2019 
Page 7 of 39 
 
 
• 
12 months post last treatment – 12m FU ± 2 weeks (Efficacy & Safety). 
STUDY OBJECTIVES AND END POINTS 
Primary Objective  
To evaluate the efficacy of a series of CO2RE treatments to improve the symptoms, clinical signs, 
and architectural changes associated with vulvar lichen sclerosus, at 6 weeks, 3 months, 6 
months and 12 months after the final treatment.  
 
Secondary Objectives 
1. Evaluate sexual function at the 3-month and 6-month follow-ups compared to baseline. 
2. Evaluate histological markers at the 6-week and 6-month follow-up compared to 
baseline. 
3. Evaluate discomfort following each treatment.  
4. Evaluate the safety of CO2RE treatments for VLS during the study. 
5. Evaluate subject satisfaction at the 6-week, 3-month, 6-month and 12-month follow-up 
visits. 
 
Primary Endpoint 
 
Change from baseline in presence and severity of symptoms (5-point severity scale), clinical 
signs (3-point severity scale) and architectural changes (3-point severity scale) at the 6-week, 3-
month, 6-month and 12-month follow-up visits.  (Appendices I & II). 
 
Secondary Safety Endpoints  
Evaluate the safety of the treatment: 
1. Clinical evaluation of treated area at each study visit. Clinical photography will be 
performed for study documentation (Appendix IV). 
2. Pain/discomfort level using a 10-point Numerical Scale Response (NSR) after each 
treatment (Appendix V). 
3. Number, severity and type of adverse events recorded throughout course of the study. 
4. 1 week ± 2 days post first treatment safety phone call (review of 1-week patient diary) – 
(Appendix VI). 

 
Candela Corporation 
Confidential 
Clinical Study of the CO2RE Laser Device for Treatment of Vulvar Lichen 
Sclerosus 
Protocol # 
DHF25211 
Rev. Date 
February 19, 2019 
Page 8 of 39 
 
 
Secondary Efficacy Endpoints 
1. Sexual function, using the Female Sexual Function Index (Appendix III), at baseline and 
at the 3-month and 6-month follow-ups. An overall score ≤ 26.55 is classified as Female 
Sexual Disorder (FSD).15 
2. Histological signs (degree of hyperkeratosis, epidermal atrophy and dermal 
inflammation) at baseline and at 6 weeks and 6 months after the final treatment. 
3. Subject satisfaction, using a 5-point Likert scale (-2=very dissatisfied; 2=Very satisfied), 
will be assessed at the 6-week, 3-month, 6-month and 12-month follow-up visits 
(Appendix VII). 
SUBJECT POPULATION 
Up to 45 female subjects who meet the following inclusion / exclusion criteria may be enrolled.   
Subject Withdrawal and Replacement 
Subjects enrolled in the study can discontinue their participation at any time for any reason 
without prejudice or reduction in the quality of their medical care.  The investigator or sponsor 
can terminate a subject’s participation in this study to protect the subject’s health or if the 
subject fails to follow directions resulting in noncompliance to study procedures.  Subjects who 
withdraw or are terminated from the study may be replaced to allow up to 45 subjects to 
complete the study.  Subjects who fail to complete the treatment will be replaced and will not 
be evaluable.  
Inclusion Criteria 
1. Able to read, understand and sign informed consent for study participation; 
2. Female subjects with age 18-80 years; 
3. Biopsy demonstrates biopsy-proven lichen sclerosus and/or there are characteristic 
changes for vulvar lichen sclerosus on physical examination; 
4. Treatment of LS has been recalcitrant to mid to high-potent topical corticosteroid 
treatment or subject refuses topical corticosteroid treatment. Recalcitrance to therapy 
is defined as no response to topical corticosteroids of an adequate potency (i.e. 
clobetasol propionate 0.05% ointment or other steroids) and a sufficient duration (12 
weeks of use) or lack of symptomatic control of the disease with a maintenance 
therapy; 
5. Topical corticosteroid treatment, if any, will be continued during the study period; 
6. Exogenous hormone treatment, if any, will be continued during the study period (type 
and dose must stay consistent throughout the study); 

 
Candela Corporation 
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Clinical Study of the CO2RE Laser Device for Treatment of Vulvar Lichen 
Sclerosus 
Protocol # 
DHF25211 
Rev. Date 
February 19, 2019 
Page 9 of 39 
 
 
7. One or more of the following symptoms: itch; pain unrelated to intercourse; pain, skin 
tearing or bleeding with intercourse; changes/decrease in sexual function; 
8. Characteristic changes for vulvar lichen sclerosus on physical examination; 
9. No breaks, tears or lesions, malodorous discharge or strawberry cervix present on 
gynecological exam. 
Exclusion Criteria 
1. Presence of clinically atypical appearing nevi in the area to be treated; 
2. Unexplained vaginal bleeding; 
3. Active infection, specifically: urinary tract infection, vulvar or vaginal infection 
(candidiasis, genital herpes/HSV, bacterial vaginosis, trichomonas); 
4. History of vulvar or any gynecological malignancy, as well as history of pelvic radiation 
therapy or stem cell transplant; 
5. Pelvic organ prolapse > stage 2; 
6. Pregnancy or planning pregnancy during the study; 
7. Systemic treatment with immuno-modulatory drugs.  
8. Use of vaginal dilators during study. 
STUDY PROCEDURES 
Enrollment and Screening 
During the first visit, the investigator will screen the subject for eligibility to participate in the 
clinical study.  The inclusion/exclusion criteria will be reviewed, the subject’s medical history, an 
examination of the subject’s treatment areas will be conducted.   
The subject will review the informed consent form (ICF) and the study will be explained to the 
subject including all risks, potential benefits, procedures, visit requirements, and other 
alternative treatment options. If the subject qualifies and wishes to participate they will 
complete the ICF with a signature and date.  The original will be retained with subject’s records 
and a copy will be provided to the subject. 
The following measurements will be performed and recorded at the specified times throughout 
the study (as specified in Error! Reference source not found.). 
 
 

 
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Clinical Study of the CO2RE Laser Device for Treatment of Vulvar Lichen 
Sclerosus 
Protocol # 
DHF25211 
Rev. Date 
February 19, 2019 
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Table 2. Study Measurements 
 
 
Assessment 
When to conduct 
Method 
Complete the Inform Consent 
form and Eligibility Screening 
and Medical History 
During the screening visit / 
prior to the 1st treatment  
Physician or staff will complete the form 
with the study subject 
PAP smear if not up-to-date 
(within 3 years according to 
ACOG guidelines) 
Patient should provide lab results of up-to-
date normal cell cytology 
Urine pregnancy test for women 
capable of becoming pregnant 
Patient should have a negative pregnancy 
test  
Gynecological exam 
Physician will examine the vulvar and 
vaginal area for any signs of active 
infection or atypical nevi 
Vulvar biopsy of treatment area 
(optional) 
Prior to the 1st treatment and 
at the 6-week and 6-month 
follow-ups 
Biopsies will be obtained from up to 10 
subjects to conduct histological 
assessment. Lab reports will be provided 
to show changes in markers compared to 
baseline.  
Subject assessment of symptoms 
• Baseline or pre-Tx. 1 
• At the 6-week, 3-month, 6-
month and 12-month 
follow-up visits 
Subjects will complete the Symptom 
Severity Questionnaire, according to the 
pre-defined scales (Appendix I) 
Physician assessment 
• Baseline or pre-Tx. 1 
• Prior to treatments  
• At the 6-week, 3-month, 6-
month and 12-month 
follow-up visits 
Physician will assess clinical signs 
associated with VLS, according to the pre-
defined scales (Appendix II) 
Subject assessment of sexual 
function 
• Baseline or pre-Tx. 1 
• At the 3-month and 6-month 
follow-up visits 
Subjects will complete the Female Sexual 
Function Index (FSFI) – Appendix III 
Clinical evaluation and 
photographs of treated area  
• Baseline or pre-Tx. 1 
• Prior to treatments  
• At the 6-week, 3-month, 6-
month and 12-month 
follow-up visits 
Physician will evaluate the treatment area. 
Physician or staff will take photographs of 
the treatment area (Appendix IV) 
Treatment pain assessment 
Immediately after each 
treatment 
NSR Scale (Appendix V) 
Subject 1-week daily diary - 
reviewed at the 1wk FU after the 
first treatment 
The daily diary will be provided 
at the 1st treatment visit and 
reviewed by phone during the 
1-week safety evaluation  
Subjects will be requested to complete a 
daily diary with data regarding their 
comfort, AE, and activity (7 days of follow-
up post 1st treatment) – Appendix VI 

 
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Clinical Study of the CO2RE Laser Device for Treatment of Vulvar Lichen 
Sclerosus 
Protocol # 
DHF25211 
Rev. Date 
February 19, 2019 
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Subject satisfaction rating 
At the 6-week, 3-month, 6-
month and 12-month follow-up 
visits 
Subject will complete the Subject 
Satisfaction Questionnaire, according to 
the pre-defined scale – Appendix VII   
Adverse Events and Serious 
Adverse Events 
During the entire study period: 
prior to and immediately after 
the treatments, during all 
follow-up visits, and whenever 
a safety concern is reported by 
the subject 
Examination of the treated area, interview 
subjects for Adverse Events 
 
 
 
Pre-Treatment Procedures 
Screening procedures may be conducted on a separate day prior to the 1st treatment, but 
preferably within 2 weeks.  
Screening / Initial Evaluation and Baseline 
1. ICF - Prior to any study procedures, written informed consent will be obtained.  Once 
the subject fully understands the possible benefits and risks of the study, the subject will 
be asked to sign and date the informed consent form (ICF).  The subject will be given a 
copy of the signed ICF. 
2. Subject ID - Prior to treatment, the subjects will be assigned a study subject number. 
3. Medical History - A medical history will be obtained to determine if the subject meets 
the study criteria, including a list of all prescribed and over-the-counter medications 
taken within the previous 6 months will be recorded.   
4. PAP smear – each patient should provide up-to-date results of PAP smear with normal 
cell cytology. 
5. Gynecological exam – The study physician will examine the vulvar and vaginal area for 
any signs of active infection, atypical nevi, or breaks, tears or lesions.  
6. Urinalysis - Negative urine pregnancy test for women capable of becoming pregnant.  
7. Patients will complete questionnaires (Subject assessment of symptoms & FSFI). 
8. For up to 10 subjects, a vulvar biopsy will be taken at baseline.    
Vulvar Biopsy Procedure 
For subjects participating in the biopsy subset of the study, a punch, or scissor snip, biopsy will 
be obtained prior to the first treatment and again at the 6-week and 6-month follow up visits.     
The study patient should be informed on the benefits and risks of the procedure and written 
consent obtained. The risks include pain, bleeding, infection, scarring, inadequate sample 
possibly requiring another biopsy procedure, or allergic reaction to anesthetic. 

 
Candela Corporation 
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Clinical Study of the CO2RE Laser Device for Treatment of Vulvar Lichen 
Sclerosus 
Protocol # 
DHF25211 
Rev. Date 
February 19, 2019 
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The biopsy specimen should be taken from the area of the vulva or peri-anal skin that clinically 
appears to have the most active or developed VLS changes.  A 3-mm or 4-mm punch can be 
used in most cases.  A 3-mm punch biopsy is generally thought to be the smallest size that will 
provide an adequate sample of tissue for pathologic analysis.  However, certain locations where 
there is little subcutaneous adipose tissue, such as the labia minora and the clitoral hood, may 
be best sampled by scissor snip technique.  The chosen location and biopsy technique should be 
based on the provider’s best judgment of potential histological change as well as patient 
comfort and healing. Adjacent skin of the same area should be sampled for post-treatment 
follow-up biopsies. 
  
 
Mark the biopsy site with surgical skin marker and photograph the marked location.  To 
minimize patient discomfort, apply topical anesthetic prior to injecting local anesthetic. Then, 
draw 1ml of 1% lidocaine with 1:100,000 epinephrine into a 1ml syringe. Slowly inject the 
anesthetic with a 30-gauge needle.  While this amount of local anesthetic is adequate for the 
majority of patients, additional anesthetic can be injected as clinically warranted. When 
anesthetizing the area, insert the needle and withdraw the plunger to decrease the chance that 
injection occurs into a vessel. Inject slowly at the base of and underneath the lesion, injecting 
enough to create a wheal. If possible, only penetrate the skin once. The wheal should be larger 
than the biopsy instrument that will be used. Adequate anesthesia for the procedure should be 
present in 1-2 minutes. Test for appropriate anesthesia prior to making any incision. As in most 
clinical situations, biopsy is performed shortly after injection. 
 
Once an adequate biopsy sample has been excised, the specimen should be placed carefully in a 
fixative solution, such as 10% formalin. Confirm that the sample is in the container after closing 
the lid. The tissue should to be sent to pathology along with the properly completed pathology 
forms. Insurance information should not be included on the form, as study subjects will not be 
billed for biopsies. Patient Initials and Subject Code should be included on the specimen labels 
(i.e. 001_AMK). 
 
Hemostasis may be achieved with pressure only for small specimens.  In addition to pressure, 
bleeding also may be controlled with suture or gel foam for punch biopsies or with aluminum 
chloride or silver nitrate for scissor snip biopsies.  
 

 
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Clinical Study of the CO2RE Laser Device for Treatment of Vulvar Lichen 
Sclerosus 
Protocol # 
DHF25211 
Rev. Date 
February 19, 2019 
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Petrolatum jelly should be applied to the healing wound after the procedure and at least twice 
daily.  Petrolatum jelly promotes healing and acts as a protective barrier preventing irritation 
from contact with urine, sweat, and friction.  Given the location and difficulties in keeping a 
dressing in place, most vulvar biopsies are not bandaged. Use of a pad or pantyliner may be 
needed for a few days after the biopsy. Mild spotting can be expected for the few days following 
a vulvar biopsy and if bleeding occurs, it can generally be stopped by direct pressure from the 
patient.  
 
Showers are permitted 24 hours after biopsy and the biopsy site should be cleansed once daily 
with a gentle cleanser. Alternatively, the patient may take sitz baths. The use of washcloths, buff 
puffs, soaps, and any type of vigorous cleaning should be avoided while the biopsy site is 
healing.  Swimming and hot tub baths should be avoided until healing is completed.  
 
Prior to Each Treatment Procedure 
1. Hair that exists in the treatment area can be removed by shaving, using a razor or an 
electric razor, or alternatively, hair can be wetted with saline. Hair can also be removed 
by waxing 72 hours before treatment.  
2. Pre-treatment photographs of the treatment area should be taken. 
3. Clinical signs of VLS will be reported. 
4. The device arm should be thoroughly cleaned and washed. 
5. A new disposable external handpiece should be used for each treatment and disposed 
of following the treatment.  
Treatment Procedure (Tx.1 – Tx.5) 
The treatment procedure should be conducted according to the following guidelines, as 
described in the CO2RE User’s Manual: 
Pre-Treatment Instructions 
1. Prior to beginning treatment, a topical anesthetic may be applied to the external labia 
and introitus. EMLA or a compounded formulation can be used. Duration of application 
and anesthetic type is at the discretion of the investigator. Topical anesthetic must be 
thoroughly removed, and the area cleaned prior to beginning treatment. 
2. Dedicated eye protection must be worn during treatment by both the subject and staff. 
3. Care must be taken to avoid unintended exposure of the treatment beam to the 
subject's eye or surrounding skin. Such exposure can cause possible damage. 
Accordingly, the eyes should be protected with non-reflective eye shields. 

 
Candela Corporation 
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Clinical Study of the CO2RE Laser Device for Treatment of Vulvar Lichen 
Sclerosus 
Protocol # 
DHF25211 
Rev. Date 
February 19, 2019 
Page 14 of 39 
 
 
4. Treatment should be performed while the subject is lying down comfortably; the 
operator should have easy access to the subject’s treatment area. 
5. Affected areas of the vulva (vestibule, introitus, medial labial majora, intralabial sulcus, 
labia minora and clitoral hood) will be treated. 
6. Subject should remove their pants and underwear. 
7. Prepare the CO2RE device for the treatment procedure, including cleaning the 
handpiece’s reflecting mirror (wiped and dried well with ≥70% alcohol). 
8. Turn the CO2RE device on and select the treatment parameters. 
Treatment  
1. The distal part of the External handpiece should be clean and dry. The handpiece should 
be held perpendicular to and in close contact with the skin. In the same manner, the 
distal end of the handpiece should be moved to the designated spot. 
2. Prior to treating the entire area, several test spots should be performed in a small 
section within the area to assess the skin for unwanted effects.  
3. The choice of treatment settings should take into consideration the subject’s skin type, 
tendency to bruise, and the specific anatomical location (vulva).  
4. Set the CO2RE treatment parameters according to investigator decision taking into 
consideration the necessary ablation depth (which is influenced from the amount of 
water in the vaginal tissue). 
5. Single pass laser exposures will be performed at a Repeat Rate of 0.5 – 1 seconds, using 
the following parameters: 
Deep Mode 
• 
Core (mJ): 40 – 50  
• 
Fractional Coverage: 3 – 5%  
• 
Pattern size (mm): 7.8 X 7.8 (Square) 
And/or  
Fusion Mode 
• 
Core (mJ): 40 – 70  
• 
Pattern size (mm): ANY, except 7.8 X 7.8 
• 
Ring Fluence (J/cm2): 46 – 87.3 
• 
Fractional Coverage: 20 – 30%  
 
6. Consider dialing down the energy or changing the fractional density if more than pin-
point bleeding occurs.  
7. Do not use pulse stacking or more than a single pass. 

 
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Clinical Study of the CO2RE Laser Device for Treatment of Vulvar Lichen 
Sclerosus 
Protocol # 
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Rev. Date 
February 19, 2019 
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8. Once the user has selected the laser operating parameters and had located the 
handpiece at the proper treatment area, he / she can use the footswitch to activate the 
laser treatment.  
Immediately Post Treatment 
1. The immediate responses, for the desired effect, are erythema, edema and a distinct 
stippled gray fractional epidermolysis pattern that aids in visualization of treatment 
progress. The treatment parameters and treatment response should be noted in the 
CRFs. 
2. Subject will be given a pain (NSR) scale to record the pain level they felt during the 
treatment. 
Post-treatment Instructions for Subject 
Subject will be provided with the following instructions for care of the treated areas as 
described in the informed consent form.   
Following the first treatment: 
1. Subjects will receive a daily diary, which they will be requested to complete, regarding 
their comfort and any adverse events for the 7-day period following treatment.  
Following each treatment session 
1. If the subject experiences itch or discomfort after treatment, ice packs may be applied 
to the treatment area. 
2. Temporary erythema (redness) and edema (swelling), as well as heat and tightening 
sensations, may occur up to a few hours after the treatment. If the subject feels 
significant discomfort longer than a few hours, an over-the-counter pain medication 
such as Tylenol® (Acetaminophen) may be used. Nonsteroidal anti-inflammatory drugs 
(NSAID), such as aspirin, Ibuprofen (Advil, Motrin), naproxen (Aleve, Anaprox, Naprelan, 
Naprosyn), etc. should be avoided unless the patient does not experience symptomatic 
relief with or is contraindicated to acetaminophen.   
3. On the evening after the treatment, subjects should wash the treated areas gently with 
lukewarm water and avoid very hot or cold water in these areas. Generally, subjects 
may use their regular cleanser after treatment, as long as these are not mechanical 
scrubs or exfoliants.  
4. Subject should refrain from sexual activities for a period of 7 days. 
5. Any pain, fever or unusual discharge should be immediately reported. 
 

 
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Follow-up Visits 
1. All subjects will be requested to return to the clinic at the following time-points during 
the study to assess the clinical safety and performance of the device: 
• 
6 weeks post last treatment – 6wk FU ± 2 weeks. 
• 
3 months post last treatment – 3m FU ± 2 weeks. 
• 
6 months post last treatment – 6m FU ± 2 weeks. 
• 
12 months post last treatment – 12m FU ± 2 weeks. 
 
2. At the follow-up visits, the following assessments will be performed, and data recorded: 
o Review changes in medication, medical history and AE, if applicable, from last 
visit. 
o Photographs of treated area. 
o Optional biopsy of treated area (6-week and 6-month follow-up only). 
o Subject assessment of symptom severity. 
o Investigator assessment of clinical signs. 
o Subject Satisfaction. 
DATA ANALYSIS 
Recording 
All data will be recorded on Case Report Forms (CRFs) or transcribed from source 
documentation, where applicable (i.e. lab reports). The site will be monitored by Syneron 
Candela staff or designees to assure adherence to the clinical trial requirements, subject safety, 
protocol procedures, and for data accuracy. The Case Report Forms and images will be reviewed 
and retrieved during the monitoring visit.  All source documentation will remain in the subject's 
files at the site. 
Review and Analysis of all data collected will be conducted by the Sponsor or designee as 
described for this protocol with the following data: 
Demography and Baseline Measurements 
Demographic and baseline/screening measurements (e.g., age, weight, clinical VLS signs and 
digital images) will be collected and descriptively presented. 

 
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Treatment Visits 
Clinical VLS signs as assessed by the study investigator, photographs of the treated region, and 
NSR scores will be collected and compared to baseline to assess efficacy and safety. Any 
potential adverse events will be documented. 
Follow-up Visit Measurements 
Follow-up measurements, efficacy and satisfaction assessment scores, and digital images will be 
used for comparative measurements with their respective data at baseline.  Primary endpoints 
will be evaluated at the 6-week, 3-month, 6-month and 12-month follow-up visit.  
Safety 
Safety of device procedure will be evaluated throughout the study. Any side effects to the 
treated area will be reported by the subject, the study investigator and the research staff.  The 
occurrence and severity of all complications from the start of the study will be recorded. 
ADVERSE EVENTS (AE) 
An adverse event (AE) is any adverse change in health or side effect that occurs in a study 
participant during their participation in the study. 
Anticipated Adverse Effects 
An adverse event (AE) is any undesired clinical occurrence in a study subject as indicated by 
signs, symptoms, illnesses, events that develop or worsen in severity in association with the 
study when deemed by the Investigator to be related to use of the device or study procedures.  
Anticipated post-treatment adverse effects which could result from the CO2RE treatment 
include pain, swelling, bruising (ecchymosis), blistering, burn, and infection. 
The Investigator will document all adverse signs and symptoms regardless of severity or 
frequency that are either volunteered by subjects or observed during the course of the study 
that are related to the device.  The Investigator will also record adverse experiences of subjects 
resulting from concurrent illnesses, reactions to concurrent medications, or progression of 
disease states that the Investigator deems related to the device. Included in the description will 
be the nature of the sign or symptom, the date of onset, whether the event was serious, the 
severity, the relationship to study procedures or investigational device, the action taken, the 
date of resolution, and the outcome. The Principal Investigator will determine the relationship 
of the adverse device effect to the investigational device. 

 
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Clinical Study of the CO2RE Laser Device for Treatment of Vulvar Lichen 
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Rev. Date 
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Unanticipated Adverse Device Effects 
For device studies, part 21 CRF 812.3(s) uses the term unanticipated adverse device effect which 
is defined as any serious adverse effect on health or safety or any life-threatening problem or 
death caused by, or associated with, a device, if that effect, problem, or death was not 
previously identified in nature, severity, or degree of incidence in the investigational plan or 
application (including a supplementary plan or application), or any other unanticipated serious 
problem associated with a device that relates to the rights, safety, or welfare of subjects. 
All unanticipated adverse effects will be graded as follows: 
Mild: 
Sign or symptom, usually transient, non-life-threatening requiring no special 
treatment and generally not interfering with usual activities. 
Moderate: 
Sign or symptom, non-life-threatening which may be ameliorated by simple 
therapeutic measures and may interfere with usual activity. 
Severe: 
Sign or symptom that is intense or debilitating but non-life-threatening and 
that interferes with usual activities. Recovery is usually aided by therapeutic 
measures and the discontinuation of the study device may be required. 
Serious: 
Any untoward medical occurrence that at any time results in death or life-
threatening illness, resulting in persistent or significant disability/incapacity.   
 
The relationship of the adverse effect to the study is defined as follows: 
 
Probable: 
An adverse event has a strong temporal relationship to study device, and 
another etiology is unlikely or significantly less likely. 
Possible: 
An adverse event has a strong temporal relationship to the study device, and 
an alternative etiology is equally or less likely compared to the potential 
relationship to study device.  
Probably not: 
An adverse event has little or no temporal relationship to the study device 
and/or a more likely alternative etiology exists. 
Not related: 
An adverse event has no temporal relationship to study device or has a much 
more likely alternative etiology.  
Reporting Adverse Events (AE) and Serious Adverse Events (SAE) 
 
The Investigator must report all unanticipated adverse device events that are serious in nature 
to the clinical study monitor immediately or within twenty-four hours by telephone (see below). 
If such an unanticipated adverse device event is reported after normal working hours, the 

 
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Clinical Study of the CO2RE Laser Device for Treatment of Vulvar Lichen 
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Investigator will leave a voice message at the monitor’s telephone number with accompanying 
report of the unanticipated adverse device event sent to the e-mail address below:  
 
Sharon Timberlake, Global VP of Clinical and Regulatory Affairs 
Candela Corporation 
Telephone Number (mobile): +1 (617) 957-1434 
 Email: sharont@syneron-candela.com 
   
 
A written report prepared by the Principal Investigator must follow within five working days to 
both the IRB and to Candela Corporation and should include a full description of the event and 
sequence. 
 
Research records will be available to study personnel, the sponsor, Ethics Review 
Committee/Institutional Review Board (IRB) and regulatory agencies as required.  Research 
records may be used for purposes of medical education, after removal of subject names or other 
identifying information.  In the Informed Consent, the subjects will be informed that the 
photographs and video taken of them during the study may be made available to the sponsor 
for marketing and instructional purposes, after removal of identifying information.  All images 
collected will be stored without personal subject identifiers at the site and at Syneron Candela. 
Device Failures and Malfunctions 
Definitions of Device Failure 
Device Failure: A device has failed if it is used according to the Sponsor's instructions but has 
failed to perform as expected.  
Device Malfunction: A device malfunction is an unexpected malfunction of the device that is 
contrary to expectations when operated according to the Sponsor's instructions.  
Device Misuse: A failure of a misused device, namely one that is used by the Investigator in a 
manner which is contradictory to the Sponsor's instructions, will not be considered a device 
malfunction. 
Precautions to Minimize Complications 
Every precaution should be taken pre-, during and post-procedure to minimize technical and 
procedural complications. 
• 
All conventional precautions relating to this type of procedure must be taken, as with 
any other procedure. 

 
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• 
All failures and malfunctions of the device will be documented in the database, and the 
device MUST be returned to the Sponsor for analysis. Device failures and malfunctions 
should also be documented in the subject’s medical record. (NOTE: Device failures or 
malfunctions are NOT to be reported as adverse events. However, if there is an adverse 
event that results from a device failure or malfunction, that specific event would be 
recorded accordingly). 
RISK/ BENEFIT ANALYSIS 
Risks 
Candela Corporation has determined that the CO2RE system is a non-significant risk in 
accordance with 21 CFR 812.3 for the intended use in this study. 
During design and development of the mentioned device, design measures were taken, and 
tests were performed to ensure treatment safety. These included selection of biocompatible 
materials, directions for appropriate cleaning to prevent cross-infection, electromechanical 
safety testing and electromagnetic compatibility testing. A large amount of clinical data (clinical 
studies and post-marketing data) using different devices for dermatological and gynecological 
procedures, including Syneron Candela devices, which are like the CO2RE device, demonstrate a 
very good safety and efficacy profile. Nevertheless, potential risks for adverse effects of the 
treatment procedure include, but are not limited to pain, swelling, bruising (ecchymosis), 
blistering, burn, and infection. 
Potential benefits to participating individuals and to society 
Subjects may or may not benefit from improvement in lichen sclerosus.  All subjects in the study 
are expected to have some benefit from the treatment procedures. Subject will receive 
treatment procedures at no cost.  This study will benefit the advancement of medicine by 
generating data on safety and efficacy that will aid in the development of an alternative 
treatment options to ultra-potent topical corticosteroids (such as clobetasol propionate).  This 
study will benefit the advancement of medicine by generating data on safety and efficacy that 
will aid in the development of an alternative or adjunctive treatment option for female patients 
who do not improve with topical corticosteroid use for vulvar lichen sclerosus. 
 
 

 
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Clinical Study of the CO2RE Laser Device for Treatment of Vulvar Lichen 
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Protocol # 
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Rev. Date 
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Payment for Participation 
Subjects will be paid a total of up to $200 for up to 10 study visits ($20 per visit) for all study 
visits and evaluations. Subjects will not pay for office visits, examinations or procedures that are 
part of this clinical study. Subjects who do not complete all study-related procedures and 
requirements will receive partial payments according to the treatment and follow-up visits that 
were completed ($20 per visit). Subjects who are biopsied at baseline, at the 6-week follow-up 
and the 6-month follow-up will receive an additional $200 (~$67 per visit). Payments will be 
issued upon study completion. 
ETHICS AND GOOD CLINICAL PRACTICE 
This study will be carried out in compliance with the following: 
o Syneron Candela’s Standard Operating Procedures (SOPs). 
o Declaration of Helsinki (current version). 
o US Code of Federal Regulations (Title 21CFR including parts 50, 56 and 812 governing 
informed consent and IRB regulations). 
o International Conference on Harmonization (ICH) Harmonized Tripartite Guideline for 
Good Clinical Practice (GCP), 1996. 
 
QUALITY ASSURANCE AND STUDY MONITORING 
Study Monitoring/Auditing/Inspection 
The Study Monitor will be responsible for monitoring the study sites to review the data being 
collected. The sponsor shall implement and maintain quality control and quality assurance 
procedures with written standard operating procedures (SOPs) to ensure that the trial is being 
conducted and data are generated, documented and reported in compliance with the protocol, 
Good Clinical Practice (GCP) and applicable regulatory requirements. Visits will be made prior to 
the initiation of the study, at scheduled intervals throughout the study, and at termination of 
the study. 
Once enrollment and treatments have begun, monitoring visits will take place more frequently 
pending enrollment and study activities.    
The sponsor and site will maintain regular phone and e-mail correspondence throughout the 
study to confirm compliance of study procedures.   
 The investigator/institution agrees to allow the study monitor and other authorized personnel 
direct access to source data/documents for trial related monitoring, the clinical supplies 

 
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Clinical Study of the CO2RE Laser Device for Treatment of Vulvar Lichen 
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storage/dispensing area and to provide all documents in the Investigator Regulatory Binder for 
review, and to assist site auditors in their activities if requested. Requests by the United Stated 
Food and Drug Administration (FDA) or regulatory agencies of other countries to inspect the 
study site may be made after adequate notification. The investigator may be required to assist 
the regulatory inspectors in their duties, if requested. 
ADMINISTRATIVE PROCEDURES 
Supply and Disposition of Study Devices 
The CO2RE Intima disposable external handpieces will be supplied to the participating clinics. 
Unused equipment will be returned to the sponsor at the end of the study.   
Control & Disposition of the Investigational Device 
The CO2RE system will be used according to the instructions of the Sponsor, Candela 
Corporation, and the manufacturer, Syneron Medical Ltd.  At the end of this study, any materials 
provided specifically for use in this study must be returned to the Sponsor, as described in the 
Clinical Trial Agreement and study budget.  
Informed Consent 
The Study Personnel will obtain written Informed Consent prior to the subject’s participation in 
any study procedures.  The Study Personnel will inform the subjects of the experimental 
procedure to be utilized and assure the subjects that their decision regarding participation in the 
study will have no bearing on the quality of medical care received and that their decision 
whether to participate in the study is strictly voluntary.  
During the initial interview, the subject will be assured that they are free to change their mind 
and will be allowed to participate in the study or withdraw from the study with no adverse 
effect on their standard medical care.   
Monitoring Plan 
At least 3 monitoring visits are projected during the whole study. The frequency of which will be 
based on enrollment, study activities and the study visit scheduled.  The first visit is scheduled at 
the initiation of the study prior to the first subject treatment in the study.  The second visit is 
scheduled after enrollment and treatment has been initiated and a third visit will be for a close-
out visit for the study.  Interim visits may be conducted as needed to assure compliance to the 
study protocol and regulatory requirements.   The number and frequency of monitoring visits 
may also be increased per the sponsor decision to collect data and images post treatment. 

 
Candela Corporation 
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Clinical Study of the CO2RE Laser Device for Treatment of Vulvar Lichen 
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Protocol # 
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Rev. Date 
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Case Report Forms 
Paper case report forms will be used in this trial. All protocol-required information collected 
during the study must be entered in the appropriate field of the case report form (CRF). The 
investigator, or designated representative, should complete the appropriate CRF fields as soon 
as possible after information is collected. The information must match the information that 
exists as source documents in the clinic chart, hospital chart, and/or investigator’s files. An 
explanation should be given for all missing data. 
It is the investigator’s responsibility to assure the accurate completion, review, and approval of 
all CRFs and the timely completion and submission of all adverse event forms. 
Record Maintenance 
The investigator shall retain a copy of all study documents in accordance with FDA regulations 
which specify that records should be kept for a period of two years: 1) following the date a 
marketing application either is approved or disapproved for use, or 2) following notification to 
the FDA that no application is being filed and/or that the study has been discontinued.  
If an investigator leaves the study site before record retention obligations have expired, the 
sponsor should be notified in writing of the person designated to retain the study documents 
during and after the study. 
Handling of clinical data.  The data are entered into a secure database to which only the Sponsor 
has access.  Admission to the database should require access to a password-protected network 
secured by the Sponsor. This database is maintained by Syneron Corporation who performs 
backups, data verification, and application upgrades. All equipment housing the clinical data 
should be located in locked rooms or a secure computer network.  The only individuals, who 
view, extract and analyze data for protocol reports and publications are physicians and nurses 
who are members of the study team or sponsors. Only authorized personnel of the sponsors will 
have access to databases.  
Any paper copies of subject medical records or research records should be stored in secure 
cabinets at the study site.  
PUBLICATION POLICY 
The investigator will not publish the study results and will not disclose confidential information 
received from Candela Corporation without prior written agreement from Syneron. Such 
confidential information shall include any and all information relating to this study as described 
in the Clinical Trial Agreement.  In the event that Candela Corporation consents to the 
publication of data from this study, the investigator will provide Candela Corporation 
manuscripts for review sixty (60) days before submission for publication. Candela Corporation 

 
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Clinical Study of the CO2RE Laser Device for Treatment of Vulvar Lichen 
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Rev. Date 
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will have no editorial rights over manuscripts. The investigator will also provide Candela 
Corporation with advance notice of at least sixty (60) days, of any presentation, lecture, abstract 
session, etc., in which any results from the study will be disclosed. 
REFERENCES 
 
1. Fistarol SK, Itin PH. Diagnosis and treatment of lichen sclerosus: an update. Am J Clin 
Dermatol. 2013 Feb;14(1):27-47. 
2. Pugliese JM, Morey AF, Peterson AC. Lichen sclerosus: review of the literature and 
current recommendations for management. J Urol. 2007;178(6):2268-2276. 
3. Halonen P, Jakobsson M, Heikinheimo O, et al. Lichen sclerosus and risk of cancer. Int J 
Cancer. 2017 May 1;140(9):1998-2002. 
4. Chi CC, Kirtschig G, Baldo M, Lewis F, Wang SH, Wojnarowska F. Systematic review and 
meta-analysis of randomized controlled trials on topical interventions for genital lichen 
sclerosus. J Am Acad Dermatol. 2012;67(2):305-312. 
5. Pérez-López FR, Vieira-Baptista P. Lichen sclerosus in women: a review. Climacteric. 
2017 Aug;20(4):339-347.  
6. Thorstensen KA, Birenbaum DL. Recognition and management of vulvar dermatologic 
conditions: lichen sclerosus, lichen planus, and lichen simplex chronicus. J Midwifery 
Womens Health. 2012 May-Jun;57(3):260-75. 
7. Berlin AL, Hussain M, Phelps R, Goldberg DJ. A prospective study of fractional scanned 
nonsequential carbon dioxide laser resurfacing: a clinical and histopathologic evaluation. 
Dermatol Surg. 2009 Feb;35(2):222-8.  
8. Arroyo C. Fractional CO2 laser treatment for vulvovaginal atrophy symptoms and vaginal 
rejuvenation in perimenopausal women. Int J Womens Health. 2017 Aug 28;9:591-595. 
9. Athanasiou S, Pitsouni E, Antonopoulou S, et al. The effect of microablative fractional 
CO2 laser on vaginal flora of postmenopausal women. Climacteric. 2016 Oct;19(5):512-
8.  
10. Salvatore S, Leone Roberti Maggiore U, et al. Histological study on the effects of 
microablative fractional CO2 laser on atrophic vaginal tissue: an ex vivo study. 
Menopause. 2015 Aug;22(8):845-9. 
11. Lee A, Lim A, Fischer G. Fractional carbon dioxide laser in recalcitrant vulval lichen 
sclerosus. Australas J Dermatol. 2016 Feb;57(1):39-43. 
12. D. Chhieng and P. Hui (eds.), Cytology and Surgical Pathology of Gynecologic Neoplasms. 
Current Clinical Pathology, DOI 10.1007/978-1-60761-164-6_2. 

 
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13. Sheinis M, Selk A. Development of the Adult Vulvar Lichen Sclerosus Severity Scale-A 
Delphi Consensus Exercise for Item Generation. J Low Genit Tract Dis. 2018 Jan;22(1):66-
73.  
14. Rosen R, Brown C, Heiman J, et al. The Female Sexual Function Index (FSFI): a 
multidimensional self-report instrument for the assessment of female sexual function. J 
Sex Marital Ther. 2000 Apr-Jun;26(2):191-208. 
 
 
 
 
 

 
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APPENDIX I – SUBJECT SYMPTOMS SEVERITY SCALE* 
 
At baseline and at the four follow-up visits, the study subject will complete assessments for 
severity of the following symptoms associated with their vulvar lichen sclerosus. 
 
Subject Symptoms 
 
Symptom 
Presence of symptoms 
Severity 
Itch  
Yes / No 
1, absent/never  
2, sometimes/occasionally  
3, often  
4, most of the time  
5, all the time 
Pain unrelated to intercourse 
(burning, soreness, 
discomfort, etc.) 
Yes / No 
1, absent/never  
2, sometimes/occasionally  
3, often  
4, most of the time  
5, all the time 
 
Superficial (introital) 
dyspareunia (pain occurring 
at the moment of 
penetration)  
Yes / No 
1, absent/never  
2, sometimes/occasionally  
3, often  
4, most of the time  
5, all the time 
 
 

 
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Skin tearing or external 
bleeding with intercourse  
Yes / No 
1, absent/never  
2, sometimes/occasionally  
3, often  
4, most of the time  
5, all the time 
Quality of life  
Yes / No 
1, no impact 
2, barely affected 
3, slightly affected 
4, moderately affected 
5, strongly affected 
Decrease in sexual function – 
desire to have sexual 
intercourse is decreased due 
to physical appearance or 
self-esteem 
Yes / No 
1, no impact 
2, barely affected 
3, slightly affected 
4, moderately affected 
5, strongly affected 
 
 
 
*Based on: Sheinis M, Selk A. Development of the Adult Vulvar Lichen Sclerosus Severity Scale-A 
Delphi Consensus Exercise for Item Generation. J Low Genit Tract Dis. 2018 Jan;22(1):66-73. doi: 
10.1097/LGT.0000000000000361. 
 
 
 
 
 
 
 

 
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APPENDIX II – CLINICAL SIGNS AND ARCHITECTURAL CHANGES SEVERITY SCALE* 
 
At baseline, prior to treatments and at the four follow-up visits, the study investigator will 
complete assessments for severity of the following clinical signs associated with vulvar lichen 
sclerosus. 
 
 
Sign 
Presence of signs 
Severity 
Fissures 
Yes / No 
1, mild  
2, moderate  
3, severe  
Whitening 
Yes / No 
1, mild  
2, moderate  
3, severe  
Crinkly/fine wrinkling of 
skin/parchment-like skin 
Yes / No 
1, mild  
2, moderate  
3, severe  
Extent of disease (figure of 
eight vs localized to labia, 
localized to 
clitoris, localized to perineum 
or combined) 
 
Yes / No 
1, mild  
2, moderate  
3, severe  
Erosions 
Yes / No 
1, mild  
2, moderate  
3, severe  
Ulcerations 
Yes / No 
1, mild  
2, moderate  
3, severe  
 
 

 
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Hyperkeratosis 
Yes / No 
1, mild  
2, moderate  
3, severe  
Excoriations 
Yes / No 
1, mild  
2, moderate  
3, severe  
Lichenification 
Yes / No 
1, mild  
2, moderate  
3, severe  
Elasticity (or loss of elasticity) 
Yes / No 
1, mild  
2, moderate  
3, severe  
Sclerosis 
Yes / No 
1, mild  
2, moderate  
3, severe  
Telangiectasia 
Yes / No 
1, mild  
2, moderate  
3, severe  
 
 
Architectural changes 
Presence of changes 
Severity 
Clitoral hood fusion  
Yes / No 
1, mild  
2, moderate  
3, severe  
Labial fusion/resorption  
Yes / No 
1, mild  
2, moderate  
3, severe  
 
 

 
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Narrowing of the introitus  
Yes / No 
1, mild  
2, moderate  
3, severe  
Anterior changes (fusion 
anteriorly below the clitoris, 
causing 
Yes / No 
1, mild  
2, moderate  
3, severe  
urethral occlusion at its 
extreme) 
Yes / No 
1, mild  
2, moderate  
3, severe  
Perianal involvement  
Yes / No 
1, mild  
2, moderate  
3, severe  
Formation of posterior 
commissure 
bands/fourchette webs 
Yes / No 
1, mild  
2, moderate  
3, severe  
 
*Sheinis M, Selk A. Development of the Adult Vulvar Lichen Sclerosus Severity Scale-A Delphi 
Consensus Exercise for Item Generation. J Low Genit Tract Dis. 2018 Jan;22(1):66-73. doi: 
10.1097/LGT.0000000000000361. 
 
 

 
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APPENDIX III – FEMALE SEXUAL FUNCTION INDEX* 
 
 
 

 
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* Rosen R, Brown C, Heiman J, et al. The Female Sexual Function Index (FSFI): a 
multidimensional self-report instrument for the assessment of female sexual function. J Sex 
Marital Ther. 2000 Apr-Jun;26(2):191-208. 
 
 

 
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APPENDIX IV – PHOTOGRAPHY GUIDELINES 
 
 
At each time point (before the treatments and at the follow‐up visits), photographs of the 
treated area should be taken in a standardized manner. 
o Photographs should be taken in a private room or area of the clinic under controlled 
conditions, including the distance from the camera to the subject, height of the camera, 
background, camera positioning, subject's positioning and lighting in order to achieve 
high quality before & after sets. 
o For consistency purposes, the same person should ideally take all study photographs, 
especially per subject. 
o Small plain labels (with the date, subject ID, subject initials, Investigator name, and 
identity of the specific area photographed, if necessary) should be placed in the same 
location within each frame at each photography timepoint. The presence of the label 
should not impair the photo’s desired effect or obscure the treated area. 
o The digital files should be labeled in a standardized manner (subject number, subject 
initials, study visit). For example: 001JS_Tx1, 001JS_FU1, etc. 
 
 
 

 
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Rev. Date 
February 19, 2019 
Page 37 of 39 
 
 
APPENDIX V – TREATMENT-ASSOCIATED PAIN ASSESSMENT 
 
 
Immediately after each treatment, the subject will be asked to rate pain/discomfort associated 
with the treatment, based on the following Numerical Scale Response (NSR).  The subject will be 
given a horizontal line scale and asked to make a mark along the scale. The subject will be asked 
to rate pain from 0 to 10, with 0 equaling no pain and 10 equaling the worst possible pain. A 
number is obtained by measuring up to the point the subject has indicated. 
 
 
 
 
 
 
 
 
 

 
Candela Corporation 
Confidential 
Clinical Study of the CO2RE Laser Device for Treatment of Vulvar Lichen 
Sclerosus 
Protocol # 
DHF25211 
Rev. Date 
February 19, 2019 
Page 38 of 39 
 
 
APPENDIX VI – SUBJECT POST-TREATMENT DAILY DIARY QUESTIONNAIRE 
 
At the 1st treatment study visit, subjects will be provided with a 1-week daily diary and 
instructed to rate the discomfort they experienced on the day of treatment and each day 
following treatment, according to the following scale:  
 
 
Score and Rate 
❑ 
0 - No Discomfort 
❑ 
1 - Mild Discomfort 
❑ 
2 - Moderate Discomfort, but 
tolerable 
❑ 
3 - Very Painful, barely tolerable 
 
Additionally, subjects will be instructed to report any adverse (side) effects during the 
first week post-treatment and to describe the event on the questionnaire.   
 
 
 
 

 
Candela Corporation 
Confidential 
Clinical Study of the CO2RE Laser Device for Treatment of Vulvar Lichen 
Sclerosus 
Protocol # 
DHF25211 
Rev. Date 
February 19, 2019 
Page 39 of 39 
 
 
APPENDIX VII – SUBJECT SATISFACTION SCALE 
 
Subject satisfaction will be assessed at the 6-week, 3-month, 6-month and 12-month follow-up 
visits, according to the following scale:  
Score 
Improvement Rate 
-2 
Very dissatisfied 
-1 
Dissatisfied 
0 
Uncertain 
1 
Satisfied 
2 
Very satisfied