Clinical trial NCT04058054
Conditions: Hypersensitivity
Sponsor: KeraNetics, LLC
Start date: 2019-07-29; Completion date: 2019-08-02
Enrollment: 22 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
To evaluate the potential for a humoral reaction to KeraStat Cream compared to a predicate device using the skin prick test.

Detailed description:
Study Overview:

Study Periods:

The length of study participation for a subject is about 2-3 days depending on availability for the final site check. There are two skin prick site checks during the course of Day 1 with a final follow up between Days 2 and 3.

Study Evaluations:

Initial screening (Screening Visit; Visit 1) will be performed on the day of the Skin Prick Test (SPT) administration and will include obtaining demographic information, brief medical history, and abbreviated physical exam.

On Day 1 (Visit 1) the SPT will be performed on the infrascapular region of the back to the right of the midline. Test articles will include the subject device (KeraStat Cream), predicate devices (KeraStat Gel, Biafine), positive control (histamine), and negative control (saline). Each test article will have a single administration, only the re-test will utilize a triplicate administration. The SPT will be ready for initial reading after approximately 15 minutes (but no sooner than 10 minutes and no longer than 20 minutes) following the final SPT administration in the series. When reading the test, the investigator will note the presence or absence of a wheal at all five sites and will measure the diameter of each wheal present. In order for the SPT to be valid, the wheal at the positive control site must exceed that at the negative control by 4 mm. If the above criteria are not met, the SPT will be repeated in triplicate on the infrascapular region of the back to the left of the midline, following the same protocol. Following the initial reading, the subject will remain at the testing facility.

A second reading will be conducted approximately 6 hours (+/- 15 minutes) after SPT administration on Day 1 (Visit 1). When reading the test, the investigator will note the presence or absence of a wheal at all five sites and will measure the diameter of each wheal present. Subjects are free to leave the clinical site after the second reading. Subjects will be instructed to promptly contact the PI and go to the ER if symptoms of an allergic reaction or shock occur.

Subjects will return to the office one to two days after initial administration for a third test reading (Visit 2). When reading the test, the investigator will note the presence or absence of a wheal in all five sites and will measure the diameter of each wheal present. Each site of test article administration will be measured for a positive reaction. A positive reaction is present when there is a measurable wheal of 3 mm or more, surrounded by a flare. Small wheals are to be confirmed by palpation. A flare alone is disregarded.

Arms: arm 1: KeraStat® Cream is a non-sterile, non-implantable wound dressing intended to provide a moist environment in the management of a variety of partial thickness dermal wounds. arm 2: KeraStat® Gel is a sterile, non-implantable water-based gelatinous (hydrogel) wound dressing intended to act as a protective covering in the management of a variety of partial thickness dermal wounds. arm 3: Wound dressing for management of partial and full thickness wounds. arm 4: Histamine is provided as a solution of histamine base (6.0 mg/mL). arm 5: Saline (sterile) is provided as a 0.9% NaCl solution.
Interventions: intervention 1: KeraStat® Cream intervention 2: KeraStat Gel intervention 3: Biafine intervention 4: Histamine intervention 5: Saline (0.9% NaCl)
Intervention descriptions: intervention 1: Administered 0.025 gm of KeraStat Cream per subject on day 1 of the study. intervention 2: Administered 0.025 gm of KeraStat Gel per subject on day 1 of the study. intervention 3: Administered 0.025 gm of Biafine per subject on day 1 of the study. intervention 4: Administered 1 drop of Histamine Dihydrocl (6 mg/mL) per subject on day 1 of the study. intervention 5: Administered 1 drop of saline per subject on day 1 of the study.

Protocol documents:
Prot_SAP_000.pdf: 
 
KeraNetics 
CONFIDENTIAL 
Page 1 
DN: PRO-KSCM-CRD-002 
 
 
 
 
 
STUDY DEVICE: KeraStat® CREAM  
STUDY NUMBER:  KSCM-CRD-002 
VERSION:  01 
EFFECTIVE DATE:  17 JUL 19 
 
SKIN PRICK TEST OF KERASTAT® CREAM  
 
 
 
 
Sponsor: KeraNetics 
200 East 1st Street, Suite 102 
Winston-Salem, North Carolina 27101 
USA 
Tel: 336 725 0621 
Fax: 336 725 0619 




 
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KERANETICS CLINICAL STUDY PROTOCOL 
Skin Prick Test of KeraStat® Cream  
Study Number: KSCM-CRD-002 
 
CONTACT INFORMATION 
 
Sponsor Contact: 
 
Ryan Clohessy 
KeraNetics 
200 East 1st Street, Suite 102 
Winston-Salem, North Carolina 27101 
USA 
Tel: 410-251-3049 
Fax: 336-725-0619 
Email rclohessy@kerabiosci.com 
 
Investigator Site Network: PMG Research, Inc. 
4505 Country Club Road, Suite 110 
Winston Salem, NC 27104 
USA 
Tel: 336.608.3500 
 
Principal Investigator: Dr. Jonathan Wilson 
1901 S. Hawthorne Rd.  
Ste. 306 
Winston-Salem, NC 27103 
Tel: 336.768.8062 
  
 
This study will be conducted according to the protocol and in compliance with Good Clinical 
Practice (GCP) and other applicable regulatory requirements. 
 
 
 


 
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INVESTIGATOR’S AGREEMENT 
 
I agree: 
• 
To assume responsibility for the proper conduct of the study at this site. 
• 
To conduct the study in compliance with applicable regulatory requirements, this protocol, any future 
amendments, and with any other study conduct procedures provided by KeraNetics (KN). 
• 
Not to implement any changes to the protocol without agreement from the sponsor and prior review and written 
approval from the Institutional Review Board (IRB) or Independent Ethics Committee (IEC), except where 
necessary to eliminate an immediate hazard to the subjects, or for administrative aspects of the study (where 
permitted by all applicable regulatory requirements). 
• 
That I am thoroughly familiar with the appropriate use of the study device(s), as described in this protocol, and 
any other information provided by the sponsor including, but not limited to, the following: the current directions 
for use/product labeling or equivalent document, and approved product label (if the product is marketed in this 
country and the label is not already provided). 
• 
That I am aware of, and will comply with, “good clinical practices” (GCP) and all applicable regulatory 
requirements. 
• 
That I will provide full and unencumbered access to source documents and medical records needed for KN, 
representatives of KN and regulatory authorities to verify source data and related documentation with respect to 
this trial. 
• 
To ensure that all persons assisting me with the study are adequately informed about the KN study device(s) and 
of their study-related duties and functions as described in the protocol.   
• 
That I have been informed that certain regulatory authorities require the Sponsor to obtain and supply, as 
necessary, details about the Investigator’s ownership interest in the Sponsor or the study device, and more 
generally about his/her financial ties with the Sponsor.  KN will use and disclose the information solely for the 
purpose of complying with regulatory requirements. 
 
Hence I: 
• 
Agree to supply KN with any necessary information regarding ownership interest and financial ties (including 
those of my spouse and dependent children); 
• 
Agree to promptly update this information if any relevant changes occur during the course of the study and for 
1 year following completion of the study; and 
• 
Agree that KN may disclose any information it has about such ownership interests and financial ties to regulatory 
authorities. 
 
 
Investigator Name:    
 
________________________________________________________ 
 
 
 
 
Investigator Signature 
 
Date 
 
 
 


 
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1. 
SYNOPSIS 
Name of Company: 
KeraNetics 
Name of Product: 
KeraStatâ Cream 
Type of Study: 
Clinical Safety 
Title of Study:  Skin Prick Test of KeraStat® Cream  
Investigator(s):  Dr. Jonathan Wilson 
Study Period:  Estimated FPFV July 2019; Expected LPLVAugust 2019 
Phase of Development:  Verification & Validation (Phase 3 of Design Control) 
Objective(s):  
• 
To evaluate the potential for a humoral reaction to KeraStat Cream compared to a predicate device  
Methodology:  This is a within subject, open-label comparison study. 
Number of Subjects:  
Sufficient subjects will be screened such that approximately 20 total subjects will complete the study. Sample size 
for the study is not based on statistical considerations. A total of 20 subjects were deemed sufficient to assess the 
potential for a humoral response to KeraStat Cream compared to the predicate device in support of establishing 
substantial equivalence. 
Study Overview: 
Study Periods: 
The length of study participation for a subject is about 2-3 days depending on availability for the final site check.  
There are two skin prick site checks during the course of Day 1 with a final follow up between Days 2 and 3.    
Study Evaluations:   
Initial screening (Screening Visit; Visit 1) will be performed on the day of the Skin Prick Test (SPT) 
administration and will include obtaining demographic information, brief medical history, and abbreviated 
physical exam. 
 
On Day 1 (Visit 1) the SPT will be performed on the infrascapular region of the back to the right of the 
midline. Test articles will include the subject device (KeraStat Cream), predicate devices (KeraStat Gel, 
Biafine), positive control (histamine), and negative control (saline). Each test article will have a single 
administration, only the re-test will utilize a triplicate administration. The SPT will be ready for initial 
reading after approximately 15 minutes (but no sooner than 10 minutes and no longer than 20 minutes) 
following the final SPT administration in the series.  When reading the test, the investigator will note the 
presence or absence of a wheal at all five sites and will measure the diameter of each wheal present.  In order 
for the SPT to be valid, the wheal at the positive control site must exceed that at the negative control by 4 
mm. If the above criteria are not met, the SPT will be repeated in triplicate on the infrascapular region of the 
back to the left of the midline, following the same protocol. Following the initial reading, the subject will 
remain at the testing facility.    
 
A second reading will be conducted approximately 6 hours (+/- 15 minutes) after SPT administration on Day 
1 (Visit 1).  When reading the test, the investigator will note the presence or absence of a wheal at all five 
sites and will measure the diameter of each wheal present.  Subjects are free to leave the clinical site after the 
second reading.  Subjects will be instructed to promptly contact the PI and go to the ER if symptoms of an 
allergic reaction or shock occur.   
 
Subjects will return to the office one to two days after initial administration for a third test reading (Visit 2).  
When reading the test, the investigator will note the presence or absence of a wheal in all five sites and will 
measure the diameter of each wheal present.  
 


 
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Name of Company: 
KeraNetics 
Name of Product: 
KeraStatâ Cream 
Type of Study: 
Clinical Safety 
Each site of test article administration will be measured for a positive reaction.  A positive reaction is present 
when there is a measurable wheal of 3 mm or more, surrounded by a flare. Small wheals are to be confirmed 
by palpation.  A flare alone is disregarded.  
Inclusion Criteria: 
Subjects must meet all of the following criteria: 
1. Men and women, age 18-65 
2. Able to understand the informed consent and provide written informed consent  
3. Healthy, unmarked skin at the test area 
4. Agreement to avoid consumption of antihistamines until completion of third test reading (Visit 2)  
 
Exclusion Criteria: 
To participate in the study, subjects must not meet any of the following criteria: 
1. Women who are pregnant, lactating/nursing or plan to become pregnant 
2. Presence of skin disease, such as widespread urticaria or eczema 
3. Diagnosis of infectious disease 
4. Receiving corticosteroids, immunosuppressive agents, radiation or chemotherapy, topical growth 
factors, anxiolytics, imipramine, phenothiazine, dopamine, phenergen, clonidine, montelukast, 
immunotherapy, UV light therapy, H-2 antagonist, cyclosporine or any other medication the 
investigator feels will affect the test within the last month 
5. Medical history of hypotension, severe hypertension, vasomotor instability, asthma, autoimmune 
disease, severe cardiac, pulmonary or renal disease 
6. Tattoo in the intrascapular test area 
7. History of surgical procedure/skin graft in the intrascapular test area 
8. Employee or relative of employee of KeraNetics 
9. Consumption of an anti-histamine within 7 days of the screening visit 
10. History of hypersensitivity to histamine products 
11. Any condition the investigator determines will compromise subject safety or prevent the subject 
from completing the study 
12. Participated in an investigational study within 30 days of the screening visit 
 


 
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Name of Company: 
KeraNetics 
Name of Product: 
KeraStatâ Cream 
Type of Study: 
Clinical Safety 
Test Product(s), Dose, and Mode of Administration:  
Subject Device: KeraStat® Cream is a non-sterile, non-implantable wound dressing intended to act as a protective 
covering and provide a moist environment in the management of a variety of partial thickness dermal wounds.  
KeraStat® Cream is provided in a screw top tube for multiple uses.  Each tube contains 1 oz (29.6 mL) of KeraStat® 
Cream, which contains 5% keratin protein incorporated into a cream base.  KeraStat Cream will be provided in its 
final device form and sourced by the sponsor. 
Predicate Devices: KeraStat Gel is a sterile, non-implantable, water-based gelatinous (hydrogel) wound dressing 
intended to act as a protective covering in the management of a variety of partial thickness dermal wounds. It is 
provided in a single-use (5 mL), collapsible aluminum tube. KeraStat Gel will be provided in its final device form 
and sourced by the sponsor. 
BIAFINE is a water-based emulsion formulated for the dressing and management of superficial wounds, minor 
abrasions, dermal ulcers, donor sites, 1st and 2nd degree burns, including sunburns, and radiation dermatitis.  Biafine 
will be provided in its final device form and sourced by the clinical site.  
Positive Control: Histamine will be provided as a solution of histamine base (6.0 mg/mL). Histamine will be sourced 
by the clinical site. 
Negative Control: Saline (sterile) will be provided as 0.9% NaCl. Saline will be sourced by the clinical site.  
 
For SPT, the infrascapular region of the back to the right of the midline will be cleaned with alcohol wipes and 
allowed to air dry.  Five marks will be made, at least 4 cm apart, to identify the test sites.  These marks will be 
made in a vertical line. The back will be cleaned again with alcohol wipes and allowed to air dry.  A UniTest® PC 
(Lincoln Diagnostics, Inc) will be used, according to the instructions of use, to administer each test article.  If 
blood is drawn, the test will be repeated for that specific site. The test will be repeated at an additional mark made 
along the vertical line.  One minute after completing the pricks, absorbent tissue will be applied to remove residual 
extract, and the back will be covered with a shirt or sheet to keep the back warm.  The subject will be instructed 
not to scratch the test area.   
 
Duration of Treatment:   
The length of study participation for a subject is 2-3 days. 
Concomitant Medication Restrictions:  
Corticosteroids, immunosuppressive agents, radiation or chemotherapy, topical growth factors, anxiolytics, 
imipramine, phenothiazine, dopamine, phenergen, clonidine, montelukast, immunotherapy, UV light therapy, 
H-2 antagonist, cyclosporine 
Criteria for Evaluation: 
Skin Reaction: 
Primary 
• 
Size of wheal for the subject device and predicate device at 15 minutes post SPT administration 
Secondary 
• 
Size of wheal for the subject device and predicate device at 6 hours and 1-2 days post SPT administration 
Safety Parameters: 
• 
Safety of the subjects will be monitored and adverse events recorded throughout the study  
Statistical Methods: 
No formal statistics will be performed to compare the subject device and predicate device. Data will be 
summarized for each individual subject and time point. The number of subjects that meet criteria for a positive 
skin reaction to KeraStat Cream and/or a positive skin reaction to the predicate device(s) will be reported.  
 
Safety:  
All subjects who participate in the study will be included in the safety analysis. Safety will be evaluated by 
examining the incidence and type of adverse events from the Screening Visit through study completion. 


 
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FIGURE 1: TIME AND EVENTS SCHEDULE 
 
Period 
Skin Prick Test  
Visits 
Screening 
Visit / Visit 1 Day 1 
Follow-Up Visit/ Visit 2 
(Day 2-3) 
Screening 
 
 
Informed Consent 
X 
 
Demography 
X 
 
Brief Medical History  
X 
 
Inclusion/Exclusion 
X 
 
Safety Procedures 
 
 
*Vital Signs  
X 
 
Abbreviated Physical Examination 
X 
 
Adverse Events 
X 
X 
Concomitant Medications 
X 
X 
Study Treatment/General 
 
 
Skin Prick Administration 
X 
 
Meal 
X 
 
Assessments 
 
 
Evaluation of Response (15 min) 
X 
 
Evaluation of Response (6 hrs) 
X 
 
Evaluation of Response (24-48 hrs) 
 
X 
 
*Vital signs include height, weight, blood pressure, pulse, temperature, and respirations per minute. 
 


 
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2. 
TABLE OF CONTENTS, LIST OF TABLES, AND LIST OF 
FIGURES  
TABLE OF CONTENTS 
1. 
SYNOPSIS ...................................................................................................................5 
FIGURE 1: TIME AND EVENTS SCHEDULE .............................................................................8 
2. 
TABLE OF CONTENTS, LIST OF TABLES, AND LIST OF FIGURES .................9 
3. 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS .............................12 
4. 
INTRODUCTION ......................................................................................................13 
4.1. 
Background .................................................................................................................13 
4.2. 
Rationale .....................................................................................................................13 
5. 
TRIAL OBJECTIVES AND PURPOSE ....................................................................14 
5.1. 
Objective .....................................................................................................................14 
6. 
INVESTIGATIONAL PLAN .....................................................................................14 
6.1. 
Overall Study Design ..................................................................................................14 
6.2. 
Number of Subjects ....................................................................................................16 
6.3. 
Study Endpoints ..........................................................................................................16 
6.4. 
Treatment Assignment ................................................................................................16 
6.5. 
Criteria for Study Termination ...................................................................................16 
7. 
SELECTION AND WITHDRAWAL OF SUBJECTS ..............................................17 
7.1. 
Subject Inclusion Criteria ...........................................................................................17 
7.2. 
Subject Exclusion Criteria ..........................................................................................17 
7.3. 
Subject Restrictions and Requirements ......................................................................18 
7.3.1. 
Medication and Therapy Restriction ..........................................................................18 
7.3.2. 
Food, Meals, Beverages and Fluid Intake ..................................................................18 
7.3.3. 
Contraception ..............................................................................................................18 
7.4. 
Subject Completion and Withdrawal ..........................................................................18 
7.4.1. 
Subject Completion ....................................................................................................18 
7.4.2. 
Patient Withdrawal (Premature Discontinuation from the Study) ..............................18 
7.4.3. 
Replacement of Patients .............................................................................................19 
8. 
TREATMENT OF SUBJECTS ..................................................................................19 
8.1. 
Description of Subject Device ....................................................................................19 
8.2. 
Concomitant Medications and Therapies ...................................................................21 


 
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8.2.1. 
Pharmacological Therapy ...........................................................................................21 
8.3. 
Randomization ............................................................................................................21 
9. 
STUDY DEVICE MATERIALS AND MANAGEMENT ........................................21 
9.1. 
Study Device ...............................................................................................................21 
9.2. 
Study Device Packaging and Labeling .......................................................................21 
9.3. 
Study Device Storage .................................................................................................21 
9.4. 
Study Device Preparation ...........................................................................................21 
9.5. 
Administration ............................................................................................................21 
9.6. 
Study Device Accountability ......................................................................................22 
9.7. 
Study Device Handling and Disposal .........................................................................22 
10. 
SCREENING ASSESSMENTS .................................................................................22 
10.1. 
Demographics .............................................................................................................22 
10.2. 
Medical History ..........................................................................................................22 
10.3. 
Physical Exam and Vital Signs ...................................................................................22 
11. 
STUDY ENDPOINTS ................................................................................................23 
11.1. 
Positive Reactions .......................................................................................................23 
11.2. 
Adverse and Serious Adverse Events .........................................................................23 
11.2.1. 
Definitions ..................................................................................................................23 
11.2.1.1. 
Adverse Event (AE) ....................................................................................................23 
11.2.1.2. 
Serious Adverse Event (SAE) ....................................................................................23 
11.2.2. 
Adverse Event Reporting ............................................................................................23 
11.3. 
Relationship to Study Device .....................................................................................23 
11.3.1. 
Assessment of Causality .............................................................................................23 
11.4. 
Recording Adverse Events .........................................................................................24 
11.4.1. 
Eliciting Adverse Event Reports ................................................................................24 
11.4.2. 
Assessment of Intensity ..............................................................................................24 
11.5. 
Reporting Adverse Events ..........................................................................................24 
11.5.1. 
SAE Reporting Procedures .........................................................................................25 
11.5.1.1. 
Regulatory Reporting Requirements for SAEs ...........................................................25 
11.5.2. 
Reporting Safety Information to the IRB ...................................................................25 
11.5.3. 
Protocol Deviations Due to an Emergency or Adverse Event ....................................25 
11.6. 
Follow-up of Adverse Events .....................................................................................25 


 
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12. 
STATISTICS ..............................................................................................................26 
12.1. 
Description of Statistical Methods ..............................................................................26 
12.1.1. 
Baseline Data Summary .............................................................................................26 
12.1.2. 
Responder Summary ...................................................................................................26 
12.2. 
Sample Size ................................................................................................................26 
12.3. 
Procedure for Accounting for Triplicate Data ............................................................26 
12.4. 
Analysis of Patients Withdrawing Prematurely from the Study .................................26 
13. 
DIRECT ACCESS TO SOURCE DATA/DOCUMENTS .........................................26 
13.1. 
Study Monitoring ........................................................................................................26 
13.2. 
Audits and Inspections ................................................................................................27 
13.3. 
Institutional Review Board (IRB) ...............................................................................27 
14. 
QUALITY CONTROL AND QUALITY ASSURANCE .........................................27 
14.1. 
Regulatory Authority Approval ..................................................................................28 
14.2. 
Protocol Modifications ...............................................................................................28 
15. 
ETHICS ......................................................................................................................28 
15.1. 
Ethics Review .............................................................................................................28 
15.2. 
Ethical Conduct of the Study ......................................................................................28 
15.3. 
Written Informed Consent ..........................................................................................29 
16. 
DATA HANDLING AND RECORDKEEPING .......................................................29 
16.1. 
Case Report Form Completion and Source Documentation .......................................29 
16.2. 
Data Management .......................................................................................................30 
16.3. 
Study Site Close-Out ..................................................................................................30 
16.4. 
Retention of Study Documents and Records ..............................................................30 
16.5. 
Inspection of Records .................................................................................................31 
17. 
INVENTION AND PUBLICATION POLICY ..........................................................31 
17.1. 
Ownership ...................................................................................................................31 
17.2. 
Confidentiality ............................................................................................................31 
17.3. 
Publication ..................................................................................................................31 
18. 
LIST OF REFERENCES ............................................................................................32 


 
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3. 
 LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS 
The following abbreviations and specialist terms are used in this study protocol. 
Table 1: 
Abbreviations and Specialist Terms  
Abbreviation or Specialist Term 
Explanation 
AE 
Adverse Event 
CRF 
Case Report Form 
CRO 
Clinical Research Organization 
ER 
Emergency Room 
EPA 
Environmental Protection Agency 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice 
ICF 
Informed Consent Form 
ICH 
International Conference on Harmonization 
ICH-GCP 
International Conference on Harmonization – Good Clinical 
Practice 
IDE 
Investigational Device Exemption 
IEC 
Institutional Ethics Committee 
IRB 
Institutional Review Board 
KN 
KeraNetics 
NSR 
Nonsignificant Risk 
OSHA 
Occupational Safety and Health Administration 
PI 
Principal Investigator 
RIPT 
Repeat Insult Patch Test 
SAE 
Serious Adverse Event 
SPT 
Skin Prick Test 
SOPs 
Standard Operating Procedures 
SAP 
Statistical Analysis Plan 
USP 
United States Pharmacopoeia 
UV 
Ultra Violet 
 


 
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4. 
INTRODUCTION 
4.1. 
Background 
Active, healthy individuals are often involved in activities of daily living that put them at risk of 
sustaining acute skin trauma.  Superficial to partial thickness abrasions may be the most 
common,1 but other partial thickness injuries such as burns (450,000 burn injuries resulted in 
medical treatment in 2013)2 and ulcers are also common.  Due to the risk of untreated acute 
partial thickness wounds and burns becoming more serious chronic wounds or full-thickness 
burns, there is pressure on the medical community to find a cost-effective and efficacious wound 
dressing that supports healing.   
KeraStat® Cream is a non-sterile, non-implantable wound dressing intended to act as a protective 
covering and provide a moist environment in the management of a variety of partial thickness 
dermal wounds.  KeraStat® Cream is provided in a screw top tube for multiple uses.  Each tube 
contains 1 oz (29.6 mL) of KeraStat® Cream, which contains 5% keratin protein incorporated 
into a cream base.  
A biological safety profile has been established for KeraStat Cream. Biocompatibility studies 
were chosen and performed in accordance with ISO 10993-1:2007, “Biological Evaluation of 
Medical Devices Part 1: Evaluation and Testing.”  Furthermore, KeraStat Cream has been 
subjected to a human subject Repeat Insult Patch Test (RIPT) to evaluate the 
irritation/sensitization potential of the medical device when applied to uncompromised skin. No 
adverse skin reactions were observed in 50 subjects evaluated in the RIPT study and KeraStat 
Cream was considered a non-primary irritant and non-primary sensitizer to the skin. 
The current study is considered a nonsignificant risk (NSR) device study according to Food and 
Drug Administration (FDA) guidance and does not require an Investigational Device Exemption 
(IDE) in advance of study conduct.  NSR device studies must follow the abbreviated 
requirements presented in 21 CFR 812.2(b) related to labeling, Institutional Review Board (IRB) 
approval, informed consent, monitoring, records, reports, and prohibition against promotion. 
4.2. 
Rationale 
When applied, KeraStat Cream covers the wound, isolating it from the external environment, 
absorbing excess exudate and facilitating a moist wound environment for the management of 
partial thickness wounds.  KeraStat Cream contains human hair-derived keratin proteins.  
Keratin, like collagen, is a structural, intermediate filament-forming protein.3 Irrespective of 
what species they reside in, keratin proteins are functionally important for mechanical stability 
and integrity and structure of the hair shaft and cells in the epithelium. These proteins are highly 
conserved between species, with only minor differences in expressed keratin gene sets between 
species.  Human hair and sheep wool in particular are highly similar with equivalent keratin 
intermediate fibers found in each species.4 Keratin proteins have been used for multiple 
applications such as FDA cleared topical wound care products (e.g. Keratec Wound Dressings, 
KeraStat Gel),5 and multiple cosmetic and personal care applications that include hair 
straightening products, shampoos, conditioners, and styling agents, as well as skin care creams 
and ointments that are sold as cosmetics.  


 
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The intended use for KeraStat Cream is as a wound dressing for management of partial thickness 
wounds where the normal skin barrier function has been disrupted. The keratin proteins in 
KeraStat Cream are derived from human hair and represent a novel component for use in a 
wound dressing compared to a legally marketed device (KeraStat® Gel) containing keratin 
proteins derived using the same manufacturing process. Animal models used for biocompatibility 
studies may not be fully predictive of the immune, inflammatory, and irritation responses in 
human subjects. While the RIPT study resulted in no observed skin reactions, the assessment is 
conducted on intact skin and there is a need to evaluate the potential for a humoral (B-cell 
mediated) immune response to KeraStat Cream on compromised skin to support its intended use. 
Therefore, a skin prick test is being conducted to support the continued evaluation of the safety 
of this product.  
5. 
TRIAL OBJECTIVES AND PURPOSE 
5.1. 
Objective 
The objective of the present study is to evaluate the potential for a humoral reaction to KeraStat 
Cream compared to predicate devices. 
6. 
INVESTIGATIONAL PLAN 
6.1. 
Overall Study Design 
This is a single site, within subject, open-label comparison study to assess the humoral reaction 
KeraStat Cream compared to predicate devices.  The length of study participation for a subject is 
two to three days depending on when a subject returns for their final follow-up evaluation.  The 
Acceptable Study Windows is shown in Table 2. 
Sufficient subjects will be screened such that 20 total subjects will complete the study.  We 
expect excellent retention throughout the duration of the study, so we will target recruitment of 
22 subjects.  The sample size for the study is not based on any statistical considerations.  A total 
of 20 subjects were deemed sufficient to assess the potential for a humoral response to KeraStat 
Cream compared to the predicate devices in support of establishing substantial equivalence.  
Initial screening (Screening Visit; Visit 1) of the subject will take place the day of the SPT 
administration.  The Screening Visit will include collecting demographic information, a brief 
medical history, and an abbreviated physical exam.  If a subject fulfills all the inclusion criteria, 
none of the exclusion criteria, and gives their informed consent they will be admitted into the 
study.  
The SPT will be performed on Day 1 (Visit 1), after screening and consent is obtained.  The test 
will include five agents: the subject device (KeraStat Cream), predicate devices (KeraStat Gel, 
Biafine), positive control (histamine), and negative control (saline).  The SPT will be 
administered on the infrascapular region of the back to the right of the midline.  The region will 
be cleaned with alcohol wipes and allowed to air dry.  Five marks will be made using a sterile 
skin marker to identify the test sits. These marks will be at least 4 cm apart and made in a 


 
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vertical line. Once the marks are made, the back will be cleaned again with alcohol wipes and 
allowed to air dry.  All subjects will initially receive the agents in the same order, going in 
descending order from a subjects’ head to feet: subject device, predicate device (KeraStat Gel), 
predicate device (Biafine), positive control, and negative control.   
Each agent will be administered once using the UniTest® PC (Lincoln Diagnostics, Inc), 
following the manufacturer’s instructions for use.  In brief, all five agents are loaded into a well 
tray. A UniTest PC touch post is placed into a well, tip-down, to load an agent onto the touch 
post. Each well contains approximately 250-500 µL. Allow the touch post to sit in the agent for 
at least 5 seconds.  The touch post is removed and placed into contact at the appropriate mark for 
one second then pressed firmly into the skin.  With proper pressure, all test sites should show a 
circular impression with an indented circle in the center surrounded by six dot indentations.  A 
separate touch post is used for each agent. If blood is drawn, the test is repeated at an additional 
mark made along the vertical line.  One minute after completing the pricks, absorbent tissue is 
applied to remove residual extract with care taken to avoid cross contamination of sites. When 
administration of the pricks is completed, the subject’s shirt or a sheet will be used to cover the 
back and keep it warm. The subject will be instructed not to scratch the test area.  
The initial evaluation of the sites will be taken after 15 (±5) minutes following the final SPT 
administration in the series.  When reading the test, the investigator will note the presence or 
absence of a wheal at all five sites and will measure the diameter of each wheal present.  In order 
for the SPT to be valid the wheal at the positive site control must exceed that at the negative site 
control by 4 mm.  If the above criteria are not met, the SPT will be repeated in triplicate on the 
infrascapular region of the back to left of the midline, following the same protocol.  Three 
vertical lines will be made with all marks at least 4 cm apart.  If the triplicate re-administration 
fails, the subject will be removed from the study.  
Following the initial reading, the subject will remain at the testing facility. They will wait with 
the pricks covered by their shirt or a sheet for a period of approximately 6 hours. The subject will 
be instructed not to scratch the test area.  During this time, the testing facility will provide a meal 
for the subject.  
A second evaluation will be conducted 6 hours (±15 minutes) after SPT administration on Day 1 
(Visit 1).  Again, the investigator will note the presence or absence of a wheal at each site and 
measure the diameter of each wheal present.  Subjects are free to leave the clinical site after the 
second reading.  Subjects will be instructed to not scratch or irritate the test area and to promptly 
contact the PI and go to the Emergency Room (ER) if symptoms of an allergic reaction or shock 
occur.  
Subjects will return to the clinical site for a third/final test evaluation (Visit 2) one to two days 
after the initial test administration.  When reading the test, the investigator will note the presence 
or absence of a wheal in all five sites and will measure the diameter of each wheal present.  A 
subject will have completed the study after the third/final evaluation has been completed.  


 
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Table 2: 
Acceptable Study Windows 
Visit 
Day Visit 
Acceptable Visit Window 
Screening (Visit 1) 
Day -7 to  
Day 1 
None 
SPT Administration (Visit 1) 
Day 1 
None 
First evaluation (Visit 1) 
Day 1 
15 minutes ±5 minutes after SPT administration 
Second evaluation (Visit 1) 
Day 1 
6 hours ±15 minutes after SPT administration 
Third/Final evaluation (Visit 2) 
Day 2 – 3 
1 – 2 days after SPT administration 
 
6.2. 
Number of Subjects 
Enough subjects will be screened and enrolled such that a total of approximately 20 total subjects 
will be recruited into the study.  All subjects will receive all five test articles.   
Subjects at screening will be given a sequential subject number starting with 1001, 1002, etc.  
Subject initials will be collected, but not used as an identifier.  The subject number will be used 
to identify the subject and samples associated with each subject.  
6.3. 
Study Endpoints 
The primary objective of the study is to assess the humoral response of KeraStat Cream 
compared to the predicate devices utilizing the following endpoints: 
• Size of wheal for the subject device and predicate devices at 15 minutes post SPT 
administration 
• Size of wheal for the subject device and predicate devices at 6 hours and 1 – 2 days 
post SPT administration 
• Safety of the subjects will be monitored and adverse events recorded throughout the 
duration of the study 
6.4. 
Treatment Assignment 
All subjects will receive all five test agents: KeraStat Cream, KeraStat Gel, Biafine, histamine, 
saline.  
6.5. 
Criteria for Study Termination 
Sponsor reserves the right to temporarily suspend or prematurely discontinue this study at any 
time for reasons including, but not limited to, safety or ethical issues or severe non-compliance.  
If Sponsor determines such action is needed, Sponsor will discuss this with the Investigator 
(including the reasons for taking such action) at that time.  When feasible, Sponsor will provide 
advance notification to the Investigator of the impending action prior to it taking effect. 


 
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Sponsor will promptly inform the Investigator and/or institution conducting the study if the study 
is suspended or terminated for safety reasons, and will also inform the regulatory authorities of 
the suspension or termination of the study and the reason(s) for the action.  If required by 
applicable regulations, the Investigator or KeraNetics/KeraNetics designee, depending on 
whether the Institutional Review Board (IRB) is a central or local IRB, must inform the IRB 
promptly and provide the reason for the suspension or termination. 
If the study is prematurely discontinued, all study data must be returned to Sponsor.  In addition, 
arrangements will be made for all unused study device(s) to be destroyed or returned in 
accordance with the applicable procedures for the study. 
7. 
SELECTION AND WITHDRAWAL OF SUBJECTS 
7.1. 
Subject Inclusion Criteria 
At the Screening Visit (Visit 1, day of the SPT), subjects must meet all of the following criteria: 
1. Males or females aged 18 – 65 years. 
2. Able to understand the informed consent, and provide written informed consent. 
3. Healthy, unmarked skin at the test area (infrascapular regions of the back). 
4. Agreement to avoid consumption of antihistamines until completion of the third test 
reading (Visit 2).  
7.2. 
Subject Exclusion Criteria 
To participate in the study, subjects must not meet any of the following criteria: 
1. Women who are pregnant, lactating/nursing or plan to become pregnant. 
2. Presence of skin disease, such as widespread urticaria or eczema. 
3. Diagnosis of infectious disease. 
4. Receiving corticosteroids, immunosuppressive agents, radiation or chemotherapy, topical 
growth factors, anxiolytics, imipramine, phenothiazine, dopamine, phenergen, clonidine, 
montelukast, immunotherapy, UV light therapy, H-2 antagonist, cyclosporine, or any 
other medication the investigator feels will affect the test within the last month. 
5. Medical history of hypotension, severe hypertension, vasomotor instability, asthma, 
autoimmune disease, severe cardiac, pulmonary or renal disease. 
6. Tattoo in the intrascapular test area. 
7. History of surgical procedure/skin graft in the intrascapular test area. 
8. Employee or relative of employee of KeraNetics. 
9. Consumption of an antihistamine within seven days of study initiation. 
10. History of hypersensitivity to histamine products. 


 
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11. Any condition the investigator determines will compromise subject safety or prevent the 
subject from completing the study. 
12. Participated in an investigational study within 30 days of the Screening Visit.  
7.3. 
Subject Restrictions and Requirements 
7.3.1. 
Medication and Therapy Restriction 
See Section 8.2.  
7.3.2. 
Food, Meals, Beverages and Fluid Intake 
Subjects will be instructed to maintain their normal level of food and fluid consumption 
throughout the trial and therefore they should not alter their fluid intake greatly over the course 
of the trial.  The testing center will provide the subject with a meal between the 15 minute and 6 
hour evaluations on Day 1.  
7.3.3. 
Contraception 
Women of childbearing potential are defined as premenopausal women who are not surgically 
sterile.  Surgically sterile is defined as women with tubal ligation, hysterectomy and/or bilateral 
oophorectomy.  
Women of childbearing potential must:  
1. Self-report that they are not pregnant or plan to become pregnant. This study does not 
require a negative urine pregnancy test.  
2. Not be lactating. 
Women of childbearing potential with male partners must: 
1. Be willing to use acceptable methods of contraception from screening through follow-up 
unless the woman is in a monogamous relationship with a sterilized male partner (e.g., 
vasectomy). 
2. Acceptable methods of birth control are systemic contraceptives (contraceptive pills, 
hormonal implants, contraceptive patches and injectable contraceptives), or intra-uterine 
devices), double-barrier methods, or as approved by the Investigator.  
7.4. 
Subject Completion and Withdrawal  
7.4.1. 
Subject Completion 
A subject will be considered to have completed the study if they complete the entire study 
through the final evaluation (Day 2 – 3, Visit 2).   
7.4.2. 
Patient Withdrawal (Premature Discontinuation from the Study) 
A documented effort must be made to determine why a subject fails to return for the necessary 
visit or is dropped from the study, and the reason for withdrawal must be recorded in the source 


 
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documents and case report form (CRF).  A subject may withdraw or be removed from the study 
for any of the following reasons and will be treated as considered appropriate by the Investigator: 
• Subject request (for any reason) 
• In the opinion of the Investigator, continuation is not in the best interest of the 
subject. 
• A serious or unexpected AE occurs such that continuation in the study is 
inappropriate. 
• Test area (infrascapular region of the back) becomes marked or affected so that the 
Investigator is unable to read the test sites.   
• Subject consumes antihistamines during the study.  
• Pregnancy 
• In the opinion of the Sponsor, continuation is not in the best interest of the subject. 
If a subject is prematurely discontinued from participation in the study for any reason, the 
Investigator must follow up on all ongoing adverse events (if any).  
In the event a subject is prematurely discontinued from the study due to an AE, or unexpected 
AE or serious adverse event (SAE) (as defined in Section 11.2.1), the procedures stated in 
Sections 11.2-11.6 must be followed.   
7.4.3. 
Replacement of Patients 
Subjects that fail the criteria for positive and negative controls in the triplicate re-administration 
will not be replaced. 
8. 
TREATMENT OF SUBJECTS 
8.1. 
Description of Subject Device 
KeraStat® Cream is a non-sterile, non-implantable wound dressing intended to act as a protective 
covering and provide a moist environment in the management of a variety of partial thickness 
dermal wounds.  KeraStat® Cream is provided in a screw top tube for multiple uses.  Each tube 
contains 1 oz (29.6 mL) of KeraStat® Cream, which contains 5% keratin protein incorporated 
into a cream base.  
The study device is described below in Table 3.


 
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Table 3: Subject Device 
 
Subject Device 
Predicate 
Device 
Predicate 
Device 
Positive Control 
Negative 
Control 
Product Name 
KeraStat Cream 
KeraStat Gel 
Biafine 
Histamine 
Saline 
Manufacturer 
KeraNetics 
KeraNetics 
Johnson and 
Johnson 
HollisterStier, 
LLC 
McKesson 
Packaging 
Multi-use tube 
Single-use tube 
Multi-use tube 
Multi-use sterile 
amber vial with 
dropper 
3ml Syringes 
Components 
5.0% keratin, 
purified water, 
glycerin, 
caprylic/capric 
triglyceride, 
dimethicone, 
mineral oil, 
sodium stearoyl 
glutamate, 
sodium 
polyacrylate/hyd
rogenated 
polydecene/tride
ceth-6, 
phenoxyethanol, 
ethylhexylglycer
in, and sodium 
hydroxide 
5.0% keratin; 
purified water, 
phenoxyethanol, 
carbomer, 
sodium 
hydroxide, and 
ethylhexylglycer
in 
Purified water, 
liquid paraffin, 
ethylene glycol 
monostearate, 
stearic acid, 
propylene 
glycol, paraffin 
wax, squalane, 
avocado oil, 
trolamine/sodiu
m alginate, 
triethanolamine, 
cetyl palmitate, 
methylparaben 
(sodium salt), 
sorbic acid 
(potassium salt), 
propylparaben 
(sodium salt), 
and fragrance 
6.0 mg/mL 
0.9% NaCl 
Route of 
Administration 
Topical 
Topical 
Topical 
Percutaneous 
Percutaneous 
Physical 
Description 
White to tan 
cream 
Hydrogel 
White to tan 
cream 
Clear liquid 
Clear liquid 
 


 
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8.2. 
Concomitant Medications and Therapies 
8.2.1. 
Pharmacological Therapy 
Concomitant medications are permitted during this study unless otherwise specified in the 
Exclusion Criteria.  
8.3. 
Randomization  
All subjects receive the same test agents in the same location (infrascapular region of the back) 
in the same order.  The test agents will be administered going in descending order from a 
subject’s head to feet: subject device, predicate device, positive control, and negative control. 
9. 
STUDY DEVICE MATERIALS AND MANAGEMENT 
9.1. 
Study Device 
KeraStat® Cream is a non-sterile, non-implantable wound dressing intended to act as a 
protective covering and provide a moist environment in the management of a variety of partial 
thickness dermal wounds.  KeraStat® Cream is provided in a screw top tube for multiple uses.  
Each tube contains 1 oz (29.6 mL) of KeraStat® Cream, which contains 5% keratin protein 
incorporated into a cream base. 
9.2. 
Study Device Packaging and Labeling 
KeraStat Cream will be provided in a multi-use (1 oz), collapsible aluminum tube. Study device 
supplies will be maintained at the site under controlled conditions and dispensed by qualified 
personnel at the study site.  Study device labels will contain information to meet the applicable 
regulatory requirements. 
9.3. 
Study Device Storage 
The study device must be stored at room temperature (15 to 30ºC [59-86ºF]). Study device must 
be dispensed or administered according to procedures described herein.  Only subjects enrolled 
in the study may receive the study device, in accordance with all applicable regulatory 
requirements.  Only authorized site staff may supply or administer the study device. 
9.4. 
Study Device Preparation 
KeraStat Cream final product will be manufactured by Dexios for KeraNetics in the form of a 
cream and packaged in a multi-use tube as detailed in Section 9.2. T 
9.5. 
Administration 
During the SPT, the study device (KeraStat Cream) will be administered on the infrascapular 
region of the back to the right of the midline by qualified personnel.  The region will be cleaned 
with alcohol wipes and allowed to air dry.  Five marks will be made using a marker to identify 
the test sets. These marks will be at least 4 cm apart and made in a vertical line. Once the marks 
are made, the back will be cleaned again with alcohol wipes and allowed to air dry.  All subjects 


 
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will initially receive the agents in the same order, going in descending order from a subjects’ 
head to feet: subject device, predicate devices, positive control, and negative control.   
Each agent will be administered once using the UniTest® PC (Lincoln Diagnostics, Inc), 
according to procedures described herein. If blood is drawn, the test is repeated at an additional 
mark made along the vertical line.  One minute after completing the pricks, absorbent tissue is 
applied to remove residual extract with care taken to avoid cross contamination of sites. When 
administration of the pricks is completed, the subject’s shirt or a sheet will be used to cover the 
back and keep it warm. The subject will be instructed not to scratch the test area.  
9.6. 
Study Device Accountability 
The Investigator is responsible for the study device accountability and record maintenance.   
9.7. 
Study Device Handling and Disposal 
Unused supplies will be disposed of using appropriate documentation according to International 
Conference on Harmonization-Good Clinical Practice (ICH-GCP), local requirements, applicable 
Occupational Safety and Health Administration (OSHA) and Environmental Protection Agency 
(EPA) regulations, and applicable study-specific procedures. 
10. 
SCREENING ASSESSMENTS 
The following assessments will be used for screening purposes only and taken after informed 
consent is obtained.   
10.1. 
Demographics 
Basic demographic information will be collected from the subject. This information includes age, 
gender, and race/ethnicity.  
10.2. 
Medical History 
Each subject will provide a brief medical history (e.g. history of allergic reactions) to ensure they 
meet the inclusion/exclusion criteria.  The Investigator will review the completed medical history 
form prior to enrolling the subject in the study.  The Investigator may ask the subject for 
additional information, as necessary.  
10.3. 
Physical Exam and Vital Signs 
An abbreviated physical exam and documentation of vital signs will be conducted by the site 
following the site’s standard policy, prior to enrolling the subject in the study. The abbreviated 
physical exam includes measuring a subject’s height, weight, blood pressure, pulse, temperature, 
and respiratory rate as well as an examination of the skin prick test region of the back.  


 
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11. 
STUDY ENDPOINTS 
11.1. 
Positive Reactions 
During all evaluations, each site will be measured for a positive reaction. A positive reaction is 
present when there is a measurable wheal of 3 mm or more, surrounded by a flare. In cases 
where the wheal diameter is non-uniform, the longest wheal diameter should be used for the 
evaluation of the SPT.6,7 Small wheals are to be confirmed by the investigator via palpation.  
11.2. 
Adverse and Serious Adverse Events 
The Investigator is responsible for the detection and documentation of events meeting the criteria 
and definition of a non-serious AE or SAE as provided in this protocol.  During the study, as 
defined from the time of informed consent until completion of study-related procedures, the 
Investigator or site staff will be responsible for detecting and following AEs and SAEs, as 
detailed in this section of the protocol.  Adverse events will be reported by the subject (or, when 
appropriate, by a caregiver, surrogate, or the subject’s legally acceptable representative). 
11.2.1. 
Definitions 
11.2.1.1. Adverse Event (AE) 
An adverse event (AE) is defined as any unfavorable or unintended change in body structure, 
body function, laboratory result (e.g., chemistry, ECG), or worsening of a pre-existing condition 
associated temporally with the use of the test product, whether or not considered related to the 
test product. 
11.2.1.2. Serious Adverse Event (SAE) 
A serious adverse event (SAE) is any untoward medical occurrence that occurs irrespective of 
study treatment assignment, if it satisfies any of these criteria: results in death; is life-threatening; 
requires inpatient hospitalization or prolongs existing hospitalization; results in persistent or 
significant disability or incapacity or substantial disruption of the ability to conduct normal life 
functions; or if the event results in a congenital anomaly or birth defect.  All SAEs should be 
reported to the study sponsor within 24 hours of the investigator being aware of the event. 
11.2.2. 
Adverse Event Reporting 
Subjects will be encouraged to spontaneously report any changes in baseline health from the time 
the subject enters the study through study completion.  Study staff also will inquire about AEs on 
each visit while the subject is in the research center.  All AEs/SAEs will be recorded in the 
source document and the case report form (CRF).   
11.3. 
Relationship to Study Device 
11.3.1. 
Assessment of Causality 
The Investigator is obligated to assess the relationship between study device and the occurrence 
of each AE/SAE.  The Investigator will use clinical judgment to determine the relationship.  


 
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Alternative causes, such as natural history of the underlying diseases, concomitant therapy, other 
risk factors, and the temporal relationship of the event to the study device will be considered and 
investigated.   
The Investigator will assess causality based on the following definitions: 
• Not Related (the AE was more likely explained by causes other than the study 
treatment). 
• Related (the study treatment and AE were closely related in time and the AE may be 
explained by exposure to study product: e.g., known adverse effect or recurrence on re-
challenge). 
11.4. 
Recording Adverse Events 
When an AE occurs, it is the responsibility of the Investigator to review all documentation (e.g., 
medical progress notes, laboratory, and diagnostics reports) relative to the event.  The 
Investigator will then record all relevant information regarding an AE in the CRF.  
The Investigator will attempt to establish a diagnosis of the AE based on signs, symptoms, 
and/or other clinical information.  In such cases, the diagnosis should be documented as the 
AE/SAE and not the individual signs/symptoms. 
11.4.1. 
Eliciting Adverse Event Reports 
At each visit, subjects will be asked about AEs by means of a non-leading question, such as 
“how have you been since your last visit?” or “how has the treatment been?”  In this way, 
possibly more mild, but clinically important, side effects of the study device can be detected.  
SAEs will be reported promptly to KeraNetics as described in the following table once the 
Investigator determines that the event meets the protocol definition of a SAE. 
11.4.2. 
Assessment of Intensity 
The Investigator will make an assessment of intensity for each AE/SAE reported during the 
study.  The assessment will be based on the Investigator’s clinical judgment.  The intensity of 
each AE/SAE recorded in the CRF should be assigned to one of the following categories: 
• Mild:  An event that is easily tolerated by the subject, causing minimal discomfort 
and not interfering with everyday activities. 
• Moderate:  An event that is sufficiently discomforting to interfere with normal 
everyday activities. 
• Severe:  An event that prevents normal everyday activities. 
An AE that is assessed as severe should not be confused with a SAE.  Severity is a category 
utilized for rating the intensity of an event; both AEs and SAEs can be assessed as severe.   
11.5. 
Reporting Adverse Events 
An unexpected event is one that is not consistent with the subject’s past medical history and is 
not evident from previous clinical experience with the test product or reasonably anticipated 


 
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from information known about the test product.  Events that are deemed both serious and 
unexpected involve special handling and reporting requirements to the IRB and FDA. All SAEs 
will be followed until stabilization or improvement. 
11.5.1. 
SAE Reporting Procedures 
Once an Investigator becomes aware that a SAE has occurred in a study subject, she/he will 
report the information as thoroughly as possible with all available details of the event to 
KeraNetics within 24 hours. If the Investigator does not have all information regarding an SAE, 
he/she will not wait to receive additional information before notifying KeraNetics of the event.  
The information regarding the event will be updated when additional information is received. 
The Investigator will always provide an assessment of causality at the time of the initial event 
report as described in Section 11.3.1. An email is the preferred method to transmit this 
information regarding a SAE to the project contact for SAE receipt.  In rare circumstances and in 
the absence of email equipment, notification by telephone is acceptable, with a copy of the event 
details sent by overnight mail.  Initial notification via the telephone does not replace the need for 
the Investigator to complete the SAE report via email within 24 hours. 
11.5.1.1. Regulatory Reporting Requirements for SAEs 
KeraNetics has a legal responsibility to notify, as appropriate, both the local regulatory authority 
and other regulatory agencies about the safety of a product under clinical investigation.  Prompt 
notification of SAEs by the Investigator to the appropriate project contact for SAE receipt is 
essential so that legal obligations and ethical responsibilities towards the safety of other subjects 
are met. 
11.5.2. 
Reporting Safety Information to the IRB 
The Investigator, or responsible person according to local requirements, will comply with the 
applicable local regulatory requirements related to the reporting of SAEs to the Institutional 
Review Board (IRB) / Institutional Ethics Committee (IEC). 
11.5.3. 
Protocol Deviations Due to an Emergency or Adverse Event 
Any subject experiencing an emergency or adverse event requiring immediate medical attention 
will receive appropriate medical management by medical staff at the site and at other clinical 
sites as indicated.  These events will be reported to KeraNetics as soon as possible.  If the 
medical management results in departure from the study protocol, the Sponsor will be 
responsible for granting permission for the subject to continue in the trial if the subject is able to 
return to study protocol adherence in a timely fashion.  If the subject cannot return to the study 
protocol in a timely fashion, then the subject will be discontinued from the study. 
11.6. 
Follow-up of Adverse Events 
After the initial AE/SAE report, the Investigator is required to proactively follow each subject 
and provide further information to Sponsor on the subject’s condition. All AEs and SAEs 
documented at a previous visit/contact and designated as ongoing, will be reviewed at 
subsequent visits/contacts. 


 
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All AEs and SAEs will be followed until resolution, until the condition stabilizes, until the event 
is otherwise explained, or until the subject is lost to follow-up.  Once resolved, the appropriate 
CRF entries will be updated.   
12. 
STATISTICS 
12.1. 
Description of Statistical Methods 
This is an observational study only; no formal statistics will be performed.  
12.1.1. 
Baseline Data Summary 
Demographic data and subjects’ characteristics (e.g. vital signs) at screening will be listed and 
summarized using descriptive statistics.  Any deviations from inclusion/exclusion criteria will be 
listed. 
12.1.2. 
Responder Summary 
The total number of subjects with a positive skin reaction (i.e. wheal diameter > 3mm) will be 
determined for the subject device and predicate device for each evaluation time point.  The 
proportion of subjects who have a positive response to the subject device will be compared to the 
proportion of subjects who have a positive response to the predicate device.   
12.2. 
Sample Size 
A total of 20 subjects were deemed sufficient to assess the potential for a humoral response to 
KeraStat Cream compared to the predicate devices in support of establishing substantial 
equivalence.  The sample size for the study is not based on any statistical considerations.  
Approximately 22 subjects will be enrolled to assure completion of at least 20 subjects.  
12.3. 
Procedure for Accounting for Triplicate Data 
In the case that a triplicate re-administration is required, wheal diameter will be averaged for 
each test agent.  A subject will be considered to show a positive reaction to the subject device or 
predicate device when the average wheal diameter is greater than 3 mm.   
12.4. 
Analysis of Patients Withdrawing Prematurely from the Study 
All information for withdrawing subjects will be included in the analyses.  Subjects who 
withdraw prematurely from the study will have any completed assessments included in the data 
summary.  
13. 
DIRECT ACCESS TO SOURCE DATA/DOCUMENTS 
13.1. 
Study Monitoring 
In accordance with applicable regulations, ICH-GCP and procedures covering the study, a 
monitor will contact the site prior to the subject enrollment to review the protocol and data 


 
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collection procedures with site staff.  In addition, the monitor will periodically contact the site, 
including conducting on-site visits at an appropriate frequency to ensure data quality and to 
ensure the safety and rights of subjects are being protected.   
The Investigator agrees to allow the monitor direct access to all relevant documents and to 
allocate his/her time and the time of his/her staff to the monitor to discuss findings and any 
relevant issues. 
At study closure, monitors will also conduct all activities described in Section 16.3. 
13.2. 
Audits and Inspections 
To ensure compliance with Good Clinical Practices and all applicable regulatory requirements, 
quality assurance audits may occur during the study or after the study is complete.  Authorized 
representatives of KeraNetics, a regulatory authority, an IRB may visit the site to perform audits 
or inspections to 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, ICH-GCP, and any applicable regulatory requirements.  
If an audit or inspection occurs, the Investigator and institution agree to allow the 
auditor/inspector direct access to all relevant documents and to allocate his/her time and the time 
of his/her staff to the auditor/inspector to discuss findings and any relevant issues.  The 
Investigator should contact KeraNetics immediately if contacted by a regulatory agency about an 
inspection. 
13.3. 
Institutional Review Board (IRB) 
This study will be conducted in full compliance with the Institutional Review Board (IRB) 
regulations in 21 CFR 56 and applicable local regulatory guidance.  
IRB approval for the investigation must be obtained before the study is initiated.  Initial IRB 
approval, and all materials approved by the IRB for this study including the patient consent form 
and recruitment materials must be maintained by the Investigator and made available for 
inspection. 
The current study is considered a nonsignificant risk (NSR) device study according to FDA 
guidance and does not require an Investigational Device Exemption (IDE) in advance of study 
conduct.  NSR device studies must follow the abbreviated requirements presented in 21 CFR 
812.2(b) related to labeling, Institutional Review Board (IRB) approval, informed consent, 
monitoring, records, reports, and prohibition against promotion. 
14. 
QUALITY CONTROL AND QUALITY ASSURANCE 
To ensure compliance with Good Clinical Practices and all applicable regulatory requirements, 
KeraNetics (or representative of KeraNetics) may conduct a quality assurance audit.  Please see 
Section 13.2 and 16.5 for more details regarding the audit process at any time during the conduct 
of the study or after study completion. 


 
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14.1. 
Regulatory Authority Approval 
Not applicable. 
14.2. 
Protocol Modifications 
The initial protocol as well as all protocol amendments must be signed and dated by the 
Investigator and approved by the IRB prior to implementation of the original protocol and any 
amendment.  The Principal Investigator must submit all protocol modifications to the IRB, as 
applicable for specific Investigators, or applicable local regulatory authority.   
Departures from the protocol will be determined as allowable on a case-by-case basis or in event 
of an emergency involving subject safety.  The Investigator or other physician in attendance 
must contact KeraNetics as soon as possible to discuss the circumstances of the emergency.  
KeraNetics, in concurrence with the Investigator, will decide whether the subject should continue 
to participate in the study.  All protocol deviations and the reason for such deviations must be 
noted on the source document and in the CRF, and reported to the IRB as appropriate. 
15. 
ETHICS  
15.1. 
Ethics Review 
The Investigator is responsible for ensuring that this protocol, the site’s informed consent form 
(ICF), and any other information that will be presented to potential subjects (e.g., advertisements 
or information that supports or supplements the informed consent) are reviewed and approved by 
the appropriate IRB.  The Investigator agrees to allow the IRB direct access to all relevant 
documents.  The IRB must be constituted in accordance with all applicable regulatory 
requirements.  KeraNetics will provide the Investigator with relevant document(s)/data that are 
needed for IRB review and approval of the study.  The IRB must approve the study and ICF 
before study device(s) and other study material can be supplied to the site. 
If the protocol, the ICF, or any other information that the IRB has approved for presentation to 
potential subjects is amended during the study, the Investigator is responsible for ensuring the 
IRB reviews and approves, where applicable, these amended documents.  The Investigator must 
follow all applicable regulatory requirements pertaining to the use of an amended ICF including 
obtaining IRB approval of the amended form before new subjects consent to take part in the 
study using this version of the form.  Copies of the IRB approval of the amended ICF/other 
information and the approved amended ICF/other information must be maintained in the 
regulatory files at the site. 
15.2. 
Ethical Conduct of the Study 
This study will be conducted in accordance with ICH-GCP guidelines and all applicable 
regulatory requirements, including, where applicable, the Declaration of Helsinki. 


 
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15.3. 
Written Informed Consent 
This study will be conducted in full compliance with the informed consent regulations in 21 CFR 
50.  The consent form must be reviewed and approved by the Sponsor prior to submission to the 
IRB.  The consent form must be approved by the IRB prior to initiation of the study.   
No Investigator may involve a human being as a subject in research unless the Investigator has 
obtained the legally effective informed consent of the subject or the subject's legally authorized 
representative.  An Investigator may seek such consent only under circumstances that provide the 
prospective subject or the representative sufficient opportunity to consider whether to participate 
and that minimize the possibility of coercion or undue influence.  The information given to the 
subject or the representative must be in a language understandable to the subject or the 
representative.  No informed consent, whether oral or written, may include any exculpatory 
language through which the subject or the representative is made to waive or appear to waive any 
of the subject's legal rights, or releases or appears to release the Investigator, the institution, the 
Sponsor, or its agents from liability for negligence. 
An IRB-approved consent form should inform each prospective subject or the legally authorized 
representative of each prospective subject of the purpose and the nature of the study, it’s possible 
hazards and benefits, and the subject's right to withdraw from the study at any time without 
prejudice to further treatment.  Exemptions to the requirement for informed consent in the United 
States are described in 21 CFR 50.23. 
The Investigator(s) at each center will ensure that the patient is given full and adequate oral and 
written information about the nature, purpose, possible risk and benefit of the study.  Patients 
must also be notified that they are free to discontinue from the study at any time.  The patient 
should be given the opportunity to ask questions and allowed time to consider the information 
provided. 
The Investigator is responsible for obtaining written consent (signed and dated ICF) from 
potential subjects prior to performing any tests or assessments required by the protocol.  A copy 
of the signed consent document will be given to the subject and the original retained by the 
Investigator. 
16. 
DATA HANDLING AND RECORDKEEPING 
16.1. 
Case Report Form Completion and Source Documentation 
The Investigator is required to prepare and maintain adequate and accurate case histories 
designed to record all observations and other data pertinent to the study for each study 
participant.  Subject data are collected by the Investigator or designee using source documents 
that are transferred to a CRF, defined by KeraNetics. Subject data necessary for analysis and 
reporting will be entered onto the source documents and then provided to the Sponsor as an 
electronic compilation of raw data from source documents via secure file exchange. 
All information entered in the CRFs must be consistent with the subject's source documentation 
(i.e., medical records).  The Investigator is responsible for the accuracy of the data transcribed 
from all source documentation. CRF entries should be made within a reasonable timeframe from 


 
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the time of a subject’s visit.  A monitor representing the Sponsor will verify the CRF 
documentation for each subject against the source documents at the study center.  Instances of 
missing or uninterpretable data will be brought to the attention of the Investigator and/or Sponsor 
for resolution.   
16.2. 
Data Management 
Clinical data management will be performed in accordance with applicable study standards and 
data cleaning procedures.  Database lock will occur when data management quality control 
procedures are completed.   
16.3. 
Study Site Close-Out 
Upon completion of the study, the monitor may conduct the following activities in conjunction 
with the Investigator or site staff, as appropriate: 
1. Resolve data queries. 
2. Accountability, reconciliation, and return of unused study device(s). 
3. Review of final site study records for completeness. 
4. Return all study-specific equipment to KeraNetics. 
16.4. 
Retention of Study Documents and Records 
Following closure of the study, the Investigator must maintain all site study records in a safe and 
secure location.  All study-related data will be retained by and are the sole property of 
KeraNetics.  The Investigator will retain a copy of all source documents and CRF data (i.e., 
DVD-ROM containing pdf files of data) for the subjects enrolled at the site.  The records must be 
maintained to allow easy and timely retrieval, when needed (e.g., audit or inspection).  Where 
permitted by local laws/regulations or institutional policy, some or all of these records can be 
maintained in a format other than hard copy (e.g., microfiche, scanned, electronic); however, 
caution needs to be exercised before such action is taken.  The Investigator must assure that all 
reproductions are legible and are a true and accurate copy of the original and meet accessibility 
and retrieval standards, including re-generating a hard copy, if required.  Furthermore, the 
Investigator must ensure there is an acceptable back-up of these reproductions and that an 
acceptable quality control process exists for making these reproductions. 
KeraNetics will inform the Investigator of the time period for retaining these records to comply 
with all applicable regulatory requirements.  The minimum retention time will meet the strictest 
standard applicable to that site for the study, as dictated by any institutional requirements or local 
laws or regulations, or KeraNetics standards/procedures; otherwise, the retention period will 
default to 5 years. 
The Investigator must notify KeraNetics of any changes in the archival arrangements, including, 
but not limited to, the following: archival at an off-site facility, transfer of ownership of the 
records in the event the Investigator leaves the site. 


 
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16.5. 
Inspection of Records 
KeraNetics (or a representative of KeraNetics) will be allowed to conduct site visits to the 
investigation facilities for the purpose of monitoring any aspect of the study.  The Investigator 
agrees to allow the monitor to inspect the drug storage area, study device stocks, study material 
accountability records, subject charts and study source documents, and other records relative to 
study conduct. 
17. 
INVENTION AND PUBLICATION POLICY 
In the event of a conflict between the provisions of this section and a written contract regarding 
the conduct of the study between Sponsor (or a contract research organization) and the site, the 
Investigator or any person assisting Investigator with the Study, the terms of that contract shall 
control. 
17.1. 
Ownership 
All information provided by or on behalf of Sponsor and all data and information generated by 
the site, the Investigator or any person assisting Investigator with the study as part of or in 
connection with the study (other than a subject’s medical records), is the sole and exclusive 
property of Sponsor.  All rights, title, and interests in and to any inventions, discoveries or know-
how made, conceived, learned or first reduced to practice by the site, Investigator or any person 
assisting Investigator with the study during the course of, in relation to, or as a result of the study 
(and any intellectual property rights related thereto) are the sole and exclusive property of the 
Sponsor, and are hereby assigned to Sponsor. 
17.2. 
Confidentiality 
All information provided by KeraNetics and all data and information generated by the site as part 
of or in relation to the study (other than a subject’s medical records) will be kept confidential by 
the Investigator, the site, and any person assisting Investigator with the study.  This information 
and data shall not be used by the site, Investigator, or any person assisting Investigator with the 
study for any purpose other than conducting the study.  These restrictions do not apply to:  1) 
information which becomes publicly available through no fault of the site, Investigator or any 
person assisting Investigator with the study; 2) information which it is necessary to disclose in 
confidence to an IRB solely for the evaluation of the study;  3) information which it is necessary 
to disclose in order to provide appropriate medical care to a study subject; or 4) study results 
which are permitted to be published as described in the next section.  
17.3. 
Publication 
If the study is a multi-center study, the first publication or disclosure of study results shall 
include data from all sites.    
Investigator may publish the results of the study only for noncommercial, educational or 
academic purposes provided that: 1) said publication is made after the multi-center publication; 
and 2) prior to making the publication, or otherwise disclosing the study results, Investigator 


 
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provides Sponsor with a copy of the proposed publication and allows Sponsor a reasonable 
period to review.  Proposed publications shall not include KeraNetics confidential information 
(other than the study results) or personal data with respect to any subject (such as name or 
initials) and if KeraNetics identifies any such KeraNetics confidential information in a proposed 
publication, it shall be removed. 
At the request of KeraNetics, the submission, publication or other disclosure of a proposed 
publication will be delayed a sufficient time to allow KeraNetics to seek patent or similar 
protection of any inventions, know-how or other intellectual or industrial property rights 
contained in such proposed publication. 
18. 
LIST OF REFERENCES  
1.  
Beam JW. Management of superficial to partial-thickness wounds. J Athl Train. 
2007;42(3):422-424. 
2.  
http://www.ameriburn.org/resources_factsheet.php. 
3.  
Bragulla HH, Homberger DG. Structure and functions of keratin proteins in simple, 
stratified, keratinized and cornified epithelia. In: Journal of Anatomy. Vol 214. ; 
2009:516-559. doi:10.1111/j.1469-7580.2009.01066.x. 
4.  
Yu Z, Wildermoth JE, Wallace OAM, et al. Annotation of sheep keratin intermediate 
filament genes and their patterns of expression. Exp Dermatol. 2011;20(7):582-588. 
doi:10.1111/j.1600-0625.2011.01274.x. 
5.  
M.P. T, R.A. S, C. H, et al. Keratin-based wound care products for treatment of resistant 
vascular wounds. J Clin Aesthet Dermatol. 2012;5(12):31-35. 
http://www.embase.com/search/results?subaction=viewrecord&from=export&id=L36619
1166\nhttp://jcadonline.epubxp.com/title/9606. 
6.  
Bousquet J, Heinzerling L, Bachert C, et al. Practical guide to skin prick tests in allergy to 
aeroallergens. Allergy Eur J Allergy Clin Immunol. 2012;67(1):18-24. doi:10.1111/j.1398-
9995.2011.02728.x. 
7.  
Konstantinou GN, Bousquet PJ, Zuberbier T, Papadopoulos NG. The longest wheal 
diameter is the optimal measurement for the evaluation of skin prick tests. Int Arch 
Allergy Immunol. 2010;151(4):343-345. doi:10.1159/000250443.