A Prospective Triple-Blinded Single-Center Study of Laser-Assisted 5-Fluorouracil Versus Laser-Assisted Corticosteroid Treatment for Keloids
Phase: PHASE4
Conditions: Keloid Scar
Sponsor: NYU Langone Health

 
 
Official Title: 
A Prospective Triple-Blinded Single-Center Study of Laser-Assisted 5-
Fluorouracil Versus Laser-Assisted Corticosteroid Treatment for Keloids   
NCT Number: 
NCT04786210 
Study Number: 
20-01172 
Document Type:  
Study Protocol and Statistical Analysis Plan 
Date of the 
Document: 
• 
December 16, 2021 
 
 

 
 
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A PROSPECTIVE SINGLE-SUBJECT TRIPLE-BLINDED SINGLE-
CENTER STUDY OF LASER-ASSISTED 5-FLUOROURACIL VERSUS 
LASER-ASSISTED CORTICOSTEROID TREATMENT FOR KELOIDS 
 
 
Principal Investigator: 
 
Nayoung Lee, MD  
The Ronald O. Perelman Department of Dermatology  
240 East 38th Street, 11th Floor, Manhattan, NY 10016 
Nayoung.lee@nyulangone.org  
212-263-7019  
Additional Investigators: 
 
Lisa Akintilo, MD, MPH 
The Ronald O. Perelman Department of Dermatology  
240 East 38th Street, 11th Floor, Manhattan, NY 10016 
Lisa.akintilo@nyulangone.org 
 
Daniel Gutierrez, MD 
The Ronald O. Perelman Department of Dermatology  
240 East 38th Street, 11th Floor, Manhattan, NY 10016 
Daniel.gutierrez2@nyulangone.org 
 
Kristen Lo Sicco, MD 
The Ronald O. Perelman Department of Dermatology  
240 East 38th Street, 11th Floor, Manhattan, NY 10016 
Kristen.losicco@nyulangone.org 
 
Marleigh Stern, MD 
The Ronald O. Perelman Department of Dermatology  
240 East 38th Street, 11th Floor, Manhattan, NY 10016 
Marleigh.stern@nyulangone.org 
 
Rachel Sally, Research Fellow 
NYU Grossman School of Medicine 
550 First Avenue, Manhattan, NY 10016 
Rachel.sally@nyulangone.org 
 
Benjamin A. Levinson, PhD, Biostatistician 
NYU Grossman School of Medicine 
Department of Population Health  
Benjamin.levinson@nyulangone.org 
 
NYULMC Study Number: 
s-20-01172 
 
Initial version: December 30, 2020 
 

Study number: s20-01172 
 
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Statement of Compliance 
  
This study will be conducted in accordance with the Code of Federal Regulations on the Protection of 
Human Subjects (45 CFR Part 46), 21 CFR Parts 50, 56, 312, and 812 as applicable, any other applicable 
US government research regulations, and institutional research policies and procedures. The International 
Conference on Harmonisation (“ICH”) Guideline for Good Clinical Practice (“GCP”) (sometimes referred to 
as “ICH-GCP” or “E6”) will be applied only to the extent that it is compatible with FDA and DHHS regulations. 
The Principal Investigator will assure that no deviation from, or changes to the protocol will take place 
without documented approval from the Institutional Review Board (IRB), except where necessary to 
eliminate an immediate hazard(s) to the trial participants. All personnel involved in the conduct of this study 
have completed Human Subjects Protection Training. 
 
 

Study number: s20-01172 
 
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Table of Contents 
 
STATEMENT OF COMPLIANCE ................................................................................................................. II 
LIST OF ABBREVIATIONS......................................................................................................................... VI 
PROTOCOL SUMMARY .............................................................................................................................. 1 
1 
KEY ROLES ......................................................................................................................................... 3 
2 
INTRODUCTION, BACKGROUND INFORMATION AND SCIENTIFIC RATIONALE ....................... 4 
2.1 
BACKGROUND INFORMATION AND RELEVANT LITERATURE ................................................................ 4 
2.2 
NAME AND DESCRIPTION OF THE INVESTIGATIONAL AGENTS  ............................................................ 5 
2.2.1 
Clinical Data to Date ................................................................................................................ 6 
2.2.2 
Dose Rationale (if applicable) ................................................................................................. 7 
2.3 
RATIONALE .................................................................................................................................... 7 
2.4 
POTENTIAL RISKS & BENEFITS ........................................................................................................ 8 
2.4.1 
Known Potential Risks ............................................................................................................. 8 
2.4.2 
Known Potential Benefits ........................................................................................................ 8 
3 
OBJECTIVES AND PURPOSE ........................................................................................................... 8 
3.1 
PRIMARY OBJECTIVES .................................................................................................................... 8 
3.2 
SECONDARY OBJECTIVE ................................................................................................................. 8 
4 
STUDY DESIGN AND ENDPOINTS .................................................................................................... 9 
4.1 
DESCRIPTION OF STUDY DESIGN .................................................................................................... 9 
4.2 
STUDY ENDPOINTS....................................................................................................................... 10 
4.2.1 
Primary Study Endpoints ....................................................................................................... 10 
4.2.2 
Secondary Study Endpoint .................................................................................................... 10 
5 
STUDY ENROLLMENT AND WITHDRAWAL .................................................................................. 11 
5.1 
INCLUSION CRITERIA .................................................................................................................... 11 
5.2 
EXCLUSION CRITERIA ................................................................................................................... 11 
5.3 
STRATEGIES FOR RECRUITMENT AND RETENTION .......................................................................... 11 
5.4 
DURATION OF STUDY PARTICIPATION ............................................................................................ 11 
5.5 
TOTAL NUMBER OF PARTICIPANTS AND SITES ................................................................................ 11 
5.6 
PARTICIPANT WITHDRAWAL OR TERMINATION ................................................................................ 12 
5.6.1 
Reasons for Withdrawal or Termination ................................................................................ 12 
5.6.2 
Handling of Participant Withdrawals or Termination ............................................................. 12 
5.7 
PREMATURE TERMINATION OR SUSPENSION OF STUDY .................................................................. 12 
6 
STUDY AGENT (STUDY DRUG, DEVICE, BIOLOGIC, VACCINE ETC.) AND/OR PROCEDURAL 
INTERVENTION ......................................................................................................................................... 12 
6.1 
STUDY AGENT(S) AND CONTROL DESCRIPTION .............................................................................. 12 
6.1.1 
Acquisition ............................................................................................................................. 12 
6.1.2 
Formulation, Appearance, Packaging, and Labeling ............................................................ 12 
6.1.3 
Product Storage and Stability ................................................................................................ 13 
6.1.4 
Preparation ............................................................................................................................ 13 
6.1.5 
Dosing and Administration .................................................................................................... 13 
6.1.6 
Route of Administration ......................................................................................................... 13 
6.1.7 
Dose Adjustments/Modifications/Delays ............................................................................... 13 
6.1.8 
Duration of Therapy ............................................................................................................... 13 
6.1.9 
Tracking of Dose ................................................................................................................... 13 
6.1.10 
Device Specific Considerations ........................................................................................ 13 
6.2 
STUDY PROCEDURAL INTERVENTION(S) DESCRIPTION ................................................................... 13 
6.2.1 
Administration of Procedural Intervention ............................................................................. 13 

Study number: s20-01172 
 
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6.2.2 
Procedures for Training of Clinicians on Procedural Intervention ......................................... 14 
7 
STUDY PROCEDURES AND SCHEDULE ....................................................................................... 14 
7.1 
STUDY PROCEDURES/EVALUATIONS ............................................................................................. 14 
7.1.1 
Study Specific Procedures .................................................................................................... 14 
- 
STUDY SCHEDULE RESEARCH COORDINATOR (SC WILL ASSIST WITH FIELDING PATIENT CALLS AND 
ORGANIZING PATIENT SCHEDULING. ............................................................................................................ 14 
7.1.2 
Pre-Screening Phone Call (Dermatology Clinical Studies Unit, 240 East 38th Street, 11th floor, 
New York, NY 10016) ......................................................................................................................... 14 
7.2 
SCREENING (VISIT 0, TO BE COMPLETED AT 222 EAST 41ST STREET, NEW YORK NY 10017) ........... 15 
7.2.1 
Treatment Visits..................................................................................................................... 15 
7.2.2 
Final Study Visit ..................................................................................................................... 15 
7.2.3 
Withdrawal/Early Termination Visit........................................................................................ 15 
7.2.4 
Unscheduled Visit .................................................................................................................. 15 
7.3 
PROPHYLACTIC MEDICATIONS, TREATMENTS, AND PROCEDURES ................................................... 16 
8 
ASSESSMENT OF SAFETY ............................................................................................................. 16 
8.1.1 
Definition of Adverse Events (AE) ......................................................................................... 16 
8.1.2 
Definition of Serious Adverse Events (SAE) ......................................................................... 16 
8.1.3 
Definition of Unanticipated Problems (UP) ............................................................................ 16 
8.2 
CLASSIFICATION OF AN ADVERSE EVENT ....................................................................................... 17 
8.2.1 
Severity of Event ................................................................................................................... 17 
8.2.2 
Relationship to Study Agent .................................................................................................. 17 
8.2.3 
Expectedness ........................................................................................................................ 17 
8.3 
TIME PERIOD AND FREQUENCY FOR EVENT ASSESSMENT AND FOLLOW-UP .................................... 17 
9 
DATA SAFETY MONITORING PLAN ............................................................................................... 18 
10 
STATISTICAL CONSIDERATIONS .................................................................................................. 18 
10.1 SAMPLE SIZE CONSIDERATIONS ......................................................................................................... 18 
10.2 STATISTICAL METHODS ..................................................................................................................... 19 
10.2.1 General Methods ..................................................................................................................... 19 
10.2.2 Demographics and Baseline Characteristics .......................................................................... 19 
10.2.3 Primary Analysis ...................................................................................................................... 19 
10.1 
MEASURES TO MINIMIZE BIAS ....................................................................................................... 20 
10.1.1 
Enrollment/Randomization/Masking Procedures .............................................................. 20 
11 
QUALITY ASSURANCE AND QUALITY CONTROL ....................................................................... 21 
12 
ETHICS/PROTECTION OF HUMAN SUBJECTS ............................................................................. 21 
12.1 
ETHICAL STANDARD ..................................................................................................................... 21 
12.2 
INSTITUTIONAL REVIEW BOARD ..................................................................................................... 21 
12.3 
INFORMED CONSENT PROCESS .................................................................................................... 21 
12.3.1 
Consent and Other Informational Documents Provided to Participants ........................... 21 
12.3.2 
Consent Procedures and Documentation ......................................................................... 21 
12.4 
PARTICIPANT AND DATA CONFIDENTIALITY .................................................................................... 22 
13 
DATA HANDLING AND RECORD KEEPING ................................................................................... 23 
13.1 
DATA COLLECTION AND MANAGEMENT RESPONSIBILITIES .............................................................. 23 
13.2 
STUDY RECORDS RETENTION ....................................................................................................... 23 
13.3 
PROTOCOL DEVIATIONS ............................................................................................................... 23 
 
PUBLICATION AND DATA SHARING POLICY.............................................................................................. 23 
13.4 ......................................................................................................................................................... 23 
14 
STUDY FINANCES ............................................................................................................................ 24 
14.1 
FUNDING SOURCE ........................................................................................................................ 24 
14.2 
COSTS TO THE PARTICIPANT ......................................................................................................... 24 

Study number: s20-01172 
 
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14.3 
PARTICIPANT REIMBURSEMENTS OR PAYMENTS ............................................................................ 24 
15 
STUDY ADMINISTRATION ............................................................................................................... 24 
15.1 
STUDY LEADERSHIP ..................................................................................................................... 24 
16 
CONFLICT OF INTEREST POLICY .................................................................................................. 24 
17 
REFERENCES ................................................................................................................................... 25 
18 
ATTACHMENTS ................................................................................................................................ 27 
19 
SCHEDULE OF EVENTS .................................................................................................................. 28 
 
 

Study number: s20-01172 
 
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List of Abbreviations 
AE 
Adverse Event/Adverse Experience 
HIPAA 
Health Insurance Portability and Accountability Act 
ICF 
Informed Consent Form 
IRB 
Institutional Review Board 
N 
Number (typically refers to participants) 
PI 
Principal Investigator 
US 
United States 
  
5FU 
 
5-fluorouracil 
 
TAC 
 
Triamcinolone 
 
POSAS  
Patient and Observer Scar Assessment Scale

Study number: s20-01172 
 
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Protocol Summary 
Title 
A Prospective Single-Subject Triple-Blinded Single-Center Study of Laser-
Assisted 5-Fluorouracil Versus Laser-Assisted Corticosteroid Treatment for 
Keloids 
Short Title 
Treatment of Keloids with Fractional Erbium Laser-Assisted 5-Fluorouracil 
Versus Laser-Assisted Corticosteroid 
Brief Summary 
This is a single-subject split-scar study with a target sample size of 20. There 
are two interventions: fractional erbium:YAG-assisted drug delivery of 5-
fluorouracil and fractional erbium:YAG-assisted drug delivery of triamcinolone 
acetonide. Patients will undergo treatments in a series of 4 treatments at 
approximately 4 week ± 1 week intervals. We will continue to follow them 
after the end of the interventional treatment to monitor for safety and 
continued benefit.  
 
Phase 
n/a  
Objectives 
Primary Objectives 
1. To estimate the mean difference between Sites treated with laser-
assisted 5-FU delivery versus laser-assisted TAC in the changes 
from the first POSAS score (before initiating treatment series) to the 
final POSAS score.  
2. To estimate the mean difference between Sites treated with laser-
assisted 5-FU delivery versus laser-assisted TAC in the modified 
Hamilton score at the final visit 
 
Secondary Objectives  
The secondary objective is to assess the differences between Sites treated 
with laser-assisted 5-FU delivery versus laser-assisted TAC in the changes in 
size of keloids post treatment   
 
Exploratory objective 
The exploratory objective is to assess the differences between Sites treated 
with laser-assisted 5-FU delivery versus laser-assisted TAC in the patients 
subjective experiences, such as pain related to treatment, healing time. 
 
 
 
Methodology 
Triple-blinded prospective study 

Study number: s20-01172 
 
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Endpoints 
Primary Endpoint 
1. The first primary endpoint is the POSAS score in Site A and Site B at first 
visit (pre-treatment) and last visit (post-treatment). 
2. The second primary endpoint is a modified Hamilton score based on 
comparing clinical photographs of the scarred skin and healthy skin next to 
each other in Site A and Site B. 
 
Secondary Study Endpoints 
The secondary endpoint is measurements of the scar in both Sites of the 
keloid. The measurements will be calculated as the total volume (length x 
width x height) in cm3 of the scar, or length x width in cm2 if the scars are 
flush with the surrounding skin scar surface will be differences in change in 
size for in the two Sites of the keloid treated with laser-assisted 5-FU delivery 
as compared to laser-assisted TAC.  
 
 
Exploratory Endpoints 
Patient’s subjective experiences measured as follows: 
1. Patient perceived side effects after each treatment at visits 1, 2, 3, 
and 4 in Site A and Site B, in terms of dyspigmentation, pain, itch, 
swelling. 
2. Pain grade after each laser treatment at visits 1, 2, 3, and 4, 
measured on a scale of 1 to 10 (10 being the worst pain), in Site A 
and Site B, recorded at the subsequent follow up visit. 
3. Perceived speed of healing at final visit (visit 5) will be compared 
between both Sites using the following answers: Site A healed faster 
than Site B, Site B healed faster than Site A, Same speed of healing 
in both Sites 
 
Study Duration 
2 years 
Participant Duration 
1 year 
Duration of IP 
administration 
Up to 6 months 
Population 
Healthy men and women ages 18-89 in the United States.  
Study Sites 
NYU Dermatologic Surgery Associates.  
Number of participants 
20 participants.  
Description of Study 
Agent/Procedure 
The intervention will be a split-scar fractional ablative erbium laser-assisted 
delivery of 50mg/mL of 5-fluorouracil solution to one half of the scar and 10 
mg/mL of triamcinolone acetonide solution to the other half of the scar. 
Patients will undergo 4 treatments.  
Reference Therapy 
N/A  
Key Procedures 
Laser therapy as above.  

Study number: s20-01172 
 
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Statistical Analysis 
 
Demographic data, baseline scar characteristics, POSAS scores, and modified 
Hamilton scores will be summarized at baseline and consecutive visits as 
appropriate. 
 
For the primary analysis, a two-sided paired Wilcoxon Signed-Rank test at a 
0.05 significance level will be used to compare Site A and Site B of the keloid 
in the change from the first POSAS score (before initiating treatment series) to 
the final POSAS score. Similarly, a two-sided paired Wilcoxon Signed-Rank 
test at a 0.05 significance level will be used to compare the modified Hamilton 
score in Site A and Site B of the keloid. 
For the secondary analysis, measurements of the scar will be summarized by 
visit and compared between the two Sites of the keloid.   
For the exploratory analysis patient’s subjective experiences will be 
summarized and compared between both Sites of the keloid as follows: 
1. Patient perceived side effects after each treatment will be 
summarized by type (dyspigmentation, pain, itch, swelling), visit (1, 2, 
3, 4) and treatment Site (A, B).  
 
2. Pain  after each laser treatment will be summarized by grade (scale 
of 1 to 10 (10 being the worst pain)), visit (1, 2, 3, 4) and treatment 
Site (A, B). 
 
3. Speed of healing after completion of laser treatments at final visit 
(visit 5) will be compared between both Sites (Site A healed faster 
than Site B, Site B healed faster than Site A, Same speed of healing 
in both Sites) 
 
 
1 Key Roles 
Nayoung Lee, MD, Principal Investigator 
The Ronald O. Perelman Department of Dermatology 
NYU Grossman School of Medicine 
Nayoung.lee@nyulangone.org 
 
Lisa Akintilo, MD/MPH, Team Member 
The Ronald O. Perelman Department of Dermatology 
NYU Grossman School of Medicine 
Lisa.akintilo@nyulangone.org 
 
Daniel Gutierrez, MD, Co-Investigator 
The Ronald O. Perelman Department of Dermatology 
NYU Grossman School of Medicine 
Daniel.gutierrez2@nyulangone.org 
 
Kristen Lo Sicco, MD, Study monitor 
The Ronald O. Perelman Department of Dermatology  
240 East 38th Street, 11th Floor, Manhattan, NY 10016 
Kristen.losicco@nyulangone.org 
 
Marleigh Stern, MD, Team Member 
The Ronald O. Perelman Department of Dermatology  

Study number: s20-01172 
 
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240 East 38th Street, 11th Floor, Manhattan, NY 10016 
Marleigh.stern@nyulangone.org 
 
Rachel Sally, Team Member 
NYU Grossman School of Medicine 
Rachel.sally@nyulangone.org  
 
Benjamin A. Levinson, PhD, Biostatistician 
NYU Grossman School of Medicine 
Department of Population Health  
Benjamin.levinson@nyulangone.org 
2 Introduction, Background Information and Scientific Rationale 
2.1 Background Information and Relevant Literature 
 
Scars are ubiquitous and create significant morbidity for millions of people across all demographics.1 
Pathologic scarring in particular may result in diminished quality of life due to cosmetic appearance, 
disfigurement, pruritis, pain, restricted functional capabilities, and decreased emotional health.1-3 Pathologic 
scar treatment may also represent a significant financial burden for patients, with high costs associated 
with the often multiple medical and surgical interventions necessary to return functionality and cosmetic 
appearance to the site.1  
 
Keloids are pathological scars characterized as an overgrowth of scar tissue past the original wound 
boundaries, but unlike malignant lesions, they are confined to the dermis and thus are considered benign.4 
Keloids are common in genetically predisposed individuals, and their treatment is especially challenging: 
once keloids are formed, they never regress spontaneously and commonly recur after treatment.5,6 In fact, 
in individuals predisposed to keloid formation, surgical debulking can result in the generation of an even 
larger scar.1  
 
The pathophysiology of keloid formation is still incompletely understood and the most commonly used 
therapeutic options return inconsistent and suboptimal results.4 There is a need for clinicians to complement 
current treatment options with new modalities in order to better manage pathological scarring, improve 
patient experiences, and decrease costs.1  
 
Common treatments for keloids include intralesional corticosteroid injections, silicone sheeting, 
cryotherapy, surgical manipulation, and radiotherapy.7 Intralesional triamcinolone acetonide (TAC) 
injection, the most commonly utilized first-line therapy, has been shown to inhibit TGF-β1 expression and 
induce apoptosis in fibroblasts.8-10 Though it is the prototypical treatment, the efficacy of intralesional TAC 
is not completely satisfactory in the treatment of keloids.11 Additionally, intralesional TAC treatments involve 
injecting into the mid-dermis where there are thick collagen bundles, which frequently causes extreme pain 
for patients.12   
 
Low-dose 5-fluorouracil (5-FU) has also emerged as a method of keloid treatment.13 5-FU is a pyrimidine 
analogue and antineoplastic agent that halts fibroblast proliferation and induces fibroblast apoptosis.14,15 
Furthermore, 5-FU and TAC have been used off-label mixed together and injected into keloids with good 
results and no known adverse drug interaction; in fact, they are synergistic.7,16  
 
More recently, there has been increased interest in and usage of laser for treatment of pathological scarring. 
Ablative fractional laser (AFXL) therapy causes micropatterns of thermal injury to the dermis, thus 
stimulating the complex process of tissue remodeling; however, these microscopic thermal wounds 
generally heal without scarring.17-19 Fractional laser devices have demonstrated benefits in the debulking 
and resurfacing of scars and keloids without adverse events, and are associated with functional 
improvements, as well as cosmetic benefits.20,21  
 

Study number: s20-01172 
 
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There is growing evidence that combination therapy regimens are more effective than monotherapy.22,23 
Multimodal combination therapies with synergistic effects have an advantage in that the agents can be used 
at lower doses compared to monotherapy, thus improving the side effect profile.22 For example, the 
combination of 5-FU and TAC has been shown to have a higher scar response rate, as well as a reduction 
of undesirable effects when compared to each alone.7 Post-laser therapy with topical corticosteroids has 
been demonstrated to enhance the effects of fractional lasers. This is likely through efficient delivery and 
uniform distribution of the corticosteroid to the desired level of the skin through the microscopic channels 
created by laser ablation.8,12 Additionally, the combination of AFXL and topical triamcinolone may reduce 
the incidence of pain compared to intralesional corticosteroid injection monotherapy.12 
 
Laser-assisted 5-FU and laser-assisted TAC have shown similar efficacies in treating hypertrophic scars, 
though laser-assisted 5-FU has fewer side effects.1 Laser-assisted topical triamcinolone is associated with 
the side effects of topical corticosteroids, including sporadic erythema, telangiectasias, hyperpigmentation, 
hypopigmentation, and a risk of dermal atrophy and fat atrophy.8,24  
 
Building upon previous research, in our study we will investigate the effectiveness of laser-assisted 5-FU 
and laser-assisted triamcinolone in the treatment of keloids. We will measure “effectiveness” by taking 
measurements of the height, width, and length of treated lesions prior to, during, and after laser-assisted 
drug delivery. Analyzing keloids on height, width, and length with calipers allows for 3-dimensional statistical 
analysis of the effects of the treatments. Similar scar measurement protocols have been used in other 
studies on pathological scarring.1  
 
2.2 Name and Description of the Investigational Agents  
In this study we will be utilizing laser-assisted drug delivery of 5-FU and TAC. The laser we will be using is 
Sciton Joule (see Figure 1 below), the ProFractional XC handpiece, which is a fractional ablative 
Erbium:yttrium-aluminum-garnet (Er:YAG) laser with a wavelength of 2940nm. Sciton Joule ProFractional 
System is FDA approved for use in soft tissue (skin, cutaneous tissue, subcutaneous tissue, striated and 
smooth tissue, muscle, cartilage meniscus, mucous membrane, lymph vessels and nodes; organs, and 
glands) such as, but not limited to: Dermatology and Plastic Surgery: Skin resurfacing Treatment of 
wrinkles; Epidermal nevi; Telangiectasia; Spider veins; Actinic chelitis; Keloids; Verrucae; Skin tags; Anal 
tags; Keratoses; Scar revision (including acne scars). The use of fractional Er:YAG in keloids is FDA 
approved. The use of fractional Er:YAG for transdermal delivery of medications is off-label.  
5-FU is a chemotherapeutic agent that can inhibit fibroblast proliferation. TAC is an anti-inflammatory 
corticosteroid that inhibits multiple inflammatory cytokines. Both topical and intralesional TAC ranging 
from 1-40 mg/mL is FDA-indicated for skin disorders, including keloids. Off label, 5-FU 50mg/mL solution 
is often mixed with TAC 10-40mg/mL by the physician and injected simultaneously into hypertrophic scars 
and keloids for synergistic effect, as previously mentioned. 
 
Er:YAG-assisted delivery of 5-FU 50mg/mL solution or 5% cream has been performed safely in scars,25 
as well as other cutaneous diseases such as vitiligo26 and Bowen’s disease.27 Topical 5-FU 5% cream is 
FDA-approved for actinic keratoses and superficial basal cell carcinomas, and because topical 5-FU often 
leads to cutaneous erosions on the area of application, continued application of 5-FU cream for two 
weeks, as is FDA-indicated, results in application of 5-FU over open wounds. In addition, intravenous 5-
FU at a higher dose of 10-30mg/kg/day depending on the disease is FDA-approved for breast, colorectal, 
gastric and pancreatic cancer. Given the extensive data of safe use of 5-FU in scars in the dermatologic 
literature, both FDA-indicated and non-FDA-indicated conditions, such as keloids, and the FDA-approved 
indication of systemic use in cancer patients in much higher doses, the localized and relatively superficial 
introduction of 1mL of 5-FU 50mg/mL by fractional Er:YAG does not present a significant risk to the 
health, safety, or welfare of a subject. Additionally, as fractional Er:YAG does not involve use of an 
implant, is not purported or represented to be for a use in supporting or sustaining life, and is not for a 
substantial use in diagnosing, curing, mitigating, or treating disease, or otherwise preventing impairment 
of human health in a way that would present a potential for serious risk to the health, safety, or welfare of 
a subject, the use of the Sciton Joule ProFractional System in this study is non-significant risk (NSR) in 
accordance with 21 CFR 812.3(m). 

Study number: s20-01172 
 
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The maximum depth of ablation by ProFractional system is 1.5 mm, which is more superficial than when a 
needle is inserted to inject 5-FU or TAC intralesionally in the clinic. Furthermore, we do not plan to ablate 
deeper than 1 mm in our study. Fractional ablation with the Sciton Joule ProFractional system using 1mL 
of 5-FU 50mg/mL solution or 10mg/mL of TAC therefore does not involve a route of administration or 
dosage level that significantly increases the risks associated with the use of the two drugs. 
Additionally, as the study involves the use of lawfully marketed drugs and the study: 
is not intended to be reported to FDA as a well-controlled study in support of a new indication for use 
nor intended to be used to support any other significant change in the labeling for the drug; 
is not intended to support a significant change in the advertising for the product; 
is conducted in compliance with the requirements for institutional review set forth in part 56 and with 
the requirements for informed consent set forth in part 50; and 
is conducted in compliance with the requirements of §312.7, 
this study meets the criteria for IND exemption in accordance with 21 CFR 312.2(b)(1) 
 
 
 
 
 
Figure 1. Sciton Joule Laser 
2.2.1 Clinical Data to Date 
In 2013, Waibel et al. used ablative fractional photo-thermolysis CO2 laser treatments to aid corticosteroid 
delivery in hypertrophic scars. Three to five laser treatments at 2-month to 3-month intervals were combined 
with a thin topical layer of TAC suspension of 10 or 20 mg/mL, depending on the location and thickness of 
the skin. They observed an overall scar improvement, with the therapy having the greatest impact on texture 
but also improved dyschromia and overall appearance.8  
 
Park et al. compared laser-assisted topical corticosteroid with intralesional corticosteroid injections in 
keloids. First, the entire keloid was treated with fractional ablative Er:YAG laser. The lesions were 
subsequently divided into two halves, with the first half receiving intralesional TAC injection (10 mg/mL) and 
the second receiving topical application of desoxymethasone 0.25% ointment. Four treatments at 6-week 

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intervals were conducted. They found a statistically significant improvement in the Vancouver Scar Scale 
(VSS) for both modalities, but the corticosteroid injection was associated with much more severe pain.12  
 
In 2019, Waibel et al. compared clinical outcomes of hypertrophic scars treated with laser-assisted 
corticosteroid delivery versus laser-assisted 5-FU delivery. Subjects underwent 3 treatment sessions at 1-
month intervals consisting of fractional ablative CO2 laser treatment followed by postoperative application 
of either TAC solution (20 mg/mL) or 5-FU solution (50 mg/mL). Scars treated with both modalities 
demonstrated reduction in overall scar surface area. There was no statistically significant difference 
between the arms, suggesting that neither agent possesses superior efficacy over the other. However, 5-
FU was not associated with the side effect risks that topical corticosteroids foster such as dermal atrophy 
or telangiectasia formation.1  
 
Sabry et al. evaluated the effectiveness of combining ablative fractional CO2 laser and topically applied 5- 
FU or verapamil hydrochloride in the treatment of hypertrophic scars and keloids. They found that 
combination therapy of ablative fractional CO2 and topical 5-FU or verapamil hydrochloride is more effective 
than ablative fractional CO2 monotherapy. Significant cosmetic improvement was seen in all subjects based 
on VSS score. The improvements achieved in scar pliability and erythema were especially notable. In 
contrast to laser-assisted delivery of 5-FU or verapamil hydrochloride, CO2 monotherapy showed no 
significant improvement in scar height. Pigmentation showed minimal improvement in all three groups. They 
observed no negative side effects with 5-FU topical treatment.28  
 
2.2.2 Dose Rationale (if applicable)  
5-FU comes in one available dose (50mg/mL) and we will be using 10 mg/mL of TAC, due to the 
higher risk of adverse effects such as dyspigmentation and atrophy with higher doses.  
 
2.3 Rationale 
The primary objective of this study is to determine the differences in clinical outcome and side effect profile 
for keloids treated with laser-assisted 5-FU delivery as compared to laser-assisted corticosteroid delivery. 
Transdermal delivery of drugs is limited by permeation through the stratum corneum, where high-molecular 
weight and hydrophilic compounds often cannot penetrate.29-31 Topical medications have been found to 
have a total absorption with only 1% to 5% bioavailability of the applied dose. Intralesional injection requires 
multiple needle punctures, which can be difficult to tolerate. Laser-assisted drug delivery can improve 
cutaneous penetration while being less painful.12 
 
We hypothesize that efficacy is greater in keloids treated with laser-assisted delivery of 5-FU as compared 
to those treated with laser-assisted delivery of TAC 10mg/mL, and we expect to see less adverse effects 
such as hypopigmentation with 5-FU.  
 
Er:YAG laser operates at a wavelength of 2940 nm and is an ablative laser as its energy is highly absorbed 
by water-containing tissue.9,32 Er:YAG has been shown to enhance permeation of 5-FU by 53-fold to 133-
fold in mouse models.33 Er:YAG has also been shown to increase the penetration of lipophilic and 
hydrophilic compounds through the skin.34 Er:YAG laser has demonstrated safety as a transdermal 
transport enhancer, with studies showing the depths of the stratum corneum and epidermis recovering to 
normal conditions within 3-5 days.33,34 Once the stratum corneum and epidermis are surpassed, the depth 
of the ablation does not affect drug delivery.35,36 Of importance in our study, fractional Er:YAG laser is 
associated with decreased risk of post-inflammatory hyperpigmentation (PIH) as compared to CO2 
laser.37,38 Skin of color (Fitzpatrick skin types IV, V, VI) is more prone to developing keloids and has a 
generally increased risk of PIH compared to lighter skin types. As such, the fractional erbium laser is the 
safer choice for our target population.   
 
 
5-FU will be used at the dose of 50 mg/mL and TAC will be used at the dose of 10mg/mL; the amount will 
depend on the size of the keloid treated. 

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2.4 Potential Risks & Benefits 
2.4.1 Known Potential Risks 
Known potential risks of laser treatment include pain, bleeding and swelling. Known potential risks of 
laser-assisted delivery of each medication is no different than the potential risks of injecting each 
medication intradermally. There is no known risk of cross-reaction if both 5-FU and TAC are injected in 
the same scar; in fact, both have been mixed and injected into keloids at the same for enhanced clinical 
efficacy.16 Keloids treated with erbium laser have been shown to have a good safety profile.37,39 As 
aforementioned, 5-FU can be applied on open wounds for actinic keratoses as approved by the FDA 
(sometimes followed by TAC in case of brisk reaction) or even given intravenously in even higher doses 
for GI malignancies.40,41  
 
TAC is used to treat a wide variety of dermatologic conditions (including open wounds/ulcers like pyoderma 
gangrenosum) and is the prototypical corticosteroid used to treat pathological scarring.42 Topical side 
effects 
include 
dermal 
atrophy, 
fat 
atrophy, 
erythema, 
telangiectasias, 
hypopigmentation, 
hyperpigmentation, scarring, easy bruising, and certain inflammatory skin conditions.8,29  
 
5-FU is an anti-metabolite widely used in cancer chemotherapy, both intravenously (FOLFOX in 
gastrointestinal malignancies) and topically.40 Sabry et al. found that topical application of 5-FU after laser 
sessions showed no side effects, though others report topical side effects of 5-FU include local pain, 
dermatitis, pruritus, burning, photosensitivity, pigmentation changes, and scarring.25,29 A review of 
intralesional injections of 5-FU found negative side effects that may include pain at the injection site, 
ulceration, burning, and hyperpigmentation; no systemic complications such as anemia, leukopenia, and 
thrombocytopenia were reported.37 
 
2.4.2 Known Potential Benefits 
Potential benefits include decrease in keloid size, improved skin texture overlying the keloid, improved 
pliability and mobility, and decrease in symptoms of itch and/or pain due to keloid.   
3 Objectives and Purpose 
3.1 Primary Objectives 
As noted in section 4.1, Site A and Site B will be randomized to either laser-assisted delivery of 5-FU or 
laser-assisted delivery of TAC. We hypothesize that there is a significant difference between the two 
treatments with respect to the clinical outcomes of the POSAS scar scores and the Hamilton scores.   
Hence, the primary objectives are: 
1. To estimate the mean difference between both Sites in the changes from the first POSAS score 
(before initiating treatment series) to the final POSAS score.  
2. To estimate the mean difference between both Sites in the modified Hamilton score at the final 
visit. 
  
 
 
3.2 Secondary Objective 
The secondary objective is to assess the differences between both Sites in change in size of keloids post 
treatment. 
 
3.3 
Exploratory objective 
 
The exploratory objective is to assess the differences between both Sites in patients subjective 
experiences, such as pain related to treatment, healing time.  

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4 Study Design and Endpoints 
4.1 Description of Study Design 
This study will be a triple-blinded single-center study of keloid therapies. The intervention will be laser-
assisted drug delivery of TAC or 5-FU. When selecting patients, preference will be for two separate scars; 
however, if a patient presents with a single long scar, we will treat one half of the scar with laser-assisted 
delivery of TAC and the other half of the scar with laser-assisted delivery of 5-FU. The keloid on the 
patient’s right side or the patient’s right half of the keloid (in a single keloid) or the superior keloid (of 2 
keloids) will be designated Site A. The keloid on the patient’s left side or the patient’s left half of the keloid 
(in a single keloid) or the inferior keloid (of 2 keloids) will be designated Site B.  Randomization of which 
treatment (5-FU or TAC) will be applied to Site A will be performed in RedCap by statistician (BL). The 
treating physician (NL) will enter the patient ID in RedCap, answer a number of eligibility verification 
questions and retrieve the assignment for that patient. No patient-identifiable data will be entered in 
RedCap. All patient data will be entered in paper forms.  All patients will undergo 4 treatments total. The 
patients will be blinded to the treatment. Their eyes will be shut and they will have protective laser 
goggles on during the treatment portion of their visit. The treating physician will treat Site A and Site B 
based on the randomized treatment allocation. The treating physician (NL) will not be blinded to the 
medication being administered after laser treatment nor to the AEs assessment. The treating physician 
cannot be blinded to the treatments, because TAC is an opaque white solution and 5-FU is a clear 
colorless solution. A blinded dermatologist (DG) will record the POSAS every visit. Physician observers 
blinded to the treatment allocation will grade the photographs taken at the final follow-up visit using a 
modified version of a photograph-based scale, the Hamilton Scale. De-identified data (aside from the 
patient ID) will be entered in Excel for purposes of statistical analysis. 
 
COVID-19 Safety Precautions  
 
In light of the COVID-19 pandemic, the study team will utilize a verbal recruitment template and COVID19 
information sheet to make patients aware of risks of completing an in-person research study. The study 
team and patients will be protected by complying with all NYU safety measures, including screening, 
social distancing, PPE, cleaning/disinfecting.  
 
Daily symptoms screening for research personnel 
- 
Each faculty member, employee, and student will complete a “Daily Symptom Check” one to 
three hours ahead of the start of their time as part of the research study.  
Screening research participants for symptoms 
- 
The study team will be responsible for screening research participants in alignment with clinical 
screening of patients: upon scheduling, appointment reminders, and arrival at the research 
location.  
- 
Patients will be asked 1. Do you have two or more Covid-19-like symptoms (cough, shortness of 
breath, fever, chills, shaking chills, muscle pain, headache, sore throat, new loss of taste or 
smell)? 2. Have you or anyone in household tested positive in the last 10 days? If either question 
is answered yes, the participant cannot come to their in-person appointment. 
- 
During the screening process study teams must notify research participants that they are required 
to wear a mask/face covering.  
- 
Upon arrival to NYULH locations, research participants are subject to the same screening 
procedures as patients. 
Social distancing 
- 
Office visits will be staggered to minimize number of individuals in waiting areas 
- 
Waiting rooms/public areas will have seats spread to 6 feet of separation 
- 
The number of study personnel in exam rooms will be minimized 
Personal Protective Equipment for research personnel 
- 
All NYU Langone staff, faculty, students, and trainees will wear a face mask at all times  
- 
Researchers will also follow any additional PPE guidelines for our clinical area 
- 
Masks will be worn in all public and work spaces and patient care areas, worn correctly to cover 
the mouth and nose 

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- 
Only NYU Langone-issued masks or personal protective equipment will be worn, no cloth masks 
or non-NYU Langone issued masks or PPE will be utilized  
Personal Protective Equipment for research participants 
- 
All participants and visitors >4 years of age will be offered a face mask upon entry to the 
ambulatory site 
- 
Patients will be informed to arrive with a face mask during the pre-visit phone call 
- 
Masks will be worn throughout participant’s appointments 
Cleansing and disinfecting 
- 
All personnel will wash hands or use hand sanitizer often, especially when entering work areas 
from public spaces and after contacting high-touch surfaces like doorknobs and handles, 
refrigerator and freezer handles, and elevator buttons 
 
4.2 Study Endpoints 
4.2.1 Primary Study Endpoints 
We will measure the non-blinded POSAS score at every visit. The POSAS was created in 2004 and takes 
both the patient and the provider perspectives into account. The POSAS scar scale has been found to be 
more reliable and less variable than other scar scales utilized in clinical practice43.  
POSAS has two components, the observer (physician) portion and the patient portion. The observer grades 
on a scale of 1 to 10, 10 being the worst scar imaginable, six measures: vascularity, pigmentation, 
thickness, relief, pliability and surface area. The patient answers six questions regarding the characteristics 
of the scar, with each question being on a scale of 1 to 10. The scores of each category are summed to get 
the total POSAS score, with 120 being the highest score and representing the worst scar.  
 
1. The first primary endpoint is the POSAS score in Site A and Site B at first visit (pre-treatment) and last 
visit (post-treatment). 
 
2. The second primary endpoint is a modified Hamilton score based on comparing clinical photographs of 
the scarred skin and healthy skin next to each other in Site A and Site B.  
 
4.2.2 Secondary Study Endpoint 
The secondary endpoint is measurements of the scar in both Sites of the keloid. The measurements will 
be calculated as the total volume (length x width x height) in cm3 of the scar, or length x width in cm2 if the 
scars are flush with the surrounding skin scar surface in the two Sites of the keloid.   
 
4.2.3 Exploratory Endpoints  
Patient’s subjective experiences measured as follows: 
 
1. Patient perceived side effects after each treatment at visits 1, 2, 3, and 4 in Site A and Site B, in 
terms of dyspigmentation, pain, itch, swelling. 
2. Pain grade after each laser treatment at visits 1, 2, 3, and 4, measured on a scale of 1 to 10 (10 
being the worst pain), in Site A and Site B, recorded at the subsequent follow up visit. 
3. Perceived speed of healing at final visit (visit 5) will be compared between both Sites using the 
following answers: Site A healed faster than Site B, Site B healed faster than Site A, Same speed 
of healing in both Sites 
 
 
 

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5 Study Enrollment and Withdrawal 
5.1 Inclusion Criteria 
In order to be eligible to participate in this study, an individual must meet all of the following criteria: 
1. Age 18-89 
2. Has one large keloid scar or at least two similar but separate keloid scars  
3. Keloid present for at least 1 year 
5.2 Exclusion Criteria 
An individual who meets any of the following criteria will be excluded from participation in this study: 
1. Currently pregnant 
2. Currently breastfeeding 
3. Have taken oral retinoids within 6 months of study initiation  
4. Has had keloid treatment within 1 month of study initiation 
5. Has active infection at treatment site 
6. Has active malignancy  
7. Presence of pedunculated keloid(s) or keloid(s) that are judged to be best treated with surgical 
excision first 
8. Hypertrophic scars 
9. Known hypersensitivity to TAC or 5-FU 
10. Chronic systemic corticosteroid or immunosuppressive medication use 
11. Has intolerance to anesthesia 
12. Has known connective tissue disease  
13. Has known infectious disease 
5.3 Strategies for Recruitment and Retention 
Participants will be recruited from the outpatient clinics of NYU Dermatology Faculty Group Practice. We 
will reach out to clinicians via word of mouth and email for subject referrals. Please see our email 
template and recruitment flyer attached as appendices. We will not utilize NYULMC media services or 
social media. Clinician-referred patients who are possibly eligible for participation in the study will be 
instructed to email research coordinator SC for pre-screening and permission to access electronic 
medical records. SC will describe the study and pre-screening process to potential subjects via telephone 
using an IRB-approved script and obtain verbal consent to ask the pre-screening questions and give 
permission for the study investigators to review the patient’s electronic medical record. If a patient is 
deemed ineligible or they pass pre-screening but later decide not to participate in the study, the pre-
screening data will be immediately destroyed. Target sample size is 15, we will attempt to screen 30-40 in 
order to obtain the target enrollment. 
5.4 Duration of Study Participation 
Duration of study participation will be 1 year.  
5.5 Total Number of Participants and Sites  
Recruitment will end when approximately 30 participants are enrolled. It is expected that approximately 
30 participants will be enrolled in order to produce 20 evaluable participants (projected accrual is 20).   
 
The site of this study will be at 222 East 41st Street, New York NY 10017. Treatments will take place on 
the 24th floor.  

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5.6 Participant Withdrawal or Termination 
5.6.1 Reasons for Withdrawal or Termination 
Participants are free to withdraw from participation in the study at any time upon request. An investigator 
may terminate participation in the study if: 
• 
Any clinical adverse event (AE), laboratory abnormality, or other medical condition or situation 
occurs such that continued participation in the study would not be in the best interest of the 
participant 
• 
The participant meets an exclusion criterion (either newly developed or not previously 
recognized) that precludes further study participation 
Participants will be terminated from the study if there is no clinical response noted by Visit #3.  
5.6.2 Handling of Participant Withdrawals or Termination 
If a participant withdraws from the study, the investigator(s) will ask if the information already collected 
can still be used as part of the study.  
5.7 Premature Termination or Suspension of Study 
This study may be temporarily suspended or prematurely terminated if there is sufficient reasonable 
cause. Written notification, documenting the reason for study suspension or termination, will be provided 
by the suspending or terminating party to the primary investigator. If the study is prematurely terminated 
or suspended, the PI will promptly inform the IRB and will provide the reason(s) for the termination or 
suspension. 
Circumstances that may warrant termination or suspension include, but are not limited to: 
• 
Determination of unexpected, significant, or unacceptable risk to participants 
 
Study may resume once concerns about safety, protocol compliance, and data quality are addressed and 
satisfy the IRB and/or FDA. 
6 Study Agent (Study drug, device, biologic, vaccine etc.) and/or 
Procedural Intervention  
6.1 Study Agent(s) and Control Description 
5-FU is a chemotherapeutic drug. This medication is kept routinely in the dermatology clinic for 
intradermal injection. The needles and syringes involved will be disposed of in the labeled clinic sharps 
container.  
 
For TAC solution, the needles and syringes involved will be disposed of in the labelled clinic sharps 
container. 
6.1.1 Acquisition 
Both 5-FU and TAC are routinely available at the NYU Dermatology Faculty Group Practice. These 
medications are ordered from the Henry Schein medical supplier.  
6.1.2 Formulation, Appearance, Packaging, and Labeling 
5-FU is a opaque white liquid that comes in a clear glass bottle. This medication comes in the dose 
50mg/mL. 
 
TAC solution is a clear colorless solution that comes in a clear glass bottle in the dose 10mg/mL. We will 
use this medication at the dose 10mg/mL.  

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6.1.3 Product Storage and Stability 
Both 5-FU and TAC are stable at room temperature.  
6.1.4 Preparation 
Neither 5-FU or TAC will need to be reconstituted; as such, both medications will be drawn up as is.  
6.1.5 Dosing and Administration 
5-FU will be used at the dose of 50 mg/mL and TAC will be used at the dose of 10mg/mL.  
6.1.6 Route of Administration 
Planned route of administration is laser-assisted delivery topically 
6.1.7 Dose Adjustments/Modifications/Delays 
Dose adjustments will be not be made to TAC or 5-FU. Adjustments will be made to the laser settings 
(density, depth) depending on the thickness of the keloid at the time of treatment. 
6.1.8 Duration of Therapy 
Therapy duration is 4 total treatments spaced 4 weeks ± 1 week apart.  
6.1.9 Tracking of Dose 
Dose will be fixed at 50 mg/mL for 5-FU and 10 mg/mL for TAC.  
6.1.10 Device Specific Considerations 
The laser utilized in our study is the Sciton Joule. Settings depend on the keloid thickness and will range 
from 400micron – 1mm in depth, 5.5-11% density, single pass, without coagulation. Contraindications to 
using this device are as follows:  
 
- 
Patients intolerant of anesthesia 
- 
Patients with infectious disease 
- 
Patients with connective tissue disease 
- 
Patients with history of immunocompromise 
- 
Patients who are pregnant 
- 
Patients who have used isotretinoin within the past year 
- 
Patients with a medical condition that may affect wound healing  
- 
Patients who use anticoagulant medications 
6.2 Study Procedural Intervention(s) Description 
The procedural intervention in this study is laser-assisted drug delivery with use of fractional ablative 
erbium laser.  
6.2.1 Administration of Procedural Intervention 
Participants will be anesthetized with intralesional 1% lidocaine with epinephrine 1:100,000.  Patients will 
be provided safety goggles. All personnel present during the laser treatment will don the appropriate laser 
goggles protective for 2940 nm. The PI (NL) will then administer the fractional ablative erbium laser 
intervention to the entire keloid of interest. After treatment of the keloid, a fixed amount of 5-FU solution 
and TAC solution will each be gently rubbed over two separate keloids or halves of the laser-treated 
area(s). Site A (which represents the right keloid or right half of the keloid or superior keloid) will be 
treated with 5-FU, and Site B (which represents the left keloid or left half of the keloid or inferior keloid) 
will be treated with TAC. Only after the application of these two medications will patients’ safety googles 
be removed. Patients will not be made aware of which medication was applied to which half of the lesion. 
The patients will be observed for 10 minutes after the procedure. Each intervention will last about 30 
minutes. The entire visit will last about 1 hour. 

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6.2.2 Procedures for Training of Clinicians on Procedural Intervention 
The procedural intervention will be provided by a single operator (NL) for standardization purposes. NL 
completed a procedural fellowship and was trained in Mohs surgery and was trained specifically on the 
Sciton Joule during fellowship. 
7 Study Procedures and Schedule 
7.1 Study Procedures/Evaluations 
7.1.1 Study Specific Procedures 
 
• 
Medical history (from both interview and medical records): history of keloids, known allergies 
(describe what is included for history, e.g., time-frame considerations, whether history will be 
obtained by interview or from medical records) 
• 
Medication history: currently taken prescription and over the counter medications 
• 
Urine pregnancy test if female of child-bearing age at every visit.  
• 
Physical examination of lesion of interest. 
• 
Photography of lesion of interest 
• 
Measurement of lesion of interest 
• 
Counseling procedures regarding what to expect during and after interventional treatment 
including post-procedure care  
- 
Study Schedule Research coordinator (SC will assist with fielding patient 
calls and organizing patient scheduling. 
- 
Patients will be scheduled in the PI’s clinic. 
- 
Patients will not be charged for treatments.  
7.1.2 Pre-Screening Phone Call (Dermatology Clinical Studies Unit, 240 East 38th Street, 
11th floor, New York, NY 10016) 
- 
Review verbal consent to pre-screen 
- 
Ensure patient provided consent for study team to review medical record, including medical history 
and photos  
- 
Assess inclusion and exclusion criteria 
- 
Collect basic demographic information including: 
o 
Full Name ________________________ 
o 
DOB: ______________ 
o 
Sex: _______________ 
o 
Email Address: ______________________________ 
o 
Current Permanent Address: __________________________ 
o 
Home Phone (if applicable): ____________________________ 
o Mobile Phone (if applicable): ____________________________  
o Emergency Contact information if they agree to provide 
The collection of basic demographic information is required in order to properly schedule 
their research screening visit (visit 0) in EPIC for the doctor’s EPIC schedule.  
- 
Schedule Screening (Visit 0) 

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7.2 Screening (Visit 0, to be completed at 222 East 41st Street, New York NY 10017) 
• 
Obtain informed consent of potential participant verified by signature on study informed consent 
form. Informed consent will be obtained by the PI, sub-I (DG), study team member (LA) or 
research coordinator (SC) only. 
• 
Verify inclusion/exclusion criteria. 
• 
Pregnancy urine test for non-menopausal women. 
• 
Obtain demographic information, medical history, medication history, alcohol and tobacco use 
history. 
• 
Randomization of either which side of lesion (Right or Left) or which lesion (if two comparable 
lesions present) will be treated with laser-assisted TAC v laser-assisted 5-FU.  
• 
Subjects Passing Screening will immediately have visit one as outlined in Visits 1-4 
7.2.1 Treatment Visits 
 
Visits 1 - 4 
• 
Urine pregnancy test if female of child-bearing age. (visits 2-4) 
• 
Physical examination of lesion of interest. 
• 
Photography of lesion (keloid) of interest, taken before any treatment is performed 
• 
Measurement (height, length, width) of lesion (keloid) of interest performed at the start of the visit, 
before treatment 
• 
Completion of POSAS (including monitoring of adverse events) by patient and providers at the 
start of the visit 
• 
Administer the study treatment (to be performed by PI): laser assisted drug-delivery treatment of 
both 5-FU and TAC.  
• 
Monitoring of adverse events 
• 
Patients will be asked about side effects (non-serious adverse events) from laser treatment on 
visits 2-4 
• 
Patients will be asked to grade their post-procedure pain on a scale of 1 to 10 on visits 2-4 
• 
Patients will be asked which side healed faster after the laser treatment on visits 2-4 
• 
Post-treatment instructions will be provided to patients on an after-treatment instruction sheet: 
gentle cleansing of area with soap and water twice a day, apply petrolatum jelly and keep area 
covered for 1 week, avoid sun exposure to treated area(s) for study duration.  
• 
Visits will take place every 4 weeks ± 1 week.  
7.2.2 Final Study Visit 
Visit 5 
• 
Photography of lesion (keloid) of interest to be reviewed by blinded physician observers 
• 
Measurement (height, length, width) of lesion (keloid) of interest  
• 
Completion of POSAS (including monitoring of adverse events)   
• 
Patients will be asked about side effects (non-serious adverse events) from laser treatment 
• 
Patients will be asked to grade their post-procedure pain on a scale of 1 to 10  
• 
Patients will be asked which side healed faster after the laser treatment  
7.2.3 Withdrawal/Early Termination Visit 
Photography and lesion measurements (length, width, height) should be done at a termination visit if a 
subject withdraws or if early termination occurs, provided the participant is willing.   
7.2.4  Unscheduled Visit 
Unscheduled visits pertaining to the lesion of interest will be documented as an extra visit. 

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7.3 Prophylactic Medications, Treatments, and Procedures 
Intralesional 1% lidocaine with epinephrine 1:100,000 will be used for anesthesia prior to each laser-
assisted drug delivery treatment session.  
8 Assessment of Safety 
8.1.1 Definition of Adverse Events (AE) 
An adverse event (AE) is any symptom, sign, illness or experience that develops or worsens in severity 
during the course of the study.  Intercurrent illnesses or injuries should be regarded as adverse events.  
Abnormal results of diagnostic procedures are considered to be adverse events if the abnormality: 
• results in study withdrawal 
• is associated with a serious adverse event 
• is associated with clinical signs or symptoms 
• leads to additional treatment or to further diagnostic tests 
• is considered by the investigator to be of clinical significance 
8.1.2 Definition of Serious Adverse Events (SAE) 
 
Serious Adverse Event 
Adverse events are classified as serious or non-serious.  A serious adverse event is any AE that is:  
• fatal 
• life-threatening 
• requires or prolongs hospital stay 
• results in persistent or significant disability or incapacity 
• a congenital anomaly or birth defect 
• an important medical event 
 
Important medical events are those that may not be immediately life threatening, but are clearly of major 
clinical significance. They may jeopardize the subject, and may require intervention to prevent one of the 
other serious outcomes noted above. For example, drug overdose or abuse, a seizure that did not result 
in in-patient hospitalization, or intensive treatment of bronchospasm in an emergency department would 
typically be considered serious.  
 
All adverse events that do not meet any of the criteria for serious should be regarded as non-serious 
adverse events.  
8.1.3 Definition of Unanticipated Problems (UP) 
 
Unanticipated Problems Involving Risk to Subjects or Others 
Any incident, experience, or outcome that meets all of the following criteria:  
• Unexpected in nature, severity, or frequency (i.e. not described in study-related documents such 
as the IRB-approved protocol or consent form, the investigators brochure, etc) 
• Related or possibly related to participation in the research (i.e. possibly related means there is a 
reasonable possibility that the incident experience, or outcome may have been caused by the 
procedures involved in the research) 
• Suggests that the research places subjects or others at greater risk of harm (including physical, 
psychological, economic, or social harm). 
This definition could include an unanticipated adverse device effect, 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 

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unanticipated serious problem associated with a device that relates to the rights, safety, or welfare of 
subjects (21 CFR 812.3(s)). 
8.2 Classification of an Adverse Event 
8.2.1 Severity of Event 
 
For AEs not included in the protocol defined grading system, the following guidelines will be used to 
describe severity. 
 
• Mild – Events require minimal or no treatment and do not interfere with the participant’s daily 
activities. 
• Moderate – Events result in a low level of inconvenience or concern with the therapeutic 
measures. Moderate events may cause some interference with functioning. 
• Severe – Events interrupt a participant’s usual daily activity and may require systemic drug 
therapy or other treatment. Severe events are usually potentially life-threatening or incapacitating. 
8.2.2 Relationship to Study Agent 
 
The clinician’s assessment of an AE's relationship to study agent (drug, biologic, device) is part of the 
documentation process, but it is not a factor in determining what is or is not reported in the study. If there 
is any doubt as to whether a clinical observation is an AE, the event should be reported. All AEs must 
have their relationship to study agent assessed. In a clinical trial, the study product must always be 
suspect. To help assess, the following guidelines are used. 
 
• Related – The AE is known to occur with the study agent, there is a reasonable possibility that the 
study agent caused the AE, or there is a temporal relationship between the study agent and event. 
Reasonable possibility means that there is evidence to suggest a causal relationship between the 
study agent and the AE. 
• Not Related – There is not a reasonable possibility that the administration of the study agent 
caused the event, there is no temporal relationship between the study agent and event onset, or 
an alternate etiology has been established.  
8.2.3 Expectedness 
 
Dr. Nayoung Lee (PI) will be responsible for determining whether an AE is expected or unexpected. An 
AE will be considered unexpected if the nature, severity, or frequency of the event is not consistent with 
the risk information previously described for the study agent. 
 
8.3 Time Period and Frequency for Event Assessment and Follow-Up 
The occurrence of an AE or SAE may come to the attention of study personnel during study visits and 
interviews of a study participant presenting for medical care, or upon review by a study monitor (KL). All 
AEs including local and systemic reactions not meeting the criteria for SAEs will be captured on the 
appropriate RF. Information to be collected includes event description, time of onset, clinician’s 
assessment of severity, relationship to study product (assessed only by those with the training and 
authority to make a diagnosis), and time of resolution/stabilization of the event. All AEs occurring while on 
study must be documented appropriately regardless of relationship. All AEs will be followed to adequate 
resolution. 
 
Any medical condition that is present at the time that the participant is screened will be considered as 
baseline and not reported as an AE. However, if the study participant’s condition deteriorates at any time 

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during the study, it will be recorded as an AE. UPs will be recorded in the data collection system 
throughout the study. 
 
Changes in the severity of an AE will be documented to allow an assessment of the duration of the event 
at each level of severity to be performed. AEs characterized as intermittent require documentation of 
onset and duration of each episode. 
 
The PI will record all reportable events with start dates occurring any time after informed consent is 
obtained until 7 (for non-serious AEs) or 30 days (for SAEs) after the last day of study participation. At 
each study visit, the investigator will inquire about the occurrence of AE/SAEs since the last visit. Events 
will be followed for outcome information until resolution or stabilization.  
 
All unresolved adverse events should be followed by the investigator until the events are resolved, the 
subject is lost to follow-up, or the adverse event is otherwise explained.  At the last scheduled visit, the 
investigator should instruct each subject to report any subsequent event(s) that the subject, or the 
subject’s personal physician, believes might reasonably be related to participation in this study.  The 
investigator should notify the IRB  of any death or adverse event occurring at any time after a subject has 
discontinued or terminated study participation that may reasonably be related to this study.  The IRB  
should also be notified if the investigator should become aware of the development of cancer or of a 
congenital anomaly in a subsequently conceived offspring of a subject that has participated in this study.  
9 Data Safety Monitoring Plan 
The safety monitor (KL) will be conduct quarterly reviews of aggregate data and adverse events. KL is 
currently a PI for a Pfizer-sponsored phase 2A trial on hidradenitis suppurativa and a PI for a multi-center 
trial studying an oral BTK inhibitor in pemphigus vulgaris sponsored by Principia Biopharma. She is also a 
Co-PI for three sponsored clinical trials androgenetic alopecia, alopecia areata and dermatomyositis. KL 
will review all visit source documents and photographs every quarter to ensure adherence to the protocol 
and monitor adverse events. 
The study will be prematurely terminated in the event of any unexpected, significant, or unacceptable risk 
to participants. A summary of the outcomes of these reviews along with all AEs and deviations will be 
submitted to the IRB on an annual basis with the Continuing Review submission. 
10 Statistical Considerations 
 
 
10.1 Sample Size Considerations 
 
We will recruit and screen 30-40 participants with a projected accrual of 20 evaluable patients.  
 
  
A sample size of 20 patients with a significance level (alpha) of 0.05 using a two-sided paired Wilcoxon 
Signed-Rank test (assuming that the actual distribution of paired differences is normal) can achieve 80% 
power to detect the following means of the paired difference between both Sites in the change from the first 
POSAS score (before initiating treatment series) to the final POSAS score. 
We present in the table below a number of detectable means based on various estimated standard 
deviations (SD) of the paired differences between both treatments in the change from the first POSAS 
score to the final POSAS score. The estimated SD’s are based on various assumptions of Pearson’s 
correlation coefficients between the first POSAS score and the final POSAS score and between both 
treatments of the keloid (we assumed that the correlation between the first POSAS score and the final 
POSAS score is similar to the correlation between both treatments). Additionally, for an estimation of 

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standard deviation of the POSAS score, we used the difference in its range divided by 4, i.e. (120-
12)/4=27. 
 : 
 
Correlation coefficient between 
the first POSAS score (before 
initiating treatment series) and 
the final POSAS score and 
between both treatments 
Estimated SD of the paired 
difference between both 
treatments in the change from 
the first POSAS score (before 
initiating treatment series) to the 
final POSAS score 
Detectable mean of paired 
difference between both 
treatments in the change from 
the first POSAS score (before 
initiating treatment series) to the 
final POSAS score  
0.1 
 48.6 
 |33.0| 
0.25 
 40.5 
 |27.5| 
0.5 
27.0 
|18.4| 
0.75 
 13.5 
 |9.2| 
0.9 
 5.4 
 |3.7| 
 
10.2 Statistical Methods  
10.2.1 General Methods  
Continuous variables will be summarized using descriptive statistics (n, mean, standard deviation, 
median, minimum, and maximum). Categorical variables will be summarized showing the number and 
percentage (n, %) of patients within each classification. Graphical displays will be provided where useful 
in the interpretation of results. 
10.2.2 Demographics and Baseline Characteristics  
Demographic data (gender, age [years], age group, race, ethnicity), baseline scar characteristics and 
POSAS scores at baseline will be summarized. 
10.2.3 Primary Analysis  
Prior to the analysis, distributions of the POSAS scores will be summarized by visit and the distributions of 
the modified Hamilton scores will be summarized at the final visit.  
 
A two-sided paired Wilcoxon Signed-Rank test at a 0.05 significance level will be used to compare Site A 
and Site B of the keloid in the change from the first POSAS score (before initiating treatment series) to the 
final POSAS score. 
 
A two-sided paired Wilcoxon Signed-Rank test at a 0.05 significance level will be used to compare the 
modified Hamilton score in Site A and Site B of the keloid. 
10.2.4 Secondary Analysis 
The measurements of the scar will be defined as the total volume (length x width x height) in cm3 of the 
scar, or length x width in cm2 if the scars are flush with the surrounding skin scar surface. 
Measurements of the scar will be summarized by visit and compared between the two Sites of the keloid.   
10.2.5 Exploratory Analysis 
Patient’s subjective experiences will be summarized and compared between both Sites of the keloid as 
follows: 

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1. Patient perceived side effects after each treatment will be summarized by type (dyspigmentation, 
pain, itch, swelling), visit (1, 2, 3, 4) and treatment Site (A, B).  
 
2. Pain  after each laser treatment will be summarized by grade (scale of 1 to 10 (10 being the worst 
pain)), visit (1, 2, 3, 4) and treatment Site (A, B). 
 
3. Speed of healing after completion of laser treatments at final visit (visit 5) will be compared 
between both Sites (Site A healed faster than Site B, Site B healed faster than Site A, Same 
speed of healing in both Sites) 
 
  
10.1 Measures to Minimize Bias 
10.1.1 Enrollment/Randomization/Masking Procedures 
The keloid on the patient’s right side or the patient’s right half of the keloid or the superior keloid will be 
designated Site A. The keloid on the patient’s left side or the patient’s left half of the keloid or the inferior 
keloid will be designated Site B.  Randomization of which treatment (5-FU or TAC) will be applied to Site 
A will be performed in in RedCap by the study statistician (BL). The treating physician (NL) will enter the 
patient ID in RedCap, answer a number of eligibility verification questions and retrieve the assignment for 
that patient. No patient-identifiable data will be entered in RedCap. All patient data will be entered in 
paper forms.  Study participants will be blinded to the type of drug delivered via laser. Because they will 
need to wear protective opaque metal laser eye shields during the treatment, they will not be able to see 
the treatment being performed. The providers involved in the intervention (NL, LA) will not be blinded to 
the type of drug delivered, given that the two drugs are clearly identifiable based on their color.  For this 
reason, a separate blinded dermatologist (DG) will complete the POSAS score at each visit. NL or LA will 
indicate which keloid is Site A and which is Site B with a surgical marking pen, when DG is not present. 
DG will then enter the treatment room and grade each Site A and Site B with the observer portion of the 
POSAS score. We will also have multiple blinded dermatologist observers on faculty at NYU rate non-
identifiable photographs of the keloids that have undergone 4 treatments and complete the Hamilton scar. 
De-identified data (aside from the patient ID) will be entered in Excel for purposes of statistical analysis. 
 
 
Source Documents and Access to Source Data/Documents 
Source data is all information, original records of clinical findings, observations, or other activities in a 
clinical trial necessary for the reconstruction and evaluation of the trial.  Source data are contained in 
source documents.  Examples of these original documents, and data records include: hospital records, 
clinical and office charts, laboratory notes, memoranda, subjects’ diaries or evaluation checklists, 
pharmacy dispensing records, recorded data from automated instruments, copies or transcriptions 
certified after verification as being accurate and complete, microfiches, photographic negatives, microfilm 
or magnetic media, x-rays, subject files, and records kept at the pharmacy, at the laboratories, and at 
medico-technical departments involved in the clinical trial. It is acceptable to use CRFs as source 
documents. If this is the case, it should be stated in this section what data will be collected on CRFs and 
what data will be collected from other sources. 
 
The study case report form (CRF) is the primary data collection instrument for the study.  All data 
requested on the CRF must be recorded.  All missing data must be explained.  If a space on the CRF is 
left blank because the procedure was not done or the question was not asked, write “N/D”.  If the item is 
not applicable to the individual case, write “N/A”.  All entries should be printed legibly in black ink.  If any 
entry error has been made, to correct such an error, draw a single straight line through the incorrect entry 
and enter the correct data above it.  All such changes must be initialed and dated.  DO NOT ERASE OR 
WHITE OUT ERRORS.  For clarification of illegible or uncertain entries, print the clarification above the 
item, then initial and date it. 
 

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Access to study records will be limited to IRB-approved members of the study team. The investigator will 
permit study-related monitoring, audits, and inspections by the IRB/EC, government regulatory bodies, 
and University compliance and quality assurance groups of all study related documents (e.g. source 
documents, regulatory documents, data collection instruments, study data etc.).  The investigator will 
ensure the capability for inspections of applicable study-related facilities (e.g. pharmacy, diagnostic 
laboratory, etc.). 
 
Participation as an investigator in this study implies acceptance of potential inspection by government 
regulatory authorities and applicable University compliance and quality assurance offices. 
11 Quality Assurance and Quality Control 
QC procedures will be implemented beginning with the data entry system and data QC checks that will be 
run on the database will be generated. Any missing data or data anomalies will be communicated to the 
site(s) for clarification/resolution. 
12 Ethics/Protection of Human Subjects 
12.1 Ethical Standard 
The investigator will ensure that this study is conducted in full conformity with Regulations for the 
Protection of Human Subjects of Research codified in 45 CFR Part 46, 21 CFR Part 50, 21 CFR Part 56, 
and/or the ICH E6. 
12.2 Institutional Review Board 
The protocol, informed consent form(s), recruitment materials, and all participant materials will be 
submitted to the IRB for review and approval. Approval of both the protocol and the consent form must be 
obtained before any participant is enrolled. Any amendment to the protocol will require review and 
approval by the IRB before the changes are implemented to the study. All changes to the consent form 
will be IRB approved; a determination will be made regarding whether previously consented participants 
need to be re-consented. 
12.3 Informed Consent Process 
12.3.1 Consent and Other Informational Documents Provided to Participants 
Consent forms describing in detail the study agent, study procedures, and risks are given to the 
participant and written documentation of informed consent is required prior to starting 
intervention/administering study product. The consent form will be submitted with this protocol. 
12.3.2 Consent Procedures and Documentation 
Informed consent is a process that is initiated prior to the individual’s agreeing to participate in the study 
and continues throughout the individual’s study participation. Extensive discussion of risks and possible 
benefits of participation will be provided to the participants and their families. Consent forms will be IRB-
approved and the participant will be asked to read and review the document in addition to the key 
information sheet. The investigator (PI and/or co-investigator) will explain the research study to the 
participant and answer any questions that may arise. Informed consent to review medical records to 
assess exclusion and inclusion criteria will take place over the phone and subject privacy will be 
protected. All participants will receive a verbal explanation in terms suited to their comprehension of the 
purposes, procedures, and potential risks of the study and of their rights as research participants. At the 
screening visit, participants will have the opportunity to carefully review the written consent form and ask 
questions prior to signing. The participants should have the opportunity to discuss the study with their 
surrogates or think about it prior to agreeing to participate. The participant will sign the informed consent 
document prior to any procedures being done specifically for the study. The participants may withdraw 
consent at any time throughout the course of the trial. A copy of the signed informed consent document 

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will be given to the participants for their records. The rights and welfare of the participants will be 
protected by emphasizing to them that the quality of their medical care will not be adversely affected if 
they decline to participate in this study. 
 
A copy of the signed informed consent document will be stored in the subject’s research record. The 
consent process, including the name of the individual obtaining consent, will be thoroughly documented in 
the subject’s research record. Any alteration to the standard consent process (e.g. use of a translator, 
consent document presented orally, etc.) and the justification for such alteration will likewise be 
documented.  
12.4 Participant and Data Confidentiality 
 
Information about study subjects will be kept confidential and managed according to the requirements of 
the Health Insurance Portability and Accountability Act of 1996 (HIPAA).  Those regulations require a 
signed subject authorization informing the subject of the following:  
• What protected health information (PHI) will be collected from subjects in this study 
• Who will have access to that information and why 
• Who will use or disclose that information  
• The rights of a research subject to revoke their authorization for use of their PHI.  
 
In the event that a subject revokes authorization to collect or use PHI, the investigator, by regulation, 
retains the ability to use all information collected prior to the revocation of subject authorization.  For 
subjects that have revoked authorization to collect or use PHI, attempts should be made to obtain 
permission to collect at least vital status (i.e. that the subject is alive) at the end of their scheduled study 
period. 
 
Participant confidentiality is strictly held in trust by the participating investigators and their staff. This 
confidentiality is extended to cover testing of biological samples and genetic tests in addition to the 
clinical information relating to participants. Therefore, the study protocol, documentation, data, and all 
other information generated will be held in strict confidence. No information concerning the study or the 
data will be released to any unauthorized third party. 
 
The study monitor, representatives of the IRB or pharmaceutical company supplying study product may 
inspect all documents and records required to be maintained by the investigator, including but not limited 
to, medical records (office, clinic, or hospital) and pharmacy records for the participants in this study. The 
clinical study site will permit access to such records. 
 
The study participant’s contact information will be securely stored at each clinical site for internal use 
during the study. At the end of the study, all records will continue to be kept in a secure location for as 
long a period as dictated by local IRB and Institutional regulations. 
 
Study participant research data, which is for purposes of statistical analysis and scientific reporting, will 
be transmitted to and stored at NYU Langone Medical Center. This will not include the participant’s 
contact or identifying information. Rather, individual participants and their research data will be identified 
by a unique study identification number. The study data entry and study management systems used by 
clinical sites and by NYU Langone Medical Center research staff will be secured and password protected. 
At the end of the study, all study databases will be de-identified and archived at the NYU Langone 
Medical Center. Photographs will be non-identifiable in content and labeling. Photographs will be stored 
on a secured drive on a password protected computer in Room 24-033 in 222 E 41st St and only 
representative non-identifiable photos will be used for publication and/or teaching purposes.  

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13 Data Handling and Record Keeping 
13.1 Data Collection and Management Responsibilities 
 
Data collection is the responsibility of the clinical trial staff at the site under the supervision of the PI. The 
PI is responsible for ensuring the accuracy, completeness, legibility, and timeliness of the data reported. 
Data to be recorded include patient’s age, gender, keloid measurements (length, width, height), scar 
scores. All data will be stored on paper to be stored in a locked file cabinet in the PI’s office at 222 E 41st 
st, and only the PI (NL) will have a copy of the key. All source documents will be  moved to a double-
locked storage space in the DCSU after study completion.  
 
Copies of the electronic CRF (eCRF) will be provided for use as source documents and maintained for 
recording data for each participant enrolled in the study. Data reported in the eCRF will be consistent with 
the source documents or the discrepancies will be explained and captured in a progress note and 
maintained in the participant’s official electronic study record. 
 
Clinical data (including AEs, concomitant medications, and expected adverse reactions data) and clinical 
laboratory data will be entered on paper to be stored in a locked file cabinet.  Clinical data will be entered 
directly from the source documents. De-identified data (aside from the patient ID) will be entered in Excel 
for purposes of statistical analysis. 
13.2 Study Records Retention 
Study documents will be retained for 5 years after final reporting/publication.  
13.3 Protocol Deviations 
A protocol deviation is any noncompliance with the clinical trial protocol, GCP, or Manual of Procedures 
(MOP) requirements. The noncompliance may be either on the part of the participant, the investigator, or 
the study site staff. As a result of deviations, corrective actions are to be developed by the site and 
implemented promptly. 
 
These practices are consistent with ICH E6: 
• 4.5 Compliance with Protocol, sections 4.5.1, 4.5.2, and 4.5.3 
• 5.1 Quality Assurance and Quality Control, section 5.1.1 
• 5.20 Noncompliance, sections 5.20.1, and 5.20.2. 
 
The PI/study will identify and report deviations within 30 working days of identification of the protocol 
deviation, or within 30 working days of the scheduled protocol-required activity per IRB guidelines. 
 
All protocol deviations will be addressed in study source documents. 
13.4 Publication and Data Sharing Policy 
The International Committee of Medical Journal Editors (ICMJE) member journals have adopted a clinical 
trials registration policy as a condition for publication. The ICMJE defines a clinical trial as any research 
project that prospectively assigns human subjects to intervention or concurrent comparison or control 
groups to study the cause-and-effect relationship between a medical intervention and a health outcome. 
Medical interventions include drugs, surgical procedures, devices, behavioral treatments, process-of-care 
changes, and the like. Health outcomes include any biomedical or health-related measures obtained in 
patients or participants, including pharmacokinetic measures and adverse events. The ICMJE policy, and 
the Section 801 of the Food and Drug Administration Amendments Act of 2007, 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. Other biomedical journals are considering adopting similar policies. For interventional 
clinical trials performed under NIH IC grants and cooperative agreements, it is the grantee’s responsibility 
to register the trial in an acceptable registry, so the research results may be considered for publication in 

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ICMJE member journals. The ICMJE does not review specific studies to determine whether registration is 
necessary; instead, the committee recommends that researchers who have questions about the need to 
register err on the side of registration or consult the editorial office of the journal in which they wish to 
publish. 
 
FDAAA mandates that a "responsible party" (i.e., the sponsor or designated principal investigator) register 
and report results of certain "applicable clinical trials": 
 
• Trials of Drugs and Biologics: Controlled, clinical investigations, other than Phase I investigations 
of a product subject to FDA regulation; 
• Trials of Devices: Controlled trials with health outcomes of a product subject to FDA regulation 
(other than small feasibility studies) and pediatric postmarket surveillance studies. 
14 Study Finances 
14.1 Funding Source 
We have received funding from the Rudin Family pilot grant and the Skin of Color Society grant.  
14.2 Costs to the Participant 
There are no costs to the participant as part of this study.  
14.3 Participant Reimbursements or Payments 
There are no participant reimbursements or payments.  
15 Study Administration 
15.1 Study Leadership 
The Study Team will govern the conduct of the study. The Steering Committee will be composed of the 
Principal Investigator, the Sub-investigator, and the Research Fellow. The Study Team will meet virtually 
or in person at least biannually.  
16 Conflict of Interest Policy 
 
The independence of this study from any actual or perceived influence, such as by the pharmaceutical 
industry, is critical. Therefore, any actual conflict of interest of persons who have a role in the design, 
conduct, analysis, publication, or any aspect of this trial will be disclosed and managed. Furthermore, 
persons who have a perceived conflict of interest will be required to have such conflicts managed in a 
way that is appropriate to their participation in the trial.  
 
Any investigator who has a conflict of interest with this study (patent ownership, royalties, or financial gain 
greater than the minimum allowable by their institution, etc.) must have the conflict reviewed by the NYU 
Langone Conflict of Interest Management Unit (CIMU) with a Committee-sanctioned conflict management 
plan that has been reviewed and approved by the study sponsor prior to participation in this study. All 
NYULMC investigators will follow the applicable conflict of interest policies. 
 
 

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17 References 
 
1. 
Waibel JS, Wulkan AJ, Rudnick A, Daoud A. Treatment of Hypertrophic Scars Using Laser-
Assisted Corticosteroid Versus Laser-Assisted 5-Fluorouracil Delivery. Dermatologic surgery : official 
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2. 
Rumsey N, Clarke A, White P. Exploring the psychosocial concerns of outpatients with disfiguring 
conditions. Journal of wound care 2003;12:247-52. 
3. 
Brown BC, McKenna SP, Siddhi K, McGrouther DA, Bayat A. The hidden cost of skin scars: 
quality of life after skin scarring. Journal of plastic, reconstructive & aesthetic surgery : JPRAS 
2008;61:1049-58. 
4. 
Wolfram D, Tzankov A, Pülzl P, Piza-Katzer H. Hypertrophic scars and keloids--a review of their 
pathophysiology, risk factors, and therapeutic management. Dermatologic surgery : official publication for 
American Society for Dermatologic Surgery [et al] 2009;35:171-81. 
5. 
Stucker FJ, Shaw GY. An approach to management of keloids. Archives of otolaryngology--head 
& neck surgery 1992;118:63-7. 
6. 
Chen MA, Davidson TM. Scar management: prevention and treatment strategies. Current opinion 
in otolaryngology & head and neck surgery 2005;13:242-7. 
7. 
Khan MA, Bashir MM, Khan FA. Intralesional triamcinolone alone and in combination with 5-
fluorouracil for the treatment of keloid and hypertrophic scars. JPMA The Journal of the Pakistan Medical 
Association 2014;64:1003-7. 
8. 
Waibel JS, Wulkan AJ, Shumaker PR. Treatment of hypertrophic scars using laser and laser 
assisted corticosteroid delivery. Lasers Surg Med 2013;45:135-40. 
9. 
Cavalie M, Sillard L, Montaudie H, Bahadoran P, Lacour JP, Passeron T. Treatment of keloids 
with laser-assisted topical steroid delivery: a retrospective study of 23 cases. Dermatol Ther 2015;28:74-
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Boyadjiev C, Popchristova E, Mazgalova J. Histomorphologic changes in keloids treated with 
Kenacort. J Trauma 1995;38:299-302. 
11. 
Mustoe TA, Cooter RD, Gold MH, et al. International clinical recommendations on scar 
management. Plastic and reconstructive surgery 2002;110:560-71. 
12. 
Park JH, Chun JY, Lee JH. Laser-assisted topical corticosteroid delivery for the treatment of 
keloids. Lasers in medical science 2017;32:601-8. 
13. 
Haurani MJ, Foreman K, Yang JJ, Siddiqui A. 5-Fluorouracil treatment of problematic scars. 
Plastic and reconstructive surgery 2009;123:139-48; discussion 49-51. 
14. 
Shridharani SM, Magarakis M, Manson PN, Singh NK, Basdag B, Rosson GD. The emerging role 
of antineoplastic agents in the treatment of keloids and hypertrophic scars: a review. Annals of plastic 
surgery 2010;64:355-61. 
15. 
Huang L, Wong YP, Cai YJ, Lung I, Leung CS, Burd A. Low-dose 5-fluorouracil induces cell cycle 
G2 arrest and apoptosis in keloid fibroblasts. The British journal of dermatology 2010;163:1181-5. 
16. 
Alexandrescu D, Fabi S, Yeh LC, Fitzpatrick RE, Goldman MP. Comparative Results in 
Treatment of Keloids With Intralesional 5-FU/Kenalog, 5-FU/Verapamil, Enalapril Alone,Verapamil Alone, 
and Laser: A Case Report and Review of the Literature. Journal of drugs in dermatology : JDD 
2016;15:1442-7. 
17. 
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fractional resurfacing device. Lasers in surgery and medicine 2007;39:96-107. 
18. 
Manstein D, Herron GS, Sink RK, Tanner H, Anderson RR. Fractional photothermolysis: a new 
concept for cutaneous remodeling using microscopic patterns of thermal injury. Lasers in surgery and 
medicine 2004;34:426-38. 
19. 
Wind BS, Meesters AA, Kroon MW, et al. Formation of fibrosis after nonablative and ablative 
fractional laser therapy. Dermatologic surgery : official publication for American Society for Dermatologic 
Surgery [et al] 2012;38:437-42. 
20. 
Hultman CS, Edkins RE, Wu C, Calvert CT, Cairns BA. Prospective, before-after cohort study to 
assess the efficacy of laser therapy on hypertrophic burn scars. Annals of plastic surgery 2013;70:521-6. 
21. 
Anderson RR, Donelan MB, Hivnor C, et al. Laser treatment of traumatic scars with an emphasis 
on ablative fractional laser resurfacing: consensus report. JAMA dermatology 2014;150:187-93. 

Study number: s20-01172 
 
Page 26 
Version: February 24, 2021 
 
 
 
CONFIDENTIAL 
This material is the property of the NYU School of Medicine and Langone Medical Center.  Do not disclose or use except as 
authorized in writing by the study sponsor 
Interventional Template Version: 11 January 2019 
22. 
Lee YI, Kim J, Yang CE, Hong JW, Lee WJ, Lee JH. Combined Therapeutic Strategies for Keloid 
Treatment. Dermatologic surgery : official publication for American Society for Dermatologic Surgery [et 
al] 2019;45:802-10. 
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Heppt MV, Breuninger H, Reinholz M, Feller-Heppt G, Ruzicka T, Gauglitz GG. Current 
Strategies in the Treatment of Scars and Keloids. Facial plastic surgery : FPS 2015;31:386-95. 
24. 
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evolving technology. Lasers in surgery and medicine 2014;46:249-62. 
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5 fluorouracil and fractional erbium YAG laser for treatment of severe hypertrophic scars. Clin Cosmet 
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Abdelwahab M, Salah M, Samy N, Rabie A, Farrag A. Effect of Topical 5-Fluorouracil Alone 
versus Its Combination with Erbium:YAG (2940 nm) Laser in Treatment of Vitiligo. Clin Cosmet Investig 
Dermatol 2020;13:77-85. 
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Wang KH, Fang JY, Hu CH, Lee WR. Erbium:YAG laser pretreatment accelerates the response 
of Bowen's disease treated by topical 5-fluorouracil. Dermatol Surg 2004;30:441-5. 
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Sabry HH, Abdel Rahman SH, Hussein MS, Sanad RR, Abd El Azez TA. The Efficacy of 
Combining Fractional Carbon Dioxide Laser With Verapamil Hydrochloride or 5-Fluorouracil in the 
Treatment of Hypertrophic Scars and Keloids: A Clinical and Immunohistochemical Study. Dermatologic 
surgery : official publication for American Society for Dermatologic Surgery [et al] 2019;45:536-46. 
29. 
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barrier. Advances in lipid research 1991;24:1-26. 
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Morrow DI, Garland MJ, McCarron PA, Woolfson AD, Donnelly RF. Innovative drug delivery 
strategies for topical photodynamic therapy using porphyrin precursors. Journal of environmental 
pathology, toxicology and oncology : official organ of the International Society for Environmental 
Toxicology and Cancer 2007;26:105-16. 
31. 
Zaleski-Larsen LA, Fabi SG. Laser-Assisted Drug Delivery. Dermatologic surgery : official 
publication for American Society for Dermatologic Surgery [et al] 2016;42:919-31. 
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Manaloto RM, Alster T. Erbium:YAG laser resurfacing for refractory melasma. Dermatologic 
surgery : official publication for American Society for Dermatologic Surgery [et al] 1999;25:121-3. 
33. 
Lee WR, Shen SC, Wang KH, Hu CH, Fang JY. The effect of laser treatment on skin to enhance 
and control transdermal delivery of 5-fluorouracil. Journal of pharmaceutical sciences 2002;91:1613-26. 
34. 
Lee WR, Shen SC, Lai HH, Hu CH, Fang JY. Transdermal drug delivery enhanced and controlled 
by erbium:YAG laser: a comparative study of lipophilic and hydrophilic drugs. Journal of controlled 
release : official journal of the Controlled Release Society 2001;75:155-66. 
35. 
Haak CS, Farinelli WA, Tam J, Doukas AG, Anderson RR, Haedersdal M. Fractional laser-
assisted delivery of methyl aminolevulinate: Impact of laser channel depth and incubation time. Lasers in 
surgery and medicine 2012;44:787-95. 
36. 
Forster B, Klein A, Szeimies RM, Maisch T. Penetration enhancement of two topical 5-
aminolaevulinic acid formulations for photodynamic therapy by erbium:YAG laser ablation of the stratum 
corneum: continuous versus fractional ablation. Experimental dermatology 2010;19:806-12. 
37. 
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recommendations for Fitzpatrick skin types V and VI. The British journal of dermatology 2013;169 Suppl 
3:91-7. 
38. 
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North America 2011;19:405-16. 
39. 
Ali FR, Forbat E, Al-Niaimi F. Laser Treatment of Keloid Scars. Dermatologic surgery : official 
publication for American Society for Dermatologic Surgery [et al] 2017;43:318. 
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Prince GT, Cameron MC, Fathi R, Alkousakis T. Topical 5-fluorouracil in dermatologic disease. 
International journal of dermatology 2018;57:1259-64. 
41. 
Prince GT, Cameron MC, Fathi R, Alkousakis T. Intralesional and Laser-Assisted 5-Fluorouracil 
in Dermatologic Disease: A Systematic Review. Journal of drugs in dermatology : JDD 2018;17:274-80. 
42. 
Manuskiatti W, Fitzpatrick RE. Treatment response of keloidal and hypertrophic sternotomy 
scars: comparison among intralesional corticosteroid, 5-fluorouracil, and 585-nm flashlamp-pumped 
pulsed-dye laser treatments. Archives of dermatology 2002;138:1149-55. 
43. 
Nguyen TA, Feldstein SI, Shumaker PR, Krakowski AC. A review of scar assessment scales. 
Seminars in cutaneous medicine and surgery 2015;34:28-36. 

Study number: s20-01172 
 
Page 27 
Version: February 24, 2021 
 
 
 
CONFIDENTIAL 
This material is the property of the NYU School of Medicine and Langone Medical Center.  Do not disclose or use except as 
authorized in writing by the study sponsor 
Interventional Template Version: 11 January 2019 
 
 
 
 
 
 
 
18 Attachments 
These documents are relevant to the protocol, but they are not considered part of the protocol.  They are 
stored and modified separately. As such, modifications to these documents do not require protocol 
amendments. 
 
Please see the sample consent form, COVID19 information documents, and key information sheet 
attached.  

Study number: s20-01172 
 
Page 28 
Version: 0.1 
 
 
CONFIDENTIAL 
This material is the property of the NYU School of Medicine and Langone Medical Center.  Do not disclose or use except as authorized in writing by the study sponsor 
Interventional Template Version: 11 JAN 2019 
 
19 Schedule of Events 
 
Activity 
 
 
 
 
Screening 
Visit 1 
 
 
 
 
Visit 2 
 
 
 
 
Visit 3 
Visit 4 
Visit 5 
Study team procedures 
 
  
 
 
  
  
Informed Consent 
X 
 
 
 
 
 
Urine pregnancy test (if applicable)  
X 
X 
X 
X 
X 
X 
Medical History 
 
X 
 
 
 
 
 
Physical Exam 
X 
X 
X 
X 
X 
X 
Randomization 
X 
 
 
 
 
 
Study drug/device dispensation 
 
X 
X 
X 
X 
 
Dermatology assessments 
 
 
 
 
 
 
Photography 
 
X 
X 
X 
X 
X 
Caliper measurements 
 
X 
X 
X 
X 
X 
POSAS 
 
X 
X 
X 
X 
X