Clinical trial NCT01459666
Conditions: Scar
Keywords: Scar Forehead Skin Cancer MOHS Surgery Dermatology
Sponsor: University Hospitals Cleveland Medical Center
Start date: 2011-09-01; Completion date: 2019-08-01
Enrollment: 9 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This study will test if the use of DysportTM (abobotulinumtoxinA) improves wound healing and scarring after Mohs surgery. Research in the laboratory as well as previous studies in humans have shown improved wound healing and scarring with the use of a similar medication called Botox.

Dysport may improve wound healing and scarring by relaxing facial muscles and therefore minimizes the muscle tension and possibly the inflammation around the wound.

Detailed description:
Primary Objective:

-To evaluate the efficacy of using aboBTX-A to improve wound healing prior to Mohs micrographic surgery and reconstruction for skin cancer as measured by the Visual Analogue Scale (VAS) at 6 weeks post surgery.

Secondary Objectives:

* To evaluate efficacy of using aboBTX-A to improve wound healing prior to Mohs micrographic surgery and reconstruction for skin cancer as measured by the Patient and Observer Assessment Scale (POSAS) at week 1, 6, and 24.
* To evaluate the efficacy of using aboBTX-A to improve wound healing prior to Mohs micrographic surgery and reconstruction for skin cancer as measured by the Visual Analogue Scale (VAS) at week 1 and 24 post surgery.
* To evaluate patient satisfaction
* To evaluate safety (adverse events)

This is a 6 month, prospective, multicenter, double-blinded, randomized, placebo-controlled study. A total of 40 male or female healthy volunteers, 20 in each arm, will be enrolled. Up to 10 more patients can be enrolled to account for patient drop-out. Subjects will all undergo Mohs micrographic surgical removal of a skin cancer lesion on the forehead followed by reconstruction. Subjects will be randomized to receive either aboBTX-A injection or placebo injection in the frontalis, procerus, and corrugator muscles prior to reconstruction. Photographs, POSAS, and clinical assessments will be taken immediately after initial wound closure, at 1 week follow-up, at 6 weeks follow-up, and at 6 months follow-up. Adverse events will also be reviewed at each study visit. After the completion of the study, the photographs will be assessed (blinded as to the patient identifiers) using a 10 cm visual analog scale (VAS). The first few photographs will be evaluated by the surgeons together to calibrate the VAS and ensure inter-reliability.

Arms: arm 1: Each patient will be able to receive up to 120 units of Dysport/placebo at the initial visit to treat the entire forehead area (the frontalis, procerus, and corrugator muscles) to insure cosmetic symmetry. Injections will be placed a minimum of 1.5cm above the orbital rim at the mid papillary line to minimize the risk of lid ptosis. The actual amount to be injected will be at the discretion of the Mohs surgeon based on his or her opinion of what amount is needed for sufficient wound paralysis and cosmetic symmetry. arm 2: None
Interventions: intervention 1: Dysport (abobotulinumtoxinA) intervention 2: Bacteriostatic 0.9% Sodium Chloride (vehicle)
Intervention descriptions: intervention 1: Intramuscular injection effects lasting up to 3 months intervention 2: Intramuscular injection

Protocol documents:
Prot_SAP_000.pdf: 
CASE 1Z12
V1.3 (10.19.2016)
CASE COMPREHENSIVE CANCER CENTER
__________________________________________________________________
STUDY NUMBER: 
CASE 1Z12
STUDY TITLE: 
A prospective, multi-center, double-blind, randomized, placebo-controlled 
study to evaluate the efficacy of abobotulinumtoxinA (BTX-A) in improving 
forehead wounds after Mohs micrographic surgery and reconstruction for 
skin cancer
 
PRINCIPAL INVESTIGATORS:
Kevin Cooper, MD
Department of Dermatology
University Hospitals Cleveland Medical Center
Case Western Reserve University
11100 Euclid Avenue
Cleveland, OH 44106
(216) 844-8200
CO- INVESTIGATORS:
Joel Cohen, MD
AboutSkin Dermatology and DermSurgery
Englewood, CO
David Ozog, MD
Department of Dermatology
Henry Ford Health Systems
Detroit, MI
Roy Moy, MD 
Department of Dermatology, UCLA
Moy-Fincher-Chipps Facial Plastics & Dermatology
Los Angeles, CA
SPONSOR:
Investigator Initiated
SUPPORT:
Medicis Pharmaceutical Corporation
CLINICAL FACILITY:
University Hospitals Cleveland Medical Center
UH- Bolwell Clinic
UH- Westlake
APPROVALS:
Protocol Review and Monitoring Committee: Approved July 3, 2012
Case Cancer IRB: Pending


CASE 1Z12 Protocol v1.2  10.23.2012
2
SCHEMA
Procedure
Visit 1:
Screening & 
Dysport 
Administration
Visit 2:
Op 
Visit
Visit 3:
1-2 wk 
f/u
Visit 4:
6 wk f/u
Visit 5:
6 month 
f/u
Informed Consent
X
Pre-op Evaluation
X
Injection of Dysport or  
Placebo
X
Adverse Events
X
X
X
X
X
Medical/Medication History
X
X
X
X
X
Photography
X
X
X
X
X
Skin Evaluation
X
X
X
X
Urine Pregnancy Test
X
X
Assessments
Physician VAS
X
X
Patient POSAS
X
X
X
X
Physician POSAS
X
X
X
X
Patient survey
X


CASE 1Z12 Protocol v1.2  10.23.2012
3
TABLE OF CONTENTS
       
SCHEMA
1.0
INTRODUCTION
1.1 Name of Study Disease
1.2 Investigational Agents 
1.3 Pre-clinical Data
1.4 Clinical Data
1.5 Clinical Pharmacokinetics
1.6 Rationale
2.0
OBJECTIVES
2.1 Primary Objective
2.2 Secondary Objective
3.0
STUDY DESIGN
4.0
PATIENT SELECTION
4.1 Inclusion Criteria
4.2 Exclusion Criteria
4.3 Inclusion of Women and Minorities 
5.0
REGISTRATION
6.0
TREATMENT PLAN
6.1 Name of Agent Administration
6.2 Definition of Dose-Limiting Toxicity
6.3 General Concomitant Medications and Supportive Care Guidelines
6.4 Duration of Therapy
6.5 Duration of Follow-up
7.0
DOSE DELAYS/DOSE MODIFICATIONS
8.0
ADVERSE EVENTS: LIST AND REPORTING REQUIREMENTS
8.1 Adverse Events and Potential Risk List
8.1.1
Name of Agent
8.2 Definitions
8.2.1
Adverse Events
8.2.2
Significance of an Adverse Event
8.2.3
Serious Adverse Events
8.2.4
Expectedness
8.2.5
Attribution
8.3 Reporting Procedures for All Adverse Events
8.4 Serious Adverse Event Reporting Procedures
8.4.1
Reporting
8.4.2
FDA Reporting
8.4.3
Multi-Center Trials
8.5 Data Safety Toxicity Committee
9.0
PHARMACEUTICAL INFORMATION


CASE 1Z12 Protocol v1.2  10.23.2012
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10.0 CORRELATIVE/SPECIAL STUDIES
11.0 STUDY PARAMETERS AND CALENDAR
11.1  Study Parameters
11.2  Calendar
12.0 MEASUREMENT OF EFFECT
13.0 DATA REPORTING/REGULATORY CONSIDERATIONS
13.1 Data Reporting
13.2 Regulatory Considerations
14.0 STATISTICAL CONSIDERATIONS
REFERENCES
APPENDICES       
APPENDIX 1
Visual Analogue Scale
APPENDIX 2
Patient and Observer Scar Assessment Scale
APPENDIX 3
Patient Satisfaction Survey
APPENDIX 4
Dysport Prescribing Information


CASE 1Z12 Protocol v1.2  10.23.2012
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1.0 INTRODUCTION
1.1
Scarring after Mohs Surgery
A common and significant risk and side effect of surgery is scarring.  A major obstacle in wound 
healing is the tension caused by the surrounding muscles.  Although surgeons can close a wound to 
minimize this tension, the repeated contraction of the surrounding muscles in every day movement put 
recurrent stress on the wound, prolonging the healing process.  This can also lead to the formation of 
hypertrophic scars.  Botulinum toxin is a protein produced by the bacterium Clostridium botulinum, 
and it is well known as a neurotoxin.  It blocks neuromuscular transmission, thereby preventing the 
affected muscle group from contracting.  It was postulated that the injection of a botulinum toxin into 
the surrounding area of a scar would decrease contraction and thereby improve wound healing and 
scarring.  Since then, there have been several studies describing the benefit of using botulinum toxin A 
(BTX-A) in improving aesthetic outcomes in facial wounds.  The use of BTX-A is becoming an 
increasing part of common practice to minimize scarring.  To date, no such studies exist using 
abobotulinumtoxinA (aboBTX-A, Dysport) nor are there studies looking specifically at post-Mohs 
reconstruction for skin cancer removal.  Mohs surgery is a specific technique of dermatologic surgery 
used to treat skin cancer.  A specific study on the use of aboBTX-A prior to repair of skin cancer 
defects on the forehead would be valuable and may prove to facilitate this practice into more general 
use among skin cancer surgeons to help in optimizing scar appearance.
1.2
Investigational Agents 
1.2.1
Dysport
Dysport (abobotulinumtoxinA) contains botulinim toxin A. It is a purified neurotoxin type A 
complex that is produced from fermentation of the bacterium Clostridium botulinum type A, 
Hall strain.  Dysport is currently indicated for use in reducing glabellar lines and in cervical 
dystonia.
Dysport is supplied in single-use, sterile vials for intramuscular injection. Each vial contains 
300 units of lyophilized abobotulinumtoxinA with 125mcg of human serum albumin and 
2.5mg of lactose.  Prior to use, it is reconstituted with 2.5 ml of sterile, bacteriostatic 0.9% 
sodium chloride solution.  This yields a solution equivalent to 10 units per 0.08cc.  
1.2.1.1
Mechanism of Action
Dysport inhibits release of the neurotransmitter, acetylcholine, from peripheral 
cholinergic nerve endings. Toxin activity occurs in the following sequence: Toxin heavy 
chain mediated binding to specific surface receptors on nerve endings, internalization of 
the toxin by receptor mediated endocytosis, pH-induced translocation of the toxin light 
chain to the cell cytosol and cleavage of SNAP25 leading to intracellular blockage of 
neurotransmitter exocytosis into the neuromuscular junction. This accounts for the 
therapeutic utility of the toxin in diseases characterized by excessive efferent activity in 
motor nerves.  Recovery of transmission occurs gradually within 3 months as the 
neuromuscular junction recovers from SNAP25 cleavage and as new nerve endings are 
formed.
1.2.1.2
Summaries of and clinical significance of non-clinical and clinical 
studies
Please see below and the Dysport package insert for more information.
1.2.1.3
Non-clinical and Clinical Pharmacokinetics
Please see below and the Dysport package insert for more information.


CASE 1Z12 Protocol v1.2  10.23.2012
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1.2.1.4
Major route of Elimination
Please see below and the Dysport package insert for more information.
1.2.1.5
Safety Profile
Dysport is an acetylcholine release inhibitor and a neuromuscular blocking agent 
indicated for the temporary improvement in the appearance of moderate to severe 
glabellar lines associated with procerus and corrugator muscle 
Contraindications:  Dysport is contraindicated in individuals with any allergy to any 
component of the preparation, including milk allergy. It is also contraindicated if 
there is a current infection at the proposed injection site. 
Pregnancy: Dysport is Pregnancy category C.  Dysport produced embryo-fetal toxicity 
when given to pregnant rats at doses similar to or greater than the maximum 
recommended human dose (MRHD) of 1000 Units on a body weight (Units/kg) basis.  In 
an embryo-fetal development study in which pregnant rats received intramuscular 
injections daily (2.2, 6.6, or 22 Units/kg on gestation days 6 through 17) or intermittently 
(44 Units/kg on gestation days 6 and 12 only) during organogenesis, increased early 
embryonic death was observed with both dosing schedules. The no-effect dose for 
embryo-fetal developmental toxicity was 2.2 Units/kg (one-tenth the MRHD on a body 
weight basis). Maternal toxicity was seen at 22 and 44 Units/kg. In a pre-and post-natal 
development study in which female rats received 6 weekly intramuscular injections (4.4, 
11.1, 22.2, or 44 Units/kg) beginning on day 6 of gestation and continuing through 
parturition to weaning, an increase in stillbirths was observed at the highest dose, which 
was maternally toxic. The no-effect dose for pre- and post-natal developmental toxicity 
was 22.2 Units/kg (approximately equal to the MRHD on a body weight basis).
There are no adequate studies in pregnant women, and therefore, no one pregnant or 
that could possibly become pregnant will be in enrolled in the study unless they use 
adequate contraception.  It is unknown whether Dysport is excreted in human milk.
Dysport has not been shown to be associated with male-mediated fetal toxicity. The 
reproductive NOEL following intramuscular injection of 0, 4, 8, and 16 U/kg was 4 
U/kg in male rats and 8 U/kg in female rats. Higher doses were associated with dose-
dependent reductions in fertility in male rats (where limb weakness resulted in the 
inability to mate), and an altered estrous cycle in female rats. There were no adverse 
effects on the viability of the embryos. In clinical practice, male contraception is not 
required with Dysport administration.
1.2.1.6
Rationale for the Proposed starting doses and dose escalation 
scheme
Please see below.
1.2.1.7
Metabolism of Investigational study agent in humans and its 
potential for drug interactions.
Not applicable.  
1.3
Pre-Clinical Data
Not applicable.


CASE 1Z12 Protocol v1.2  10.23.2012
7
1.4
Clinical Data
Three double-blind, randomized, placebo-controlled, clinical studies have evaluated the efficacy 
of Dysport for use in the temporary improvement of the appearance of moderate to severe glabellar lines. 
These three studies enrolled healthy adults (ages 19–75) with glabellar lines of at least moderate severity at 
maximum frown. Subjects were excluded if they had marked ptosis, deep dermal scarring, or a substantial 
inability to lessen glabellar lines, even by physically spreading them apart. The subjects in these studies 
received either Dysport or placebo. The total dose was 50 units delivered in equally divided aliquots to 
specified injection sites.  Additional endpoints for each of the studies were post-treatment glabellar line 
severity of none or mild with at least a 1-grade improvement from baseline for separate investigator and 
subject assessments at Day 30. 
Investigators and subjects assessed efficacy at maximum frown by using a 4-point scale (none, mild, 
moderate, severe).  Overall treatment success was defined as post-treatment glabellar line severity of none 
or mild with at least 2 grade improvements from Baseline for the combined investigator and subject 
assessments (composite assessment) on Day 30 (see Table 6). Additional endpoints for each of the studies 
were post-treatment glabellar line severity of none or mild with at least a 1 grade improvement from 
Baseline for the separate investigator and subject assessments on Day 30.
After completion of the randomized studies, subjects were offered participation in a two-year, open-label re-
treatment study to assess the safety of multiple treatments.
 Please see attached package insert for more information.  
1.5 Clinical Pharmacokinetics of Dysport
Using currently available analytical technology, it is not possible to detect Dysport in the peripheral 
blood following intramuscular injection at the recommended doses.
1.6
Placebo:  Sterile Bacteriostatic 0.9% sodium chloride solution
Sterile, bacteriostatic 0.9% sodium chloride solution will be used as the placebo agent since 
abobotulinumtoxinA is reconstituted with the same solution.  An equivalent unit to volume ratio will be 
used (10 units per 0.08cc).  i.e. if the patient would be receiving 30 units, 0.25cc of bacteriostatic 0.9% 
sodium chloride would be drawn.  See Standard Reconstitution table below.


CASE 1Z12 Protocol v1.2  10.23.2012
8
Standard Reconstitution Table
Mix 1 vial of Dysport (300 units) with 2.5cc’s of Bacteriostatic 0.9% Sodium Chloride
Concentration = 10 units per 0.08cc.
Dysport
Volume
6 units
0.05cc
12 units
0.1cc
15 units
0.125cc
24 units
0.2cc
30 units
0.25cc
36 units
0.3cc
54 units
0.4cc
60 units
0.5cc
1.7
Rationale
The use of botulinum toxin A (BTX-A) induced chemoimmobilization of facial wounds to minimize 
scarring is becoming an increasing part of common practice.  Several case reports and small clinical trials 
describe the benefit of using BTX-A in improving aesthetic outcomes in facial wounds. 1-5  
The major factor impeding successful wound healing and therefore improved cosmesis is wound tension 
caused by surrounding muscles.  Although surgeons can approximate wound edges to minimize this 
tension, repeated contractions of the surrounding muscle cause recurrent microtrauma.  This prolongs the 
inflammatory response and increases localized metabolic activity, which can lead to hypertrophic scars. 
A recent prospective clinical study evaluated the use of botulinum toxin A (Botox, Allergan, Irvine, CA) 
in improving facial wound healing found a statistically significant improvement in scar outcome 
compared with placebo.2  No serious adverse events were reported.
To date, no such studies exist using abobotulinumtoxinA (aboBTX-A, Dysport) nor are there studies 
looking specifically at post-Mohs reconstruction for skin cancer removal.  
A specific study on the use of aboBTX-A prior to repair of skin cancer defects on the forehead would be 
valuable and may prove to facilitate this practice into more general use among skin cancer surgeons to 
help in optimizing scar appearance.
In this study, each patient will be able to receive up to 120 units of Dysport/placebo at the initial visit to 
treat the entire forehead area (the frontalis, procerus, and corrugator muscles) to insure cosmetic 
symmetry.  Toxin will be placed a minimum of 1.5cm above the orbital rim at the mid papillary line to 
minimize the risk of lid ptosis.  The actual amount to be injected will be at the discretion of the Mohs 
surgeon based on his or her opinion of what amount is needed for sufficient wound paralysis and cosmetic 
symmetry.  At the completion of the study, all subjects will be offered additional Dysport at no cost to the 
glabella as an on-label indication for improvement of glabella frown lines. 
2.0
OBJECTIVES
To quantify the improvement in scar appearance, we propose the use of two well-established methods of 
measurement:  The Visual Analogue Scale (VAS) and the Patient and Observer Scar Assessment Scale 
(POSAS)6,7 The VAS will be used as the primary end point.  It consists of a 10 point scale to assess global scar 
assessment.  Scar photographic images are assessed by independent physicians, and previous studies have shown 
very high intrarater consistency.  The POSAS consists of two numeric scales. One scale is completed by the 
patients, the other by the clinician. This scale is different than previous scales because it takes the patient’s input 
into consideration. It has good internal consistency and interobserver reliability.8,9  


CASE 1Z12 Protocol v1.2  10.23.2012
9
2.1
Primary Objective:
To evaluate the efficacy of using aboBTX-A to improve wound healing prior to Mohs 
micrographic surgery and reconstruction for skin cancer as measured by the Visual Analogue Scale 
(VAS) at 6 weeks post surgery.
2.2
Secondary Objective:
To evaluate efficacy of using aboBTX-A to improve wound healing prior to Mohs 
micrographic surgery and reconstruction for skin cancer as measured by the Patient and 
Observer Assessment Scale (POSAS) at week 1, 6, and 24.
To evaluate the efficacy of using aboBTX-A to improve wound healing prior to Mohs 
micrographic surgery and reconstruction for skin cancer as measured by the Visual 
Analogue Scale (VAS) at week 1 and 24 post surgery.
To evaluate patient satisfaction
To evaluate safety (adverse events)
3.0
STUDY DESIGN
3.1
Study Design including dose escalation/cohorts/subject numbers
This is a 6 month, prospective, multicenter, double-blinded, randomized, placebo-controlled study. A 
total of 40 male or female healthy volunteers, 20 in each arm, will be enrolled.  Up to 10 more patients 
can be enrolled to account for patient drop-out. Subjects will all undergo Mohs micrographic surgical 
removal of a skin cancer lesion on the forehead followed by reconstruction.  Subjects will be 
randomized to receive either aboBTX-A injection or placebo injection in the frontalis, procerus, and 
corrugator muscles prior to reconstruction.  Photographs, POSAS, and clinical assessments will be 
taken immediately after initial wound closure, at 1 week follow-up, at 6 weeks follow-up, and at 6 
months follow-up.  Adverse events will also be reviewed at each study visit.  After the completion of 
the study, the photographs will be assessed (blinded as to the patient identifiers) using a 10 cm visual 
analog scale (VAS). The first few photographs will be evaluated by the surgeons together to calibrate 
the VAS and ensure inter-reliability.
40 Patient undergoing Mohs Surgery 
for NMSC on the forehead region
(Additional 10 patients to account for 
dropout)
Total for All Sites = 50 patients
UHCMC Total= 20 patients
Dysport Arm
N = 20 (additional 5 for dropout)
UHCMC= Up to 10 patients
Placebo Arm
N = 20 (additional 5 for dropout)
UHCMC= Up to 10 patients


CASE 1Z12 Protocol v1.2  10.23.2012
1
0
Procedure
Visit 1:
Screening & 
Dysport 
Administration
Visit 2:
Op Visit
Visit 3:
1 wk f/u
Visit 4:
6 wk f/u
Visit 5:
6 month f/u
Informed Consent
X
Pre-op Evaluation
X
Injection of Dysport or  
Placebo
X
Adverse Events
X
X
X
X
X
Medical/Medication History
X
X
X
X
X
Photography
X
X
X
X
X
Skin Evaluation
X
X
X
X
Urine Pregnancy Test
X
X
Assessments
Physician VAS
X
X
Patient POSAS
X
X
X
X
Physician POSAS
X
X
X
X
Patient survey
X
3.2
Number of subjects
Subjects for this study will be recruited from up to five clinical sites. A total of forty healthy evaluable 
subjects will participate in this study.  Up to fifty subjects will be enrolled to account for projected 
dropout.  It is anticipated that at least 10 subjects will be enrolled in the first year at UHCMC.  An 
evaluable subject is one who has passed the inclusion and exclusion criteria; given informed consent; 
received and followed the treatment schedule, and has been adequately followed to establish valid 
endpoints of efficacy and tolerance.  
3.3
Replacement of subjects
If a subject withdraws from the study prior to the 6 month follow-up, a replacement subject will be 
enrolled and will be assigned to the same drug or placebo group.
3.4
Expected Duration of Subject Participation  
3.4.1
Duration of Therapy
Study subjects will be given a one time treatment with Dysport at their first visit.  This one 
time injection of Dysport is expected to cause an effect for approximately 3 months.
3.4.2
Duration of Follow-up
Patients will be followed for toxicity and effect for 6 months after treatment the one time 
treatment with Dysport.  If there are adverse events the clinical course of each event will be 
followed until resolution, stabilization, or until it has been determined that the study treatment 
or participation is not the cause.  Serious adverse events that are still ongoing at the end of the 
study period will necessitate follow-up to determine the final outcome. Any serious adverse 
event that occurs after the study period and is considered to be possibly related to the study 
treatment or study participation will be recorded and reported immediately.


CASE 1Z12 Protocol v1.2  10.23.2012
1
1
4.0    PATIENT SELECTION
4.1
Inclusion Criteria:
Patients must meet all of the following inclusion criteria to be eligible for enrollment: 
1. Adults 18 years or older.  
2. Ability to understand the risks, benefits, and alternative to participation and give informed 
consent
3. Have biopsy proven skin cancer on the medial forehead that is amenable to Mohs surgery.  
Medial forehead is defined as the area superiorly from the hairline, inferiorly at the eyebrow, 
and laterally to the tip of the lateral brow (see diagram). 
4. Undergoing elective reconstruction of biopsy proven skin cancer that is amenable to Mohs 
surgery with defect size measuring 1.0 cm or greater
5. If female, not currently pregnant, no potential for pregnancy, or if of child-bearing age, must 
agree to use adequate contraception (e.g., hormonal or barrier method of birth control; 
abstinence) for 30 days after the last dose of study drug.  A negative urine pregnancy test is 
required at study entry for female subjects of childbearing potential: a woman is considered to 
be of child bearing potential unless she has had a tubal ligation, total hysterectomy, bilateral 
oopherectomy, or is postmenopausal (without a menstrual period for at least one year)
6. Agrees to not use disallowed concomitant medications (retinoids)
4.2
Exclusion Criteria
The presence of any of the following will exclude a patient from study enrollment.
1. Pregnant women, women who are breastfeeding, or women of child bearing age who are 
unwilling to use adequate contraception (described above) during the study period
2. Current or past history of a neuromuscular disease (such as myasthenia gravis, amyotrophic 
lateral sclerosis, Eaton-Lambert syndrome)
3. Currently taking aminoglycosides or other agents interfering with neuromuscular transmission 
(e.g., curare-like agents)
4. History of radiation therapy or chemotherapy
5. History of keloid or other hypertrophic scar formation
6. Current or past history of scleroderma
7. Has used botulinum toxin in the forehead area within one year.
8. Has significant resting eyebrow ptosis
9. Has used any topical retinoids to the forehead area within the past 4 weeks
10.Undergo any scar revision procedure for the duration of the study including intralesional 
kenalog, laser treatment, and/or scar revision surgeries
11.Any hypersensitivity to any component of abobotulinumtoxinA (i.e. cow milk protein) or any 
previous hypersensitivity to any botulinum toxin A or related product.
12.Non-English speaking:  These patients are excluded since translation of the informed consent 
into other languages is time-consuming and expensive as it requires a bona fide translator for 
the particular language of interest and this type of person may be difficult to locate.
13.House staff and students, medical students on a clerkship, and employees related to study 
personnel or who work for any study personnel, and members of the study team are not 
eligible to participate in this study as a subject. 
14.The investigator feels that for any reason the subject is not eligible to participate in the study
4.3
Inclusion of Women and Minorities
Both men and women  and members of all races and ethnic groups are eligible for this trial.


CASE 1Z12 Protocol v1.2  10.23.2012
1
2
5.0
REGISTRATION 
5.1
Registration 
All subjects who have been consented will be registered in the OnCore Database. For those 
subjects who are consented, but not enrolled, the reason for exclusion will be recorded.  All 
subjects from Collaborating Centers will also be registered through UHCMC and will be provided 
a study number by calling the telephone number of the Study Coordinator. 
5.2
Randomization 
Block randomization will be used to ensure equal or near equal numbers of subjects per study arm.  
Subjects from Collaborating Centers will be randomized upon receiving a study number from 
UHCMC.   
6.0
TREATMENT PLAN
6.1
Dysport
Each patient will be able to receive up to 120 units of Dysport/placebo at the initial visit to 
treat the entire forehead area (the frontalis, procerus, and corrugator muscles) to insure 
cosmetic symmetry.  Injections will be placed a minimum of 1.5cm above the orbital rim at the 
mid papillary line to minimize the risk of lid ptosis.  The actual amount to be injected will be 
at the discretion of the Mohs surgeon based on his or her opinion of what amount is needed for 
sufficient wound paralysis and cosmetic symmetry. 
Appropriate dose modifications for Dysport are described in Section 7.0.  
Reported adverse events and potential risks of Dysport are described in Section 8.0 
No investigational or commercial agents or therapies other than those described below may be 
administered with the intent to treat the patient's Mohs incision site.
6.2
Definition of Dose-Limiting Toxicity
Not applicable to this study as a single dose of disport/placebo will be administered.  There 
will be no dose escalations.  Reported adverse events and potential risks of Dysport are 
described in Section 8.0.
6.3
General Concomitant Medications and Supportive Care Guidelines
Aminoglycosides or other agents interfering with neuromuscular transmission (e.g., curare-like 
agents) may potentiate the effects of Botox.   Patients currently receiving these agents are 
excluded from the study.  
Using currently available analytical technology, it is not possible to detect Dysport in the 
peripheral blood following intramuscular injection at the recommended doses. Dysport is not 
known to interfere with cytochrome P450.  
Patients should receive full supportive care, including transfusions of blood and blood products, 
cytokines, antibiotics, antiemetics, etc when appropriate.
6.4
Duration of Therapy
Study subjects will be given a one time treatment with Dysport at their first visit.  This one 
time injection of Dysport is expected to cause an effect for approximately 3 months.


CASE 1Z12 Protocol v1.2  10.23.2012
1
3
6.5
Duration of Follow Up
Patients will be followed for toxicity and effect for 6 months after treatment the one time 
treatment with Dysport.  If there are adverse events the clinical course of each event will be 
followed until resolution, stabilization, or until it has been determined that the study treatment 
or participation is not the cause.  Serious adverse events that are still ongoing at the end of the 
study period will necessitate follow-up to determine the final outcome. Any serious adverse 
event that occurs after the study period and is considered to be possibly related to the study 
treatment or study participation will be recorded and reported immediately.
7.0
DOSE DELAYS/DOSE MODIFICATIONS
Not applicable.  No dose delays or modifications are anticipated. 
8.0
 ADVERSE EVENTS: LIST AND REPORTING REQUIREMENTS
8.1
Adverse Events and Potential Risk List
The following is a list of AEs (Section 8.1) and the reporting requirements associated with 
observed AEs (Sections 8.3 and 8.4). 
The clinical course of each event will be followed until resolution, stabilization, or until it has been 
determined that the study treatment or participation is not the cause. 
Serious adverse events that are still ongoing at the end of the study period will necessitate follow-
up to determine the final outcome. Any serious adverse event that occurs after the study period and 
is considered to be possibly related to the study treatment or study participation will be recorded 
and reported immediately.
8.1.1
Dysport
8.1.1.1
Adverse events most likely to occur in this study

Bleeding

Bruising

Infection

Asymmetric / Unsatisfactory results

Injection site pain or reaction
8.1.1.2
Reported common adverse events (>=2%) in placebo-controlled clinical 
trials of Dysport for glabellar lines

Nasopharyngitis

Headache

Injection site pain or reaction

Upper respiratory infection

Eyelid edema

Eyelid ptosis

Sinusitis

Nausea
8.1.1.3
AEs identified from extensive post-marketing data

Vertigo

Eyelid psosis

Diplopia

Amyotrophy


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
Photophobia

Dysphagia

Nausea

Malaise

Flu like illness

Hypersensitivity

Burning sensation

Facial paresis

Hypoesthesia

Erythema

Excessive granulation tissue
8.1.1.4
The most current version of the prescribing information sheet should be 
consulted for more detailed information on adverse events.  As with all therapeutic 
proteins, there is always a chance for immunogenecity and the production of anti-
bodies.  No formal drug interactions have been identified in studies using Dysport.   
Excessive overdose of the drug may be expected to produce neuromuscular weakness 
with a variety of symptoms.  Depending on the extent of overdose, respiratory arrest 
requiring respiratory support may occur.  In the event of an overdose, an antitoxin is 
available.  However, it will not reverse toxin-induced effects already apparent by the 
time of antitoxin administration. The antitoxin is available from the Centers for 
Disease Control and Prevention in Atlanta, GA.
8.1.2
Adverse Events and Potential Risks- Mohs Surgery and Reconstruction
There are risks involved with Mohs and reconstruction surgical procedure that are 
independent of this study including but not limited to:  

Pain

Infection

Bleeding

Swelling

Hematoma

Scar Formation

Wound Dehiscence

Failure of flap or skin graft

Temporary or Permanent Nerve Damage

Distortion/Alteration of surrounding anatomic features

Tumor Recurrence
8.1.3
Adverse Events and Potential Risks- Questionnaires
There may be risks involved with completing the questionnaires.  Some of the questions 
may be upsetting, or the patient may feel uncomfortable answering them (e.g. regarding 
how their scar looks). If they do not wish to answer a question, they will be offered the 
opportunity of skipping it and going on to the next question. The patient may also become 
bored when answering the questions and if so, will be offered the opportunity to stop and 
resume completing the questionnaire after a rest period.
8.2
Definitions
8.2.1
Adverse Events  
An adverse event (AE) is any unfavorable or unintended event, physical or psychological, 
associated with a research study, which causes harm or injury to a research participant as a result 
of the participant’s involvement in a research study. The event can include abnormal laboratory 


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findings, symptoms, or disease associated with the research study. The event does not necessarily 
have to have a causal relationship with the research, any risk associated with the research, the 
research intervention, or the research assessments. 
Adverse events may be the result of the interventions and interactions used in the research; the 
collection of identifiable private information in the research; an underlying disease, disorder, 
or condition of the subject; and/or other circumstances unrelated to the research or any 
underlying disease, disorder, or condition of the subject. In general, adverse events that are at 
least partially the result of (a) or (b) would be considered related to the research, whereas 
adverse events solely related to (c) or (d) would be considered unrelated to the research. 
External adverse events are adverse events experienced by subjects enrolled in multicenter 
clinical trials at sites other than the site(s) over which the Institutional Review Board has 
jurisdiction. 
Internal adverse events are adverse events experienced by subjects enrolled at the site(s) 
under the IRB’s jurisdiction for either multicenter or single-center research projects. 
8.2.2 The significance of an adverse event is used to describe the patient/event outcome or 
action criteria associated with events that pose a threat to a patient’s life or functioning (i.e., 
moderate, severe or life threatening).  Based on the National Cancer Institute Guidelines for 
the Cancer Therapy Evaluation Program, severity can be defined by the following grades of 
events:
Grades 1 are mild adverse events. (e.g., minor event requiring no specific medical 
intervention; asymptomatic laboratory findings only; marginal clinical relevance)
Grades 2 are moderate adverse events (e.g., minimal intervention; local intervention; 
non-invasive intervention; transfusion; elective interventional radiological procedure; 
therapeutic endoscopy or operation).
Grades 3 are severe and undesirable adverse events (e.g., significant symptoms 
requiring hospitalization or invasive intervention; transfusion; elective interventional 
radiological procedure; therapeutic endoscopy or operation).
Grades 4 are life threatening or disabling adverse events (e.g., complicated by acute, 
life-threatening metabolic or cardiovascular complications such as circulatory failure, 
hemorrhage, sepsis; life–threatening physiologic consequences; need for intensive 
care or emergent invasive procedure; emergent interventional radiological procedure, 
therapeutic endoscopy or operation).
Grades 5 are fatal adverse event resulting in death.    
8.2.3  
Serious Adverse Events 
A serious adverse event (SAE) is any adverse experience occurring at any dose that 
results in any of the following outcomes: 
Results in death. 
Is a life-threatening adverse experience.  The term life-threatening in the 
definition of serious refers to an adverse event in which the subject was at risk of 
death at the time of the event.  It does not refer to an adverse event which 
hypothetically might have caused death if it were more severe. 
Requires inpatient hospitalization or prolongation of existing hospitalization.  
Any adverse event leading to hospitalization or prolongation of hospitalization will 


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be considered as Serious, UNLESS at least one of the following expectations is 
met:
o The admission results in a hospital stay of less than 12 hours OR
o The admission is pre-planned (i.e., elective or scheduled surgery arranged 
prior to the start of the study) OR
o The admission is not associated with an adverse event (e.g., social 
hospitalization for purposes of respite care.
However it should be noted that invasive treatment during any 
hospitalization may fulfill the criteria of “medically important” and as 
such may be reportable as a serious adverse event dependant on clinical 
judgment.  In addition where local regulatory authorities specifically 
require a more stringent definition, the local regulation takes precedent. 
Results in persistent or significant disability/incapacity.  The definition of 
disability is a substantial disruption of a person’s ability to conduct normal life’s 
functions.
Is a congenital anomaly/birth defect. 
Is an important medical event.  Important medical events that may not result 
death, be life-threatening, or require hospitalization may be considered a serious 
adverse experience when, based upon appropriate medical judgment, they may 
jeopardize the patient or subject and may require medical or surgical intervention 
to prevent one of the outcomes listed in this definition.  Examples of such medical 
events include allergic bronchospasm requiring intensive treatment in an 
emergency room or at home, blood disease or disorders, or convulsions that do not 
result in inpatient hospitalization, or the development of drug dependency or drug 
abuse.
8.2.4
Expectedness
Adverse Events can be Expected or Unexpected.
An expected adverse event is an event previously known or anticipated to result from 
participation in the research study or any underlying disease, disorder, or condition of the 
subject. The event is usually listed in the Investigator Brochure, consent form or research 
protocol. 
An unexpected adverse event is an adverse event not previously known or anticipated to result 
from the research study or any underlying disease, disorder, or condition of the subject. 
8.2.5
Attribution
Attribution is the relationship between an adverse event or serious adverse event and the study 
drug.  Attribution will be assigned as follows:

Definite – The AE is clearly related to the study drug.

Probable – The AE is likely related to the study drug.

Possible – The AE may be related to the study drug.

Unlikely – The AE is doubtfully related to the study drug.

Unrelated – The AE is clearly NOT related to the study drug.
8.3
Reporting Procedures for All Adverse Events
All participating investigators will assess the occurrence of AEs throughout the subject’s participation in the 
study.  Subjects will be followed for toxicity for 6 months after treatment has been discontinued.  The 
clinical course of each event will be followed until resolution, stabilization, or until it has been determined 
that the study treatment or participation is not the cause.  


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Participants will be given a phone number to call if they suspect they may be experiencing an adverse 
event.  In addition, we will telephone the participant at 24 hrs following the procedure. If the 
participant reports any such reaction, they will be asked to return for an examination and any needed 
treatment. This visit will be considered a research visit and no clinical charge will be entered. The 
event will be followed until the event resolves, the subject does not desire further follow-up, the subject 
withdraws from the study, or the subject is lost to follow-up.
The investigator is responsible for ensuring that all adverse events observed by the investigator or reported 
by the subject which occur after the subject has signed the informed consent are fully recorded in the 
subject’s case report form, subject’s medical records, and/or any other institutional requirement. Source 
documentation must be available to support all adverse events. 
A laboratory test abnormality considered clinically relevant (e.g., causing the subject to withdraw from the 
study), requiring treatment or causing apparent clinical manifestations, or judged relevant by the 
investigator, should be reported as an adverse event.  
The investigator will provide the following for all adverse events:
Description of the event
Date of onset and resolution
Grade of toxicity 
Attribution of relatedness to the investigational agent
Action taken as a result of the event
Outcome of event
In this study, descriptions and grading scales found in the NCI Common Terminology Criteria for Adverse 
Events (CTCAE) version 4.0 available at http://ctep.cancer.gov will be utilized for AE reporting. 
Investigative sites will report adverse events to their respective IRB according to the local IRB’s policies 
and procedures in reporting adverse events.
8.4
Serious Adverse Event Reporting Procedures
Serious adverse events that occur beginning with the signing of the informed consent form, during 
treatment, or within 6 months of the last dose of treatment must be reported to the UHCMC Principal 
Investigator.
Investigative sites will report serious adverse events to their respective IRB according to the local IRB’s 
policies and procedures in reporting serious adverse events.
8.4.1
Medicis Reporting
Not applicable.
8.4.2
FDA Reporting
There is no IND for this study, therefore this is not applicable.
8.4.3
Multi-Center Trials with UHCMC Investigator as Principal Investigator
For multi-site trials where a UHCMC investigator is serving as the Principal Investigator, each 
participating investigator is required to abide by the reporting requirements set by the protocol.  
Participating investigators must report all serious adverse events that occur after the subject has signed 
the informed consent form to the UHCMC Principal Investigator within 24 hours of discovery or 
notification of the event.  Initial serious adverse event information and all amendments or additions 
must be recorded in Oncore.  Relevant medical records should be faxed as soon as they become 
available.  The UHCMC Principal Investigator will review and assess the SAE and follow the 


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reporting requirements in Section 8.4.1 and 8.4.2 and communicate results to all investigational sites.  
The participating investigator must provide follow-up information on the SAE.  Report Serious 
Adverse Events by telephone, email or facsimile to:  
Contact Name: Kevin Cooper, MD.
Contact Email: Kevin.Cooper@gmail.com
Telephone: 216-844-7834
Fax: 216-844-8993
Serious adverse events occurring after conclusion of the study AND thought to be possibly related to 
the investigational agent will be collected and reported within 24 hours of discovery or notification of 
the event.
Each investigative site will be responsible to report SAEs that occur at that institution to their 
respective IRB.  It is the responsibility of each participating investigator to report serious adverse 
events to the study sponsor and/or others as described above. 
8.4.4
Data Safety Toxicity Committee
It is the Case Comprehensive Cancer Center’s Principal Investigator’s responsibility to ensure that ALL 
serious adverse events are reported to the Case Comprehensive Cancer Center’s Data Safety Toxicity 
Committee. This submission is simultaneous with their submission to the Sponsor or other Regulatory 
body. 
9.0
PHARMACEUTICAL INFORMATION
A list of the adverse events and potential risks associated with the investigational or commercial agents 
administered in this study can be found in Section 8.0   
Name of Agent
Dysport
Chemical Name:     
abobotulinumtoxinA
Other Names:        
 Clostridium botulinum type toxin A toxin-haemagglutinin 
complex
Classification:         
Prescription Medicine
Molecular Formula: 
Botulinum toxin type A, the active ingredient in Dysport 
(abobotulinumtoxinA), is a purified neurotoxin type A 
complex produced by fermentation of the bacterium 
Clostridium botulinum type A, Hall Strain. It is purified 
from the culture supernatant by a series of precipitation, 
dialysis, and chromatography steps. The neurotoxin complex 
is composed of the neurotoxin, hemagglutinin proteins and 
non-toxin non-hemagglutinin protein.
Mode of Action:     
Dysport inhibits release of the neurotransmitter, 
acetylcholine, from peripheral cholinergic nerve endings. 
Toxin activity occurs in the following sequence: Toxin 
heavy chain mediated binding to specific surface receptors 
on nerve endings, internalization of the toxin by receptor 
mediated endocytosis, pH-induced translocation of the toxin 
light chain to the cell cytosol  and cleavage of SNAP25 


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leading to intracellular blockage of neurotransmitter 
exocytosis into the neuromuscular  junction. This accounts 
for the therapeutic utility of the toxin in diseases 
characterized by excessive efferent activity in motor nerves.
Metabolism:   
Using currently available analytical technology, it is not 
possible to detect Dysport in the peripheral blood following 
intramuscular injection at the recommended doses
Product description:  
Dysport is supplied in a single-use, sterile vial for 
reconstitution intended for intramuscular injection. Each vial 
contains 300 Units of freeze-dried lyophilized 
abobotulinumtoxinA, 125 micrograms human serum 
albumin and 2.5 mg lactose.  Box containing 1 vial—NDC 
99207-500-30
Solution preparation: 
Prior to use, it is reconstituted with 2.5 ml of sterile, 
bacteriostatic 0.9% sodium chloride solution.  This yields a 
solution equivalent to 10 units per 0.08cc.  
Storage requirements: 
 Dysport is stored under refrigeration at 2–8°C, protected 
from light.
Stability:  
         Not Applicable.
Route of administration:  
Intramuscular injection into the desired muscle.
Drug Procurement: 
Dysport will be supplied for this study by Medicis and is 
available in 3 ml vials containing 300 units of freeze-dried 
abobotulinumtoxinA.  Dysport is being provided at no 
cost to the study subject.   Dysport will be directly 
supplied to each participating site for this study by Medicis. 
Drug Accountability: 
  The investigator or designated study personnel are 
responsible for maintaining accurate dispensing records of 
the study drug at their site.  All study drugs must be 
accounted for, including study drug accidentally or 
deliberately destroyed.    
Drug Destruction: 
   At the completion of the study, there will be a final reconciliation of 
drug shipped, drug consumed, and drug remaining. This reconciliation 
will be logged on the drug reconciliation form, signed and dated. Any 
discrepancies noted will be investigated, resolved, and documented 
prior to return or destruction of unused study drug. Drug destroyed on 
site will be documented in the study files.
Other Information: 
         Not Applicable.
10.0
   CORRELATIVE/SPECIAL STUDIES
Not applicable.


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11.0
STUDY PARAMETERS AND CALENDAR
11.1
Study Parameters
11.1.1.1
Screening Evaluation and Initial Visit (1 hr)
Screening studies and evaluations will be used to determine the eligibility of each 
subject for study inclusion. All evaluations must be completed < 28 days  prior to 
administration of protocol therapy. 
Informed consent: Prior to study initiation, each subject will be screened to ensure 
they meet all of the inclusion and none of the exclusion criteria outlined above. 
Potential subjects will be interviewed and examined by the investigator or his 
designee to establish their eligibility for inclusion in the study.  Subjects will be given 
a full description of the nature and purpose of the study. If a subject is willing to 
participate, they must provide written informed consent before proceeding with the 
study. 
Inclusion and Exclusion criteria
Demographics
Medical History
Pre-op evaluation by Mohs surgeon, which includes focal skin exam
Vital signs including: blood pressure, pulse, respiratory rate
Concomitant Medications Assessment including aminoglycoside, or other agents 
interfering with neuromuscular transmission (e.g., curare-like agents) 
Urine pregnancy test
Randomization
Injection of Dysport or placebo
Review AEs
This visit will take place 2-4 weeks prior to planned Mohs procedure, + or – 3 days
Baseline photographs
11.2
Treatment Period
Visits 2-5 can be scheduled +/- 5 days from indicated date.
Visit 2: Op Visit (30 minutes)    
Localized skin evaluation
Vital signs including: blood pressure, pulse, respiratory rate
Concomitant Medications Assessment including aminoglycoside, or other 
agents interfering with neuromuscular transmission (e.g., curare-like agents) 
Mohs procedure 
Reconstruction
Photograph of wound before and after reconstruction
POSAS
Patient and Observer Scar Assessment Scale (POSAS): The Patient and Observer 
Scar Assessment Scale (POSAS) consist of two numeric scales. One scale is 
completed by the patients, the other by the clinician. This scale is different than 
previous scales because it takes the patient’s input into consideration. It has good 
internal consistency and interobserver reliability8-10. Patient POSAS will be 
collected at visit 2, 3, 4, and 5.  Physician POSAS will be collected by each surgeon 
at visit 2, 3, 4, and 5.  In addition, at the conclusion of the study, all four 
participating investigators will evaluate the photos of the wound at closure, at 6 
weeks, and at 6 months for PSOAS scores in vascularity, pigmentation, thickness, 


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and surface area.  Relief and pliability will not be assessed as photographs do not 
allow for measurement of these values.   
Review AEs, medical history, medications
Visit 3: 1 week follow-up (30 minutes)
Localized skin evaluation
Vital signs including: blood pressure, pulse, respiratory rate
Concomitant Medications Assessment including aminoglycoside, or other agents 
interfering with neuromuscular transmission (e.g., curare-like agents) 
Suture removal
Photograph of wound
POSAS
Review AEs, medical history, medications
Visit 4: 6 weeks follow-up (30 minutes)
Localized skin evaluation
Vital signs including: blood pressure, pulse, respiratory rate
Concomitant Medications Assessment including aminoglycoside, or other agents 
interfering with neuromuscular transmission (e.g., curare-like agents) 
Photograph of wound 
POSAS
Review AEs, medical history, medications
Visit 5: 6 months follow-up/End of study visit (45 minutes)
Localized skin evaluation
Vital signs including: blood pressure, pulse, respiratory rate
Concomitant Medications Assessment including aminoglycoside, or other agents 
interfering with neuromuscular transmission (e.g., curare-like agents) 
Photograph of wound
POSAS, VAS
Visual Analog Scale (VAS): This is a 10 point scale to assess global scar 
assessment.  At the conclusion of the study, photographs will be assessed in an 
independent and blinded fashion.  After reviewing the photos of the wound at 
closure, at 6 weeks, and at 6 months, the participating raters will be asked to rate the 
cosmetic outcome at 6 weeks and 6 months on a 10-cm visual analog scale .  The 
rater will be asked to assess the first patient together to establish a reference score 
for their respective further scores.   Prior studies have shown very high intrarater 
consistency from VAS7.  
Review AEs, medical history, medications
Option: additional Dysport to glabella/forehead to reduce lines.  Females of 
childbearing potential will undergo a urine pregnancy test. 
Patient Satisfaction Survey: This survey will ask the patient’s opinion of using 
Dysport and if they would recommend the procedure to other patients.


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11.3
Calendar
Procedure
Visit 1:
Screening & 
Dysport 
Administration
Visit 2:
Op Visit
Visit 3:
1 wk 
f/u
Visit 4:
6 wk f/u
Visit 5:
6 month 
f/u
Informed Consent
X
Pre-op Evaluation
X
Injection of Dysport or  Placebo
X
Adverse Events
X
X
X
X
X
Medical/Medication History
X
X
X
X
X
Photography
X
X
X
X
X
Skin Evaluation
X
X
X
X
Urine pregnancy test
X
X
Assessments
Physician VAS
X
X
Patient POSAS
X
X
X
X
Physician POSAS
X
X
X
X
Patient survey
X
12.0
MEASUREMENT OF EFFECT
  
12.1
VAS:  Visual Analog Scale.  This is a 10 point scale to assess global scar assessment.  At the 
conclusion of the study, photographs will be assessed in an independent and blinded fashion.  After 
reviewing the photos of the wound at closure, at 6 weeks, and at 6 months, the participating raters will 
be asked to rate the cosmetic outcome at 6 weeks and 6 months on a 10-cm visual analog scale .  The 
rater will be asked to assess the first patient together to establish a reference score for their respective 
further scores.   Prior studies have shown very high intrarater consistency from VAS7.  See statistical 
section for more information.
12.2
POSAS:  Patient and Observer Scar Assessment Scale.  The Patient and Observer Scar Assessment 
Scale (POSAS) consist of two numeric scales. One scale is completed by the patients, the other by the 
clinician. This scale is different than previous scales because it takes the patient’s input into 
consideration. It has good internal consistency and interobserver reliability8-10. Patient POSAS will be 
collected at visit 2, 3, 4, and 5.  Physician POSAS will be collected by each surgeon at visit 2, 3, 4, 
and 5.  In addition, at the conclusion of the study, all four participating investigators will evaluate the 
photos of the wound at closure, at 6 weeks, and at 6 months for PSOAS scores in vascularity, 
pigmentation, thickness, and surface area.  Relief and pliability will not be assessed as photographs do 
not allow for measurement of these values.   
13.0
DATA REPORTING/REGULATORY CONSIDERATIONS
Adverse event lists, guidelines, and instructions for AE reporting can be found in Section 8.0 (Adverse 
Events: List and Reporting Requirements).
13.1
Data Reporting
The OnCore Database will be utilized, as required by the Case Comprehensive Cancer Center, to 
provide data collection for both accrual entry and trial data management.  OnCore is a Clinical Trials 
Management System housed on secure servers maintained at Case Western Reserve University.  
OnCore properly used is compliant with Title 21 CFR Part 11.  Access to data through OnCore is 
restricted by user accounts and assigned roles.  Once logged into the OnCore system with a user ID and 


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password, OnCore defines roles for each user which limits access to appropriate data. User information 
and 
password 
can be 
obtained 
by contacting 
the OnCore Administrator 
at 
oncore-
registration@case.edu.
OnCore is designed with the capability for study setup, activation, tracking, reporting, data monitoring 
and review, and eligibility verification. This study will utilize electronic Case Report Form completion 
in the OnCore database.  A calendar of events and required forms are available in OnCore.
13.2
Regulatory Considerations
The study will be conducted in compliance with ICH guidelines and with all applicable federal (including 
21 CFR parts 56 & 50), state or local laws. 
13.2.1
Written Informed Consent
Provision of written informed consent must be obtained prior to any study-related procedures.  The 
Principal Investigator will ensure that the subject is given full and adequate oral and written 
information about the nature, purpose, possible risks and benefits of the study as well as the 
subject’s financial responsibility.  Subjects will also be notified that they are free to discontinue 
from the study at any time.  The subject will be given the opportunity to ask questions and allowed 
time to consider the information provided. 
The original, signed written Informed Consent Form will be kept with the Research Chart in 
conformance with the institution’s standard operating procedures. A copy of the signed written 
Informed Consent Form will be given to the subject.
Withdrawal of consent: Subjects may choose to discontinue their participation in the study at any 
time by notifying the PI. They will be asked to send a written letter to the PI listed on the informed 
consent. No further research data will be obtained nor clinical data entered into the research 
database. Data gathered until the time of withdrawal will be maintained.
Illiterate subjects: In the event that illiterate individuals who understand English present 
themselves as potential study participants and meet all inclusion/exclusion criteria, the consent 
form will be read to that individual in the presence of a witness and all questions answered. The 
study participant will sign the consent document by “making their mark” in the signature space.  
Both the person obtaining the consent (either the PI or his/her official delegate) and the witness 
will co-sign and date the consent form, noting that the informed consent process has taken place.
Non-English speaking patients, house staff and students, medical students on a clerkship, and 
employees related to study personnel or who work for any study personnel, and members of the 
study team are not eligible to participate in this study as a subject.
13.2.2
    Subject Data Protection
In accordance with the Health Information Portability and Accountability Act (HIPAA), each 
subject will sign an authorization to release medical information to the sponsor and/or allow the 
sponsor, a regulatory authority, or Institutional Review Board access to subject’s medical 
information that includes all hospital records relevant to the study, including subjects’ medical 
history.
All data will be recorded in patient specific study binders. These binders will be kept in a locked 
room only accessible to research personnel. This data will then be transferred to an electronic 
database stored on the UHCMC secure drive that will be password protected and only accessible to 
research personnel. The research team, authorized UH personnel, the study sponsor (if applicable), 
and regulatory entities such as the Food and Drug Administration (FDA) and the Office of Human 
Research Protections (OHRP), may have access to the study records to protect the subject’s safety 


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and welfare. Any information derived from this research project that personally identifies the 
subject will not be voluntarily released or disclosed by these entities without a separate consent, 
except as specifically required by law.  Research records provided to authorized, non-UH entities 
will not contain identifiable information about the subject. Publications and/or presentations that 
result from this study will not include identifiable information.
Digital photographs of the wound will be taken at each visit. The digital files will be stored on 
the UHCMC secure drive that only research personnel will have access to.
13.2.3
Accessing Electronic Medical Records for University Hospitals Health System
Not applicable
13.2.4
Retention of Records
The Principal Investigator at UHCMC supervises the retention of all documentation of adverse 
events, records of study drug receipt and dispensation, and all IRB correspondence for as long as 
needed to comply with national and international regulations. No records will be destroyed until 
the Principal Investigator confirms destruction is permitted. 
13.2.5
Audits and Inspections
Authorized representatives of the sponsor, a regulatory authority, an Independent Ethics 
Committee (IEC) or an Institutional Review Board (IRB) may visit the study site to perform audits 
or inspections, including source data verification.  The purpose of an audit or inspection is to 
systematically and independently examine all study-related activities and documents to determine 
whether these activities were conducted, and data were recorded, analyzed, and accurately reported 
according to the protocol, Good Clinical Practice (GCP), guidelines of the International 
Conference on Harmonization (ICH), and any applicable regulatory requirements.  
13.2.6
Data Safety and Monitoring Plan
This protocol will adhere to the policies of the Case Comprehensive Cancer Center Data and 
Safety Monitoring Plan in accordance with NCI regulations.
13.2.7
Multicenter Guidelines
                          Responsibility of the Coordinating Center 

The Coordinating Center is responsible for the coordination, development, submission, and 
approval of the protocol as well as its subsequent amendments.  The protocol must not be 
rewritten or modified by anyone other than the Coordinating Center.  There will be only one 
version of the protocol, and each participating institution will use that document.  The 
Coordinating Center is responsible for assuring that all participating institutions are using 
the correct version of the protocol.

The Coordinating Center is responsible for the overall conduct of the study at all 
participating institutions and for monitoring its progress.  All reporting requirements are the 
responsibility of the Protocol Chair. 

The Coordinating Center is responsible for the timely review of Adverse Events (AE) to 
assure safety of the patients.

The Coordinating Center will be responsible for the review of and timely submission of data 
for study analysis.

Each participating institution will have an appropriate assurance on file with the Office for 
Human Research Protection (OHRP).  The Coordinating Center is responsible for assuring 
that each participating institution has an OHRP assurance and must maintain copies of IRB 
approvals from each participating site. 

 Prior to the activation of the protocol at each participating institution, an OHRP form 310 
(documentation of IRB approval) must be submitted to the Coordinating Center.


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
The Coordinating Center is responsible for central patient registration.  The Coordinating 
Center is responsible for assuring that IRB approval has been obtained at each participating 
site prior to the first patient registration from that site.

The Coordinating Center is responsible for the preparation of all submitted data for review.

The Coordinating Center will maintain documentation of AE reports.  

Audits may be accomplished in one of two ways:  (1) source documents and research 
records for selected patients are brought from participating sites to the Coordinating Center 
for audit, or (2) selected patient records may be audited on-site at participating sites.  If the 
funding or regulatory agency chooses to have an audit at the Coordinating Center, then the 
Coordinating Center is responsible for having all source documents, research records, all 
IRB approval documents, Drug Accountability Record forms, patient registration lists, 
response assessments scans, x-rays, etc. available for the audit.
Agent Ordering

Except in very unusual circumstances, each participating institution will order 
Dysport directly from Medicis.  Investigational agents may be ordered by a 
participating site only after the initial IRB approval for the site has been forwarded 
by the Coordinating Center to Medicis. 
14.0 STATISTICAL CONSIDERATIONS
To quantify the improvement in scar appearance, we propose the use of two well-established methods 
of measurement:  The Visual Analogue Scale (VAS) and the Patient and Observer Scar Assessment 
Scale (POSAS)6,7  The VAS will be used as the primary end point.  It consists of a 10 point scale to 
assess global scar assessment.  Scar photographic images are assessed by independent physicians, and 
previous studies have shown very high intrarater consistency.  The POSAS consists of two numeric 
scales. One scale is completed by the patients, the other by the clinician. This scale is different than 
previous scales because it takes the patient’s input into consideration. It has good internal consistency 
and interobserver reliability.8,9  
14.1
Visual Analog Scale: This is a 10 point scale to assess global scar assessment.  VAS has been 
used in previous studies to assess cosmetic outcome of scars.  In this study, we plan to evaluate the efficacy 
of using aboBTX-A to improve wound healing prior to Mohs micrographic surgery and reconstruction for 
skin cancer as measured by the Visual Analogue Scale (VAS) at 6 weeks post surgery as the primary 
endpoint.
14.1.1
Meaningful clinically important difference:  Using the data from 2 previously 
published clinical trials, Quinn et al7 reported that the minimal clinically important 
difference on the VAS cosmesis scale is 1.5 on a 10 point VAS11 
14.1.2
Sample size calculation:  Prior authors have reported a pooled SD of 1.4 and 2.2 
among VAS scores for surgical scars, yielding an effect size (mean difference/SD) of  
0.7 to 1.1.  A sample size of 20 patients per treatment group would provide an 80% 
chance (statistical power) of detecting an effect size of 1.0, using a two-sided t-test, 
with a type I error level of 5%.  Assuming a 5-10% dropout rate with follow-up visit 
and given the efficiency of the 2-sample t test relative to the Wilcoxon rank sum test 
is 95%, a total of 25 patients will be enrolled per group.
14.1.3
Data Analysis:  The VAS ratings at 6 weeks and at 6 months for each patient will be 
based on the average of all four physician scores.  The average of the VAS scores 
will then be compared between the 2 treatment groups using the Wilcoxon rank sum 
test.  All calculated P values are 2-sided, and P<0.5 is considered statistically 
significant.
14.1.4
Patient Accrual is anticipated that at least 10 subjects will be enrolled in the first year 
at UHCMC.  


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14.2
Patient and Observer Scar Assessment Scale: This scale will allow us to assess the patient 
and observer’s opinion of his/her scar as a secondary endpoints.  In comparison to the VAS, this scale takes 
the patient’s input into consideration.  In addition, multiple parameters are evaluated including vascularity, 
pigmentation, thickness, and surface area.  Parameters.  Prior studies have shown good internal consistency 
and interobserver reliability8-10.   The average PSAS and OSAS scores for each parameter will be compared 
between the 2 treatment groups using the Wilcoxon rank sum test.  All calculated P values are 2-sided, and 
P<0.5 is considered statistically significant.
15.0
REFERENCES
1.
Flynn TC. Use of intraoperative botulinum toxin in facial reconstruction. Dermatol Surg. Feb 
2009;35(2):182-188.
2.
Gassner HG, Brissett AE, Otley CC, et al. Botulinum toxin to improve facial wound healing: A 
prospective, blinded, placebo-controlled study. Mayo Clin Proc. Aug 2006;81(8):1023-1028.
3.
Gassner HG, Sherris DA, Friedman O. Botulinum toxin-induced immobilization of lower facial 
wounds. Arch Facial Plast Surg. Mar-Apr 2009;11(2):140-142.
4.
Sherris DA, Gassner HG. Botulinum toxin to minimize facial scarring. Facial Plast Surg. Feb 
2002;18(1):35-39.
5.
Xiao Z, Zhang F, Cui Z. Treatment of hypertrophic scars with intralesional botulinum toxin type A 
injections: a preliminary report. Aesthetic Plast Surg. May 2009;33(3):409-412.
6.
Draaijers LJ, Tempelman FR, Botman YA, et al. The patient and observer scar assessment scale: a 
reliable and feasible tool for scar evaluation. Plast Reconstr Surg. Jun 2004;113(7):1960-1965; 
discussion 1966-1967.
7.
Duncan JA, Bond JS, Mason T, et al. Visual analogue scale scoring and ranking: a suitable and 
sensitive method for assessing scar quality? Plast Reconstr Surg. Sep 15 2006;118(4):909-918.
8.
Truong PT, Lee JC, Soer B, Gaul CA, Olivotto IA. Reliability and validity testing of the Patient and 
Observer Scar Assessment Scale in evaluating linear scars after breast cancer surgery. Plast Reconstr 
Surg. Feb 2007;119(2):487-494.
9.
van de Kar AL, Corion LU, Smeulders MJ, Draaijers LJ, van der Horst CM, van Zuijlen PP. Reliable 
and feasible evaluation of linear scars by the Patient and Observer Scar Assessment Scale. Plast 
Reconstr Surg. Aug 2005;116(2):514-522.
10.
Bianchi FA, Roccia F, Fiorini P, Berrone S.  Use of Patient and Observer Scar Assessment Scale for 
Evaluation of Facial Scars Treated With Self-Drying Silicone Gel.  J Craniofac Surg 2010;21: 719-723.
11.
Quinn J, Wells G, Sutcliffe T, et al. Tissue adhesive versus suture wound repair at 1 year: randomized 
clinical trial correlating early, 3-month, and 1-year cosmetic outcome. Ann Emerg Med. Dec 
1998;32(6):645-649.


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Appendices
Appendix 1 : Visual Analog Scale 
|-----|------|------|-------|--------|-------|-------|--------|--------|-------|
1cm                                                                                   10cm
(Not drawn to scale)
(1 bring lowest acceptable cosmetic result, 10 being best cosmetic result)
Appendix 2: Patient and Observer Scar Assessment Scale


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Appendix 3: Patient Satisfaction Questionnaire
1. Please rate how satisfied you are with the result of scar (wound?):
1: Excellent 2: Very good 3: Good 4: Fair 5: Poor
2. Would you recommend using Dysport (botulinum toxin A) to help reduce scarring?
1: Yes 2: No
Appendix 4:  Dysport Prescribing Information