Clinical trial NCT03346902
Conditions: Mohs Surgery
Sponsor: Bonti, Inc.
Start date: 2018-02-06; Completion date: 2018-10-08
Enrollment: 12 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This study will evaluate the safety and efficacy of EB-001 in improving wound healing and reducing scar formation in patients undergoing Mohs surgery for skin lesions in the forehead area following a single treatment of EB-001 when injected into the muscles underlying the incision area.

Detailed description:
This study will evaluate the safety and efficacy of EB-001 in improving wound healing and reducing scar formation in patients undergoing Mohs surgery for skin lesions in the forehead area following a single treatment of EB-001 when injected into the muscles underlying the incision area.

The safety objective is to determine the safety and tolerability of single treatment of EB-001 when injected into facial muscles underlying a surgical wound during Mohs surgery.

The efficacy objective is to evaluate the efficacy of a single treatment of EB-001 when injected into the facial muscles (frontalis) underlying the surgical wound in improving wound healing, and reducing scar formation.

Arms: arm 1: Drug: : Placebo: 0.9% Sodium Chloride Injection

Injection of Placebo into area of scarring (forehead) arm 2: Drug: EB-001 Injection of EB-001 into area of scarring (forehead)
Interventions: intervention 1: EB-001 intervention 2: 0.9% Sodium Chloride Injection
Intervention descriptions: intervention 1: Injection of EB-001 into area of scarring (forehead) intervention 2: Injection of Saline into area of scarring (forehead)

Protocol documents:
Prot_SAP_000.pdf: 
Protocol EB001-SR201 
Version 2.0 
IND 130880 
02 May 2018 
 
 
 
Confidential / Trade Secret 
 
 
 
 
 
Page 1 of 15 
 
 
 
CLINICAL STUDY PROTOCOL 
 
 
A Phase 2 Study to Evaluate Safety and Efficacy of EB-001 Injections in Facial 
Scar Reduction After Undergoing Mohs Surgery 
 
 
Study Number: EB001-SR201 
 
 
 
IND Sponsor: Bonti, Inc. 
 
 
Version Number:  
 
2.0 
Amendment:   
 
1 
Amendment 1 Date:   
02 May, 2018 
Original Protocol Date: 
16 November, 2017 
 
CONFIDENTIALITY STATEMENT 
The information in this document contains trade secrets and commercial information that are 
confidential and may not be disclosed unless such disclosure is required by applicable laws 
and regulations. In any event, persons to whom the information is disclosed must be informed 
that the information is confidential and may not be further disclosed by them. These 
restrictions on disclosure will apply equally to all future information supplied to you which is 
indicated as confidential.  
 
 
 
 


Protocol EB001-SR201 
Version 2.0 
IND 130880 
02 May 2018 
 
 
 
Confidential / Trade Secret 
 
 
 
 
 
Page 2 of 15 
 
SUMMARY OF CHANGES RATIONALE 


Protocol EB001-SR201 
Version 2.0 
IND 130880 
02 May 2018 
 
 
 
Confidential / Trade Secret 
 
 
 
 
 
Page 3 of 15 
 
SIGNATURE PAGE 
 
Approved by: 
 
 
 


Protocol EB001-SR201 
Version 2.0 
IND 130880 
02 May 2018 
 
 
 
Confidential / Trade Secret 
 
 
 
 
 
Page 4 of 15 
 
STATEMENT OF COMPLIANCE 
 
By signing below, I confirm that I have read this protocol and agree: 
• to assume responsibility for the proper conduct of the study at this site, 
• to conduct the study according to the procedures described in this protocol and any 
future amendments,  
• not to implement any deviation from, or changes to, the protocol without 
agreement of the sponsor and written approval from the Institutional Review Board 
or Independent Ethics Committee, except where necessary to eliminate an 
immediate hazard to subject(s), and 
• that I am aware of and will comply with all applicable regulations and guidelines on 
clinical trials, Good Clinical Practice (GCP), and protection of human subjects 
 
 
 
 
 
 _______________________  
 _______________________  
 ____________________  
 Investigator Printed Name 
Signature  
Date 
 
 
 


Protocol EB001-SR201 
Version 2.0 
IND 130880 
02 May 2018 
 
 
 
Confidential / Trade Secret 
 
 
 
 
 
Page 5 of 15 
 
TABLE OF CONTENTS 
TABLE OF CONTENTS ................................................................................................................. 5 
LIST OF TABLES ........................................................................................................................... 5 
LIST OF FIGURES ........................................................................................................................ 5 
 
LIST OF ABBREVIATIONS AND GLOSSARY OF TERMS ................................................................ 6 
 
LIST OF TABLES 
Table 1 
Schedule of Study Procedures ......................................................................... 15 
 
LIST OF FIGURES 
Figure 1 
Injection Sites .................................................................................................. 13 
Figure 2 
Study Design of EB001-SR201 ......................................................................... 14 
  
 
 
 


Protocol EB001-SR201 
Version 2.0 
IND 130880 
02 May 2018 
 
 
 
Confidential / Trade Secret 
 
 
 
 
 
Page 6 of 15 
 
LIST OF ABBREVIATIONS AND GLOSSARY OF TERMS 
Term 
Definition 
AE 
adverse event 
ALT (SGPT) 
alanine aminotransferase (= serum glutamic pyruvic transaminase) 
ATC 
Anatomical Therapeutic Chemical 
AST (SGOT) 
aspartate aminotransferase (= serum glutamic oxaloacetic 
transaminase) 
BoNT 
botulinum neurotoxin 
BoNT/A 
botulinum neurotoxin serotype A 
BoNT/E 
botulinum neurotoxin serotype E 
BP 
blood pressure 
BUN 
blood urea nitrogen 
CBL 
change from baseline 
CFR 
Code of Federal Regulations 
CMP 
clinical monitoring plan 
CRO 
Contract Research Organization 
DAS 
digital abduction score 
EB-001 
botulinum neurotoxin serotype E drug product 
ECG 
electrocardiogram 
eCRF 
electronic case report form 
ED50 
effective dose to product 50% DAS effect 
EDC 
electronic data capture 
EOS 
end of study 
ET 
early termination 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice 
GGT 
gamma-glutamyl transferase 
GLP 
Good Laboratory Practices 
GMP 
Good Manufacturing Practices 
HBsAg 
hepatitis B surface antigen 
HC 
heavy chain 
HDL 
high density lipoprotein 
HEENT 
head, eye, ear, nose, throat 


Protocol EB001-SR201 
Version 2.0 
IND 130880 
02 May 2018 
 
 
 
Confidential / Trade Secret 
 
 
 
 
 
Page 7 of 15 
 
Term 
Definition 
HIV 
human immunodeficiency virus 
HR 
heart rate 
HSA 
human serum albumin 
ICF 
informed consent form 
ICH 
International Conference on Harmonization  
ICH E6 
International Conference on Harmonization Guidance for Industry, 
Good Clinical Practice: Consolidated Guidance 
IM 
Intramuscular 
IRB 
institutional review board 
IUD 
intrauterine device 
LC 
light chain 
LDH 
lactate dehydrogenase 
LDL 
low density lipoprotein 
MCH 
mean cell hemoglobin 
MCHC 
mean cell hemoglobin concentration 
MCV 
mean (red) cell volume 
MedDRA 
Medical Dictionary for Regulatory Activities 
mITT 
modified Intent to Treat 
mL 
Milliliter 
mouse LD50 
lethal dose to 50% of mice after intraperitoneal injection 
msec 
millisecond 
NA 
not applicable 
ng 
nanogram  
NOAEL 
no observable adverse effects limit 
OHRP 
Office for Human Research Protections 
PCV 
packed cell volume 
PI 
principal investigator 
POSAS 
Patient and Observer Scar Assessment Scale 
PR interval 
time between the onset of atrial depolarization and the onset of 
ventricular depolarization 
PRN 
as-needed 
RBC 
red blood cell 


Protocol EB001-SR201 
Version 2.0 
IND 130880 
02 May 2018 
 
 
 
Confidential / Trade Secret 
 
 
 
 
 
Page 8 of 15 
 
Term 
Definition 
RDW 
red (cell) distribution width 
RR interval 
time elapsed between two consecutive R-waves 
QRS duration 
the interval from the beginning of the Q wave to the termination 
of the S wave, representing the time for ventricular depolarization 
QT interval 
interval representing the time for both ventricular depolarization 
and repolarization to occur 
QTc 
corrected QT (interval) 
QTcB interval 
QTc interval using Bazett’s correction (msec) = QT/(RR)½, where the 
QT interval is measured in msec and the RR interval is measured in 
seconds 
QTcF interval 
QTc interval using Fridericia’s correction (msec) = QT/(RR)⅓, where 
the QT interval is measured in msec and the RR interval is 
measured in seconds 
SAE 
serious adverse event/experience 
SAP 
statistical analysis plan 
SCARS 
Scar Cosmesis Assessment and Rating Scale 
SNAP 
synaptosomal-associated protein 
SOT 
spread of toxin 
SUSAR 
suspected unexpected serious adverse reactions 
RR interval 
time elapsing between two consecutive R waves in the 
electrocardiogram. It is used to assess the ventricular rate. 
TCA 
trichloroacetic acid 
TEAE 
treatment emergent adverse event 
µg 
microgram 
UP 
unanticipated problem 
US 
United States 
VAS 
Visual Analog Scale 
WBC 
white blood cell (Leukocyte) 
WHO 
World Health Organization 
 


Protocol EB001-SR201 
Version 2.0 
IND 130880 
02 May 2018 
 
 
 
Confidential / Trade Secret 
 
 
 
 
 
Page 9 of 15 
 
PROTOCOL SUMMARY 
Study Number: 
EB001-SR201 
Study Title: 
A Phase 2 Study to Evaluate Safety and Efficacy of EB-001 Injections in Facial Scar Reduction 
After Mohs Surgery 
Investigational Drug Product: 
EB-001 (Botulinum Neurotoxin Serotype E, BoNT/E) for injection 
Study Objectives: 
Safety Objective: To determine the safety and tolerability of single treatment of EB-001 when 
injected into forehead muscles underlying a surgical wound during Mohs surgery. 
Efficacy Objective: To evaluate the efficacy of EB-001 intramuscular (IM) injection into the 
forehead muscles underlying the surgical wound in improving wound healing, and reducing 
scar formation. 
 
Phase of Trial: 
Phase 2 
Clinical Hypothesis: 
Safety: In patients undergoing Mohs surgery for skin lesions in the forehead area, a single 
treatment with EB-001 when injected into the muscles underlying the incision area will have 
an acceptable safety and tolerability profile. 
Efficacy: In patients undergoing Mohs surgery for skin lesions in the forehead area, a single 
treatment with EB-001 when injected into the muscles underlying the incision area will 
improve wound healing and reduce scar formation. 
Study Population: 
Healthy subjects 18 to 75 years of age, inclusive, undergoing dermatological surgical 
procedures to remove single skin lesions in the forehead. 
Outcome Measures: 
Safety Measures:  
• Incidence and severity of treatment emergent adverse events (TEAEs) and serious 
adverse events (SAEs) 
• Focused neurologic examination for potential spread of toxin (SOT) 
• Incidence of abnormal findings in laboratory tests, electrocardiogram (ECG), physical 
exam, and vital signs (pulse rate, respiratory rate and blood pressure) 
• Urine pregnancy test for women of childbearing potential 


Protocol EB001-SR201 
Version 2.0 
IND 130880 
02 May 2018 
 
 
 
Confidential / Trade Secret 
 
 
 
 
 
Page 10 of 15 
 
Efficacy Measures: 
• Scar assessment using a Visual Analog Scale (VAS) 
 
 
 
 
 
 
 
 
Study Design: 
This will be a randomized, placebo-controlled, single blind (to subject and study site 
personnel), parallel arm study with placebo or active treatment with IM injections. Subjects 
will be randomized to receive either a single dose (treatment) of EB-001 or placebo.  
The study will be conducted at one center that specializes in dermatological surgical 
procedures. The study will include a visit for the surgical procedure (Day 1). Follow up visits 
will be scheduled at Days 2, 8, 30, and 90 (Table 1). The study will enroll approximately 12 
subjects, randomly assigned to EB-001 or placebo in a 2:1 ratio for a total of 8 subjects in the 
EB-001 arm, and 4 subjects in the placebo arm (Figure 2). 
Investigational (Study) Sites: 
One dermatology site specialized in Mohs surgery. 
 
 
 
 
 
 
 
 
 
 
 
 
 
Duration: 
The expected duration for each subject participation is approximately 13 weeks from the day 
of surgery to the last visit.  
Inclusion Criteria: 
An individual must meet ALL the following criteria to participate in this study: 


Protocol EB001-SR201 
Version 2.0 
IND 130880 
02 May 2018 
 
 
 
Confidential / Trade Secret 
 
 
 
 
 
Page 11 of 15 
 
1. Between 18 and 75 years of age, inclusive  
2. In good health, or with stable treated medical condition, as determined by the 
investigator.   
3. Scheduled to undergo Mohs surgery to remove a single skin lesion in the forehead. 
This could be 
 
 
 
 
5. Women of non-childbearing potential must be postmenopausal (at least 12 
consecutive months of amenorrhea) 
6. Women of childbearing potential must not be pregnant, lactating, or planning to 
become pregnant during the study 
7. Women of childbearing potential agreeing to use either  
a. a highly effective method of contraception with failures rates less than 1% per 
year such as implant, intrauterine device (IUD), or sterilization from the day of 
dosing for 3 months (subjects who underwent sterilization must have initiated 
the procedure at least 3 months prior to the day of dosing) or  
b. dual methods of contraception with overall failures rates less than 1% per year 
such as injectable, pill, patch, ring, and diaphragm from the day of dosing for 
3 months (subjects using oral contraception must have initiated treatment at 
least 2 months prior to the day of dosing) 
8. Willing and able to complete and comply with procedures, protocol requirements and 
instructions, which includes completion of all required visits 
9. Willing and able to sign and date IRB-approved informed consent 
10. Able to speak, read, and understand the language of the informed consent form (ICF) 
and study questionnaires 
Exclusion Criteria: 
An individual who meets ANY of the following criteria will be excluded from participation in 
this study: 
1. Pregnant or breast feeding, or planning a pregnancy 
2. Body weight less than 50 kg (110 pounds) 
3. Reported use of any botulinum toxin of any serotype within last 6 months before study 
drug administration 
4. Anticipated use of any botulinum toxin of any serotype during the study  
5. Known hypersensitivity to any botulinum toxin serotype 
6. Known allergy or sensitivity to any of the components of the study treatments, or any 
materials used in the study procedures 
7. Aminoglycoside intake within 48 hours prior to or during surgery  
8. Pre-existing disorders of the neuromuscular junction (myasthenia gravis, Eaton-
Lambert syndrome, or amyotrophic lateral Sclerosis) 


Protocol EB001-SR201 
Version 2.0 
IND 130880 
02 May 2018 
 
 
 
Confidential / Trade Secret 
 
 
 
 
 
Page 12 of 15 
 
9. Any uncontrolled medical condition that in opinion of investigator, puts subject at 
undue safety risk 
10. Any clinically significant psychiatric condition that, in opinion of investigator, may 
interfere with study assessments or protocol compliance 
11. Any cosmetic procedure, laser resurfacing treatment, or retinoid therapy in the 
forehead area in the past 30 days before study drug administration 
12. Any eyebrow or eyelid ptosis at baseline as determined by the Investigator 
13. History of hypertrophic scars or keloid formation or other wound abnormalities as 
assessed by the investigator 
14. History of alcohol or drug abuse in the last 3 years, based on investigator judgement 
  
 
 
 
 
 
 
 
 
 
 
 
Study Drug: 
 
 
Placebo: 
Preservative free, sterile saline solution 0.9% Sodium Chloride Injection, USP.  
Dosage: 
 
  


Protocol EB001-SR201 
Version 2.0 
IND 130880 
02 May 2018 
 
 
 
Confidential / Trade Secret 
 
 
 
 
 
Page 13 of 15 
 
Figure 1 
Injection Sites 
Pre-Surgery Assessments: 
Written informed consent form (ICF), demographics, inclusion/exclusion criteria, medical 
history, physical and focused neurological examinations, height/weight, prior and 
concomitant medications, triplicate ECG, clinical laboratory tests (serum chemistry, lipids, 
hematology), 
immunogenicity 
sample 
collection, 
blood 
collection 
for 
human 
immunodeficiency virus (HIV) and hepatitis B and C, urine collection for drugs of abuse, and 
urine pregnancy test for premenopausal women.  
Safety Assessments: 
Adverse events, physical and focused neurologic examinations, prior and concomitant 
medications, triplicate ECG, vital signs, clinical laboratory tests, medical history, and urine 
pregnancy test. 
Efficacy Assessments 
Scar assessment using VAS,
 
 
 
 
Other Assessments 
Standardized facial photography will be performed to aid efficacy assessments.  


Protocol EB001-SR201 
Version 2.0 
IND 130880 
02 May 2018 
 
 
 
Confidential / Trade Secret 
 
 
 
 
 
Page 14 of 15 
 
General Statistical Considerations: 
Analysis will be performed when all patients have completed the Day 90 visit or exited early 
from the study. The statistical analysis plan detailing all analyses will be signed off before 
the primary database lock. 
For efficacy analysis, modified intent to treat (mITT) population including all randomized 
and treated patients with at least one post-injection efficacy assessment will be used. The 
safety analysis will be performed using safety population including all randomized and 
treated patients. All analysis will be performed on “as treated” basis. 
For main safety analysis, incidence of all adverse events, TEAEs, and serious adverse events 
will be summarized for each treatment group. The efficacy variables are scar assessment 
multiple scales. The data will be summarized by descriptive statistics and 95% confidence 
interval (based on t-test) for treatment group will also be presented. 
The planned sample size will be approximately 12 subjects (8 for EB-001 and 4 for placebo, 
Figure 2). For this pilot study, no formal sample size computations were made. 
 
All statistical analysis will be descriptive summary statistics.  
 
Figure 2 
Study Design of EB001-SR201 
 
 


Protocol EB001-SR201 
Version 2.0 
IND 130880 
02 May 2018 
 
 
 
Confidential / Trade Secret 
 
 
 
 
 
Page 15 of 15