Assessment of Wound Closure Comparing Synthetic Hybrid-Scale Fiber Matrix With Standard of Care in Treating Diabetic Foot Ulcer
Phase: NA
Conditions: Diabetic Foot Ulcer
Sponsor: Acera Surgical, Inc.

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Page 1 of 39 
 
 
Assessment of Wound Closure Comparing Synthetic 
Hybrid-Scale Fiber Matrix with Standard of Care in 
Treating Diabetic Foot Ulcer 
 
 
 
 
                                         Protocol Number: 21-RES-002 
Revision: 02 
Approval Date: 07NOV2022  
 
 
 
Acera Surgical, Inc. 
10880 Baur Blvd. 
Saint Louis, MO 63132 
844-879-2237 
 
 
 
 
 
This document contains confidential information belonging to Acera Surgical. Except as 
may be otherwise agreed to in writing, by accepting or reviewing these materials, you agree 
to hold such information in confidence and not to disclose it to others (except where 
required by applicable law), nor to use it for unauthorized purposes. In the event of actual or 
suspected breach of this obligation, Acera Surgical should be promptly notified. 
 
 

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PROTOCOL APPROVAL SIGNATURE PAGE 
 
Assessment of Wound Closure Comparing Synthetic Hybrid-
Scale Fiber Matrix with Standard of Care in Treating 
Diabetic Foot Ulcer 
Protocol Number:  21-RES-002 
Revision: 02 
 
 __________________________________________________________________ 
Matthew MacEwan, PhD  
 
 
 
 
 
Date 
Chief Science Officer 
Acera Surgical, Inc. 
 
 
__________________________________________________________________ 
Pamela McKeown  
       
 
 
 
 
 
Date                      
Vice President, Health Policy and Reimbursement 
Acera Surgical, Inc.                                                                                                                                        
 
__________________________________________________________________ 
Khalid Husain, DPM, FACFAS, FACCWS   
 
 
Date  
Principal Investigator      
Midwest Foot & Ankle Clinics                                                                                             
 
 
 

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PRINCIPAL INVESTIGATOR SIGNATURE PAGE 
 
Assessment of Wound Closure Comparing Synthetic Hybrid-
Scale Fiber Matrix with Standard of Care in Treating 
Diabetic Foot Ulcer 
Protocol Number:  21-RES-002 
Revision: 02 
 
The trial will be conducted in accordance with the ethical principles that have their 
origin in the Declaration of Helsinki and in compliance with this protocol, Good 
Clinical Practice (GCP) guidelines, and applicable regulatory requirements and 
laws. 
 
 
I hereby confirm that I approve of this Clinical Study Protocol and agree to comply 
with its terms as laid out in this document. I agree to ensure that all staff members 
involved in the conduct of this study are informed about their obligations in 
meeting the above commitments. 
 
 
 
_______________________________________________________________ 
 
Printed Name                                     Signature                                             Date 
 
 
 
 
 
 
 
 
 
 
 
 

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TABLE OF CONTENTS 
1. PROTOCOL SUMMARY .............................................................................. 6 
2. INTRODUCTION & PURPOSE .................................................................... 7 
2.1. Background and Purpose ........................................................................... 7 
2.2. Purpose ...................................................................................................... 9 
2.3. Intended Use/Indications ........................................................................... 9 
2.4. Standard of Care ...................................................................................... 10 
3. STUDY DESIGN.......................................................................................... 10 
4. PATIENT SELECTION ............................................................................... 12 
4.1. Inclusion Criteria ..................................................................................... 12 
4.2. Exclusion Criteria .................................................................................... 13 
5. STUDY CONDUCT ..................................................................................... 14 
5.1. Schedule of Events .................................................................................. 14 
5.2. Screening ................................................................................................. 14 
5.3. Informed consent ..................................................................................... 14 
5.4. Run-in Period ........................................................................................... 15 
5.4.1. First Visit of Run-In Period (14 to 17 days before randomization) ... 15 
5.4.2. Second Visit of Run-In Period (7 days ± 3 days After First Visit) .... 16 
5.5. Point of Enrollment ................................................................................. 16 
5.6. Randomization ......................................................................................... 16 
5.7. Blinding ................................................................................................... 17 
5.8. Enrollment Procedures ............................................................................ 17 
5.9. Device Application / Follow-up Care Procedures ................................... 17 
5.10. Standard of Care .................................................................................... 18 
5.11. Post-Application Procedures ................................................................. 19 
5.12. Follow-Up Procedures ........................................................................... 20 
5.13. Study Exits ............................................................................................. 20 
5.13.1. Study Participation Exit Points ........................................................ 20 
5.13.2. Patient Withdrawal ........................................................................... 20 
5.13.3. Patient Lost To Follow-Up............................................................... 21 
5.13.4. Patient Death .................................................................................... 21 
5.13.5. Sponsor Discontinues Study ............................................................ 21 
6. ADVERSE EVENT ...................................................................................... 21 
6.1. Principal Investigator Responsibilities .................................................... 21 
6.2. Adverse Event Definitions ...................................................................... 22 
6.3. Adverse Event Assessment ...................................................................... 23 
6.4. Adverse Event Reporting ........................................................................ 23 
7. STATISTICAL CONSIDERATION ............................................................ 24 

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7.1. Hypotheses to be Tested .......................................................................... 24 
7.1.1. Primary Endpoints: ............................................................................ 24 
7.2. Analysis Populations ............................................................................... 24 
7.3. Sample Size Calculation .......................................................................... 25 
7.4. Interim and Final Analyses ...................................................................... 25 
7.5. Statistical Analysis .................................................................................. 27 
7.5.1. Demographic and Baseline Characteristics ........................................ 27 
7.5.2. Medical History .................................................................................. 27 
7.5.3. Procedural Information ...................................................................... 28 
7.5.4. Primary Endpoints .............................................................................. 28 
7.6. Study Outcome ........................................................................................ 28 
7.6.1. Primary Endpoints .............................................................................. 28 
7.6.2. Secondary Endpoints .......................................................................... 28 
7.6.3. Tertiary Endpoints .............................................................................. 29 
7.7. Adverse Events ........................................................................................ 29 
7.7.1. All Adverse Events ............................................................................ 29 
7.7.2. Serious Adverse Events...................................................................... 30 
7.7.3. Adverse Events of Interest ................................................................. 30 
7.8. Strategies to Address Missing Data ......................................................... 30 
8. DATA HANDLING AND RECORD KEEPING ........................................ 31 
8.1. Case Report Forms (CRFs) ..................................................................... 31 
9. ETHICS......................................................................................................... 31 
9.1. Ethical Conduct of the Clinical Study ..................................................... 31 
9.2. Institutional Review Board (IRB) ........................................................... 32 
9.3. Confidentiality ......................................................................................... 32 
10. SPONSOR DISCONTINUATION CRITERIA ......................................... 32 
10.1. Termination of the study by the Sponsor .............................................. 33 
10.2. Termination of Site by the Sponsor ....................................................... 33 
10.3. Termination by the Investigator ............................................................ 33 
11. PUBLICATIONS POLICY ........................................................................ 33 
12. SUMMARY OF PROTOCOL REVISIONS .............................................. 34 
13. REFERENCES ........................................................................................... 34 
14. APPENDICES ............................................................................................ 36 
  

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1.  PROTOCOL SUMMARY 
Title 
Assessment of Wound Closure Comparing Synthetic Hybrid-Scale Fiber 
Matrix with Standard of Care in Treating Diabetic Foot Ulcer  
Protocol Number 
21-RES-002; Revision: 002 
Protocol  
Approval Date 
07NOV2022 
Study Sponsor 
Acera Surgical, Inc. 
Indications for 
Use 
Restrata® is intended for use in the management of wounds, including:  
Partial and full thickness wounds, pressure sores / ulcers, venous ulcers, 
diabetic ulcers, chronic vascular ulcers, tunneled / undermined wounds, 
surgical wounds (e.g., donor site / grafts, postlaser surgery, post-Mohs 
surgery, podiatric wounds, dehisced wounds), trauma wounds (e.g., 
abrasions, lacerations, partial thickness burns, skin tears), draining wounds. 
Study Product 
Synthetic Hybrid-Scale Fiber Matrix (Restrata®) 
Study Purpose 
Comparatively assess wound closure in diabetic foot ulcers treated 
with synthetic hybrid-scale fiber matrix or standard of care in a 
randomized clinical trial. 
Enrollment Size 
48 subjects (24 subjects in the experimental arm and 24 subjects in the 
control arm) 
Study Design 
Prospective, randomized, controlled, single-blind clinical trial 
Primary Outcome 
Measure 
• Diabetic Foot Ulcers: Complete re-epithelialization of wounds within 
12 weeks after the initial application of the study product plus 
confirmation of no drainage or need for additional dressing 2 weeks 
after complete re-epithelialization 
Secondary 
Outcome Measure 
1. Decrease in wound area 
2. Time from initial application of study product to complete re-
epithelialization of wound 
3. Total number of product applications 
Tertiary Outcome 
Measure  
1. Quality of Life - SF-36 Questionnaire 
2. Incidence of adverse events 
3. Cost effectiveness / economic model (amount of product usage, length 
of treatment) 
Assessment 
Timepoints 
➢ Run-In Period to verify enrollment criteria: 2 weeks before initial 
application of study product 
➢ Product Application: Weekly application (or as needed based on the 
clinician discretion and ongoing wound assessment) for either 12 weeks or 
until complete reepithelialization (whichever occurs first) 

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➢ Wound assessment, measurement, and AEs: Day of initial product 
application and weekly for either 12 weeks or until complete re-
epithelialization (whichever occurs first) 
➢ Quality of Life and Pain Assessments: Day of initial product 
application and at either complete reepithelialization or 12 weeks 
(whichever occurs first) 
➢ For patients with complete re-epithelialization: 
o Clinic visit two weeks after complete re-epithelialization to 
verify wound closure, drainage, and need for additional dressing 
 
2. INTRODUCTION & PURPOSE 
2.1. Background and Purpose 
Diabetes and peripheral vascular disease are both growing healthcare problems that 
can lead to chronic wounds by compromising skin integrity and impairing the wound 
healing process1. Chronic wounds affect more than 6.5 million patients annually in 
the United States2. In particular, many diabetic foot ulcers (DFUs) fail to heal with 
standard options such as debridement, dressings, and infection control1. Skin 
substitutes can regenerate tissue and replace lost skin for wounds that are otherwise 
difficult to treat2. 
The process of wound healing requires a coordinated effort of cellular recruitment 
and tissue growth. Regenerative matrix materials have been used as a skin substitute 
to promote this coordination and provide immediate wound coverage to minimize 
the risks associated with infection and fluid loss3. An ideal material for these 
purposes would serve as a healing scaffold, limit infection risk, minimize 
inflammation, be readily available for use, and be conformable to diverse wound 
surfaces. 
To support the infiltration of fibroblasts, the deposition of new collagen, and 
reepithelialization of the wound surface, the wound matrix material should persist 
in the wound for several weeks4. The timing of wound matrix degradation is 
therefore critical, as the wound matrix should resist degradation until sufficient new 
tissue growth has occurred. The susceptibility of biologic wound matrix materials to 
enzymatic degradation leads to a resorption rate that is poorly controlled, risking the 
premature degradation of the wound matrix prior to sufficient wound healing. 
There remains a need for materials that minimize inflammation and promote 
complete wound healing. Electrospun fibrous scaffolds may meet this need by 

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mimicking the structure of native extracellular environment while enabling resident 
cells to perform their roles in the healing cascade5. 
In 2018, a retrospective study was completed to evaluate clinical efficacy and utility 
of Restrata, a synthetic skin substitute2. The study examined 82 chronic wounds 
including 34 DFUs, 34 VLUs, and 14 other chronic wounds (pressure ulcers, 
traumatic and postsurgical wounds, nonvenous vascular wounds and necrotic 
wounds). Synthetic hybrid-scale fiber matrix was applied weekly, or as deemed 
appropriate for up to 12 weeks. Overall, treated wounds demonstrated progressive 
and sustained wound area reduction over the course of treatment, with 85 percent 
achieving complete closure at 12 weeks. 
Based on these clinical findings a prospective, non-randomized, single-arm, single-
blind study was conducted at 5 centers across the United States as a pilot for an 
expanded randomized controlled trial. In the study wounds were prepared using 
standard methods or debridement, and synthetic hybrid-scale fiber matrix was then 
applied to the wound so that it completely contacted the entire surface of the wound 
bed. A non-adherent primary wound dressing was then applied, followed by 
appropriate secondary dressing to manage the wound exudate and moisture. Post-
application, wounds were examined weekly for signs of infection, wound 
progression, and tissue healing for up to 12 weeks, or until complete closure, which 
was confirmed 2 weeks thereafter. The wound area was measured, wound 
appearance was photographed, and wound closure was documented if present. 
Synthetic hybrid-scale fiber matrix was then re-applied weekly or as deemed 
appropriate. 
At the end of the 12-week treatment period, complete wound closure occurred in 
75.0% (18/24) of patients who received synthetic hybrid-scale fiber matrix. The 
average wound area reduction over 12 weeks was 96%, and the average time to 
complete wound closure was 6.4 weeks. A significant increase in epithelialization 
was observed from the initial to the final assessment (p<0.0001, Wilcoxon matched-
pairs signed rank test), with nearly complete covering seen at final assessment. This 
was paralleled by a significant decrease in the amount of wound exudate (p<0.0001) 
to a nearly dry wound at the final assessment, and complete disappearance of 
necrotic tissue over time (p=0.0001). An average of 4.3 scaffolds were used per 
patient over the treatment period. Fixation was used to hold all scaffolds in place, 
with the most popular fixation technique being the use of Steri-Strips. The decision 
of the frequency of re-application was solely at the discretion of the clinician who 
was treating the wounds, and results found that half of the patients received 
reapplication of the nanofiber matrix on a weekly basis, whereas the other half of 
the patients had less frequent re-application rates. Neither fixation technique nor 
application frequency were found to have a statistically significant effect on 

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complete wound closure (p=0.41, Chi-square test and p=0.64, Fisher’s exact test, 
respectively). In total, the clinical results suggest that synthetic hybrid-scale fiber 
matrix offers a new and unique alternative in the treatment of chronic DFUs and 
assists in properly powering an expanded multi-center randomized controlled 
clinical trial. 
2.2. Purpose 
The purpose of the following prospective, randomized, controlled clinical trial is to 
compare synthetic hybrid-scale fiber matrix (Restrata®, Acera Surgical, Inc.) with 
standard of care in treating diabetic foot ulcers in human subjects. 
This study is being conducted to provide information on healing success with a new 
category of synthetic skin substitutes recently created by the Centers for Medicare 
and Medicaid Services (CMS). The study will demonstrate utilization of synthetic 
hybrid-scale fiber matrix in generating wound healing outcomes; including time to 
wound epithelialization, decrease in wound size, and total number of study product 
applications prior to healing. This data is valuable to the payor community with  
coverage decisions.  
2.3. Intended Use/Indications 
 Restrata® is a sterile, single use device intended for use in local management of 
wounds. Restrata® is a soft, white, conformable, non-friable, absorbable matrix that 
provides a moist environment for the body’s natural healing process to occur. 
Restrata® is made from synthetic biocompatible materials and was designed to 
include a fibrous structure with high porosity, similar to native extracellular matrix. 
Restrata® is a porous matrix with a defined rate of resorption that provides a scaffold 
for cellular infiltration and vascularization before completely degrading via 
hydrolysis. The device permits the ingress of cells and soft tissue formation in the 
defect space / wound bed. The device does not contain any human or animal 
materials or tissues. 
Restrata® is terminally sterilized, in a single use double peel package in a variety of 
sizes. Contents of the package are guaranteed sterile and non-pyrogenic unless the 
package has been opened or damaged.  
Restrata® is intended for use in the management of wounds, including:  Partial and 
full thickness wounds, pressure sores / ulcers, venous ulcers, diabetic ulcers, chronic 
vascular ulcers, tunneled / undermined wounds, surgical wounds (e.g., donor site / 
grafts, postlaser surgery, post-Mohs surgery, podiatric wounds, dehisced wounds), 
trauma wounds (e.g., abrasions, lacerations, partial thickness burns, skin tears), 
draining wounds.  Utilization of Restrata® in the treatment of diabetic foot ulcers, 

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as proposed in the present study, is therefore considered “on label” and is not 
considered experimental. 
The benefits and risks of participation in this study will be described in the informed 
consent form.  
2.4. Standard of Care 
The standard of care for established chronic wounds incorporates common 
principles, including: 
 
 Removing necrotic tissue through debridement. 
 Maintaining moisture balance by selecting the proper wound dressing to 
control exudate. 
 Taking measures to prevent or treat wound infections. 
 Correcting ischemia in the wound area. 
 Applying offloading device in the case of diabetic foot ulcers) 
 
Subjects randomized to the Standard of Care (control) arm will have their wounds 
debrided weekly. An appropriate dressing (foam or alginate dressing) will then be 
applied to maintain wound moisture balance in the wound, and changed daily. An 
appropriate offloading device (CAM boots or surgical shoes) will also be utilized 
depending on the wound location, condition and patient’s health status. 
 
3. STUDY DESIGN  
Condition: Diabetic Foot Ulcer (DFU) 
 
Aim: Comparatively assess wound closure in diabetic foot ulcers treated with 
synthetic hybrid-scale fiber matrix or standard of care in a randomized, controlled 
clinical trial.  
Number of Patients: 48 subjects (24 subjects in the experimental arm and 24 
subjects in the control arm) 
Number of Sites:  2 
Study Type: 
Interventional  
Study Design: 
Allocation: Randomized (1:1 ratio) 
Endpoint Classification:  Efficacy 
Intervention Model: Direct assignment 

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Masking: Single Blind (Subject) 
Primary Purpose: Treatment 
Control Group:
Treatment with Standard of Care (weekly) 
 
Test Group:
Treatment with Synthetic Hybrid-Scale Fiber Matrix (weekly or 
as needed based on the clinician discretion and ongoing wound 
assessment) 
 
Primary Outcome Measures:  
 
• 
Complete re-epithelialization of wound as assessed by the evaluator 
within 12 weeks after the initial application of the study product plus 
confirmation of no drainage or need for additional dressing 2 weeks 
after complete re-epithelialization. 
 
Secondary Outcome Measures:  
 
• 
Decrease in Wound Area From Initial Application 
Wound area measurements will be made via acetate tracing every week 
for 12 weeks or until complete reepithelialization, whichever occurs 
first. 
 
• 
Time to Complete Re-epithelialization 
The number of weeks from initial application of study product until 
complete reepithelialization is first identified. 
 
• 
Number of Product Applications 
The number of study product applications including the initial 
application until 12 weeks for DFU patients or until complete 
reepithelialization, whichever occurs first. 
 
Tertiary Outcome Measures: 
 
• 
Quality of Life (SF-36) 
Day of initial application and at either 12 weeks or at complete re-
epithelialization (whichever occurs first). 

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• 
Incidence of adverse events 
 
• 
Cost effectiveness / Economic model (amount of product usage, length 
of treatment) 
The following information will be provided for each subject: 
 
• 
CPT Codes 
• 
HCPCS Codes 
• 
ICD-10 codes 
• 
DRGs (if applicable) 
• 
Dates of Service/Range of service 
• 
Place of Service  
• 
Bill type (131, etc.) 
 
 
4. PATIENT SELECTION 
4.1. Inclusion Criteria 
1. Patient is at least 18 years old  
2. Patient is willing and capable of complying with all protocol 
requirements 
3. Patient or legally authorized representative (LAR) is willing to provide 
written informed consent prior to or at the beginning of the run-in period 
4. Patient has Type 1 or Type 2 diabetes (criteria for the diagnosis of 
diabetes mellitus per American Diabetes Association) 
5. Ulcer must be located at least in part on the foot or ankle 
6. Ulcer must be present for a minimum of 28 days prior to randomization 
and initial application of study product 
7. Wound size must be  ≤30 cm2 on the day of randomization and initial 
application of the study product, after initial debridement 
8. Patient has adequate circulation to the affected extremity, as 
demonstrated by at least ONE of the following within 60 days prior to 
enrollment/randomization: 
a. Dorsum transcutaneous oxygen test (TcPO2) of study leg with 
results ≥40mmHg, OR 
b. Ankle-Brachial Index (ABI) of study leg with results of ≥ 0.7OR 

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c. Toe-Brachial Index (TBI) of study extremity with results of > 50 
mmHg  
 
4.2.  Exclusion Criteria 
1. Patient has been previously enrolled into this study, or is currently 
participating in another drug or device study that has not reached its 
primary endpoint 
2. Patient is pregnant, breast feeding or planning to become pregnant 
3. Patient has a known allergy to resorbable suture materials, e.g. 
Polyglactin 910 (PGLA), Polydioxanone (PDS) 
4. Patient has a life expectancy less than six months as assessed by the 
investigator 
5. Patient has received skin substitutes during the run-in period or within 
14 days prior to beginning of run-in period 
6. Patient has an additional wound within 3 cm of the study wound 
7. Hgb A1c > 12% within 3 months prior to randomization in patients 
with a known history of diabetes  
8. Patient not in reasonable metabolic control in the judgment of the 
investigator 
9. Patient with a known history of poor compliance with medical 
treatments 
10. Patient currently undergoing cancer treatment 
11. Patient has been diagnosed with at least one of the following 
autoimmune connective tissue diseases: lupus, vasculitis, sickle cell, or 
uncontrolled rheumatoid arthritis 
12. Patient is taking parenteral corticosteroids or any cytotoxic agents for 7 
consecutive days during the run-in period or up to 30 days before the 
run-in period. Chronic oral steroid use is not excluded if dose is < 10 
mg per day for prednisone. 
13. Active infection, undrained abscess, or critical colonization of the 
wound with bacteria in the judgment of the investigator 
14. Osteomyelitis or exposed bone, probes to bone or joint capsule on 
investigator’s exam or radiographic evidence 
15. Patient unwilling to or unable to safely utilize appropriate offloading 
device to unweight wound 

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16. Study ulcer experiences spontaneous closure over the 2-week run in 
period 
 
5. STUDY CONDUCT 
5.1. Schedule of Events 
The schedule of events for this study is outlined in Appendix A.       
5.2. Screening 
A patient screening log will be maintained. For patients who do not meet eligibility 
criteria, the reason(s) for exclusion from the study will be documented.  
Patients will undergo the benefit insurance verification process via the third-party 
Reimbursement Support Hotline prior to or during the run-in period. Product 
Reimbursement will be confirmed for the synthetic hybrid-scale fiber matrix and 
related services and procedures incurred during the study period. 
5.3. Informed consent  
Prior to the start of the 2-week run-in period and the completion of any non-
standard of care study activities, written informed consent shall be obtained from 
the patient or the patient’s legally authorized representative (LAR). The 
investigator (or designee) must ensure that each patient (or LAR) is fully informed 
about the nature of the study, study objectives, study products, study procedures, 
and possible risks and benefits associated with participation in this study. 
Information shall be provided to the patient (or LAR) in a language and level of 
complexity so that he/she understands. The patient (or LAR) will have adequate 
time to consider participation in the study and have the opportunity to ask 
questions. The patient (or LAR) will sign and date the informed consent form, and 
he/she shall be provided a signed copy of the form. The investigator (or designee) 
will retain each patient’s original signed informed consent form. 
If significant new information is obtained after a patient is enrolled, the patient will 
be informed about the new information if the patient has not exited the study. Any 
discussions with the patient about new information should be documented. Patients 
will sign a new informed consent form at the discretion of the investigator and/or 
the IRB/EC. 
The initial informed consent form and any revisions made during the course of the 
study must be approved by both the IRB/EC and Acera Surgical, Inc. before use. 

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5.4. Run-in Period 
A 2-week run-in period will be required prior to enrollment/randomization and 
treatment in order to complete screening assessments and confirm that the wound 
has spontaneously closed. Written informed consent must be obtained prior to or at 
the beginning of the run-in period. 
5.4.1. First Visit of Run-In Period (14 to 17 days before randomization) 
An in-person visit will be completed at the beginning of the 2-week run-in 
period, and the following will be completed: 
• 
Written informed consent will be obtained 
• 
Assessment of inclusion/exclusion criteria 
• 
Collection of demographics and medical history information 
• 
Assessment of HbA1c in patients with known history of diabetes if 
it was not completed within the previous 73 days 
• 
If vascularization in the study leg was not assessed within the 
previous 42 days, then at least ONE of the following shall be 
completed: 
o Ankle-brachial index (ABI) of study leg 
o Toe-brachial index (TBI) of study extremity 
o TcPO2 of study leg 
 
• 
Assessment of ulcer size  
• 
Assessment of wound for signs of infection, wound progression, 
and tissue healing. Gross observation will be utilized to determine 
the need for change in dressing type or dressing 
replacement/change. 
NOTE: Informed consent must be obtained prior to the above 
assessments if they are not considered standard of care at this visit. 
If the patient does not continue to meet all inclusion/exclusion criteria 
by the end of the visit, then they will be considered a screen failure and 
should not proceed with additional visits/assessments. 

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5.4.2. Second Visit of Run-In Period (7 days ± 3 days After First Visit) 
An in-person visit will be completed 7 days after the first run-in visit (± 
3 days), and the following will be completed: 
• 
Assessment of ulcer size  
• 
Assessment of wound through gross observation and analysis for signs 
of infection, wound progression, and tissue healing. Gross observation 
will be utilized to determine the necessity of standard dressing change. 
• 
Continued assessment of inclusion/exclusion criteria. 
If the patient does not continue to meet all inclusion/exclusion criteria, 
then they will be considered a screen failure and should not proceed 
with additional visits/assessments. 
5.5. Point of Enrollment 
Patients will be considered enrolled after ALL of the following requirements are 
met: 
• Written informed consent is provided 
• The patient meets all inclusion criteria  
• The patient meets no exclusion criteria 
• The patient has completed the 2-week run-in period without 
spontaneous closure 
• The patient is randomized 
 
5.6. Randomization 
The randomization process will be finalized prior to enrollment of the first study 
patient. Once the patient meets all enrollment criteria and has completed the 2-week 
run-in period, the patient will be randomized. Patients will be randomized to receive 
either synthetic hybrid-scale fiber matrix (treatment group) or standard of care 
treatment (control group). Appendix B presents the randomization plan. 
Randomization will be stratified by wound size: 
Patients will fall into two groups (< 12.5 cm2) and (≥ 12.5 cm2 and ≤ 30 
cm2). Patients within each group will be randomized in a 1:1 ratio to 
receive either synthetic hybrid-scale fiber matrix or standard of care 
treatment. 
Once the patient is ready to be randomized, the randomization form will be 
completed by study personnel. Any patients that exit the study before randomization 

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are considered screen failures. A study exit CRF shall be completed if the patient is 
not eligible for randomization. 
 
5.7. Blinding 
The patient will remain blinded to the randomization assignment from the time of 
randomization assignment to the end of the treatment 
 
5.8. Enrollment Procedures 
Prior to enrollment, patients expressing an interest in participation will proceed with 
the inclusion/exclusion eligibility interview and informed consent process. An 
enrolled patient will be one who completes the eligibility interview, signs the 
Informed Consent form and receives initial treatment with either Restrata or 
Standard of Care therapy. 
 
5.9. Device Application / Follow-up Care Procedures 
Please refer to Appendix C for a list of supplies that will be provided by the 
sponsor for wound assessments / follow-up care procedures.  
 
1) WOUND BED PREPARATION: 
• Prepare the wound bed using standard methods to ensure it is free 
of exudate and devitalized tissue. An initial excision or debridement 
of the wound is necessary to ensure the wound edges contain viable 
tissue. 
• Wait for any bleeding to stop and ensure there is no active bleeding 
before applying synthetic hybrid-scale fiber matrix. 
• Cleanse the wound thoroughly with sterile saline prior to 
application of synthetic hybrid-scale fiber matrix 
 
2) PREPARATION OF SYNTHETIC HYBRID-SCALE FIBER 
MATRIX 
• Select the appropriate size sheet of synthetic hybrid-scale fiber 
matrix. 
• Heavily fenestrate with a scalpel or mesh prior to application. 
Synthetic hybrid-scale fiber matrix must be fenestrated prior to use 

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in any wound prone to exudate in order to permit effective exudate 
management. 
• Synthetic hybrid-scale fiber matrix is packaged in a nested pouch 
configuration. Peel open the outer foil pouch starting from the 
chevron sealed edge.  The inner TyVek® pouch is sterile and may 
be placed on the sterile field.  
• Rinse surgical gloves, if necessary, to remove any glove powder 
prior to touching the product.    
• Synthetic hybrid-scale fiber matrix can be cut to the desired shape 
in a wet or dry state. In order to increase pliability of the product, 
hydrate in warm, sterile, hypertonic solution (i.e. saline, water, etc.) 
for a minimum of 1 minute. 
3) APPLICATION OF SYNTHETIC HYBRID-SCALE FIBER 
MATRIX 
• Apply matrix with either side towards the wound bed, and position 
to completely contact the entire surface of the wound bed and 
extend slightly beyond wound margins. The matrix can be 
repositioned as necessary. 
• Securely anchor the matrix as needed with suture, staples or 
Steristrips. 
• Apply a non-adherent primary wound dressing over the matrix. 
• To prevent dislodgment of product, apply appropriate secondary 
dressing or compression to maintain dressing adherence (e.g., multi-
layer compression bandage system, or other appropriate dressing), 
manage the wound exudate, keep the matrix moist, and keep all 
layers securely in place. The optimum secondary dressing is 
determined by wound location, size, depth and provider preference. 
• Discard any unused pieces of study product BEFORE the curtain 
between the patient’s head and lower extremities is opened. 
• Provide appropriate offloading device as appropriate based on the 
subject’s wound location, health status etc. 
 
5.10. Standard of Care 
1) WOUND BED PREPARATION: 

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• Prepare the wound bed using standard methods to ensure it is free 
of exudate and devitalized tissue. An initial excision or debridement 
of the wound is necessary to ensure the wound edges contain viable 
tissue. 
• Wait for any bleeding to stop and ensure there is no active bleeding 
before applying an appropriate primary dressing. 
• Cleanse the wound thoroughly with sterile saline prior to 
application of an appropriate primary dressing. 
 
2) APPLICATION OF PRIMARY / SECONDARY DRESSINGS 
 
• Apply primary dressing to the wound bed, and position to 
completely contact the entire surface of the wound bed and extend 
slightly beyond wound margins.  
• Securely anchor the dressing as needed. 
• Apply appropriate secondary dressing to maintain dressing 
adherence, manage the wound exudate, and keep all layers securely 
in place. The optimum secondary dressing is determined by wound 
location, size, depth and provider preference. 
• Discard any unused pieces of standard wound therapy BEFORE the 
curtain between the patient’s head and lower extremities is opened. 
• Provide appropriate offloading device as appropriate based on the 
subject’s wound location, health status etc. 
5.11. Post-Application Procedures 
• 
Patients should be instructed on how to care for the wound site, utilize 
an appropriate offloading device (CAM boots or surgical shoes), and 
keep the wound site moist, and clean. 
 
• 
Patients are required to return to the clinic every week for post-
operative analysis of the wound site. 
  

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5.12. Follow-Up Procedures 
Weekly up to 12 weeks or until complete closure is first identified with a 
confirmation visit within 2 weeks thereafter; window for all visits is ± 3 days. 
At each of the interim timepoints subjects will return to the clinic for analysis / 
assessment of the following as indicated in the Schedule of Events in Appendix A: 
• Measurement of wound area  
• Documentation of wound appearance via photograph 
• Documentation of wound closure (if present)  
• Gross observation of wound for evidence of infection 
• Assessment of Quality of Life 
• Codes used to submit for reimbursement and amount (if any) 
reimbursed  
  
5.13. Study Exits 
5.13.1. Study Participation Exit Points 
A patient’s participation in the study will end after any of the following: 
 
• Patients with complete re-epithelialization and closure confirmation 
• Patients without complete re-epithelialization at 12 weeks 
• Patient withdrawal 
• Patient lost to follow-up 
• Amputation of all or part of the study limb 
• Closure of study 
• Patient death 
 
5.13.2. Patient Withdrawal 
A patient (or patient’s LAR) may choose to withdraw from the study at any 
time without penalty or loss of benefits. The patient should notify the 
investigator (or designee) of his/her desire to withdraw, and the investigator 
(or designee) should ask for and document the reason for withdrawal. The 
investigator may also choose to withdraw a patient from the study at any 
time if he/she considers it to be in the patient’s best interest. The reason for 
withdrawal should be recorded. Any data collected on the patient up to the 
point of withdrawal may be used in the study.  
 
If complete wound closure has not been confirmed at the time of 
withdrawal from the study, then the investigator should attempt to 

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determine the status of the wound at the time of the patient’s withdrawal to 
the best of the patient’s ability (i.e., healed, not healed, seeking additional 
treatment, not seeking additional treatment) and to complete as many of the 
patient-reported outcomes questionnaires as the patient is able and willing 
to complete. 
5.13.3. Patient Lost To Follow-Up 
The investigator should encourage patients to return for all required follow-
up visits. A patient will be considered lost to follow-up after three 
documented phone call attempts or emails plus a certified letter that is sent 
to the patient’s last known address in which no response is received. A 
patient should not be automatically exited from the study after a missed 
visit(s). Rather, the patient will remain in the study until he/she completes 
the final study visit required by the protocol, withdraws from the study, or 
is considered to be lost to follow-up.   
5.13.4. Patient Death 
If known, the cause of death should be documented. 
 
5.13.5. Sponsor Discontinues Study 
Premature termination of this clinical study may occur because of a 
regulatory authority decision, change in opinion of the IRB/EC, product 
safety concerns or at the discretion of Acera Surgical, Inc. Acera Surgical, 
Inc. reserves the right to discontinue the study prior to inclusion of the 
intended number of patients but intends only to exercise this right for valid 
scientific or administrative reasons. After such a decision, the investigator 
must contact all participating patients within 30 days. 
 
6. ADVERSE EVENT  
6.1. Principal Investigator Responsibilities  
The investigator (or designee) should record and maintain all adverse events that 
occur over the course of the patient’s participation in the study (randomization 
through study exit) during or outside of study visits. Adverse events that are 
reported to the sponsor will be assessed by an investigator. Adverse event 
assessments should include severity, seriousness, and relatedness to the product, 
study procedures and pre-existing conditions. See Section 6.4 for adverse events 
that are required to be reported to the Sponsor. 
 

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6.2. Adverse Event Definitions 
Adverse Event:  
Any untoward medical occurrence (sign, symptom, illness, abnormal laboratory 
value, or other medical event) that occurs while the patient is enrolled in the study 
whether or not it is related to the study product or study procedures. A medical 
condition (pre-existing condition) that exists at study enrollment/randomization is 
not considered an AE unless the condition worsens after enrollment. 
Serious Adverse Event:  
A serious adverse event is any undesirable adverse event or untoward medical 
occurrence (sign, symptom, illness, abnormal laboratory value, or other medical 
event) experienced by a patient during the study that: 
• Results in death;  
• Is life-threatening; 
• Requires inpatient hospitalization or prolongation of an existing 
hospitalization; 
• Results in persistent or significant disability/incapacity; or 
• Requires intervention to prevent a permanent impairment of a 
bodily function or damage to a body structure.   
Medical and scientific judgment should be exercised in determining whether an 
event is a serious adverse event. An important medical event may not be 
immediately life-threatening and/or result in death or hospitalization.  However, if 
it is determined that the event may jeopardize the patient and may require 
intervention to prevent one of the other outcomes listed in the definition above, the 
adverse event should be reported as serious. Examples of such events are intensive 
treatment in an emergency room for a bronchospasm or convulsions that do not 
result in hospitalization.  
This definition of an SAE is not intended to include hospitalization specifically to 
treat a condition that existed prior to the patient’s enrollment in the study (e.g., pre-
existing cardiovascular disease that is treated during the study) or prearranged 
elective surgery performed during this study period. 
Adverse Device Effect: 

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Any adverse event that is caused by or associated with a study product.   
Unanticipated Adverse Device Effect: 
Any serious adverse effect on health or safety or any life-threatening problem  or  
death caused  by  or  associated  with  a  study product,  if  that  effect,  problem  or  
death  was not  previously  identified  in  nature,  severity  or  degree  of  incidence  
in  the  Protocol or Instructions for Use. 
6.3. Adverse Event Assessment 
Adverse events that are required to be reported to the sponsor must be assessed by 
an investigator for severity, seriousness and relatedness to the product, study 
procedures and pre-existing conditions. 
The following scale should be used for severity assessment: 
 
The following scale should be used for an assessment of relatedness to the study 
product, study procedure(s), and pre-existing conditions: 
• 
Not Related 
• 
Possibly Related 
• 
Probably Related 
• 
Definitely Related 
6.4. Adverse Event Reporting   
The following adverse events are required to be promptly reported to the sponsor 
on the adverse event CRF: 
• 
Any serious adverse event whether or not it is related to a study 
product/procedure  

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• 
Any adverse event that in the opinion of the investigator is definitely 
related, probably related, or possibly related to a study product and/or 
study procedure 
• 
The following adverse events whether or not they are related to a study 
product/procedure:  
o Infection of wound and/or area surrounding wound 
o Complete or partial amputation of lower extremity 
o Allergic reaction 
Serious adverse product effects should be reported to the sponsor as soon as 
possible. Pre-existing conditions or adverse events that occur prior to 
randomization are not required to be reported.  
The investigator (or designee) is also required to report AEs to the IRB/EC if the 
AEs are required to be reported per the IRB/EC reporting requirements. 
7. STATISTICAL CONSIDERATION 
7.1. Hypotheses to be Tested 
7.1.1.  Primary Endpoints: 
The null hypothesis (H0) for the primary endpoint is that the difference in 
proportion of patients achieving 100% re-epithelialization by week 12 
between the synthetic hybrid-scale fiber matrix group (π1) and the control 
group (π2) is less than or equal to the superiority margin of +0.10 based on a 
one-sided Farrington & Manning test. The alternative hypothesis (H1) is that 
the difference is less than the superiority margin of +0.10. These can be seen 
in the equations below: 
H0: π1 - π2 >= +0.10 
H1: π1 - π2 < +0.10 
 
 
7.2. Analysis Populations 
Intention to Treat Population (ITT) 
The ITT population will consist of all enrolled patients. Patients are considered 
enrolled after meeting the criteria specified in Section 4. Patients in the ITT 

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population will be evaluated based on the randomized treatment group. 
 
Modified Intention to Treat Population (mITT) 
The mITT population will consist of ITT patients who have at least one product 
application. This will serve as the primary analysis population for study efficacy. 
Patients in the mITT population will be evaluated based on the randomized 
treatment group. 
 
Per Protocol (PP) 
The PP will include all ITT patients who additionally meet all study eligibility 
criteria, have available study data for the primary study endpoint and do not have a 
major protocol violation that affects primary effectiveness. Patients in the PP 
population will be evaluated based upon the treatment that they receive. 
 
7.3. Sample Size Calculation 
Sample size calculations were performed using a Farrington & Manning test for 
superiority of the synthetic hybrid-scale fiber matrix group compared to the control 
group. Under assumptions of a closure rate of 80% for the synthetic hybrid-scale 
fiber matrix group, 40% for the control group, and a superiority margin of 10%, 
this results in a sample size of 20 per group (40 total) that provides a power of 0.8 
and one-sided alpha of 0.05. After allowing for an assumed 20% lost to follow up, 
this results in a total sample size of 48 patients.  
 
7.4. Interim and Final Analyses 
An unblinded interim assessment for sample size re-estimation (SSR) will be 
performed on the primary endpoint of the study by an independent statistician. 
The analysis will be conducted when 50% of the mITT population (24 patients) 
have been enrolled and completed the primary endpoint evaluation. The analysis 
described below will be performed on the mITT population. 
The purposes of the interim analysis are (1) to calculate the power for superiority, 
conditioned on the interim-observed difference between treatments with respect to 
100% re-epithelialization rates and on the superiority margin of 10%, and (2) 
determine if the sample size needs to be increased in order to maintain the desired 
conditional power of 80%. 
 
The conditional power will be calculated under the assumption that the interim 
observed estimate of the treatment difference is the true treatment difference.  It 
will be calculated using the following formula as discussed in Lan and Wittes 
(1988) where: 

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Z1-α is the (1-α)*100% percentile of the standard normal distribution (i.e., the 
critical value used to assess superiority at the final analysis at overall one-sided 
significance level α). 
τ is the information fraction (= proportion of patients in the first interim analysis = 
r/M where r is the number of patients per group in the interim analysis and M is the 
planned number of patients per group for the final analysis); if the interim sample 
sizes per group are not equal due to randomness, the harmonic mean of the sample 
size will be used.   
Bτ = 
  where Zτ = the Farrington-Manning non-inferiority test statistic 
calculated on the interim observed data. Φ is the cumulative distribution function 
of the standard normal distribution. 
Following the “promising zone” algorithm in Mehta and Pocock (2011), if the 
conditional power based on the planned final sample size of 48 patients is <42% or 
>80% at the interim stage, the study will continue as is (there will be no stoppage 
of the study for futility nor will there be a sample size increase).  If the conditional 
power is between 42-80% (the promising zone), the sample size may then be re-
estimated using the method described by Wang et al (2002) in order to maintain 
80% conditional power without increasing the Type I error (probability of a false 
positive result) of the study. Specifically, the total revised sample size per group, 
M` required to achieve a conditional power of 80% to assess superiority at the final 
analysis using a superiority margin of 10% is found by solving the following 
equation for M`: 
𝑍𝑍0.20ට1 −𝑟𝑟
𝑀𝑀` + 𝑍𝑍𝜏𝜏ඨ𝑀𝑀`
𝑟𝑟−𝑍𝑍1−𝛼𝛼= 0 
 
where Z0.20 is the 20th percentile of the standard normal distribution 
(corresponding to the desired 80% conditional power) and where all other 
variables in this equation are defined above. M` will not exceed 70 patients for the 
DFU arm. This formula assumes the interim observed effect size between 
treatments is the true effect size between treatments. 
 
Results of the interim assessment will be presented by the independent statistician 
to the Sponsor group. The report to the Sponsor will state if additional sample is 
required to achieve a conditional power of 80%, and if so, how many additional 
patients. If additional sample size is required, the Sponsor will make a decision to 
either enroll the additional patients or not enroll and accept that the primary 

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endpoint may be under-powered.  The independent statistician’s report containing 
the results that led to the independent statistician’s recommendation will be kept 
confidential within the select Sponsor group. 
 
The following decision rules outline the possible outcomes of the interim analysis: 
1. If the test for CPni <0.42 or ≥0.8, then there is no increase in the sample size 
and the trial will be completed on a minimum of 48 enrolled patients, as 
scheduled. 
If the test for conditional power is 0.42 ≤ CPni < 0.8, then the sample size will 
be increased by just the right amount such that CPni is increased to 0.8, under a 
cap of 70 patients. The range 0.42 ≤ CPni < 0.8 is called the promising zone for 
non-inferiority. Specifically, if CPni is in its promising zone, this decision rule 
increases the sample size by the smallest of 70 patients or the number needed to 
boost CPni to 0.8. 
 
7.5. Statistical Analysis 
Data collected in this study will be reported using summary tables and patient data 
listings. Continuous variables will be summarized using descriptive statistics 
(number of patients, mean, standard deviation [SD], median, minimum, and 
maximum). Categorical variables will be summarized using frequencies and 
percentages of patients in each category. All results will be presented by treatment 
group and study arm in appropriate patient populations. SAS software version 9.4 
or similar will be used for the statistical analysis. 
7.5.1. Demographic and Baseline Characteristics 
Patient demographics for all analysis populations will be summarized in a 
table. Gender, ethnicity, and race will be summarized with frequency and 
percent. Age, height, weight, and BMI will be summarized with N, mean, 
standard deviation, median and minimum and maximum. 
 
7.5.2. Medical History 
Patient medical history, including tobacco use, comorbidities, diabetes 
history, and wound history (where applicable) for all analysis populations 
will be summarized in a table. Categorical variables will be summarized 
with frequency and percent. Continuous variables will be summarized with 
N, mean, standard deviation, median and minimum and maximum. 
 

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7.5.3. Procedural Information 
Descriptive statistics will be used to summarize the initial wound 
assessment by treatment group and procedural information. 
 
7.5.4. Primary Endpoints 
For the purpose of the primary endpoint analysis, the largest study wound 
will be analyzed. 
 
7.6. Study Outcome 
7.6.1. Primary Endpoints 
100% re-epithelialization will be assessed every week for 12 weeks or until 
100% re-epithelialization, whichever occurs first. Persistence of wound 
closure will be verified via confirmatory visit within 2 weeks after complete 
closure has been first determined.  
For the primary endpoint of 100% re-epithelialization at week 12 a two-stage 
analysis will test first if the rate of 100% re-epithelialization is superior 
between groups using a chi squared and/or Farrington & Manning test. 
Superiority for synthetic hybrid-scale fiber matrix will be demonstrated if the 
lower bound of the 90% CI of the difference in proportions lies above the 
superiority margin of +10%. 
 
7.6.2. Secondary Endpoints 
The following secondary endpoints will be summarized for exploratory 
purposes. Statistical testing may be performed at the request of the sponsor / 
investigator. 
Decrease in Wound Area from Baseline 
The difference in wound area from baseline to each time point will be 
summarized for each treatment group in each arm. The difference in mean 
percent change in size between the treatment group and control group will be 
calculated for each timepoint. Wound area measurements will be made via 
acetate tracing every week for 12 weeks, or until 100% re-epithelialization, 
whichever occurs first. 
 
Time to Wound Closure  
The time to wound closure will be summarized by proportion of patients with 
wound closure at each timepoint for each treatment group in each arm. The 
difference in proportion of patients with wound closure between the 
treatment group and control group will be calculated for each timepoint. 

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Persistence of wound closure will be verified via confirmatory visit within 2 
weeks after complete closure has been first determined. 
 
Number of Product Applications 
The number of product applications will be summarized for each treatment 
group in each arm. The difference in mean number of applications between 
the treatment group and control group will be calculated for each timepoint. 
Product applications will be defined as the number of product applications 
prior to complete wound closure within the treatment period for each study 
arm.  
 
7.6.3. Tertiary Endpoints 
The following tertiary endpoints will be summarized for exploratory 
purposes. Continuous variables will be summarized using descriptive 
statistics (number of patients, mean, median, quartiles, standard deviation 
[SD], minimum, and maximum). Categorical variables will be summarized 
using frequencies and percentages of patients in each category. Statistical 
testing may be performed at the request of the sponsor / investigator. Where 
possible, results will be summarized at each collected time point and the 
change from baseline will be presented. 
Quality of Life – SF-36  
Results will be summarized at each time point using the proportion of 
patients at each level. Change from baseline will be assessed as the number 
of levels either improved or worsened. 
 
Cost effectiveness / Economic model (Amount of product usage, length of 
treatment) 
Results will be summarized descriptively by timepoint where applicable. 
 
7.7. Adverse Events 
7.7.1. All Adverse Events 
Summaries of incidence rates of individual AEs overall will be prepared. 
Only treatment emergent AEs will be analyzed (a treatment emergent adverse 
event is one that started or worsened in severity at or after start of 
randomized treatment). Because a patient may experience more than one AE, 
summaries will provide both the number of patients experiencing at least one 
event and the number of events within a reporting period. Percentages 
provided will be the percent of patients experiencing one or more adverse 
events. In addition, incidence of AEs will be presented by severity (mild, 

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moderate, severe) and by relationship to investigational product or procedure. 
Patients experiencing an event more than once will be counted under the 
maximum severity/relationship experienced. 
A listing of all adverse events will include the patient number, AE number, 
days since index procedure, the AE name, the severity of AE, whether or not 
the AE is classified as serious (SAE), the relationship of the AE to the study 
product or procedure, the action taken, and the outcome.  
 
7.7.2. Serious Adverse Events 
Summaries of incidence rates and relationship to the study product/procedure 
of individual SAEs will be prepared. Summaries will provide both the 
number of patients and the number of events within a reporting period. 
Percentages provided will be the percent of patients experiencing one or 
more serious adverse events. A data listing of SAEs will also be provided, 
displaying details of the event(s) captured on the CRF.  
 
7.7.3. Adverse Events of Interest 
Summaries of incidence rates of the following AEs by treatment group will 
be prepared: 
o Infection of wound and/or area surrounding wound 
o Amputation of lower extremity 
o Allergic reaction  
o Excessive redness, pain, swelling or blistering of wound 
 
 
7.8. Strategies to Address Missing Data 
 
Patients who are missing complete wound closure will be considered as “missing 
data patients”. Missing complete wound closure status will be imputed using a 
logistic regression multiple imputation approach for dichotomous outcome data. In 
this approach, missing healing status will be imputed from logistic regression 
models with independent variables of age, gender, and other variables to be 
specified in the formal statistical analysis plan.  This will be performed 50 times in 
each arm in order to generate 50 “complete” datasets.  The one-sided Farrington & 
Manning test for assessing treatment difference will be carried out on each of the 
50 complete datasets, with the results being combined across the 50 complete 
datasets using standard multiple imputation theory to obtain one overall p-value 

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comparing the two treatments on the primary endpoint after accounting for missing 
data.  
 
8. DATA HANDLING AND RECORD KEEPING 
8.1. Case Report Forms (CRFs)  
Completed original CRFs are the sole property of Acera and should not be made 
available in any form to third parties, except for authorized representatives of 
appropriate regulatory authorities, without written permission from Acera. 
It is the Principal Investigator's responsibility to ensure completion of CRFs by the 
clinical research team and to review and approve the data captured on all CRFs as 
accurate.  All CRFs must be signed by the investigator.  This signature serves to 
attest that the information contained on the CRFs is true.  At all times, the 
investigator has final personal responsibility for the accuracy and authenticity of 
all data entered on CRFs.  Subject source documents are the investigator's subject 
records maintained at the study site, and will be used to verify data documented on 
CRFs.   
In some cases, a portion of the source documents for a given study/site may be the 
CRFs.  For this study, the patient questionnaires’ CRF pages will be considered 
source documents. 
Maintenance of Records: 
The Principal Investigator shall maintain the required records for a period of 2 
years after the date the study is completed or terminated or the records are no 
longer required to support a submission to a regulatory agency, whichever date is 
later. The Principal Investigator may withdraw from the responsibility to maintain 
records for the time required by transferring custody to another person who will 
accept responsibility for them. The sponsor must be notified in writing about the 
records transfer. 
 
9. ETHICS 
9.1. Ethical Conduct of the Clinical Study 
This clinical study will be conducted in accordance with the ethical principles that 
have their origin in the Declaration of Helsinki and in compliance with the protocol, 
Good Clinical Practice (GCP) guidelines, and applicable local regulatory 
requirements and laws. 

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9.2. Institutional Review Board (IRB) 
It is the responsibility of the investigator to obtain prospective approval of the 
conduct of the clinical study, the final protocol, protocol amendments, informed 
consent forms, and other relevant documents (e.g. advertisements), if applicable, 
from the IRB. Copies of the final IRB approvals must be forwarded to Acera 
Surgical, Inc. prior to enrolling patients or starting any clinical study activities. 
Protocol amendments require Acera Surgical, Inc. and IRB approval before any 
patient in this clinical study is subjected to that change. When a change is necessary 
to eliminate apparent immediate hazards to the clinical study patients, emergency 
procedures can be used with caution to prevent exposing the patient to the hazard. 
9.3. Confidentiality 
Information about study patients will be kept confidential and managed according 
to the requirements of the local regulatory authority, as well as applicable US laws 
and regulations. Personal Health Information (PHI) will be acquired during 
informed consent of the patient and from the medical records. This information will 
be utilized to identify the subject and contact the subject for emergencies and follow 
up appointments. The PHI is part of the patient clinic chart, and will be secured in a 
locked office when not in use. To ensure that confidentiality is maintained, patient 
names will not be used in this evaluation in any other way. A unique identifying 
number will be used. This identification method will be consistent for each subject 
throughout the evaluation. 
In the event that a patient revokes authorization to collect or use PHI, the 
Investigator, by regulation, retains the ability to use all information collected prior 
to the revocation of the authorization. 
 
10. SPONSOR DISCONTINUATION CRITERIA 
The Sponsor may suspend or terminate the study or part of the study at any time for 
any reason. If the investigator suspends or terminates the study at their respective 
site, the investigator will promptly inform the Sponsor and the IRB/EC and provide 
them with a detailed written explanation. 

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10.1. Termination of the study by the Sponsor 
Premature termination of this clinical study may occur because of a regulatory 
authority decision, change in opinion of the IRB/EC, product safety concerns or at 
the discretion of Acera Surgical, Inc. 
Acera Surgical, Inc., reserves the right to discontinue the study prior to inclusion of 
the intended number of patients, but intends only to exercise this right for valid 
scientific or administrative reasons. After such a decision, the investigator must 
contact all participating patients within 30 days. 
10.2. Termination of Site by the Sponsor 
Acera Surgical, Inc., reserves the option to terminate the participation of a study site 
at any time. Reasons for terminating the participation of a study site include, but are 
not limited to, the following: 
• Patient enrollment is unsatisfactory 
• Data recording is consistently inaccurate or incomplete 
• Investigator does not adhere to the protocol or applicable regulatory 
guidelines in conducting the study 
• IRB decides to terminate or suspend approval for the Investigator 
• Study site or Investigator violates GCP or the study agreements, 
disrupting the appropriate conduct of the trial. 
• Investigator asks to withdraw from study participation 
10.3. Termination by the Investigator 
If the Investigator terminates the study prematurely, the Investigator must provide 
the Sponsor and IRB/EC with a written statement describing why the study was 
terminated prematurely. 
11. PUBLICATIONS POLICY 
Acera Surgical, Inc. will be responsible for determining when the study results 
should be published. The Sponsor may work jointly with the investigators to publish 
information. The investigators shall not submit a publication to journals or 
professional societies without notification and review by the Sponsor. 

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12. SUMMARY OF PROTOCOL REVISIONS 
Revision 
Number 
Date 
Sections 
Revised 
Summary of Changes 
01 
xx/xx/21 
 
 
02 
21OCT2022 4.1 inclusion #7; 
4.1 inclusion 
#8b; 
4.2 exclusion 
#16 
5.4 
5.4.1 
5.4.2 
5.5 
5.6 
5.12 
7.6.1 
Appendix B 
Including wounds ≤30cm2, 
remove lower limit on wound 
size, remove upper ABI limit, 
run-in period revised to remove 
wound size changes limitations, 
remove acetate tracing 
requirements, data analysis will 
be conducted using chi squared  
 
 
13. REFERENCES 
1. Raghav A, Khan ZA, Labala RK, Ahmad J, Noor S, Mishra BK. 
Financial burden of diabetic foot ulcers to world: a progressive topic to 
discuss always. Ther Adv Endocrinol Metab. 2018;9(1):29-31. 
doi:10.1177/2042018817744513. 
 
2. Regulski MJ and MacEwan MR. Implantable Nanomedical Scaffold 
Facilitates Healing of Chronic Lower Extremity Wounds. Wounds. 
2018;30(8): E77-E80. 
 
3. Snyder DL, Sullivan N, Margolis DJ, Schoelles K. Skin substitutes for 
treating chronic wounds. Technology Assessment Program Project ID 
No. WNDT0818. (Prepared by the ECRI Institute-Penn Medicine 
Evidence-based Practice Center under Contract No. HHSA 290-2015-
00005-I) Rockville, MD: Agency for Healthcare Research and Quality. 
February 2020. 
 
4. Macewan M R, Macewan S, Kovacs T R, et al. (October 02, 2017) What 
Makes the Optimal Wound Healing Material? A Review of Current 

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Science and Introduction of a Synthetic Nanofabricated Wound Care 
Scaffold. Cureus 9(10): e1736. DOI 10.7759/cureus.1736 
 
5. MacEwan MR and MacEwan S et al.  Efficacy of a Nanofabricated 
Electrospun Wound Matrix in Treating Full-thickness Cutaneous 
Wounds in a Porcine Model. Wounds. 2018;30(2):E21–E24. 
 
 

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14. APPENDICES 
Appendix A: Schedule of Events 
 
Notes: 
• X – Requirement must be completed by study personnel 
• (1) – Treatment period visits will cease after complete wound re-epithelialization is confirmed 
• (2) – An in-person visit two weeks (± 3 days) after complete wound re-epithelialization is first identified after Week 0 are required for patients with complete wound re-
epithelialization. These visits are NOT required if there is not complete wound re-epithelialization at or before 12 weeks. 
• (3) – HbA1c and a vascularization assessment can be completed anytime within 60 days prior to Week 0 
• (4) – SF-36 Questionnaire and Pain Scale will be completed during the visit when complete wound re-epithelialization is first identified or at 12 weeks (whichever occurs 
first)
Start
7 days    
(±3 days)
0
1
2
3
4
5
6
7
8
9
10
11
12
2 weeks after 
wound closure     
(±3 days)
Informed Consent
X
Screening
X
X
X
Demographic and history
X
HbA1c
X(3)
Vascularization (ABI, TBI 
or TcPO2)
X(3)
Assessment of Re-
Eoithelization
X
X
X
X
X
X
X
X
X
X
X
X
SF-36 Questionnaire and 
Pain Scale
X
X(4)
Randomization
X
Visual Examination of 
Wound and imaging
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Product Application
X
X
X
X
X
X
X
X
X
X
X
X
X
Adverse events
X
X
X
X
X
X
X
X
X
X
X
X
X
X(2)
Treatment Period (1)
Week 0 is the initial application of study product and occurs 14 to 
17 days after the start of the run-in period. Visit window for 
Weeks 1 through 12 is (±3 days)
Two-Week In-
person Follow-up 
(2)
Requirement
Run-In Period

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Appendix B: Randomization Plan 
 
A Randomization Plan for patients with wound size 
< 12.5 cm2 
from 
http://www.randomization.com 
1. 
Standard of Care_______________________ 
2. 
Restrata_______________________________ 
3. 
Restrata_______________________________ 
4. 
Standard of Care_______________________ 
5. 
Restrata_______________________________ 
6. 
Standard of Care_______________________ 
7. 
Restrata_______________________________ 
8. 
Standard of Care_______________________ 
9. 
Restrata_______________________________ 
10. 
Standard of Care_______________________ 
11. 
Restrata_______________________________ 
12. 
Standard of Care_______________________ 
13. 
Standard of Care_______________________ 
14. 
Restrata_______________________________ 
15. 
Restrata_______________________________ 
16. 
Restrata_______________________________ 
17. 
Restrata_______________________________ 
18. 
Standard of Care_______________________ 
19. 
Standard of Care_______________________ 
20. 
Restrata_______________________________ 
21. 
Standard of Care_______________________ 
22. 
Restrata_______________________________ 
23. 
Standard of Care_______________________ 
24. 
Standard of Care_______________________ 
 
24 subjects randomized into 2 blocks  
To reproduce this plan, use the seed 24156  
along with the number of subjects per block/number of blocks  
and (case-sensitive) treatment labels as entered originally.  
Randomization plan created on 3/26/2021, 1:14:54 PM 
 
 
 
 
 

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Page 38 of 39 
 
A Randomization Plan for patients with wound size 
of ≥ 12.5 cm2 and ≤ 30 cm2 
from 
http://www.randomization.com 
1. Standard of Care_______________________ 
2. Restrata_______________________________ 
3. Standard of Care_______________________ 
4. Restrata_______________________________ 
5. Standard of Care_______________________ 
6. Restrata_______________________________ 
7. Restrata_______________________________ 
8. Standard of Care_______________________ 
9. Restrata_______________________________ 
10. 
Restrata_______________________________ 
11. 
Standard of Care_______________________ 
12. 
Standard of Care_______________________ 
13. 
Standard of Care_______________________ 
14. 
Restrata_______________________________ 
15. 
Restrata_______________________________ 
16. 
Standard of Care_______________________ 
17. 
Restrata_______________________________ 
18. 
Restrata_______________________________ 
19. 
Standard of Care_______________________ 
20. 
Restrata_______________________________ 
21. 
Standard of Care_______________________ 
22. 
Standard of Care_______________________ 
23. 
Standard of Care_______________________ 
24. 
Restrata_______________________________ 
 
24 subjects randomized into 2 blocks  
To reproduce this plan, use the seed 27186  
along with the number of subjects per block/number of blocks  
and (case-sensitive) treatment labels as entered originally.  
Randomization plan created on 3/26/2021, 1:17:57 PM 
 
 
 
 
 
 
 
 

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Appendix C: Supplies Provided by Sponsor 
 
- Clinical Report Forms (CRFs) 
- Study binder 
- Acetate tracing supplies