Clinical trial NCT03501043
Conditions: Equinovarus; Acquired
Sponsor: Albert Einstein Healthcare Network
Start date: 2018-06-11; Completion date: 2019-08-22
Enrollment: 11 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
This pilot study will aim to understand the potential benefit of the assessment of walking using video slow motion for muscle selection and the development of an image catalogue guide of the potential results of injection of abobotulinumtoxinA by comparing foot postures before and after injection. The objective is to evaluate the use of video assessment to improve muscle selection for the injection of botulinum toxin A to improve walking outcomes. Primary outcomes include: self-selected velocity (SSV), maximal velocity (MV) and symmetry of walking. Secondary outcomes include: passive range of motion (PROM), Modified Ashworth Scale (MAS) and the Tardieu Scale (TS). Fifteen persons post stroke or TBI over age 18 with equinovarus foot deformity who are able to ambulate will be included in the study. Dysport 1000 to 1500 units will be used to be distributed on the basis of clinical indication to ankle plantar flexors (gastrocnemius and soleus), tibialis posterior and long toe flexors. The duration of subjects' participation is 4-6 weeks.

Detailed description:
This is a prospective, single arm, non-randomized clinical study with pre-post assessment to include post-stroke and Traumatic Brain Injury (TBI) outpatients with spastic ankle / foot muscles amenable to botulinum toxin injection. Subjects must be able to walk without braces.

AbobotulinumtoxinA injection in a dose range of 500 to 1500 units one time to be distributed on the basis of clinical indication to ankle plantar flexors (gastrocnemius and soleus), knee extensors, knee flexors, tibialis posterior and long toe flexors.

Arms: arm 1: Subjects will receive 1000 to 1500 units of Dysport to be distributed on the basis of clinical indication to ankle plantar flexors (gastrocnemius and soleus), knee extensors and flexors, tibialis posterior and long toe flexors for one injection.
Interventions: intervention 1: Dysport
Intervention descriptions: intervention 1: Dysport 1000 to 1500 units to be distributed on the basis of clinical indication to ankle plantar flexors (gastrocnemius and soleus), knee extensors and flexors, tibialis posterior and long toe flexors.

Protocol documents:
Prot_SAP_001.pdf: 
Video and Temporal Spatial Parameters Assessment of Gait after Dysport Treatment: A Pilot Study 
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Title: Video and Temporal Spatial Parameters Assessment of Gait after Dysport 
Treatment: A Pilot Study 
Principal Investigator: Alberto Esquenazi, MD 
Sponsor: Alberto Esquenazi, MD 
Draft or Version Number:  7 May 2018, v.1.0 
 


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SIGNATURE PAGE 
The signature below constitutes the approval of this protocol and the attachments, and 
provides the necessary assurances that this trial will be conducted according to all stipulations 
of the protocol, including all statements regarding confidentiality, and according to local legal 
and regulatory requirements and applicable US federal regulations and ICH guidelines. 
Principal Investigator or Clinical Site Investigator: 
Signed: 
 
Date: 
 
 
Name:  Alberto Esquenazi, MD 
 
Title:  Chairman, Department of Physical Medicine and Rehabilitation;  
 


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TABLE OF CONTENTS 
PAGE 
SIGNATURE PAGE ........................................................................................................................................... I 
TABLE OF CONTENTS ..................................................................................................................................... II 
LIST OF ABBREVIATIONS .............................................................................................................................. IV 
PROTOCOL SUMMARY .................................................................................................................................. V 
KEY ROLES AND CONTACT INFORMATION.................................................................................................... 7 
1 
BACKGROUND INFORMATION ............................................................................................................ 8 
1.1 Rationale ....................................................................................................................................... 8 
1.2 Potential Risks and Benefits ......................................................................................................... 8 
1.2.1 
Potential Risks ........................................................................................................... 8 
1.2.2 
Potential Benefits ...................................................................................................... 9 
2 
OBJECTIVES…………………………………………………………………………………………………………………………………….9 
2.1  Study Objectives ........................................................................................................................... 9 
2.2  Study Outcome Measures ............................................................................................................ 9  
2.2.1 
Primary ...................................................................................................................... 9 
2.2.2 
Secondary .................................................................................................................. 9 
3 
STUDY DESIGN……………………………………………………………………………………………………………………………....9 
4 
STUDY ENROLLMENT AND WITHDRAWL………………………………………………………………………………………10 
4.1 Subject Inclusion Criteria ............................................................................................................ 10 
4.2 Subject Exclusion Criteria ........................................................................................................... 10 
4.3 Strategies for Recruitment and Retention ................................................................................. 10 
4.4 Subject Withdrawal .................................................................................................................... 10 
4.4.1 
Reasons for Withdrawal .......................................................................................... 11 
4.4.2 
Handling of Subject Withdrawals or Subject Discontinuation of Study 
Intervention ............................................................................................................ 11 
5 
STUDY INTERVENTION………………………….………………………………………………………………………………………11 
5.1 Study Product Description .......................................................................................................... 11 
5.1.1       Acquisition ................................................................................................................ 11 
5.1.2       Product Storage and Stability ................................................................................... 11 
5.2 Dosage, Preparation and Administration of Study Product ....................................................... 11 
5.3 Accountability Procedures for the Study Product ...................................................................... 12 
5.4 Concomitant Medications/Treatments ...................................................................................... 12 
5.5 Administration of Intervention ................................................................................................... 12 
6        STUDY SCHEDULE ............................................................................................................................... 12 
6.1 Screening .................................................................................................................................... 12 
6.2 Baseline ....................................................................................................................................... 13 
6.3 Follow-up Final Visit .................................................................................................................... 13 
6.4 Withdrawal Visit ......................................................................................................................... 14 


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7        STUDY PROCEDURES/EVALUATIONS ............................................................................................... 124 
7.1 Study Procedures/Evaluations .................................................................................................... 14 
8        ASSESSMENT OF SAFETY .................................................................................................................. 124 
8.1 Adverse Events ........................................................................................................................... 15 
8.2 Serious Adverse Events ............................................................................................................... 15 
8.3 Time Period and Frequency for Event Assessment and Follow-Up ............................................ 15 
8.4 Characteristics of an Adverse Event ........................................................................................... 15 
8.4.1 
Relationship to Study Intervention ......................................................................... 15 
8.4.2 
Expectedness of SAEs .............................................................................................. 16 
8.4.3 
Severity of Event ..................................................................................................... 16 
9        STATISTICAL CONSIDERATIONS ....................................................................................................... 126 
9.1 Study Hypotheses ....................................................................................................................... 16 
9.2 Sample Size ................................................................................................................................. 16 
10      SOURCE DOCUMENTS AND ACCESS TO SOURCE DATA/DOCUMENTS ............................................. 17 
11      ETHICS/PROTECTION OF HUMAN SUBJECTS ..................................................................................... 17 
11.1 Ethical Standard ........................................................................................................................ 17 
11.2 Institutional Review Board ........................................................................................................ 17 
11.3 Informed Consent Process ........................................................................................................ 17 
11.4 Subject Confidentiality .............................................................................................................. 18 
12 
DATA HANDLING AND RECORD KEEPING.......................................................................................... 18 
12.1 Data Management Responsibilities …………………………………………………….………………………….…...18  
12.2 Data Capture Methods …………………………………………………………………………………………………........18 
12.3 Types of Data………………………………………………………………………………………………….......................18 
12.4 Protocol Deviations.….………………………………………………………………………………………………………....18  
13 
LITERATURE REFERENCES .................................................................................................................. 18 
APPENDICES ................................................................................................................................................ 20 
APPENDIX A: DYSPORT (ABOBOTULINUMTOXINA) DOSING AND DILUTION GUIDE ................................ 201 
APPENDIX B: SCHEDULE OF EVENTS ........................................................................................................... 22 
 


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LIST OF ABBREVIATIONS 
AE 
Adverse Event/Adverse Experience 
CRF 
Case Report Form 
eCRF 
Electronic Case Report Form 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice 
HIPAA 
Health Insurance Portability and Accountability Act 
ICF 
Informed Consent Form 
IRB 
Institutional Review Board 
MAS 
Modified Ashworth Scale 
MV 
Maximal Velocity  
N 
Number (typically refers to subjects) 
PROM 
Passive Range of Motion (ankle)  
PI 
Principal Investigator 
SAE 
Serious Adverse Event/Serious Adverse Experience 
SOP 
Standard Operating Procedure 
SSV 
Self-Selected Velocity 
TS 
Tardieu Scale 
 


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PROTOCOL SUMMARY 
Title: 
Video and Temporal Spatial Parameters Assessment of Gait after 
Dysport treatment: A Pilot Study 
Summary:  
This pilot study will aim to understand the potential benefit of the 
assessment of walking using video slow motion for muscle selection 
and the development of an image catalogue guide of the potential 
results of injection of abobotulinumtoxinA by comparing foot 
postures before and after injection. 
Objectives: 
 
To evaluate the use of video assessment to improve muscle 
selection for the injection of botulinum toxin A to improve walking 
outcomes 
 
Primary:  SSV, MV, symmetry of walking 
 
Secondary:  PROM, MAS and TS 
Population: 
15 persons post stroke or TBI over age 18 with equinovarus foot 
deformity who are able to ambulate.  
Description of Intervention: 
Dysport 1000 to 1500 units to be distributed on the basis of clinical 
indication to ankle plantar flexors (gastrocnemius and soleus), knee 
extensors and flexors, tibialis posterior and long toe flexors 
Study Duration: 
Study set-up including IRB/EC approval: 9 months 
Final study report estimated by: March 2019 
Subject Participation Duration: 
4-6 weeks  
Estimated Time to Complete 
Enrollment: 
May 2018 to December 2018 


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Schematic of Study Design: 
 
Prior to  
Enrollment 
 
 
 
 
 
 
 
 
 
 
 
Visit 1 
Baseline 
 
 
 
 
 
 
 
 
 
 
 
Visit 2 
Follow-up  
(4-6 weeks post  
Baseline)  
 
 
 
 
 
 
 
 
 
Obtain informed consent. Screen potential subjects by inclusion and exclusion criteria; 
obtain history, document. 
Perform baseline assessments. 
Physical examination, PROM, MAS, TS for the affected ankle and knee. Slow 
motion video analysis and temporal-spatial parameters of locomotion will be 
obtained at SSV and MV with and without shoes.   
Administer initial study intervention. Subjects will be injected with 
abobotulinumtoxinA to the muscles selected based on the clinical assessment. 
Dose, muscles and technique used will be documented. 
15 subjects 
Final Assessments 
Follow-up assessments of outcome measures: 
physical examination, PROM, MAS, TS for the affected ankle and knee. Slow 
motion video analysis and temporal-spatial parameters of locomotion will be 
obtained at self-selected and maximum walking velocity with and without shoes. 
Adverse effects will be recorded.  


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KEY ROLES AND CONTACT INFORMATION 
  
Principal Investigator: 
Alberto Esquenazi, MD 
Research Associate:  
Stella Lee, MPA 
Institution:  
MossRehab 
60 Township Line Rd.  
Elkins Park, PA 19027 
(215) 663-6665 
(215) 663-6686 
 


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1 
BACKGROUND INFORMATION  
Post-stroke, ~40% of patients develop spasticity, with severe or disabling spasticity in up to 
15% of patients. 1, 2 Of those who have sustained a traumatic brain injury, approximately 75% develop 
spasticity, with nearly 50% warranting anti-spasticity treatment. 3 Spasticity is a chronic condition 
defined as “disordered sensory-motor control, resulting from an upper motor neuron lesion, presenting 
as intermittent or sustained involuntary activation of muscles” with postural limb changes. 4 Spasticity is 
characterized by muscle stiffness, paresis, muscle spasms, muscle fatigue, and in some cases rheological 
change with abnormal lower limb postures. 5 Beyond the underlying primary disorder and disease, 
spasticity negatively influences patient function, quality of life and increases caregiver burden. 6 
 
Hemiparesis from acquired brain injury can also impair mobility, related to abnormal passive and active 
antagonist muscle resistance. 4  In chronic hemiparesis, walking speed stabilizes at a low plateau level, in 
most cases inadequate to sustain community ambulation. 7 Intramuscular injection of botulinum toxin 
type A (BoNT-A), produces muscle relaxation for 12–16 weeks or longer and is an effective treatment for 
lower limb muscle overactivity in spastic paresis. 8 While botulinum toxin reduces muscle tone and 
improves spasticity-related features in lower-limb muscles, muscle selection that results in improved 
walking outcomes have not been explored. 8 
 
Currently clinical evaluation of the patient with lower limb spasticity after TBI or stroke focuses primarily 
on physical examination, and in some instances visual assessment of walking. These data, supplemented 
by registries, illustrations depicting typical patterns, and the potential muscles involved are used to 
determine the selection of the potential muscles for the injection of botulinum toxin.  
 
This pilot study will aim to understand the potential benefit of the assessment of walking using video 
slow motion for the muscle selection and develop an image catalogue of the potential results of 
injection of abobotulinumtoxinA by comparing foot postures before and after injection.  
 
1.1 Rationale 
Current FDA approved dosing for leg muscle injection with abobotulinumtoxina ranges from 1000 to 
1500 units to be distributed based on clinical indication to ankle plantar flexors (gastrocnemius and 
soleus), tibialis posterior and long toe flexors at intervals greater than 3 months. The treatment 
algorythm may be improved by a dynamic walking visual guidance. We believe visual assessment will 
improve guidance to muscle selction for treatment, which may result in improvement in foot posture 
and walking.  
1.2 Potential Risks and Benefits 
1.2.1 Potential Risks 
Lower limb spasticity injection most frequently reported adverse reactions (>2%) are: nasopharyngitis, 
muscular weakness, musculoskeletal pain, dizziness and falls. 


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1.2.2 Potential Benefits 
Potential benefits of visual assessment during walking may improve functional outcomes. While it may 
not provide direct benefit to subjects, the importance of the knowledge that may result from the study 
such as improvement in muscle selection for treatment, patient outcomes and patient satisfaction.  
2 OBJECTIVES 
2.1 Study Objectives  
Primary objectives: This is a prospective, single arm, non-randomized clinical study designed to evaluate 
pre-post walking velocity and symmetry with the use of Dysport in patients with equinovarus foot 
deformity.  
Secondary objectives: The study will also assess impact of Dysport related to the following measures: 
ankle and knee PROM, MAS and TS. 
2.2 Study Outcome Measures 
Walking velocity will be collected at baseline and at the follow-up visit using the Gait Mat evaluation. 
Ankle and knee PROM, MAS and TS data will be collected at baseline and at the follow-up visit.  
2.2.1 
Primary 
Primary endpoint: comparative walking velocity and symmetry of walking at baseline and follow-up 
visits.  
2.2.2 
Secondary 
Secondary endpoint: ankle and knee PROM, MAS and TS as well as video observational analysis at 
baseline and follow-up Visits.  
3    STUDY DESIGN 
This is a prospective, single arm, non-randomized clinical study with pre-post assessment to include 
post-stroke and TBI outpatients with spastic ankle / foot muscles amenable to botulinum toxin injection. 
Subjects must be able to walk without braces.  
abobotulinumtoxinA injection in a dose range of 1000 to 1500 units one time to be distributed on the 
basis of clinical indication to ankle plantar flexors (gastrocnemius and soleus), knee extensors, knee 
flexors, tibialis posterior and long toe flexors. Administration of the Dysport will be performed by the PI.  
 
First patient expected to be enrolled will be May 2018 and last patient expected to be enrolled will be 
December 2018. Subjects will be enrolled for a duration of 4-6 weeks.  
 


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4 STUDY ENROLLMENT AND WITHDRAWAL4.1 Subject Inclusion Criteria 
In order to be eligible to participate in this study, an individual must meet all of the following criteria: 
 
Provide signed and dated informed consent form 
 
Willing to comply with all study procedures and be available for the duration of the study  
 
Male or female, aged ≥ 18  
 
Equinovarus foot deformity appropriate for botulinum toxin treatment (naïve or non-naïve)  
 
MAS between 1 to 3 
 
Women of reproductive potential must use effective contraception for the duration of the study 
 
Able to walk a few steps without a brace for the purpose of the video observation 
4.2 Subject Exclusion Criteria 
An individual who meets any of the following criteria will be excluded from participation in this study: 
 
Previous surgical intervention to affected/ankle/foot 
 
Uncontrolled seizures  
 
Pregnancy or lactation 
 
Known allergic reactions to Dysport  
 
Treatment with another investigational drug or other intervention in the past 4 months  
 
MAS 4 
 
Anything that would place the individual at increased risk or preclude the individual’s full 
compliance with or completion of the study 
 
Lower motor neuron disorder 
 
< Four months post botulinum toxin or serial casting 
4.3 Strategies for Recruitment and Retention 
Subjects will be recruited from clinician referrals in the stroke and TBI outpatient clinics, the gait 
laboratory and patient charts. Subjects will receive the toxin free of charge. 
4.4 Subject Withdrawal 
Subjects may withdraw voluntarily from the study or the investigator may terminate a subject's 
participation. 


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4.4.1 
Reasons for Withdrawal 
Subjects are free to withdraw from participation in the study at any time upon request. 
An investigator may terminate a study subject’s participation in the study if: 
 
Any clinical adverse event (AE) or other medical condition or situation occurs such that 
continued participation in the study would not be in the best interest of the subject. 
 
The subject meets an exclusion criterion (either newly developed or not previously recognized) 
that precludes further study participation. 
4.4.2 
Handling of Subject Withdrawals or Subject Discontinuation of Study 
Intervention 
If a subject withdraws from the study, the Investigator will complete and report the observations 
as thoroughly as possible up to the date of withdrawal including the date drug treatment and the reason 
for withdrawal. If the subject is withdrawn due to an AE, the Investigator will follow the subject until the 
AE has resolved or stabilized. In all cases, the reason for and date of withdrawal must be recorded in the 
case report form and in the subject's medical records.  
 
5 STUDY INTERVENTION 
5.1 Study Product Description 
Product information can usually be obtained from package insert, for licensed drug or biologic 
(Appendix A).   
5.1.1     Acquisition 
An IMP may be supplied by the manufacturer or study sponsor.  
5.1.2 
Product Storage and Stability 
Drug will be provided by IPSEN for subject use. Dysport will be stored in the refrigerator along other 
botulinum toxins available in the gait laboratory. The refrigerator is locked and only accessible to gait 
laboratory staff. 
5.2 Dosage, Preparation and Administration of Study Product 
Drug will be prepared in the gait laboratory by staff currently trained in preparing botulinum toxins for 
clinical use. The toxin will be reconstituted with 3 cc of NSS. All vials are closed by 13 mm freeze-drying 
with a center hole, crimped over. Dysport drug product will be stored at the recommended temperature 
between 2⁰C/8⁰C.  
The product does not contain any antimicrobial agent. It is therefore recommended that the product be 
used immediately after reconstitution.  


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5.3 Accountability Procedures for the Study Product 
The PI, or other representative, will ensure that all IMP is stored in a secured area, under recommended 
temperature monitored storage conditions, in accordance with applicable regulatory requirements and 
will be reconstituted and dispensed by qualified staffed members.  
All study treatments are to be accounted for Dysport accountability log.  
5.4 Concomitant Medications/Treatments 
The following concomitant medications are not permitted during this study:  
 
Other botulinum toxin for administration into any site of the body other than Dysport. 
 
Any investigational new drug or device or off label use of any drug.  
 
Aminoglycoside antibiotics or other drugs that interfere with neuromuscular transmission.  
The following concomitant medications are permitted during this study but they must be monitored 
closely and every effort should be made to keep their dose and dose regimen constant throughout the 
course of the study.  
 
Changes in pain medication are acceptable if absolutely necessary and according to clinical 
judgement and will be recorded in the eCRF.  
 
Concomitant use of anticholinergic drugs (which may potentiate systemic anticholinergic 
effects) is permitted if the dosage has been stable for the six weeks prior to the study treatment 
and is expected to remain at this stable dose throughout the study.  
 
Concomitant treatment with dantrolene, tizanidine, gabaerigc, opiord or other antispasticity 
agents, including oal baclofen and benzodiazepines should be kept at the same dose throughout 
the study.  
5.5 Administration of Intervention 
The treatment dose will be administered by the PI to the targeted muscle at the baseline visit.  
6 STUDY SCHEDULE 
Details of the timing of each clinic visit, and the tests and procedures to be performed at each visit are 
located in Appendix B. Visits should take place as close to the visit time point as possible. Details on the 
performance of specific assessments or activities are presented in this section.  
6.1 Screening 
Screening Visit  


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Written informed consent should be obtained prior to enrollment. This visit may occur on the same day 
as the baseline visit at the discretion of the PI. The following assessments will be performed to check 
eligibility criteria:  
 
Demographics (sex, date of birth/age, ethnicity, race, height and weight) 
 
Medical/surgical history, including ongoing medical history 
 
Botulinum toxin history use 
 
Prior and concomitant medications. Prior medications will be all medications administered 
within 4 weeks before screening visit 
 
Measurement of ankle and knee PROM, MAS, TS and video and temporal-spatial parameters of 
walking 
 
Adverse event collection 
6.2 Baseline 
The screening visit and the baseline could occur on the same day at the PI’s discretion. The following 
assessments should be performed at the baseline visit prior to administration of Dysport. If the 
screening and the baseline visits occur on the same day all assessments identified in the screening visit 
should also be done at the visit, recorded in the eCRF.  
Baseline Visit  
 
Verify inclusion/exclusion criteria 
 
Adverse event collection 
 
Concomitant medications 
 
Results of physical examinations, ankle and knee PROM, MAS and TS 
 
Video assessment of temporal spatial parameters of with and without shoes at SSV and MV 
 
Study treatment administration 
6.3 Follow-up Final Visit  
The following tests and procedures will be performed/evaluated at Follow-Up Visit:  
 
 
Adverse event collection 
 
Concomitant medications 
 
Review medical and medication history 
 
Record results of physical examinations, ankle and knee PROM, MAS and TS 


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 
Video assessment of temporal spatial parameters of with and without shoes at SSV and MV 
 
Record adverse events as reported by subject or observed by investigator 
 
Record subject’s compliance with intervention 
6.4 Withdrawal Visit 
Early withdrawal for each subject, the following tests and procedures will be performed/evaluated:  
 
Adverse event collection 
 
Concomitant medications 
 
7 STUDY PROCEDURES /EVALUATIONS 
7.1 Study Procedures/Evaluations 
 
Primary Evaluations:  
SSV without and with shoes – Subjects will be advised to walk 10 meters with and without their shoes at 
their comfortable walking speed. Three trials of this test will be collected. SSV will be obtained prior to 
the study treatment at baseline and follow-up visits.  
MV without and with shoes – Subjects will be advised to walk 10 meters with and without their shoes 
and their fastest walking speed. Three trials of this test will be collected. MV will be obtained prior to 
the study treatment at baseline and follow-up visits.  
Secondary Evaluations: 
Tone will be measured for the gastrocnemius and soleus muscles with the MAS – MAS will be used to 
assess muscle tone in the grastrocnemius and soleus muscles prior to the study treatment at baseline 
and at the follow up visit.  
 
Spasticity in the gastrocnemius and soleus muscles measured with the TS - The will be used to assess 
spasticity in these muscles. Assessments will be made at slow (V1) and fast (V3) speed of stretch. The 
angle of arrest at slow speed (Xv1), the angle of catch at fast speed (Xv3) and the spasticity grade (Y) at 
fast speed will be recorded in the eCRF at each speed. The spasticity angle will be calculated by the 
difference between the angle of arrest at slow speed (XV1) and the angle of each at fast speed (Xv3). The 
TS ratings will be obtained prior to the study treatment at baseline and at the follow-up visit.  
 
PROM - will be used to assess treatment response. The ankle, knee flexed and knee extended 
measurements will be obtained prior to the study treatment at baseline and at the follow-up visit.  
 
8 ASSESSMENT OF SAFETY 


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8.1 Adverse Events 
An adverse event is any untoward or unfavorable medical occurrence in a human subject, including any 
abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, 
temporally associated with the subject’s participation in the research, whether or not considered 
related to the subject’s participation in the research. 
8.2 Serious Adverse Events 
A serious adverse event (SAE) is one that meets one or more of the following criteria: 
 
Results in death 
 
Is life-threatening (places the subject at immediate risk of death from the event as it occurred) 
 
Results in inpatient hospitalization or prolongation of existing hospitalization 
 
Results in a persistent or significant disability or incapacity 
 
Results in a congenital anomaly or birth defect   
 
An important medical event that may not result in death, be life threatening, or require 
hospitalization may be considered an SAE when, based upon appropriate medical judgment, the 
event may jeopardize the subject and may require medical or surgical intervention to prevent 
one of the outcomes listed in this definition. 
8.3 Time Period and Frequency for Event Assessment and Follow-Up 
Unanticipated problems will be recorded in the data collection system throughout the study.  
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. SAEs will be reported to 
DrugSafety.USA@ipsen.com.  
8.4 Characteristics of an Adverse Event 
8.4.1 
Relationship to Study Intervention 
To assess relationship of an event to study intervention, the following guidelines are used: 
1. Related (Possible, Probable, Definite) 
a. The event is known to occur with the study intervention. 
b. There is a temporal relationship between the intervention and event onset. 
c. The event abates when the intervention is discontinued. 


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d. The event reappears upon a re-challenge with the intervention. 
2. Not Related (Unlikely, Not Related) 
a. There is no temporal relationship between the intervention and event onset. 
b. An alternate etiology has been established. 
8.4.2 
Expectedness of SAEs 
The Study PI will be responsible for determining whether an SAE is expected or unexpected.  An adverse 
event will be considered unexpected if the nature, severity, or frequency of the event is not consistent 
with the risk information previously described for the intervention.   
8.4.3 
Severity of Event 
The following scale will be used to grade adverse events: 
1. Mild: no intervention required; no impact on activities of daily living (ADL) 
2. Moderate: minimal, local, or non-invasive intervention indicated; moderate impact on ADL 
3. Severe: significant symptoms requiring invasive intervention; subject seeks medical attention, 
needs major assistance with ADL 
9   STATISTICAL CONSIDERATIONS 
9.1 Study Hypotheses 
The statistical analysis of the data obtained from this study will be performed using SPSS v. 19.0.  
All data collected in this study will be documented using summary tables and subject data listings. 
Continuous variables will be summarized using descriptive statistics, specifically the mean, median, 
standard deviation, minimum and maximum. Categorical variables will be summarized by frequencies 
and percentages. 
Demographics, Medical History and Baseline Characteristics: 
The subjects will be summarized with respect to baseline demographics and baseline characteristics 
(e.g., age, gender, race, ethnicity, injury type and time since last injury, height and weight, etc.). These 
will be summarized by descriptive statistics including means, medians, standard deviations and ranges 
(for quantitative variables) and counts and percentages (for categorical variables). 
 
Primary Endpoint:   
The primary end point is to collect SSV and MV with and without shoes at Baseline and Follow-up Visits 
using the Gait Mat. Data will be reported descriptively and continuous data will be reported with the 
change from follow-up to baseline.  
Secondary Endpoint:  
The following are secondary endpoints:  


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 
PROM will be presented descriptively as continuous data along with the change form baseline.  
 
The TS will be presented descriptively as continuous data along with the change from baseline.  
 
The MAS will be presented descriptively as rank data along with the change from baseline.  
9.2  Sample Size  
For this pilot study, no prospective calculations of statistical power have been made. The sample size of 
15 subjects has been selected to provide information on safety, reliability and feasibility of video 
assisted muscle selection for Dysport injection.  
10     SOURCE DOCUMENTS AND ACCESS TO SOURCE DATA/DOCUMENTS 
Study staff will maintain appropriate medical and research records for this study, in compliance with IRB 
requirements for the protection of confidentiality of subjects.  Study staff will permit authorized 
representatives of the IRB to examine (and when required by applicable law, to copy) research records 
for the purposes of quality assurance reviews, audits, and evaluation of the study safety, progress and 
data validity.   
11 
  ETHICS/PROTECTION OF HUMAN SUBJECTS 
11.1 Ethical Standard 
The investigator will ensure that this study is conducted in full conformity with the principles set forth in 
The Belmont Report: Ethical Principles and Guidelines for the Protection of Human Subjects of Research, 
as drafted by the US National Commission for the Protection of Human Subjects of Biomedical and 
Behavioral Research (April 18, 1979) and codified in 45 CFR Part 46 and/or the ICH E6. 
11.2  Institutional Review Board 
The protocol, informed consent form(s), recruitment materials, and all subject 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 subject is enrolled.  Any amendment to the protocol will require review and 
approval by the IRB before the changes are implemented in the study.  
11.3    Informed Consent Process 
Informed consent is a process that is initiated prior to the individual agreeing to participate in the study 
and continues throughout study participation.  Extensive discussion of risks and possible benefits of 
study participation will be provided to subjects and their families, if applicable.  A consent form 
describing in detail the study procedures and risks will be given to the subject.  Consent forms will be 
IRB-approved, and the subject is required to read and review the document or have the document read 
to him or her.  The investigator or designee will explain the research study to the subject and answer 
any questions that may arise.  The subject will sign the informed consent document prior to any study-
related assessments or procedures.  Subjects will be given the opportunity to discuss the study with 
their surrogates or think about it prior to agreeing to participate.  They may withdraw consent at any 
time throughout the course of the study.  A copy of the signed informed consent document will be given 
to subjects for their records.  The rights and welfare of the subjects will be protected by emphasizing to 


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them that the quality of their clinical care will not be adversely affected if they decline to participate in 
this study. 
The consent process will be documented in the clinical or research record.   
11.4 Subject Confidentiality 
Subject confidentiality is strictly held in trust by the investigators, study staff, and the sponsor and their 
agents.  This confidentiality is extended to cover testing of biological samples and genetic tests in 
addition to any study information relating to subjects. 
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 without prior written approval of the sponsor. 
The study monitor or other authorized representatives of the sponsor may inspect all study documents 
and records required to be maintained by the investigator, including but not limited to, medical records 
(office, clinic, or hospital) for the study subjects.  The clinical study site will permit access to such 
records.  
12 
DATA HANDLING AND RECORD KEEPING 
The investigator is responsible for ensuring the accuracy, completeness, legibility, and timeliness of the 
data reported.  All source documents should be completed in a neat, legible manner to ensure accurate 
interpretation of data.  The investigator will maintain adequate case histories of study subjects, 
including accurate case report forms (CRFs), and source documentation. 
12.1   Data Management Responsibilities 
Data collection and accurate documentation are the responsibility of the study staff under the 
supervision of the investigator.  All source documents and laboratory reports must be reviewed by the 
study team and data entry staff, who will ensure that they are accurate and complete.  Unanticipated 
problems and adverse events must be reviewed by the investigator or designee.   
12.2 Data Capture Methods 
Data will be collected on paper and entered electronically on a password protected network computer. 
Data quality checks will be performed internally on a routine basis.  
12.3   Types of Data 
Subject medical history, demographics, concomitant medications will be collected. The following 
outcome data will be collected: ankle and knee RPOM, MAS, TS, Gait Mat data on temporal spatial data 
including SSV and MV without and with shoes.   
                  12.4   Protocol Deviations 


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A protocol deviation is any noncompliance with the clinical study protocol, Good Clinical Practice, or 
Manual of Procedures requirements.  The noncompliance may be on the part of the subject, the 
investigator, or study staff.  As a result of deviations, corrective actions are to be developed by the study 
staff and implemented promptly. 
All deviations from the protocol must be addressed in study subject source documents and promptly 
reported to the local IRB, according to their requirements.  
13 
LITERATURE REFERENCES 
 
1. Wissel J, Manack A, Brainin M. Toward an epidemiology of poststroke spasticity Neurology 
2013;80:S13-S9. 
2. Zorowitz RD, Gillard PJ, Brainin M. Poststroke spasticity: sequelae and burden on stroke survivors 
and caregivers. Neurology 2013;80:S45-S52. 
3. Frieden TR, Houry D, Baldwin G. Report to congress on traumatic brain injury in the United States: 
epidemiology and rehabilitation. Centers for Disease Control and Prevention; 2015. 
4. Burridge JH, Wood DE, Hermens HJ, Voerman GE, Johnson GR, van Wijck F et al. Theoretical and 
methodological considerations in the measurement of spasticity. Disabil Rehabil 2005;27:69-80. 
5. Kheder A, Nair K. Spasticity: pathophysiology, evaluation and management. Pract Neurol 
2012;12:289-98. 
6. Mayer NH, Esquenazi A. Muscle overactivity and movement dysfunction in the upper motoneuron 
syndrome. Phys Med Rehabil Clin N Am 2003;14:855-83, vii-viii. 
7. Moseley AM, Lanzarone S, Bosman JM, van Loo MA, de Bie RA, Hassett L et al. Ecological validity of 
walking speed assessment after traumatic brain injury: a pilot study. J Head Trauma Rehabil 
2004;19:341-8. 
8. Gracies JM, Esquenazi A, Brashear A, Banach M, Kocer S, Jech R et al. Efficacy and safety of 
abobotulinumtoxinA in spastic lower limb: randomized trial and extension. Neurology Epub 
2017;89:1-9. 
 


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APPENDICES 
Appendix A: Dysport (abobotulinumtoxinA) Dosing and Dilution Guide 
Appendix B: Schedule of Events 


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APPENDIX A: DYSPORT (ABOBOTULINUMTOXINA) DOSING AND DILUTION GUIDE 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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APPENDIX B: SCHEDULE OF EVENTS 
 
Procedures 
Screening  
Baseline  
Final Visit Follow-up 
Premature 
Discontinuation 
Signed Consent Form 
X 
X 
 
 
Assessment of Eligibility Criteria 
X 
X 
 
 
Review of Medical History 
X 
X 
 
 
Review of Concomitant Medications  X 
X 
X 
X 
Study Intervention 
 
X 
 
 
Physical 
Examination 
Complete 
X 
X 
X 
 
Assessment of Adverse Events 
 
X 
X 
X 
Drug Administration 
 
X 
 
 
Other Procedures 
PROM 
X 
X 
X 
 
MAS 
X 
X 
X 
 
TS 
X 
X 
X 
 
SSV with and 
without shoes 
X 
X 
X 
 
MV with and 
without shoes 
X 
X 
X 
 
Temporal spatial 
data 
x 
x 
x 
 
 
 
 

ICF_000.pdf: 










Albert Einstein Healthcare Network  
Institutional Review Board 
Approval Date: 3/28/2019  DO NOT SIGN AFTER:3/14/20