Clinical trial NCT02737748
Conditions: Donor Site Complication
Keywords: Donor Site Wounds
Sponsor: Transwell Biotech Co., Ltd.
Start date: 2017-07-06; Completion date: 2021-05-07
Enrollment: 48 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
Primary objective:

1. To evaluate the safety of TWB-103 in split-thickness skin graft donor site wounds (DSW) for Phase I in terms of Incidence of treatment-related AEs and SAEs (including infections and bleeding)
2. To evaluate the efficacy for Phase I+II of TWB-103 in split-thickness skin graft donor site wounds (DSW) in terms of The healing time from DSW creation to 100% re-epithelialization

Secondary objective:

1. To evaluate the efficacy of TWB-103 in split-thickness skin graft donor site wounds (DSW) in secondary efficacy endpoints
2. To evaluate the safety of TWB-103 in split-thickness skin graft donor site wounds (DSW) in secondary safety endpoints

Detailed description:
The study was designed to evaluate the safety and efficacy of the TWB-103 in adult subjects with split-thickness skin graft donor site wounds (DSW). In Phase I proportion, eligible subjects were recruited sequentially with one week staggering of treatment. Eligible subjects were randomized into TWB-103 or Placebo groups in a 1:1 ratio. Phase I was planned to recruit 3 evaluable subjects each in TWB-103 and Placebo groups. Evaluable subjects in Phase I were (1) he/she who received at least one dose and had follow-up evaluation at least 14 days after the first dose or (2) he/she who received at least one dose and had early withdrawn due to safety reasons before Day 28. When all of those 6 evaluable subjects completed the planned treatment period (14 days or till first 100% re-epithelialization, which came first), the recruitment was temporarily stopped for 14 days for safety observation. The safety data before and on Day 28 Visit were reviewed by the sponsor and the principal investigator. If no safety issue was decided, the study would enter Phase II portion and eligible subjects would be randomized into a 1:1 ratio into one of the TWB-103 and Placebo groups. The dosing regimen designed in Phase II portion was the same as it was designed in Phase I portion.

Subjects were instructed to attend scheduled visits at Screening, Day 0 (treatment start the day), Day 3, Day 7, Day 10, and Day 14 (end of treatment). All subjects were scheduled to attend a follow-up visit on Day 28 to evaluate the status of the target wound and then enter a 360-day follow-up phase. During the 360-day follow-up, four follow-up visits were scheduled at 90±14 days, 180±14 days, 270±14 days, and 360±14 days following the subject's Day 28 visit (if no Day 42 visit) or Day 42 visit.

Arms: arm 1: Subjects will receive TWB-103 2 to 3 times till 100% re-epithelialization or up to 10 days (around once every 3 days). arm 2: Subjects will receive placebo 2 to 3 times till 100% re-epithelialization or up to 10 days (around once every 3 days).
Interventions: intervention 1: TWB-103 Group intervention 2: Placebo Group
Intervention descriptions: intervention 1: Each subject received TWB-103+Tegaderm for up to 10 days or to the day of 100% re-epithelialization, whichever comes first, followed by Tegaderm alone application from Day 10 to 14 if failing to achieve 100% re-epithelialization by Day 10. intervention 2: Each subject received Placebo+Tegaderm for up to 10 days or to the day of 100% re-epithelialization, whichever comes first, followed by Tegaderm alone application from Day 10 to 14 if failing to achieve 100% re-epithelialization by Day 10.

Protocol documents:
Prot_SAP_000.pdf: 
Study Protocol 
TWB-103 for Donor Site Wounds 
(Project Number: 16-FDF-C001) 
Confidential  
Version: 3.0 
Date: 11APR2019 
 
Sponsor: TRANSWELL BIOTECH CO., LTD. 
Prepared by: A2 Healthcare Taiwan Corporation 
Page 1 of 82
 
STUDY PROTOCOL 
 
 
A Phase I/II Study to Evaluate the Safety and Efficacy of TWB-103 in 
Adult Patients with Split-Thickness Skin Graft Donor Site Wounds (DSW)  
 
 
Project Number: 
16-FDF-C001 
Investigational Product: 
TWB-103 
Sponsor: 
TRANSWELL BIOTECH CO., LTD. 
No.10. YanFa 2nd Road, HsinChu Science Park, 
30076, HsinChu, Taiwan 
Tel: +886-3-5670399 
 
Protocol Author: 
Mr. Douglas Chen and Dr. Yu-Yun Chang 
A2 Healthcare Taiwan Corporation 
10F., No. 2, Sec. 4, Renai Rd., Daan Dist., 
Taipei City 106, Taiwan 
Tel: +886-2-2325-5998 
Fax: +886-2-2325-5997 
Version: 
Current: 3.0, April 11, 2019 
Initial: 0.1, October 07, 2015 
Previous: 2.0, October 3, 2017 
 
 
Confidentiality Statement 
This protocol is provided for the purpose of conducting a clinical research study. The information contained in 
this document is confidential and, except to the extent necessary to obtain informed consent or IEC/IRB 
approval, cannot be disclosed unless required by governmental regulation. Persons to whom any portion of the 
contents of this document is disclosed must be informed that the information is confidential and may not be 
further disclosed by them. 


Study Protocol 
TWB-103 for Donor Site Wounds 
(Project Number: 16-FDF-C001) 
Confidential  
Version: 3.0 
Date: 11APR2019 
 
Sponsor: TRANSWELL BIOTECH CO., LTD. 
Prepared by: A2 Healthcare Taiwan Corporation 
Page 2 of 82
SIGNATURE PAGE 
 
The signature below constitutes the approval of this protocol and the attachments, and 
provides the necessary assurances that this trial will be conducted according to all stipulations 
of the protocol, including all statements regarding confidentiality, and according to local legal 
and regulatory requirements and ICH guidelines. 
 
Principal Investigator: 
 
 
______________________________________ 
_____________________ 
Name 
  
Date 
 


Study Protocol 
TWB-103 for Donor Site Wounds 
(Project Number: 16-FDF-C001) 
Confidential  
Version: 3.0 
Date: 11APR2019 
 
Sponsor: TRANSWELL BIOTECH CO., LTD. 
Prepared by: A2 Healthcare Taiwan Corporation 
Page 3 of 82
LIST OF ABBREVIATIONS 
ADR 
Adverse drug reaction 
AE 
Adverse event 
ALT 
Alanine transaminase 
ANC 
Absolute neutrophil count 
ANCOVA 
Analysis of covariance 
ANOVA 
Analysis of variance 
AST 
Aspartate transaminase 
bFGF 
Basic fibroblast growth factors 
BUN 
Blood urea nitrogen 
CI 
Confidence intervals 
CMH 
Cochran-Mantel-Haenszel 
CRF 
Case report form 
CRO 
Contract research organization 
CTCAE 
Common terminology criteria for adverse events 
DSMB 
Data and Safety Monitoring Board 
DSW 
Donor site wounds 
EDC 
Electronic Data Capture 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice 
HIV 
Human immunodeficiency virus 
HLA 
Human leukocyte antigen 
ICH 
International Conference on Harmonisation 
IND 
Investigative New Drug 
IP 
Investigational Product 
IQR 
Inter-quartile range 


Study Protocol 
TWB-103 for Donor Site Wounds 
(Project Number: 16-FDF-C001) 
Confidential  
Version: 3.0 
Date: 11APR2019 
 
Sponsor: TRANSWELL BIOTECH CO., LTD. 
Prepared by: A2 Healthcare Taiwan Corporation 
Page 4 of 82
IRB 
Institutional review board 
ITT 
Intent-to-treat 
MedDRA 
Medical Dictionary for Regulatory Activities 
PDGF 
platelet-derived growth factor 
PI 
Principal investigator 
PMDA 
Pharmaceuticals and Medical Devices Agency 
PP 
Per-protocol 
PRA 
Panel reactive antibodies 
RBC 
Red blood cell 
SAE 
Serious adverse event 
SOC 
System/Organ/Class 
SOP 
Standard Operating Procedure 
TFDA 
Taiwanese Food and Drug Administration 
TWBIO 
Transwell Biotech Co., Ltd. 
ULN 
Upper limit normal 
WBC 
White blood cell 
 
 


Study Protocol 
TWB-103 for Donor Site Wounds 
(Project Number: 16-FDF-C001) 
Confidential  
Version: 3.0 
Date: 11APR2019 
 
Sponsor: TRANSWELL BIOTECH CO., LTD. 
Prepared by: A2 Healthcare Taiwan Corporation 
Page 5 of 82
TABLE OF CONTENTS 
SIGNATURE PAGE ................................................................................................................. 2 
LIST OF ABBREVIATIONS ................................................................................................... 3 
TABLE OF CONTENTS .......................................................................................................... 5 
PROTOCOL SUMMARY ........................................................................................................ 7 
SCHEDULE OF ASSESSMENTS ......................................................................................... 20 
STUDY SCHEMA ................................................................................................................... 23 
1. 
BACKGROUND AND RATIONALE ......................................................................... 24 
1.1 
GENERAL INTRODUCTION ...................................................................................................................... 24 
1.2 
RATIONALE AND JUSTIFICATION FOR THE STUDY .................................................................................. 26 
2. 
OBJECTIVES AND ENDPOINTS.............................................................................. 28 
2.1 
OBJECTIVES ........................................................................................................................................... 28 
2.2 
ENDPOINTS ............................................................................................................................................ 28 
3. 
STUDY POPULATION ................................................................................................ 31 
3.1 
THE NUMBER OF PATIENTS TO BE ENROLLED ....................................................................................... 31 
3.2 
INCLUSION CRITERIA ............................................................................................................................. 31 
3.3 
EXCLUSION CRITERIA ............................................................................................................................ 32 
3.4 
WITHDRAWAL CRITERIA ........................................................................................................................ 35 
3.5 
PATIENT REPLACEMENT ........................................................................................................................ 36 
3.6 
CONCOMITANT TREATMENTS ................................................................................................................ 36 
4. 
STUDY DESIGN ........................................................................................................... 38 
4.1 
TREATMENT ASSIGNMENT ..................................................................................................................... 41 
4.2 
RANDOMIZATION AND BLINDING ........................................................................................................... 42 
4.3 
STOPPING RULES AND UNSCHEDULED VISITS ......................................................................................... 43 
5. 
TRIAL MATERIALS ................................................................................................... 46 
5.1 
TRIAL PRODUCT (S) ............................................................................................................................... 46 
5.2 
DOSAGE AND ADMINISTRATION............................................................................................................. 46 
5.3 
PACKAGE AND LABELING ...................................................................................................................... 48 
5.4 
STORAGE AND DRUG ACCOUNTABILITY ................................................................................................ 48 
5.5 
PRODUCT ACCOUNTABILITY .................................................................................................................. 48 
5.6 
ASSESSMENT OF COMPLIANCE ............................................................................................................... 49 
5.7 
TREATMENT FOR INVESTIGATIONAL PRODUCT OVERDOSE .................................................................... 49 
5.8 
OTHER CONSIDERATION FOR INVESTIGATIONAL PRODUCT ................................................................... 49 
6. 
STUDY ASSESSMENTS .............................................................................................. 50 
6.1 
INFORMED CONSENT .............................................................................................................................. 50 
6.2 
DEMOGRAPHICS ..................................................................................................................................... 50 
6.3 
PREGNANCY TEST AND CONTRACEPTION .............................................................................................. 50 
6.4 
ELIGIBILITY ........................................................................................................................................... 50 
6.5 
PHYSICAL EXAMINATIONS ..................................................................................................................... 51 
6.6 
MEDICATION HISTORY ........................................................................................................................... 51 
6.7 
MEDICAL HISTORY ................................................................................................................................ 51 
6.8 
VITAL SIGNS .......................................................................................................................................... 51 
6.9 
HEMATOLOGIC AND BIOCHEMICAL INDEXES ......................................................................................... 52 
6.10 
INVESTIGATIONAL PRODUCT ................................................................................................................. 52 
6.11 
WOUND ASSESSMENT............................................................................................................................. 52 
6.12 
PAIN ASSESSMENT .................................................................................................................................. 54 
6.13 
EXIT OF STUDY ...................................................................................................................................... 54 


Study Protocol 
TWB-103 for Donor Site Wounds 
(Project Number: 16-FDF-C001) 
Confidential  
Version: 3.0 
Date: 11APR2019 
 
Sponsor: TRANSWELL BIOTECH CO., LTD. 
Prepared by: A2 Healthcare Taiwan Corporation 
Page 6 of 82
6.14 
PANEL REACTIVE ANTIBODIES (PRA) TEST ............................................................................................ 54 
6.15 
TEGADERMTM DISPENSING AND RETURN ................................................................................................ 54 
7. 
STUDY SCHEDULE .................................................................................................... 56 
7.1 
SCREENING VISIT ................................................................................................................................... 56 
7.2 
ADMINISTRATION VISIT ......................................................................................................................... 56 
7.3 
EVALUATION VISITS .............................................................................................................................. 57 
7.4 
THE END OF TREATMENT VISIT ............................................................................................................... 59 
7.5 
FOLLOW-UP VISITS ................................................................................................................................. 60 
8. 
ADVERSE EVENTS ..................................................................................................... 62 
8.1 
DEFINITIONS .......................................................................................................................................... 62 
8.2 
AE/SAE INTENSITY AND RELATIONSHIP ASSIGNMENT ......................................................................... 63 
8.3 
COLLECTING, RECORDING AND REPORTING OF ADVERSE EVENTS ........................................................ 66 
9. 
DATA ANALYSIS ........................................................................................................ 70 
9.1 
DATA QUALITY ASSURANCE ................................................................................................................. 70 
9.2 
CLINICAL DATA MANAGEMENT ............................................................................................................. 70 
10. 
SAMPLE SIZE AND STATISTICAL METHODS ................................................... 71 
10.1 
DETERMINATION OF SAMPLE SIZE ......................................................................................................... 71 
10.2 
STATISTICAL AND ANALYTICAL PLANS ................................................................................................. 71 
11. 
ETHICAL CONSIDERATIONS ................................................................................. 76 
11.1 
INFORMED CONSENT .............................................................................................................................. 76 
11.2 
IRB REVIEW ........................................................................................................................................... 76 
11.3 
CONFIDENTIALITY OF DATA AND PATIENT RECORDS ............................................................................ 77 
12. 
PUBLICATIONS .......................................................................................................... 78 
13. 
RETENTION OF TRIAL DOCUMENTS .................................................................. 79 
14. 
REFERENCES .............................................................................................................. 80 
15. 
PROTOCOL AMENDMENT HISTORY .................................................................. 81 
 


Study Protocol 
TWB-103 for Donor Site Wounds 
(Project Number: 16-FDF-C001) 
Confidential  
Version: 3.0 
Date: 11APR2019 
 
Sponsor: TRANSWELL BIOTECH CO., LTD. 
Prepared by: A2 Healthcare Taiwan Corporation 
Page 7 of 82
PROTOCOL SUMMARY 
Full Title 
 
A Phase I/II Study to Evaluate the Safety and Efficacy of TWB-103 
in Adult Patients with Split-Thickness Skin Graft Donor Site 
Wounds (DSW) 
Short Title 
TWB-103 for Adult Patients with Split-Thickness Skin Graft Donor 
Site Wounds 
Project No 
16-FDF-C001 
Study Phase 
Phase I/II 
Sponsor 
TRANSWELL BIOTECH CO., LTD. 
Objectives 
 
Primary objective: 
1. To evaluate the safety of TWB-103 in split-thickness skin graft 
donor site wounds (DSW) for Phase I in terms of incidence of 
treatment-related AEs and SAEs (including infections and bleeding)  
2. To evaluate the efficacy for Phase I+II of TWB-103 in split-
thickness skin graft donor site wounds (DSW) in terms of the 
healing time from DSW creation to 100% re-epithelialization 
Secondary objective: 
1. To evaluate the efficacy of TWB-103 in split-thickness skin graft 
donor site wounds (DSW) in secondary efficacy endpoints 
2. To evaluate the safety of TWB-103 in split-thickness skin graft 
donor site wounds (DSW) in secondary safety endpoints 
Study Design 
This study will be designed in a Phase I/II randomized, double-blind, 
additional evaluator-blind, placebo-controlled, multi-center, multi-
nation (Taiwan and Japan), parallel manner.  
In Phase I proportion, eligible patients will be recruited sequentially 
with one week staggering in the initiation of study treatment. 
Eligible patients will also be randomized into Treatment (TWB-
103+TegadermTM) and Control (placebo+TegadermTM) groups in 1:1 
ratio. Phase I plan to recruit 3 evaluable TWB-103+TegadermTM 


Study Protocol 
TWB-103 for Donor Site Wounds 
(Project Number: 16-FDF-C001) 
Confidential  
Version: 3.0 
Date: 11APR2019 
 
Sponsor: TRANSWELL BIOTECH CO., LTD. 
Prepared by: A2 Healthcare Taiwan Corporation 
Page 8 of 82
treated and 3 evaluable placebo+TegadermTM treated patients. 
Patients in phase I are considered as evaluable when (1) he/she 
receives at least one dose and has follow-up evaluation at least 14 
days after first dose or (2) he/she receives at least one dose and has 
early withdrawn due to safety reasons before Day 28. When all of 
those 6 evaluable patients complete the planned treatment period (14 
days or till first 100% re-epithelialization, which comes first), the 
recruitment of patients will be temporarily stopped for 14 days for 
safety observation. The safety data of TWB-103 before and on Day 
28 Visit will be reviewed by the sponsor and the principal 
investigator. If no safety issue of TWB-103 is decided, the study will 
enter Phase II portion and eligible patients will be randomized into 
Treatment and Control groups in 1:1 ratio. 
All subjects are scheduled to attend a follow-up visit at Day 28 to 
evaluate the status of the target wound and then enter a 360-day 
follow-up phase. If the complete wound closure occurs by Day 14, 
the re-confirmation of wound closure should be performed on Day 
28 follow-up. In the case that complete wound closure occurs at 
some point between Day14 and Day 28, an additional follow-up visit 
will be scheduled on Day 42 for the re-confirmation before subject 
enters the 360-day follow-up phase. If the complete wound closure is 
not observed on Day 28, patients will have other appropriate 
treatment at the investigator’s discretion. The DSWs will be 
followed till 100% re-epithelialization. 
During the 360 days of follow-up, four follow-up visits will be 
scheduled on 9014 days, 18014 days, 27014 days and 36014 
days following the subject’s Day 28 visit (if no Day 42 visit) or Day 
42 visit. In total, 5~6 follow-up visits will be scheduled in this study 
for all randomized subjects. 
The study will be stopped when > 1/3 of patients in the phase I have 
developed study drug related grade 2 or above SAEs defined as in 
Section 8. The investigator will determine if SAEs are study drug 


Study Protocol 
TWB-103 for Donor Site Wounds 
(Project Number: 16-FDF-C001) 
Confidential  
Version: 3.0 
Date: 11APR2019 
 
Sponsor: TRANSWELL BIOTECH CO., LTD. 
Prepared by: A2 Healthcare Taiwan Corporation 
Page 9 of 82
related without breaking the blind. If the cause of SAE is 
inconclusive, the investigator can request to break the blind 
following the procedure stated in Section 4.2. 
Patients who experience > Grade 2 skin allergic reaction or > Grade 
2 systemic allergic reaction related to the product or placebo must 
not receive any further TWB-103 or placebo treatment. If a patient 
should develop infection at the DSW site before Day 10, he/she will 
stop the TWB-103 or placebo application at the investigator’s 
discretion. Patients with the aforementioned conditions, before or at 
Visit 8, should finish the scheduled assessments (except that 
application of TWB-103/placebo is stopped; that the application 
and dispensation of TegadermTM will be at the investigator’s 
discretion; and that the return of TegadermTM will be asked if 
applicable). Patients with allergic reaction or infection may receive 
appropriate treatments at the PI’s discretion, will be monitored 
throughout the healing process (including the recovery from allergic 
reaction or infection, and the complete closure of DSW) and will 
continue the remaining visits (application of TWB-103 or placebo 
will be stopped if planned originally). In these cases of TWB-
103/placebo discontinuation, wound assessments performed after 
onset of allergic reaction or infection will be excluded from 
statistical analysis. 
Unscheduled visits can be requested when patients require the 
investigator’s medical attention, e.g. the reopen of DSW but self-
care is insufficient, infection, or allergic reaction. Patients should 
finish the assessments of Day 14 (except that the completion of 
hemogram and serum biochemistry as well as the application and 
dispensation of TegadermTM will be at the investigator’s discretion; 
and that the return of TegadermTM is not required) during the 
unscheduled visit. Patients will resume the original planned visits 
and/or come in additional unscheduled visits at the investigator’s 
discretion. The option to choose Vaseline Gauze or Non-Stick Gauze 


Study Protocol 
TWB-103 for Donor Site Wounds 
(Project Number: 16-FDF-C001) 
Confidential  
Version: 3.0 
Date: 11APR2019 
 
Sponsor: TRANSWELL BIOTECH CO., LTD. 
Prepared by: A2 Healthcare Taiwan Corporation 
Page 10 of 82
such as silastic foam dressings only can be selected on or after Day 
14. 
Study Population 
Patient aged at 20-65 years old presenting a split-thickness skin graft 
donor site wound 
Number of Patients  
The sample size is determined to be 15 versus 15 evaluable (= per-
protocol for Phase I+II) patients (1:1 ratio) for Treatment versus 
Control groups, 30 evaluable patients in total. To ensure the 
completion of 30 evaluable patients, around 36 patients will be 
recruited.  
Study Product, Dose, 
Route, Regimen 
TWB-103, allogeneic human fibroblasts + gelatin-based hydrogel, 
applied 2 to 3 times till 100% re-epithelialization or up to 10 days 
(around once every 3 days); a matching placebo, freezing solution 
with gelatin-based hydrogel, is used as the control and applied to 
patients in the same duration and dosing frequency as TWB-103. 
Duration of Treatment During the planned treatment period (14 days), each patient will 
receive TWB-103+TegadermTM or placebo+TegadermTM for up to 
10 days or to the day of 100% re-epithelialization, whichever comes 
first, followed by TegadermTM alone application from Day 10 to Day 
14 if failing to achieve 100% re-epithelialization by Day 10. 
Study Visits 
Patients will be scheduled to attend the following visits: 
1. Screening (within 2 weeks prior to DSW creation) 
2. Day 0 (treatment begins) 
3. Day 3 ( 1 day) 
4. Day 7 ( 1 day) 
5. Day 10 ( 1 day) 
6. Day 14 ( 2 days, end of treatment) 
7. Day 28 ( 3 days, Follow-up) 
8. Day 42 ( 3 days, Follow-up) 


Study Protocol 
TWB-103 for Donor Site Wounds 
(Project Number: 16-FDF-C001) 
Confidential  
Version: 3.0 
Date: 11APR2019 
 
Sponsor: TRANSWELL BIOTECH CO., LTD. 
Prepared by: A2 Healthcare Taiwan Corporation 
Page 11 of 82
9. 90  14 days after Visit 7 or Visit 8 (Follow-up) 
10. 180  14 days after Visit 7 or Visit 8 (Follow-up) 
11. 270  14 days after Visit 7 or Visit 8 (Follow-up) 
12. 360  14 days after Visit 7 or Visit 8 (Follow-up) 
Note:  (1) For patients with complete wound closure by Day 14, the 
confirmation of wound closure will be assessed on Day 28. 
(2) Day 42 follow-up is only scheduled when the wound closure is 
not completed by Day 14 but is observed on Day 28. The wound
closure will be re-confirmed on Day 42.  
(3) If no Visit 8, Visit 9~12 should be scheduled following Visit 7. 
(4) In case patients achieve 100% re-epithelialization before or at 
Day 10, patients will finish up the assessments on the day with 
100% re-epithelialization. This day of 100% re-epithelialization 
will be the end of treatment and the remaining scheduled 
treatment visits, if applicable, will be dismissed. 
Patient Assignment 
Patients who meet all eligibility requirements for entry into the study 
will be randomized into one of the treatment group or control group 
in 1:1 ratio as shown below: 
Treatment Group: 
TWB-103 add-on TegadermTM till 100% re-epithelialization or up to 
10 days, whichever comes first, followed by TegadermTM alone 
application from Day 10 to Day 14 if failing to achieve 100% re-
epithelialization by Day 10. If 100% re-epithelialization is not 
observed on Day 14 (the end of treatment), patients will have 
application of TegadermTM up to Day 28. 
Control Group: 
Placebo+TegadermTM till 100% re-epithelialization or up to 10 days, 
whichever comes first, followed by TegadermTM alone application 
from Day 10 to Day 14 if failing to achieve 100% re-
epithelialization by Day 10. If 100% re-epithelialization is not 


Study Protocol 
TWB-103 for Donor Site Wounds 
(Project Number: 16-FDF-C001) 
Confidential  
Version: 3.0 
Date: 11APR2019 
 
Sponsor: TRANSWELL BIOTECH CO., LTD. 
Prepared by: A2 Healthcare Taiwan Corporation 
Page 12 of 82
observed on Day 14 (the end of treatment), patients will have 
application of TegadermTM up to Day 28. 
Note:  
1. TegadermTM will be renewed at each visit between Visit 3 (Day 3) to Visit 7 
(Day 28) if 100% re-epithelialization is not observed. Whenever TegadermTM falls 
off from DSW site, new TegadermTM should be applied immediately. If necessary, 
drainage is allowed, but re-application of TWB-103 or placebo is not necessary in 
this case.  
2. If the first 100% re-epithelialization is observed on Day 28, patients will be 
scheduled Day 42 follow-up and dispensed with TegadermTM. 
3. If the first 100% re-epithelialization is not observed on Day 28, patients will 
receive the application of TegadermTM on site for protection of wound site and/or 
have other appropriate treatment at the investigator’s discretion. The DSWs will 
be followed till 100% re-epithelialization. 
4. To prevent the itchiness and skin reaction caused by the long-term usage of 
TegadermTM, Vaseline Gauze or Non-Stick Gauze such as silastic foam dressings 
can be used on and after Day 14 at the investigator’s discretion. 
Patients Inclusion 
Criteria 
A patient is eligible for the study if all of the following apply:  
1. Female/male patients, aged 20-65 years old 
2. Presenting a split-thickness skin graft donor site wound with a 
minimum size of 15 cm2 but no more than 100 cm2, with a 
minimum width of 3 cm and with an approximate thickness of 
0.010~0.012 inches. The graft cannot be harvested from a site 
from which a skin graft was previously obtained. 
3. If the primary wound is a result of a thermal or chemical burn, the 
total body surface area of the said wound must be less than 15%. 
Note: The burn area is estimated based on the method used at the local site. 
The Rule of Nines Chart (1% body surface area equals one patient’s palm size) 
or Lund and Browder Chart are acceptable. 
4. Females of childbearing potential must have a documented 
negative serum pregnancy test done at the screening visit, which is 
within 2 weeks prior the DSW creation and the treatment 


Study Protocol 
TWB-103 for Donor Site Wounds 
(Project Number: 16-FDF-C001) 
Confidential  
Version: 3.0 
Date: 11APR2019 
 
Sponsor: TRANSWELL BIOTECH CO., LTD. 
Prepared by: A2 Healthcare Taiwan Corporation 
Page 13 of 82
5. Both male and female patients must agree to use highly effective 
contraceptives from signing informed consent to 30 days after the 
last dose administration. Acceptable contraceptive forms include: 
a. Established use of oral, injected or implanted hormonal 
methods of contraception 
b. Placement of an intrauterine device (IUD) or intrauterine 
system (IUS) 
c. Barrier methods of contraception: Condom or occlusive 
cap (diaphragm or cervical/vault caps)  
6. Willing to comply with the study protocol and has signed the 
Informed Consent Form 
Note: The rationale for the inclusion criteria is described in section 3.2. 
Patients Exclusion 
Criteria 
Any patient meeting any of the exclusion criteria will be excluded 
from study participation. 
1. Female patients who are pregnant or lactating or planning a 
pregnancy and any male patient whose partner (wife) planning a 
pregnancy from signing informed consent to 30 days after the last 
dose administration.  
2. Clinically significant disease or condition that may compromise 
graft taken and/or donor site healing (e.g. the presence of a 
bleeding disorder, capillary fragility, venous or arterial disorder 
directly affecting the donor site to be treated, known or suspected 
systemic malignancies, human immunodeficiency virus infection, 
renal or liver disease, uncontrolled diabetes mellitus, 
thrombocytopenia, vasculitis, poor nutritional status). 
3. Patients who are currently receiving or have received the 
following treatments within 4 weeks prior to Screening Visit are 
excluded from the study:  
a) systemic, or inhaled corticosteroids or immunosuppressant 
agents; or 


Study Protocol 
TWB-103 for Donor Site Wounds 
(Project Number: 16-FDF-C001) 
Confidential  
Version: 3.0 
Date: 11APR2019 
 
Sponsor: TRANSWELL BIOTECH CO., LTD. 
Prepared by: A2 Healthcare Taiwan Corporation 
Page 14 of 82
b) therapeutic doses of anticoagulants (e.g. Coumadin, Heparin, 
low molecular weight Heparin) for pre-existing medical 
conditions, for whom a dose interruption from Screening 
through the end of the study period is contraindicated. 
4. Autoimmune disease, e.g. lupus erythematosus, multiple sclerosis. 
5. Hematologic disease, malignancy or hypo-immunity. 
6. History of HIV infection or congenital immunodeficiency. 
Note: HIV = human immunodeficiency virus 
7. History of alcoholism or drug abuse.  
8. Have used any tobacco product within 1 week prior to Day 0. 
9. Patients previously treated with any cell-based product, including 
autologous tissue at the treatment site. 
10. Received an investigational drug, device or biological/bioactive 
treatment within 30 days prior to Screening Visit. 
11. Any clinical condition or significant concurrent disease judged 
by the investigator to complicate the evaluation of the trial 
treatment. 
12. History of sensitivity to bovine or porcine origin of materials, or 
human serum albumin. 
13. DSWs located in the face, over joints, lower legs or the buttocks 
14. Any of the following hematologic abnormalities: 
a. Hemoglobin < 10.0 g/dL 
b. ANC < 1,500/μL, 
c. Platelets < 75,000 /μL 
15. Any of the following serum chemistry abnormalities: 
a. Total bilirubin > 1.5 × ULN, 
b. AST or ALT > 3 × ULN,  


Study Protocol 
TWB-103 for Donor Site Wounds 
(Project Number: 16-FDF-C001) 
Confidential  
Version: 3.0 
Date: 11APR2019 
 
Sponsor: TRANSWELL BIOTECH CO., LTD. 
Prepared by: A2 Healthcare Taiwan Corporation 
Page 15 of 82
c. -GT > 2.5 x ULN, 
d. Alk-P > 2.5 x ULN, 
e. Serum albumin < 2.7 g/dL, 
f. Creatinine >1.5 x ULN 
g. Any other ≥ Grade 2 laboratory abnormality (based on 
CTCAE) at baseline (other than those listed above)  
16. DSWs in area with active skin infection or with skin condition 
that is considered highly susceptible to infection judged by the 
investigator  
Note: The rationale for the exclusion criteria is described in section 3.3. 
Primary Endpoint 
Phase I 
Safety:  
Incidence of treatment-related AEs and SAEs (including infections 
and bleeding) 
Note: AE = adverse event; SAE = Serious adverse event 
Phase I+II 
Efficacy: 
The healing time from DSW creation to the first 100% re-
epithelialization with confirmation for at least 10 days apart assessed 
by the investigator 
Secondary Endpoints Phase I+II 
Efficacy: 
1. The healing time from DSW creation to the first 100% re-
epithelialization with confirmation for at least 10 days apart, 
assessed by the first additional evaluator 
2. The healing rates (complete wound closure) of patients at Day 7, 
10 and 14 after DSW creation 
Note: Complete wound closure is defined as skin 100% re-


Study Protocol 
TWB-103 for Donor Site Wounds 
(Project Number: 16-FDF-C001) 
Confidential  
Version: 3.0 
Date: 11APR2019 
 
Sponsor: TRANSWELL BIOTECH CO., LTD. 
Prepared by: A2 Healthcare Taiwan Corporation 
Page 16 of 82
epithelialization without drainage or dressing requirements. 
3. The healing percentage of wounds (ratio of healing area and 
original area) at Days 7, 10 and 14 after DSW creation 
4. The pain change from baseline to post-wound creation visits based 
on short-form McGill pain questionnaire score 
Safety: 
1. Incidence of treatment-related AEs and SAEs (including 
infections and bleeding) 
2. Incidence of AEs and SAEs 
3. Changes in post-treatment physical examination, vital signs, and 
general laboratory assessment compared to baseline 
Note: The investigator will determine the end of treatment based on the healing 
progress. Wound healing will be assessed based on the wound observation by the 
investigator and an additional evaluator. An additional evaluator who is not aware 
of the treatment given will evaluate based on photos of the wound. The additional 
evaluator will receive photos of the wound from CRO and will return the 
assessment to CRO. A second additional evaluator, who is also blinded, will be 
requested when the discrepancy occurs between the investigator and the first 
additional evaluator in the determination of 100% re-epithelialization. 
Statistical Analysis 
For this study, the sample size is 30 evaluable patients in total. This 
sample size is based on clinical judgment and not based on power 
calculation. 
Two populations will be introduced for statistical analysis: 
Intent-to-treat (ITT) population:  
• 
Patients randomized 
• 
Patients ever treated by at least one dose of trial medication 
• 
Patients with any post-treatment evaluation 
Per-protocol (PP) population: 
• 
Dosed with planned dosing regimen of investigational 


Study Protocol 
TWB-103 for Donor Site Wounds 
(Project Number: 16-FDF-C001) 
Confidential  
Version: 3.0 
Date: 11APR2019 
 
Sponsor: TRANSWELL BIOTECH CO., LTD. 
Prepared by: A2 Healthcare Taiwan Corporation 
Page 17 of 82
product 
• 
With efficacy endpoint measurement at wound assessment 
(with first 100% re-epithelialization or complete Day 14 visit 
evaluation) 
• 
Fulfilling all inclusion and exclusion criteria 
• 
Without taking prohibited medication 
Since the dosing regimen designed in Phase I are exactly those 
designed for Phase II, and the procedures/schedules of assessment 
that patients receive are identical in both phases, the data collected in 
Phase I portion will be combined with those in the Phase II portion 
for statistical analysis. 
Primary endpoints and secondary efficacy endpoints in Phase I/II 
will be analyzed on ITT and PP population. Non-primary safety 
endpoints, demographics and baseline characteristics will be 
analyzed on ITT population. Conclusion of primary endpoint in 
Phase I will be made based on ITT population analysis results and 
that in Phase II will be made according to the result of ITT 
population analysis. For all assessments, the baseline will be defined 
as the most recently available data before the administration of 1st 
dose treatment. 
Descriptive statistics will be provided by treatment group/country 
and by all for all of the endpoints, including primary and secondary 
ones. Frequency table will be provided for categorical data, while 
mean, standard deviation, maximum, minimum, median, inter-
quartile range (IQR), and 95% two-sided confidence interval will be 
calculated for continuous measurements. 
AEs and SAEs will be reported by treatment group/country and 
physiological systems as appropriate. The incidence of treatment-
related AEs and SAEs between treatments will be analyzed by 
Cochran-Mantel-Haenszel test (CMH) test. 


Study Protocol 
TWB-103 for Donor Site Wounds 
(Project Number: 16-FDF-C001) 
Confidential  
Version: 3.0 
Date: 11APR2019 
 
Sponsor: TRANSWELL BIOTECH CO., LTD. 
Prepared by: A2 Healthcare Taiwan Corporation 
Page 18 of 82
Incidence of AEs and SAEs will be analyzed by CMH test. Changes 
in physical examinations will be displayed for each individual 
system. Net changes from pre-treatment laboratory test results and 
vital signs will be analyzed by descriptive statistics.  
Healing time from DSW creation to 100% re-epithelialization will 
be estimated by using Kaplan-Meier methods and compared between 
groups by using log-rank test. The healing time is defined as from 
DSW creation to the first 100% re-epithelialization with 
confirmation for at least 10 days apart, observed by the investigator 
and the first additional evaluator. 
If the first 100% re-epithelialization is observed at any visit by Day 
28 with confirmation for at least 10 days apart, the healing time is 
noted as the duration from the day of DSW creation to the day of the 
first 100% re-epithelialization. The fulfilling of the visits and/or 
follow-ups after the 100% re-epithelialization day will not be taken 
into account to determine the healing time. If the 100% re-
epithelialization is not observed by Day 28 visit, the healing time 
will be censored on day of the last visit up to Day 28 visit. If the 
100% re-epithelialization is observed by Day 28 visit but no 
confirmation is made, the healing time will be censored on day of 
the last visit up to Day 28 visit. The censoring rules will be applied 
immediately once patients leave the study regardless the 
participation and/or completion of the long-term (360 days) follow-
ups. 
If patient develops grade 2 or above SAEs and should exit the study 
prematurely before Day 14, he/she should be excluded from the 
primary efficacy analysis, because early censor will result in under 
estimation of the healing time while treatment group (TWB-
103+TegadermTM) is prone to have higher risk of developing 
treatment related SAE.  
In the cases of TWB-103/placebo discontinuation due to allergic 
reaction or infection, wound assessments performed after onset of 


Study Protocol 
TWB-103 for Donor Site Wounds 
(Project Number: 16-FDF-C001) 
Confidential  
Version: 3.0 
Date: 11APR2019 
 
Sponsor: TRANSWELL BIOTECH CO., LTD. 
Prepared by: A2 Healthcare Taiwan Corporation 
Page 19 of 82
allergic reaction or infection will be excluded from statistical 
analysis. 
Healing rates (complete wound closure) of patients at Days 7, 10 and 
14 after DSW creation will be analyzed by CMH test. Healing 
percentage of wounds (ratio of healing and original areas) at Days 7, 
10 and 14 after DSW creation will be analyzed by Analysis of 
variance (ANOVA) model with treatment group and country as 
factor. Score on short-form McGill pain questionnaire will be 
analyzed by using Analysis of covariance (ANCOVA) model with 
treatment group and country as factor and baseline characteristics as 
covariate. Vancouver Scar Scale will be analyzed by Wilcoxon 
ranked sum test. The score in each category (pigmentation, 
vascularity, pliability and height) and the sum score of all category 
in Vancouver Scar Scale will be analyzed. 
All treatment group comparisons will be conducted with significance 
level of 0.05, using 2-tailed tests. 
Demographics and baseline characteristics will be summarized for 
each group/country by using descriptive statistics. 
 


Study Protocol 
TWB-103 for Donor Site Wounds 
(Project Number: 16-FDF-C001) 
Confidential  
Version: 3.0 
Date: 11APR2019 
 
Sponsor: TRANSWELL BIOTECH CO., LTD. 
Prepared by: A2 Healthcare Taiwan Corporation 
Page 20 of 82
SCHEDULE OF ASSESSMENTS 
 
 
Screening1 
Treatment12, 13  
Follow-up 
Procedure 
Within 2 weeks 
prior to  
DSW creation 
Day 01 
Day 3 
 (± 1 
day) 
Day 7 
 (± 1 
day) 
Day 10 
(± 1 day) 
Day 14 
(± 2 
days)14 
Day 28 
(± 3 
days)2,11 
Day 42 
(± 3 
days)3,11 
90, 180, 270, 
360 days (± 
14 days) 
from visit 7 
or 84,11 
Visit 
1 
2 
3 
4 
5 
6 
7 
8 
9, 10, 11, 12 
Informed consent 
X 
 
 
 
 
 
 
 
 
Screening no. assign  
X 
 
 
 
 
 
 
 
 
Inclusion / Exclusion  
X 
 
 
 
 
 
 
 
 
Randomization19 
X 
 
 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
 
Medical History 
X 
 
 
 
 
 
 
 
 
Physical Examination 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Vital Signs 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Pregnancy Test (Serum) 
X 
 
 
 
 
 
 
 
 
PRA test: Class I HLA. 
 
X20 
 
 
 
 
X 
 
 
Hemogram 
X 
X20 
X 
X 
X 
X 
X 
X 
 
Serum Biochemistry 
X 
X20 
X 
X 
X 
X 
X 
X 
 
TWB-103+TegadermTM or 
placebo+TegadermTM 5,6 
 
X 
X 
X 
 
 
 
 
 
TegadermTM applying at site6 
 
 
 
 
X7 
X7, 22 
X7, 10, 22 
 
 
TegadermTM dispensing6, 8 
 
X 
X 
X 
X 
X22 
X22, 23 
 
 
TegadermTM return9 
 
 
X 
X 
X 
X22 
X22 
X22, 23 
 
Wound assessment15 
 
X 
X 
X 
X 
X 
X2 
X 
X16 
Pain questionnaire21 
X 
 
X 
X 
X 
X 
X 
X 
X 
AE assessment 
X17 
X 
X 
X 
X 
X 
X 
X 
X18 
Prior/Concomitant treatment 
X 
X 
X 
X 
X 
X 
X 
X 
 
1. Visit 1 (screening) and Visit 2 (Day 0) can be performed on the same day. 
2. When DSW reaches 100% re-epithelialization by Day 14, a re-confirmation of wound closure will be performed on Day 28. 


Study Protocol 
TWB-103 for Donor Site Wounds 
(Project Number: 16-FDF-C001) 
Confidential  
Version: 3.0 
Date: 11APR2019 
 
Sponsor: TRANSWELL BIOTECH CO., LTD. 
Prepared by: A2 Healthcare Taiwan Corporation 
Page 21 of 82
3. Day 42 visit is only for patients whose DSWs do not reach to 100% re-epithelialization on Day 14 but heal on Day 28 as a re-confirmation. 
4. For patients whose visit 8 (Day 42) is scheduled, these visits will be arranged at 90, 180, 270 and 360 days after visit 8 (Day 42); otherwise, these follow-ups will 
be planned at 90, 180, 270 and 360 days after visit 7 (Day28). These long-term follow-ups should be scheduled even if 100% re-epithelialization is not observed 
on Day 28 or Day 42. 
5. For treatment group: TWB-103+TegadermTM. For the control group: placebo+TegadermTM. The application will be discontinued when the 100% re-
epithelialization of DSW is observed by the investigator.  
6. The size of TegadermTM to be used for each patient will be determined by the investigator based on the size of DSW. Whenever TegadermTM falls off from DSW 
site, new TegadermTM should be applied immediately. If necessary, drainage is allowed, but re-application of TWB-103 or placebo is not necessary in this case. 
7. TegadermTM is applied to the wound site after the investigator has finished the wound assessment if the DSW has not reached 100% re-epithelialization, 
regardless the original group assignment.  
8. TegadermTM is dispensed to the patient regardless of the condition of DSWs. Patients are advised to apply TegadermTM to DSW site if the wound open remains 
or reappears, and to re-apply new TegadermTM every 2~3 days till next visit or wound closure. The amount of TegadermTM dispensed should be adequate for 
patient’s use till next visit.  
9. Unused TegadermTM is returned to the study site if TegadermTM is dispensed to the patient at the previous visit. Re-dispensing of unused TegadermTM to the 
same patient is allowed when the primary package of TegadermTM remains intact. 
10. The patient will receive the application of TegadermTM on site for protection of wound site and/or start with other treatment recommended by the investigator if 
DSW does not reached 100% re-epithelialization by Day 28.  
11. When patients are withdrawn from the study by Day 28, they are required to finish all assessments of Day 28, except the application and dispensation of 
TegadermTM. The unused TegadermTM should be returned if received from the previous visit. For patients who have initially scheduled Day 42 visit but make the 
decision between Day 28 to Day 42 to withdraw from the study, he/she should be encouraged to complete assessments planned for Day 42 visit at the earliest 
date convenient for the patients. If patients have entered the long-term follow-up period (i.e. after Day 28 or Day 42 if scheduled) and the decision of withdrawal 
is confirmed, effort must be made to understand and record the reason of withdrawal 
12. In case patients achieve 100% re-epithelialization before or at Day 10, patients will finish up the assessments on the day with 100% re-epithelialization. This 
day of 100% re-epithelialization will be the end of treatment and the remaining scheduled treatment visits, if applicable, will be dismissed. 
13. When patients experience > Grade 2 skin allergic reaction or > Grade 2 systemic allergic reaction related to the product/placebo or develop infection that the 
continuation of TWB-103/placebo is considered inappropriate at the investigator’s discretion, patients should finish the scheduled assessments (except that 
application of TWB-103/placebo is stopped; that the application and dispensation of TegadermTM will be at the investigator’s discretion; and that the return of 
TegadermTM will be asked if applicable) and will continue the remaining visits (application of TWB-103 or placebo will be stopped if planned originally). 
14. When unscheduled visits are requested, patients should finish the assessments of Day 14 (except that the completion of hemogram and serum biochemistry as 
well as the application and dispensation of TegadermTM will be at the investigator’s discretion; and that the return of TegadermTM is not required) during the 
unscheduled visit. The option to choose Vaseline Gauze or Non-Stick Gauze such as silastic foam dressings only can be selected on or after Day 14. 
15. When the first 100% re-epithelialization is not observe by Day 28, the DSWs will be followed till 100% re-epithelialization. 
16. At Visit 9~12, recording of 100% re-epithelialization and the area of target wound are not required. Instead, wound assessment will include scar assessment 
(Vancouver Scar Scale and if necessary, additional comments on scar elasticity, scar color and pigmentation), skin texture (relationship to surrounding skin, 
texture, margins, size and multiplicity) and any altered sensations. 
17. Adverse events will start recording after signing informed consent. 
18. At Visit 9~12, only TWB-103/placebo-relative and DSWs-relative adverse events will be recorded. 


Study Protocol 
TWB-103 for Donor Site Wounds 
(Project Number: 16-FDF-C001) 
Confidential  
Version: 3.0 
Date: 11APR2019 
 
Sponsor: TRANSWELL BIOTECH CO., LTD. 
Prepared by: A2 Healthcare Taiwan Corporation 
Page 22 of 82
19. Randomization will be done before DSW creation but after all baseline procedures are completed and the subject has been deemed eligible for the study. 
20. For Visit 2, the hematologic, biochemical and PRA tests conducted within 7 days prior to Day 0 are acceptable. 
21. Patients should evaluate pain level at the (future) DSW site. 
22. To prevent the itchiness and skin reaction caused by the long-term usage of TegadermTM, Vaseline Gauze or Non-Stick Gauze such as silastic foam dressings 
can be used on and after Day 14 at the investigator’s discretion. 
23. TegadermTM is dispensed only when Day 42 is scheduled. Unused TegadermTM should be returned on Day 42. 
 


Study Protocol 
TWB-103 for Donor Site Wounds 
(Project Number: 16-FDF-C001) 
Confidential  
Version: 3.0 
Date: 11APR2019 
 
Sponsor: TRANSWELL BIOTECH CO., LTD. 
Prepared by: A2 Healthcare Taiwan Corporation 
Page 23 of 82
STUDY SCHEMA 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
*Note: 
Day 42 visit is only for patients whose DSWs do not reach to 100% re-epithelialization on Day 14 but heal on Day 28 as a re-
confirmation. 
 
 
 
TegadermTM  
alone  
TegadermTM  
alone  
Randomization 
TWB-103 + TegadermTM 
up to 10 days 
Screening 
V1         Day 0 
          Day 3 
       Day 7 
    Day 10              Day 14               Day 28            Day 42* 
Treatment  
Long-term follow-ups 
at 90, 180, 270 and 360 
days after Day 28 (if no 
Day 42 visit) or Day 42 
Placebo+TegadermTM 
up to 10 days 
Follow-up 
TegadermTM  
alone  
TegadermTM  
alone 


Study Protocol 
TWB-103 for Donor Site Wounds 
(Project Number: 16-FDF-C001) 
Confidential  
Version: 3.0 
Date: 11APR2019 
 
Sponsor: TRANSWELL BIOTECH CO., LTD. 
Prepared by: A2 Healthcare Taiwan Corporation 
Page 24 of 82
1. 
BACKGROUND AND RATIONALE 
1.1 
General Introduction 
The skin is a vital organ with several major functions: protection, sensation, 
thermoregulation, excretion, absorption, and metabolism. Any breach in skin integrity 
may lead to the disruption of one or more functions as well as pain, discomfort and 
possible infection. Some wounds may be sutured (primary intention healing) whereas 
open wounds may heal by secondary intention, which is a slower process. The longer 
a wound exists, the greater the potential for infection as it will require regular dressing 
changes over a period of time; a procedure that will always carry a risk of potential 
infection. 
Depending on the healing time of a wound, it can be classified as acute or chronic: 
 
Those classified as acute wounds heal with little or no complications in the 
predicted amount of time, such as surgical, thermal and chemical or any 
traumatic type of wounds. 
 
Those classified as chronic wounds take a longer time to heal and often have 
different degree of complications, such as infectious, ischemic, diseases 
(Epidermolysis Bullosa), radiation-poisoning (therapeutic or accidental) or any 
ulceration type of wounds (pressure ulcer, venous leg ulcer, diabetic foot ulcer). 
When wounds are extensive, unsuitable for closure by suturing, or are likely to cause 
physical or psychological problems through scarring, skin grafts should be considered 
in order to accelerate healing and minimize scarring of wounds1.  
Split-thickness skin grafting is the most frequently used reconstructive technique to 
repair damaged or missing skin (e.g. burns, chronic, and traumatic wounds), including 


Study Protocol 
TWB-103 for Donor Site Wounds 
(Project Number: 16-FDF-C001) 
Confidential  
Version: 3.0 
Date: 11APR2019 
 
Sponsor: TRANSWELL BIOTECH CO., LTD. 
Prepared by: A2 Healthcare Taiwan Corporation 
Page 25 of 82
those that cannot be covered by a skin flap, which consists of skin and subcutaneous 
tissue that survives based on its own blood supply, or are not likely to be ameliorated 
by secondary intention. The wound created after harvesting the skin is called the donor 
site wound (DSW). Treatment of the split-thickness graft donor sites has been studied 
over the years, but no standard treatment for managing these sites is confirmed. 
Depending on the thickness of the split skin grafting, the DSW should spontaneously 
re-epithelialize completely in 7 to 21 days. Optimum local care for these DSWs should 
facilitate the wound healing process and be cost-effective, while it should prevent 
associated complications, such as pain, discomfort, infection, and scarring and 
consider the patients’ physical and mental well-being during the treatment process. 
Particularly pain and discomfort are reported to occur with more frequency from 
DSWs than on the recipient site2,3. 
TWB-103 is supplied as a two-component therapeutics consisting of one vial of living 
allogeneic fibroblasts (TWB-102 cells) and one vial of gelatin-based hydrogel (TWB-
103 hydrogel). While the mechanism of healing is multi-modal, TWB-103 does not 
function as a barrier dressing, but rather than a “stimulus” or “aid” to wound healing. 
TWB-102 cells do not persist as occurs in a graft. It is believed that, upon application 
to the wound, the production of cytokines and growth factors by the living cells are the 
key factors responsible for the ability of TWB-103 to enhance healing by secondary 
intention. 
Nonclinical studies have shown that the fibroblasts present within TWB-103 produce 
many of the signaling molecules, such as basic fibroblast growth factors (bFGF), 
platelet-derived growth factor (PDGF), and other growth factors and cytokines that are 
known to be beneficial to the various phases of wound healing (i.e. hemostasis, 
inflammation, proliferation, and remodeling). Additionally, TWB-103 can also 


Study Protocol 
TWB-103 for Donor Site Wounds 
(Project Number: 16-FDF-C001) 
Confidential  
Version: 3.0 
Date: 11APR2019 
 
Sponsor: TRANSWELL BIOTECH CO., LTD. 
Prepared by: A2 Healthcare Taiwan Corporation 
Page 26 of 82
provide wound site a number of matrix proteins that play key structural roles in skin 
and in healing.  
1.2 
Rationale and Justification for the Study 
1.2.1 Rationale for the Study Purpose 
Transwell Biotech Co., Ltd. (TWBIO) seeks approval of an Investigative New 
Drug (IND) for TWB-103. Specifically, TWBIO is seeking regulatory 
permission to apply the product for first-time-in-human for managing surgical 
and donor site wounds in adults due to autografting procedure. The purpose of 
the present phase I/II study is to explore the safety and efficacy profiles of 
TWB-103 in split-thickness skin graft DSW. This study will be conducted via a 
randomized, double-blind, additional evaluator-blind, placebo-controlled, 
multi-center, multi-nation (Taiwan and Japan), parallel fashion.  
1.2.2 Rationale for Doses Selected 
TWB-103 has not yet been previously approved by any regulatory authorities 
in the world. However, the overall safety of TWB-103 has been characterized 
in the animal models of cutaneous wounds. Nonclinical studies of TWB-103 in 
the burn indication have not been performed as the general acute cutaneous 
wounds have more similarities than differences to the wounds of the donor site. 
The nonclinical set of data on TWB-103 includes product characterization, cell 
migration, tumorigenicity and immune-toxicity. The results of these studies do 
not suggest a potential for immunological, toxicological, or oncogenic risks. 
Moreover, efficacy is further supported by more than 15 years of human use 
safety experience in Switzerland of FE002-SK2, the same cell line making 
TWB-103. 


Study Protocol 
TWB-103 for Donor Site Wounds 
(Project Number: 16-FDF-C001) 
Confidential  
Version: 3.0 
Date: 11APR2019 
 
Sponsor: TRANSWELL BIOTECH CO., LTD. 
Prepared by: A2 Healthcare Taiwan Corporation 
Page 27 of 82
1.2.3 Rationale for Study Population 
The study population designed to be enrolled are patients aged at 20-65 years 
old presenting a split-thickness skin graft DSW with a minimum size of 15 cm2 
but no more than 100 cm2, with a minimum width of 3 cm, and with an 
approximate thickness of 0.010~0.012 inches. Since TWB-103 is believed to 
have the ability to regenerate functional skin tissue by modulating and 
improving secondary intention wound healing, the study population is therefore 
selected. 
1.2.4 Rationale for Study Design 
This is a phase I/II study intending to explore the safety and efficacy of TWB-
103 in split-thickness skin graft DSW by adding on TWB-103 to TegadermTM, 
the standard of wound care to compare with placebo+TegadermTM. In this 
study, TWB-103 will be applied as an adjuvant therapy besides Tegaderm TM 
for safety concern since this is a first-time-in-human study for TWB-103 even 
though TWB-103 is believed to be relatively safe and also for ethical concern. 
The ethical issue is also concerned with employing placebo+Tegaderm TM as a 
control. To avoid systematic bias, the study is designed as a double-blind, 
additional evaluator-blind, randomized study.  


Study Protocol 
TWB-103 for Donor Site Wounds 
(Project Number: 16-FDF-C001) 
Confidential  
Version: 3.0 
Date: 11APR2019 
 
Sponsor: TRANSWELL BIOTECH CO., LTD. 
Prepared by: A2 Healthcare Taiwan Corporation 
Page 28 of 82
2. 
OBJECTIVES AND ENDPOINTS  
2.1 
Objectives 
2.1.1 Primary Objectives 
1. To evaluate the safety for Phase I of TWB-103 in split-thickness skin graft 
donor site wounds (DSW) for Phase I in terms of incidence of treatment-related 
AEs and SAEs (including infections and bleeding)  
2. To evaluate the efficacy for Phase I+II of TWB-103 in split-thickness skin 
graft donor site wounds (DSW) in terms of the healing time from DSW 
creation to 100% re-epithelialization 
2.1.2 Secondary Objectives 
1. To evaluate the efficacy of TWB-103 in split-thickness skin graft donor site 
wounds (DSW) in secondary efficacy endpoints 
2. To evaluate the safety of TWB-103 in split-thickness skin graft donor site 
wounds (DSW) in secondary safety endpoints 
2.2 
Endpoints 
2.2.1. Primary endpoints 
The primary endpoint for this study is: 
Phase I 
Safety:  
Incidence of treatment-related AEs and SAEs (including infections and 
bleeding) 
Phase I+II 


Study Protocol 
TWB-103 for Donor Site Wounds 
(Project Number: 16-FDF-C001) 
Confidential  
Version: 3.0 
Date: 11APR2019 
 
Sponsor: TRANSWELL BIOTECH CO., LTD. 
Prepared by: A2 Healthcare Taiwan Corporation 
Page 29 of 82
Efficacy: 
The healing time from DSW creation to the first 100% re-epithelialization with 
confirmation for at least 10 days apart, assessed by the investigator 
2.2.2. Secondary endpoints 
The endpoints used to achieve the secondary objectives of this study are listed 
below: 
Phase I+II 
Efficacy: 
1. The healing time from DSW creation to the first 100% re-epithelialization 
with confirmation for at least 10 days apart, assessed by the first additional 
evaluator 
2. The healing rates (complete wound closure) of patients at Days 7, 10 and 14 
after DSW creation 
Note: Complete wound closure is defined as skin 100% re-epithelialization 
without drainage or dressing requirements. 
3. The healing percentage of wounds (ratio of healing area and original area) at 
Days 7, 10 and 14 after DSW creation 
4. The pain change from baseline to post-wound creation visits based on short-
form McGill pain questionnaire score 
Safety: 
1. Incidence of treatment-related AEs and SAEs (including infections and 
bleeding) 


Study Protocol 
TWB-103 for Donor Site Wounds 
(Project Number: 16-FDF-C001) 
Confidential  
Version: 3.0 
Date: 11APR2019 
 
Sponsor: TRANSWELL BIOTECH CO., LTD. 
Prepared by: A2 Healthcare Taiwan Corporation 
Page 30 of 82
2. Incidence of AEs and SAEs 
3. Changes in post-treatment physical examination, vital signs, and general 
laboratory assessment compared to baseline 
Note: The investigator will determine the end of treatment based on the healing progress. 
Wound healing will be assessed based on the wound observation by the investigator and an 
additional evaluator. An additional evaluator who is not aware of the treatment given will 
evaluate based on photos of the wound. The additional evaluator will receive photos of the 
wound from CRO and will return the assessment to CRO. A second additional evaluator, who 
is also blinded, will be requested when the discrepancy occurs between the investigator and the 
first additional evaluator in the determination of 100% re-epithelialization. 
 


Study Protocol 
TWB-103 for Donor Site Wounds 
(Project Number: 16-FDF-C001) 
Confidential  
Version: 3.0 
Date: 11APR2019 
 
Sponsor: TRANSWELL BIOTECH CO., LTD. 
Prepared by: A2 Healthcare Taiwan Corporation 
Page 31 of 82
3. 
STUDY POPULATION 
3.1 
The Number of Patients to Be Enrolled 
The sample size is determined to be 15 versus 15 evaluable (per-protocol for Phase 
I+II) patients (1:1 ratio) for Treatment versus Control groups, 30 evaluable patients in 
total. To ensure the completion of 30 evaluable patients, around 36 patients will be 
recruited. 
3.2 
Inclusion Criteria 
A patient is eligible for the study if all of the following apply: 
1. Female/male patients, aged 20-65 years old 
2. Presenting a split-thickness skin graft donor site wound with a minimum size of 15 
cm2 but no more than 100 cm2, with a minimum width of 3 cm and with an 
approximate thickness of 0.010~0.012 inches. The graft cannot be harvested from a 
site from which a skin graft was previously obtained. 
3. If the primary wound is a result of a thermal or chemical burn, the total body 
surface area of the said wound must be less than 15%. 
Note: The burn area is estimated based on the method used at the local site. The Rule of Nines Chart 
(1% body surface area equals one patient’s palm size) or Lund and Browder Chart are acceptable. 
4. Females of childbearing potential must have a documented negative serum 
pregnancy test done at the screening visit, which is within 2 weeks prior the DSW 
creation and the treatment 
5. Both male and female patients must agree to use highly effective contraceptives 
from signing informed consent to 30 days after the last dose administration. 
Acceptable contraceptive forms include: 


Study Protocol 
TWB-103 for Donor Site Wounds 
(Project Number: 16-FDF-C001) 
Confidential  
Version: 3.0 
Date: 11APR2019 
 
Sponsor: TRANSWELL BIOTECH CO., LTD. 
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a. Established use of oral, injected or implanted hormonal methods of 
contraception 
b. Placement of an intrauterine device (IUD) or intrauterine system (IUS) 
c. Barrier methods of contraception: Condom or occlusive cap (diaphragm or 
cervical/vault caps) 
6. Willing to comply with the study protocol and has signed the Informed Consent 
Form 
Note: The rationale for the inclusion criteria is described as below. 
1. The lower limit of age, 20 years old is set as the age to participate in clinical trial by self-
responsibility (the legal age of consent is 20 years old in Taiwan and Japan). Upper limit 65 
years old is set because elderly patients tend to be poor in compliance and have poor skin 
quality. 
2. Maximum size of DSW, 100 cm2, is set by the standard of the investigational product, and a 
minimum size of 15 cm2 is set considering that smaller DSW can heal easily and the existing 
standard treatment is sufficient. Minimum width of 3 cm is defined based on commonly 
medical appliance used for DSW creation. The thickness (0.010 - 0.012 inches) of the split skin 
grafting is defined based on clinical practice. And then, to minimize the complexity of safety 
and efficacy evaluation, the skin graft should be obtained from the area that has no previous 
use for skin graft. 
3. To ensure the safety of patients, only mild burn patient (total burn surface area less than 15%) 
can be considered for recruitment 
4-5. The criteria are to ensure the safety of patients, patient’s partners, fetuses and infants. 
6. It is to confirm that the patient complies with this study protocol. 
3.3 
Exclusion Criteria 
Any patient meeting any of the exclusion criteria will be excluded from study 
participation. 


Study Protocol 
TWB-103 for Donor Site Wounds 
(Project Number: 16-FDF-C001) 
Confidential  
Version: 3.0 
Date: 11APR2019 
 
Sponsor: TRANSWELL BIOTECH CO., LTD. 
Prepared by: A2 Healthcare Taiwan Corporation 
Page 33 of 82
1. Female patients who are pregnant or lactating or planning a pregnancy and any 
male patient whose partner (wife) planning a pregnancy from signing informed 
consent to 30 days after the last dose administration. 
2. Clinically significant disease or condition that may compromise graft taken and/or 
donor site healing (e.g. the presence of a bleeding disorder, capillary fragility, 
venous or arterial disorder directly affecting the donor site to be treated, known or 
suspected systemic malignancies, human immunodeficiency virus infection, renal 
or liver disease, uncontrolled diabetes mellitus, thrombocytopenia, vasculitis, poor 
nutritional status). 
3. Patients who are currently receiving or have received the following treatments 
within 4 weeks prior to Screening Visit are excluded from the study:  
a) systemic, or inhaled corticosteroids or immunosuppressant agents; or 
b) therapeutic doses of anticoagulants (e.g. Coumadin, Heparin, low molecular 
weight Heparin) for pre-existing medical conditions, for whom a dose 
interruption from Screening through the end of the study period is 
contraindicated. 
4. Autoimmune disease, e.g. lupus erythematosus, multiple sclerosis. 
5. Hematologic disease, malignancy or hypo-immunity. 
6. History of HIV or congenital immunodeficiency. 
Note: HIV = human immunodeficiency virus 
7. History of alcoholism or drug abuse.  
8. Have used any tobacco product within 1 week prior to Day 0. 
9. Patients previously treated with any cell-based product, including autologous tissue 
at the treatment site. 


Study Protocol 
TWB-103 for Donor Site Wounds 
(Project Number: 16-FDF-C001) 
Confidential  
Version: 3.0 
Date: 11APR2019 
 
Sponsor: TRANSWELL BIOTECH CO., LTD. 
Prepared by: A2 Healthcare Taiwan Corporation 
Page 34 of 82
10. Received an investigational drug, device or biological/bioactive treatment within 
30 days prior to Screening Visit. 
11. Any clinical condition or significant concurrent disease judged by the investigator 
to complicate the evaluation of the trial treatment. 
12. History of sensitivity to bovine or porcine origin of materials, or human serum 
albumin. 
13. DSWs located in the face, over joints, lower legs or the buttocks 
14. Any of the following hematologic abnormalities: 
a. Hemoglobin < 10.0 g/dL 
b. ANC < 1,500/μL, 
c. Platelets < 75,000 /μL 
15. Any of the following serum chemistry abnormalities: 
a. Total bilirubin > 1.5 × ULN, 
b. AST or ALT > 3 × ULN,  
c. γ-GT > 2.5 x ULN, 
d. Alk-P > 2.5 x ULN, 
e. Serum albumin < 2.7 g/dL, 
f. Creatinine >1.5 x ULN 
g. Any other ≥ Grade 2 laboratory abnormality (based on CTCAE) at baseline 
(other than those listed above) 
16. DSWs in area with active skin infection or with skin condition that is considered 
highly susceptible to infection judged by the investigator 


Study Protocol 
TWB-103 for Donor Site Wounds 
(Project Number: 16-FDF-C001) 
Confidential  
Version: 3.0 
Date: 11APR2019 
 
Sponsor: TRANSWELL BIOTECH CO., LTD. 
Prepared by: A2 Healthcare Taiwan Corporation 
Page 35 of 82
Note: The rationale for the exclusion criteria is described as below. 
1. It is to ensure the safety of patients, patient’s partners, fetuses and infants. 
2-7., 12., 14-15. Criteria are set to ensure the safety of patients due to the potential increased 
chance of infection, prolonged wound closure, immunological over-reaction, or other 
complications resulted from these conditions. 
3., 5-8. These conditions and habits may affect the efficacy evaluation of investigational product. 
9-11., 16. Those are to minimize the complexity of safety and efficacy evaluation. 
13. DSW located on face is excluded with ethical consideration. Other locations are excluded to 
minimize the complexity of safety and efficacy evaluation. 
3.4 
Withdrawal Criteria  
Patients may be withdrawn from the trial due to any of the following conditions: 
1. The patient decides to withdraw her/his informed consent form. 
2. Investigator considers that the patient is no longer physically and/or psychologically 
feasible to remain in the study. 
3. The patient refuses to proceed with critical measures for the study endpoints, 
defined as all variables required for primary endpoint evaluation. 
4. The patient has lost to follow-up 
The reasons for discontinuation must be recorded in the Case Report Form (CRF) and 
in the patient’s medical records for all early terminated cases. All study participants 
withdrawn from the study before Day 28 will finish assessments of Visit 7 (Day 28), 
except the application and dispensation of TegadermTM. If the patient has received 
TegadermTM from the visit before withdrawal, the return of TegadermTM should be 
made. For patients who have initially scheduled Day 42 visit but make the decision 
between Day 28 to Day 42 to withdraw from the study, he/she should be encouraged 
to complete assessments planned for Day 42 visit at the earliest date convenient for the 


Study Protocol 
TWB-103 for Donor Site Wounds 
(Project Number: 16-FDF-C001) 
Confidential  
Version: 3.0 
Date: 11APR2019 
 
Sponsor: TRANSWELL BIOTECH CO., LTD. 
Prepared by: A2 Healthcare Taiwan Corporation 
Page 36 of 82
patients. If patients have entered the long-term follow-up period (i.e. after Day 28 or 
Day 42 if scheduled) and the decision of withdrawal is confirmed, effort must be made 
to understand and record the reason of withdrawal. If a patient is discontinued due to 
an AE, every effort will be made to follow the event until resolution. 
3.5 
Patient Replacement 
All patients who drop out of the study will not be replaced. New patients will be 
screened with a newly assigned patient number until the target evaluable patients are 
reached in this study. 
3.6 
Concomitant Treatments 
All medications and supplements taken by the study participant beginning four weeks 
prior to Screening Visit till Visit 8 will be recorded on the appropriate page of the 
Case Report Form (CRF). This record will include the name of the medication, 
frequency, unit dose, dates of the drug was started and stopped, and the indication for 
the use of the drug. 
Patients are allowed to receive routinely used medications or treatments for other 
indications which is judged by the investigator as not affecting the efficacy and safety 
assessments of this study.  
- Prohibited Medications/Treatment 
a) systemic, or inhaled corticosteroids or immunosuppressant, chemotherapeutic 
agents 
b) therapeutic doses of anticoagulants (e.g. Coumadin, Heparin, low molecular weight 
Heparin)  
c) Any treatment/therapy applied to wound area that may affect the efficacy evaluation 
of study medication at the investigator’s discretion 


Study Protocol 
TWB-103 for Donor Site Wounds 
(Project Number: 16-FDF-C001) 
Confidential  
Version: 3.0 
Date: 11APR2019 
 
Sponsor: TRANSWELL BIOTECH CO., LTD. 
Prepared by: A2 Healthcare Taiwan Corporation 
Page 37 of 82
d) Any treatments containing povidone-iodine, chlorhexidine, polymyxin and 
mycostatin, for DSW. 
 


Study Protocol 
TWB-103 for Donor Site Wounds 
(Project Number: 16-FDF-C001) 
Confidential  
Version: 3.0 
Date: 11APR2019 
 
Sponsor: TRANSWELL BIOTECH CO., LTD. 
Prepared by: A2 Healthcare Taiwan Corporation 
Page 38 of 82
4. 
STUDY DESIGN 
This study will be designed in a Phase I/II randomized, double-blind, additional 
evaluator-blind, placebo-controlled, multi-center, multi-nation (Taiwan and Japan), 
parallel manner. This study is to evaluate the safety and efficacy of the TWB-103 in 
adult patients with split-thickness skin graft donor site wounds (DSW). The study will 
recruit 30 evaluable patients, approximately up to 36 patients to be recruited to 
complete a total of 30 evaluable patients. Eligible patients will be randomly assigned 
in 1:1 ratio to one of the following groups: 
Treatment Group: 
TWB-103 add-on TegadermTM till 100% re-epithelialization or up to 10 days, 
whichever comes first, followed by TegadermTM alone application from Day 10 to 
Day 14 if failing to achieve 100% re-epithelialization by Day 10. If 100% re-
epithelialization is not observed on Day 14 (the end of treatment), patients will have 
application of TegadermTM up to Day 28. 
Control Group: 
Placebo+TegadermTM till 100% re-epithelialization or up to 10 days, whichever comes 
first, followed by TegadermTM alone application from Day 10 to Day 14 if failing to 
achieve 100% re-epithelialization by Day 10. If 100% re-epithelialization is not 
observed on Day 14 (the end of treatment), patients will have application of 
TegadermTM up to Day 28. 
Note:  
1. TegadermTM will be renewed at each visit between Visit 3 (Day 3) to Visit 7 (Day 28) if 100% re-
epithelialization is not observed. Whenever TegadermTM falls off from DSW site, new TegadermTM 
should be applied immediately. If necessary, drainage is allowed, but re-application of TWB-103 or 
placebo is not necessary in this case. 


Study Protocol 
TWB-103 for Donor Site Wounds 
(Project Number: 16-FDF-C001) 
Confidential  
Version: 3.0 
Date: 11APR2019 
 
Sponsor: TRANSWELL BIOTECH CO., LTD. 
Prepared by: A2 Healthcare Taiwan Corporation 
Page 39 of 82
2. If the first 100% re-epithelialization is observed on Day 28, patients will be scheduled Day 42 follow-
up and dispensed with TegadermTM. 
3. If the first 100% re-epithelialization is not observed on Day 28, patients will receive the application 
of TegadermTM on site for protection of wound site and/or have other appropriate treatment at the 
investigator’s discretion. The DSWs will be followed till 100% re-epithelialization. 
4. To prevent the itchiness and skin reaction caused by the long-term usage of TegadermTM, Vaseline 
Gauze or Non-Stick Gauze such as silastic foam dressings can be used on and after Day 14 at the 
investigator’s discretion. 
 
In Phase I proportion, eligible patients will be recruited sequentially with one week 
staggering in the initiation of study treatment. Eligible patients will also be 
randomized into 1:1 ratio into one of Treatment (TWB-103+TegadermTM) and Control 
(placebo+TegadermTM) groups. Phase I plan to recruit 3 evaluable TWB-
103+TegadermTM treated and 3 evaluable placebo+TegadermTM treated patients. 
Patients in phase I are considered as evaluable when (1) he/she receives at least one 
dose and has follow-up evaluation at least 14 days after first dose or (2) he/she 
receives at least one dose and has early withdrawn due to safety reasons before Day 
28. When all of those 6 evaluable patients complete the planned treatment period (14 
days or till first 100% re-epithelialization, which comes first), the recruitment of 
patients will be temporarily stopped for 14 days for safety observation. The safety data 
of TWB-103 before and on Day 28 Visit will be reviewed by the sponsor and the 
principal investigator. If no safety issue of TWB-103 is decided, the study will enter 
Phase II portion and eligible patients will be randomized into 1:1 ratio into one of 
Treatment and Control groups. 
Each patient will have treatment for up to 14 days or to the day of 100% re-
epithelialization, whichever comes first. Patients assigned to the Treatment Group will 
receive TWB-103 add-on TegadermTM till 100% re-epithelialization or up to 10 days, 


Study Protocol 
TWB-103 for Donor Site Wounds 
(Project Number: 16-FDF-C001) 
Confidential  
Version: 3.0 
Date: 11APR2019 
 
Sponsor: TRANSWELL BIOTECH CO., LTD. 
Prepared by: A2 Healthcare Taiwan Corporation 
Page 40 of 82
whichever comes first and will receive TegadermTM alone from Day 10 to Day 14 if 
re-epithelialization can not be attained by Day 10. Patients assigned to the Control 
Group will receive placebo+TegadermTM till 100% re-epithelialization or up to 10 
days, whichever comes first and will receive TegadermTM alone from Day 10 to Day 
14 if re-epithelialization can not be attained by Day 10. Patients from either group 
(treatment or control) will have application of TegadermTM alone up to Day 28 if 
100% re-epithelialization of DSWs is not observed on Day 14 (end of treatment).  
Patients will be required to attend scheduled visits at Screening, Day 0 (treatment start 
day), Day 3, Day 7, Day 10, Day 14 (end of treatment). In case patients achieve 100% 
re-epithelialization before or at Day 10, patients will finish up the assessments on the 
day with 100% re-epithelialization. This day of 100% re-epithelialization will be the 
end of treatment and the remaining scheduled treatment visits, if applicable, will be 
dismissed. 
All subjects are scheduled to attend a follow-up visit on Day 28 to evaluate the status 
of the target wound and then enter a 360-day follow-up phase. If the complete wound 
closure occurs by Day 14, the re-confirmation of wound closure should be performed 
on Day 28 follow-up. In the case that complete wound closure occurs at some point 
between Day14 and Day 28, an additional follow-up visit will be scheduled on Day 42 
for the re-confirmation before subject enters the 360-day follow-up phase. If the 
complete wound closure is not observed on Day 28, patients will have other 
appropriate treatment at the investigator’s discretion. The DSWs will be followed till 
100% re-epithelialization. 
During the 360-day follow-up, four follow-up visits will be scheduled at 9014 days, 
18014 days, 27014 days and 36014 days following the subject’s Day 28 visit (if no 


Study Protocol 
TWB-103 for Donor Site Wounds 
(Project Number: 16-FDF-C001) 
Confidential  
Version: 3.0 
Date: 11APR2019 
 
Sponsor: TRANSWELL BIOTECH CO., LTD. 
Prepared by: A2 Healthcare Taiwan Corporation 
Page 41 of 82
Day 42 visit) or Day 42 visit. In total, 5~6 follow-up visits will be scheduled in this 
study for all randomized subjects. 
4.1 
Treatment Assignment 
Eligible patients will be assigned a randomization number in sequential order and each 
of the randomization will determine the allocation of one of the two groups in 1:1 ratio 
as shown below: 
Treatment Group: 
TWB-103 add-on TegadermTM till 100% re-epithelialization or up to 10 days, 
whichever comes first, followed by TegadermTM alone application from Day 10 to 
Day 14 if failing to achieve 100% re-epithelialization by Day 10. If 100% re-
epithelialization is not observed on Day 14 (the end of treatment), patients will have 
application of TegadermTM up to Day 28. 
Control Group: 
Placebo+TegadermTM till 100% re-epithelialization or up to 10 days, whichever comes 
first, followed by TegadermTM alone application from Day 10 to Day 14 if failing to 
achieve 100% re-epithelialization by Day 10. If 100% re-epithelialization is not 
observed on Day 14 (the end of treatment), patients will have application of 
TegadermTM up to Day 28. 
Note:  
1.TegadermTM will be renewed at each visit between Visit 3 (Day 3) to Visit 7 (Day 28) if 100% re-
epithelialization is not observed. Whenever TegadermTM falls off from DSW site, new TegadermTM 
should be applied immediately. If necessary, drainage is allowed, but re-application of TWB-103 or 
placebo is not necessary in this case. 
2. If the first 100% re-epithelialization is observed on Day 28, patients will be scheduled Day 42 follow-
up and dispensed with TegadermTM. 


Study Protocol 
TWB-103 for Donor Site Wounds 
(Project Number: 16-FDF-C001) 
Confidential  
Version: 3.0 
Date: 11APR2019 
 
Sponsor: TRANSWELL BIOTECH CO., LTD. 
Prepared by: A2 Healthcare Taiwan Corporation 
Page 42 of 82
3. If the first 100% re-epithelialization is not observed on Day 28, patients will receive the application 
of TegadermTM on site for protection of wound site and/or have other appropriate treatment at the 
investigator’s discretion. The DSWs will be followed till 100% re-epithelialization. 
4. To prevent the itchiness and skin reaction caused by the long-term usage of TegadermTM, Vaseline 
Gauze or Non-Stick Gauze such as silastic foam dressings can be used on and after Day 14 at the 
investigator’s discretion. 
4.2 
Randomization and Blinding 
Permuted block randomization method stratified by site will be applied to generate 
randomization codes, detailed in the randomization plan. Each randomization number 
will be assigned to individual patients according to the time-sequence for screened 
patient becoming eligible.  
Blinding to patients and the investigator will be performed in this study. Besides, the 
evaluator blinding on wound healing evaluation will also be performed that an 
additional evaluator who is not aware of the treatment given will assess based on the 
photos of the wound. A second additional evaluator, who is also blinded, will be 
requested when the discrepancy occurs between the investigator and the first 
additional evaluator in the determination of 100% re-epithelialization. 
At the initiation of the study, the study center will be instructed on the method for 
breaking the blind. The emergency key (individual random code envelope) will be 
kept by the investigator. Study drug treatment may be revealed only for reasons 
relating to the subject’s safety and when critical therapeutic decisions are contingent 
on knowing the assigned study drug, including conditions listed in Section 4.3.1 and 
4.3.2. Withdrawal of a subject from the study is not a sufficient reason to break the 
blind.  


Study Protocol 
TWB-103 for Donor Site Wounds 
(Project Number: 16-FDF-C001) 
Confidential  
Version: 3.0 
Date: 11APR2019 
 
Sponsor: TRANSWELL BIOTECH CO., LTD. 
Prepared by: A2 Healthcare Taiwan Corporation 
Page 43 of 82
The reason to break the blind must be discussed with the Sponsor prior to breaking the 
blind. Investigator can request this by using the “Emergency Key Open Request 
Form” and sending it to the sponsor’s representative with the rationale described. 
After receiving authorization for unblinding from the Sponsor, the investigator will 
acknowledge with his/her signature and the date on the Emergency Key envelope, then 
open to unblind the specific subject’s treatment assignment. When the blinding code is 
broken, the reason must be fully documented as a written entry in the source 
document. 
Key information will be recorded in the “Emergency Key Open Request Form”, 
including the subject number, the date the blind was broken, the rationale, the person 
who requested the breaking of the blind, and the signatures of the Sponsor 
representative contacted, and the person who broke the blind. The incidence of blind 
broken should be documented in the subject’s case report form (CRF), but no 
emergency key should be revealed. 
4.3 
Stopping rules and unscheduled visits 
4.3.1 Stop the study 
The study will be stopped when > 1/3 of patients in the phase I have developed study 
drug related grade 2 or above SAEs defined as in Section 8. The investigator will 
determine if SAEs are study drug related without breaking the blind. If the cause of 
SAE is inconclusive, the investigator can request to break the blind following the 
procedure stated in Section 4.2. 
4.3.2 Discontinue the study product 
Patients who experience > Grade 2 skin allergic reaction or > Grade 2 systemic 
allergic reaction related to the product or placebo must not receive any further TWB-


Study Protocol 
TWB-103 for Donor Site Wounds 
(Project Number: 16-FDF-C001) 
Confidential  
Version: 3.0 
Date: 11APR2019 
 
Sponsor: TRANSWELL BIOTECH CO., LTD. 
Prepared by: A2 Healthcare Taiwan Corporation 
Page 44 of 82
103 or placebo treatment. If a patient should develop infection at DSW site before Day 
10, he/she will stop the TWB-103 or placebo application at the investigator’s 
discretion. Patients with the aforementioned conditions, before or at Visit 8, should 
finish the scheduled assessments (except that application of TWB-103/placebo is 
stopped; that the application and dispensation of TegadermTM will be at the 
investigator’s discretion; and that the return of TegadermTM will be asked if 
applicable). Patients with allergic reaction or infection may receive appropriate 
treatments at the PI’s discretion, will be monitored throughout the healing process 
(including the recovery from allergic reaction or infection, and the complete closure of 
DSW) and will continue the remaining visits (application of TWB-103 or placebo will 
be stopped if planned originally). In these cases of TWB-103/placebo discontinuation, 
wound assessments performed after onset of allergic reaction or infection will be 
excluded from statistical analysis.  
4.3.3 Withdraw from the study 
Patients may be withdrawn from the study voluntarily or at the investigator’s 
discretion. Refer to Section 3.4 for details. 
4.3.4 Unscheduled visits 
Unscheduled visits can be requested when patients require the investigator’s medical 
attention, e.g. the reopen of DSW but self-care is insufficient, infection, or allergic 
reaction. Patients should finish the assessments of Day 14 (except that the completion 
of hemogram and serum biochemistry as well as the application and dispensation of 
TegadermTM will be at the investigator’s discretion; and that the return of 
TegadermTM is not required) during the unscheduled visit. Patients will resume the 
original planned visits and/or come in additional unscheduled visits at the 


Study Protocol 
TWB-103 for Donor Site Wounds 
(Project Number: 16-FDF-C001) 
Confidential  
Version: 3.0 
Date: 11APR2019 
 
Sponsor: TRANSWELL BIOTECH CO., LTD. 
Prepared by: A2 Healthcare Taiwan Corporation 
Page 45 of 82
investigator’s discretion. The option to choose Vaseline Gauze or Non-Stick Gauze 
such as silastic foam dressings only can be selected on or after Day 14.  
 
 


Study Protocol 
TWB-103 for Donor Site Wounds 
(Project Number: 16-FDF-C001) 
Confidential  
Version: 3.0 
Date: 11APR2019 
 
Sponsor: TRANSWELL BIOTECH CO., LTD. 
Prepared by: A2 Healthcare Taiwan Corporation 
Page 46 of 82
5. 
TRIAL MATERIALS 
5.1 
Trial Product (s) 
TWB-103 is supplied as a two-component therapeutics consisting of one vial of living 
allogeneic fibroblasts and one vial of gelatin-based hydrogel. The two components are 
stored separately as the cells need to stay frozen in a -80oC freezer (with temperature 
not higher than -70oC) and the hydrogel will require a proper storage in a 4oC 
refrigerator (with temperature at 2~6oC). The cell vial and placebo vial can be stored 
approximately up to six months after receiving. The expiration date of IP is printed on 
the label attached to the package of IP as well as the data sheet companying with IP. 
5.2 
Dosage and Administration 
Patients who meet all eligibility requirements for entry into the study will be 
randomized into one of the treatment group or control group in 1:1 ratio as shown 
below: 
Treatment Group: 
TWB-103 add-on TegadermTM till 100% re-epithelialization or up to 10 days, 
whichever comes first, followed by TegadermTM alone application from Day 10 to 
Day 14 if failing to achieve 100% re-epithelialization by Day 10. If 100% re-
epithelialization is not observed on Day 14 (the end of treatment), patients will have 
application of TegadermTM up to Day 28. 
Control Group: 
Placebo+TegadermTM till 100% re-epithelialization or up to 10 days, whichever comes 
first, followed by TegadermTM alone application from Day 10 to Day 14 if failing to 
achieve 100% re-epithelialization by Day 10. If 100% re-epithelialization is not 


Study Protocol 
TWB-103 for Donor Site Wounds 
(Project Number: 16-FDF-C001) 
Confidential  
Version: 3.0 
Date: 11APR2019 
 
Sponsor: TRANSWELL BIOTECH CO., LTD. 
Prepared by: A2 Healthcare Taiwan Corporation 
Page 47 of 82
observed on Day 14 (the end of treatment), patients will have application of 
TegadermTM up to Day 28. 
Note:  
1.TegadermTM will be renewed at each visit between Visit 3 (Day 3) to Visit 7 (Day 28) if 100% re-
epithelialization is not observed. Whenever TegadermTM falls off from DSW site, new TegadermTM 
should be applied immediately. If necessary, drainage is allowed, but re-application of TWB-103 or 
placebo is not necessary in this case. 
2. If the first 100% re-epithelialization is observed on Day 28, patients will be scheduled Day 42 follow-
up and dispensed with TegadermTM. 
3. If the first 100% re-epithelialization is not observed on Day 28, patients will receive the application 
of TegadermTM on site for protection of wound site and/or have other appropriate treatment at the 
investigator’s discretion. The DSWs will be followed till 100% re-epithelialization.  
4. To prevent the itchiness and skin reaction caused by the long-term usage of TegadermTM, Vaseline 
Gauze or Non-Stick Gauze such as silastic foam dressings can be used on and after Day 14 at the 
investigator’s discretion. 
 
After the creation of DSW (Day 0), the wound site will be covered with gauze 
containing epinephrine solution (1:100000) for a few minutes and then TWB-
103+TegadermTM or placebo+TegadermTM will be applied to DSW site immediately 
after. Bipolar electrocautery can be used to stop bleeding in some spots if bleeding 
continues after applying epinephrine and compression for 15 minutes. Dressing will be 
changed every 3~4 days (on Day 3, 7, and 10) following the procedure stated below. 
(1) Remove the TegadermTM. The wound is properly cleaned by gentle wiping 
with gauze pad or cotton swab wetted with normal saline or by rinsing the 
wound with normal saline. The wound is then touched with dry gauze pad 
or cotton swab to remove excessive fluid or moisture. 
(2) Perform wound assessment. 


Study Protocol 
TWB-103 for Donor Site Wounds 
(Project Number: 16-FDF-C001) 
Confidential  
Version: 3.0 
Date: 11APR2019 
 
Sponsor: TRANSWELL BIOTECH CO., LTD. 
Prepared by: A2 Healthcare Taiwan Corporation 
Page 48 of 82
(3) Thaw TWB-102 Cells (the treatment group) or freezing solution (control 
group) at 37C water bath for 60~80 seconds. 
(4) Taking 0.4 mL cells (the treatment group) or freezing solution (control 
group) mixed with 4.6 ml gel hydrogel (pre-melted 37C water bath for ~20 
minutes) in one syringe. 
(5) The final mixture will be applied to the target wounds (0.05 mL mixture/cm2 
wound). 
(6) Cover the wound area with TegadermTM. 
5.3 
Package and Labeling 
The investigational product (IP) will be packaged in vials for each administration. All 
vials will be labeled for study number, vial identifier, prescription instructions, the 
investigator’s name, storage conditions, expiry date, and the descriptions of “Clinical 
trial use only” and “Keep out of the reach of children”.  
5.4 
Storage and Drug Accountability 
The IP shipping is to be arranged by the Sponsor to the study site and to be handled by 
the investigator or the designated pharmacist for management and administration. The 
two components are stored separately as the cells need to stay frozen in a -80oC 
freezer and the hydrogel will require a proper storage at 2~6oC. TWB-103/placebo can 
be stored up to six months before clinical application.  
5.5 
Product Accountability 
All patients are administered IP or control material at the clinical site (Visit 2~4). All 
of the unused IP and control material will be asked to be destroyed on site or returned 
from the clinical site to the sponsor. Each IP and control material shipped, used, and 


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returned will be recorded with a date in order to keep track of the IP and control 
material in precise details. 
5.6 
Assessment of Compliance 
The IP or control material will be administered at the study site at scheduled visits 
(Visit 2~4). Patient compliance should not be a severe issue. However, the study 
monitor will assure the patient’s compliance with the study protocol.  
5.7 
Treatment for Investigational Product Overdose 
Product overdose will not be of concern as the dosing regimen of TWB-103/placebo 
in this study is to be administered at the site by site medical staff and believed to be 
safe. If over dosage should occur, the patient or the person in charge of caring for the 
patient should contact the investigator as early to determine if any immediate medical 
treatment is needed. The patient should also be arranged as soon as possible for 
evaluation before any further IP treatment can be proceeded. This post-overdose visit 
can be an un-scheduled or a regular study visit. The study monitor appointed by the 
sponsor should be contacted by the investigator of any over-dose report as soon as 
being aware of the event. Any unfavorable effects caused by the overdose event must 
be reported as an AE and even SAE. 
5.8 
Other Consideration for Investigational Product 
Because nicotine interferes the wound closure, smoking is not allowed from one week 
prior to Day 0 till Day 14. 
 


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6. 
STUDY ASSESSMENTS 
6.1 
Informed Consent 
All patients must provide signed informed consent at the Screening visit, prior to any 
study-related procedures. Only the institutional review board (IRB) approved 
informed consent form can be used. 
6.2 
 Demographics 
Demographic data, including age, gender, weight and height information will be 
obtained at the Screening visit. 
6.3 
 Pregnancy Test and Contraception 
Patient with childbearing potential must be confirmed of not being pregnant at the 
Screening visit. The pregnancy test should be done at the screening visit, which is 
within 2 weeks prior the DSW creation and the treatment. Both male and female 
patients should also be informed that defined contraceptive methods must be used 
from signing informed consent to 30 days after the last dose administration.  
Acceptable contraceptive forms include: 
a. Established use of oral, injected or implanted hormonal methods of contraception 
b. Placement of an intrauterine device (IUD) or intrauterine system (IUS) 
c. Barrier methods of contraception: Condom or occlusive cap (diaphragm or 
cervical/vault caps) 
6.4 
 Eligibility 
Eligibility should be thoroughly checked by the investigator at Screening Visit. See 
Sections 3.2 and 3.3 for detailed eligibility criteria. 


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6.5 
 Physical Examinations 
The patient will be examined at each scheduled visit by standard physical examination 
items including general appearance, skin, eyes, ears, nose, throat, head and neck, 
heart, chest and lungs, abdomen, extremities, lymph nodes, musculoskeletal, 
neurological, other body systems if applicable for describing the status of the patient’s 
health. 
6.6 
 Medication History 
Previous medications are categorized into therapies relevant or not related to 
cutaneous wound/ulcer at the Screening Visit. The cutaneous wound/ulcer-irrelevant 
therapy should only be recorded up to 4 weeks before study entry. The cutaneous 
wound/ulcer therapy (all kinds of modality) should be recorded for at least 3 months 
prior to Screening Visit. 
6.7 
 Medical History 
The general medical history up to 3 months of study entry should be recorded at the 
Screening Visit. The medical history should include procedural within a 1 year time 
and major surgical history for the life time base. The history of cutaneous wound/ulcer 
for the coming DSW creation will be recorded in the “cutaneous wound/ulcer history” 
part of the CRF, separately. Medical history and cutaneous wound/ulcer history will 
include date of onset, location, and diagnosis, prior therapies, and current status. The 
cutaneous wound/ulcer history should be recorded for lifetime of the patient. 
6.8 
 Vital Signs 
Patient will be measured of blood pressures, pulse rate and body temperature at all 
scheduled visits. 


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6.9 
Hematologic and Biochemical Indexes 
The hematologic and biochemical indexes will be measured at Visit 1~8. For Visit 2, 
the hematologic and biochemical tests conducted within 7 days prior to Day 0 are 
acceptable. The items to be measured include the following: 
Hematology: hemoglobin, hematocrit, Red blood cell (RBC), platelet, White blood 
cell (WBC) with differential counts, Absolute neutrophil count (ANC) 
Biochemistry:  aspartate transaminase (AST), alanine transaminase (ALT), serum 
creatinine, blood urea nitrogen (BUN), albumin, total bilirubin, gamma-glutamyl 
transferase (γ-GT), alkaline phosphatase (Alk-P) 
6.10 
Investigational Product 
Investigational drugs will be administered to eligible patients at Visit 2~4, starting 
with the Administration visit (Day 0). Drug accountability and inventory will be 
recorded in the CRFs and the relevant study log. 
6.11 
Wound assessment 
The wound assessment will be measured at all scheduled visits except the Screening 
Visit.  
From Visit 2 (Day 0) to Visit 8 (Day 42), the investigator will determine the end of 
treatment based on the healing progress. Wound healing will be assessed based on the 
wound observation by the investigator and an additional evaluator. An additional 
evaluator who is not aware of the treatment given will evaluate based on photos of the 
wound. The additional evaluator will receive photos of the wound from CRO and will 
return the assessment to CRO. A second additional evaluator, who is also blinded, will 


Study Protocol 
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be requested when the discrepancy occurs between investigator and the first additional 
evaluator in the determination of 100% re-epithelialization. 
The photos of wound will be taken under the following guidelines. 
(a) Cameras and rulers with the same brand and model will be used throughout the 
study. 
(b) The study staff who are trained will be in charge of taking photos following 
the guidelines for each study center. 
(c) Two different photos will be taken for each wound at each visit: one for the 
calculation of wound healing and the other as the reference of the wound 
location relative to the body part. 
(d) The wound area shown in the photo specific for calculation purpose, along 
with the provided ruler, should have sufficient size and quality for evaluation. 
(e) Images will be processed by the software, Image J. 
(f) The investigator and evaluator(s) will select the boundary of said wound in the 
photo manually and by the wand tool in Image J. 
(g) Calculate the wound size by Image J based on the area selected. 
(h) The healing percentage of wounds will be calculated by the ratio of healing 
area and original area (Day 0). 
Complete wound closure is defined as skin 100% re-epithelialization without drainage 
or dressing requirements. Wound closure should be re-confirmed on Day 28 when the 
complete wound closure occurs by Day 14, or on Day 42 in the case that complete 
wound closure occurs at some point between Day14 and Day 28. 
During the 360 days of follow-up (Visit 9~12), recording of 100% re-epithelialization 
and the area of target wound are not required. Instead, potential long-term adverse 


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events will be determined and recorded, including scar assessment (Vancouver Scar 
Scale and if necessary, additional comments on scar elasticity, scar color and 
pigmentation), skin texture (relationship to surrounding skin, texture, margins, size 
and multiplicity), pain assessment (see section 6.12) and any altered sensations.  
6.12 
Pain assessment 
The pain assessment will be measured by employing short-form McGill pain 
questionnaire and will be performed at all scheduled visits, expect Visit 2 (Day 0), 
starting from the Screening visit. Patients should evaluate pain level at the (future) 
DSW site. 
6.13 
 Exit of Study 
The patient should complete the last follow-up (Visit 12) before exiting from the 
study, regardless of the treatment groups and the wound healing outcome.  
6.14 
Panel reactive antibodies (PRA) test 
All patients (Phase I + Phase II) will be tested with Class I HLA on Day 0 and Day 28. 
The same testing kit should be employed for all labs. For Visit 2, the PRA test 
conducted within 7 days prior to Day 0 is acceptable. 
Note: HLA = Human leukocyte antigen 
6.15 
TegadermTM dispensing and return 
The size of TegadermTM to be used for each patient will be determined by the 
investigator based on the size of DSW. Sufficient amount of TegadermTM will be 
dispensed to patients. The amount of TegadermTM dispensed should be adequate for 
patient’s use till next visit. Patients are advised to apply TegadermTM to DSW site if 
the wound open remains or reappears, and to re-apply new TegadermTM every 2~3 


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days till next visit or wound closure. Whenever TegadermTM falls off from DSW site, 
new TegadermTM should be applied immediately. Unused TegadermTM will be 
returned to the clinical site at the next visit. Re-dispensing of unused TegadermTM to 
the same patient is allowed when the primary package of TegadermTM remains intact.  
TegadermTM will be dispensed to patients from Visit 2 (Day 0) to Visit 7 (Day 28). 
However, at Visit 7 (Day 28), TegadermTM is dispensed only when Visit 8 (Day 42) is 
scheduled. To prevent the itchiness and skin reaction caused by the long-term usage of 
TegadermTM, Vaseline Gauze or Non-Stick Gauze such as silastic foam dressings can 
be used on and after Day 14 at the investigator’s discretion. 
 
 


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7. 
STUDY SCHEDULE 
7.1 
Screening visit  
(Visit 1: within 2 weeks prior to DSW creation) 
 
Explain the nature of the study and have patients to read and sign an Informed 
Consent Form 
 
Assign patient screening number 
 
Obtain demographic characteristics 
 
Obtain medical history 
 
Obtain vital signs 
 
Perform physical examinations 
 
Perform pregnancy test for applicable patients 
 
Obtain blood samples for hemogram and biochemical tests 
 
Screen patients for inclusion/exclusion criteria 
 
Pain questionnaire 
 
Record adverse events 
 
Record prior/concomitant treatments 
 
Randomization (before DSW creation but after all baseline procedures are 
completed and the subject has been deemed eligible for the study) 
7.2 
Administration Visit 
(Visit 2: Day 0) 
Before DSW creation 


Study Protocol 
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 
Perform physical examinations 
 
Obtain vital signs 
 
Obtain blood samples for hemogram and biochemical tests (the hematologic and 
biochemical tests conducted within 7 days prior to Day 0 are acceptable) 
 
Obtain blood samples for PRA test (the PRA test conducted within 7 days prior 
to Day 0 is acceptable) 
After DSW creation 
 
Wound assessment (including the thickness of DSW) 
 
Apply study medications (treatment group: TWB-103+ TegadermTM; control 
group: placebo+TegadermTM) 
 
Dispense TegadermTM to patients 
 
Record adverse events 
 
Record concomitant treatments 
7.3 
Evaluation Visits 
7.3.1   Visit 3: Day 3  1 day 
 
Perform physical examinations 
 
Obtain vital signs 
 
Obtain blood samples for hemogram and biochemical tests 
 
Pain questionnaire  
 
Wound assessment 


Study Protocol 
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Version: 3.0 
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 
Apply study medications (if not 100% re-epithelialization. Treatment group: 
TWB-103+ TegadermTM; control group: placebo+TegadermTM) 
 
Dispense TegadermTM to patients 
 
Return unused TegadermTM (if received at previous visit) 
 
Record adverse events 
 
Record concomitant treatments 
7.3.2   Visit 4: Day 7  1 day 
 
Perform physical examinations 
 
Obtain vital signs 
 
Obtain blood samples for hemogram and biochemical tests 
 
Pain questionnaire  
 
Wound assessment 
 
Apply study medications (if not 100% re-epithelialization. Treatment group: 
TWB-103+ TegadermTM; control group: placebo+TegadermTM) 
 
Dispense TegadermTM to patients  
 
Return unused TegadermTM (if received at previous visit) 
 
Record adverse events 
 
Record concomitant treatments 
7.3.3   Visit 5: Day 10  1 day 
 
Perform physical examinations 
 
Obtain vital signs 


Study Protocol 
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(Project Number: 16-FDF-C001) 
Confidential  
Version: 3.0 
Date: 11APR2019 
 
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Prepared by: A2 Healthcare Taiwan Corporation 
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 
Obtain blood samples for hemogram and biochemical tests 
 
Pain questionnaire  
 
Wound assessment 
 
Apply TegadermTM (if not 100% re-epithelialization, for both treatment and 
control group) 
 
Dispense TegadermTM to patients  
 
Return unused TegadermTM  
 
Record adverse events 
 
Record concomitant treatments 
7.4 
The end of treatment visit 
(Visit 6: Day 14 days  2 days) 
 
Perform physical examinations 
 
Obtain vital signs 
 
Obtain blood samples for hemogram and biochemical tests 
 
Pain questionnaire  
 
Wound assessment 
 
Apply TegadermTM, Vaseline Gauze or Non-Stick Gauze (if not 100% re-
epithelialization, for both treatment and control group) 
 
Dispense TegadermTM, Vaseline Gauze or Non-Stick Gauze to patients 
 
Return unused TegadermTM 
 
Record adverse events 


Study Protocol 
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(Project Number: 16-FDF-C001) 
Confidential  
Version: 3.0 
Date: 11APR2019 
 
Sponsor: TRANSWELL BIOTECH CO., LTD. 
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 
Record concomitant treatments 
7.5 
Follow-up visits 
7.5.1   Visit 7: Day 28  3 days 
 
Perform physical examinations 
 
Obtain vital signs 
 
Obtain blood samples for hemogram and biochemical tests 
 
Obtain blood samples for PRA test 
 
Pain questionnaire  
 
Wound assessment 
 
Apply TegadermTM, Vaseline Gauze or Non-Stick Gauze (if not 100% re-
epithelialization, for both treatment and control group) 
 
Dispense TegadermTM, Vaseline Gauze or Non-Stick Gauze to patients (only for 
patients who have Day 42 Visit) 
 
Return unused TegadermTM, Vaseline Gauze or Non-Stick Gauze 
 
Record adverse events 
 
Record concomitant treatments 
7.5.2   Visit 8: Day 42  3 days 
(Only scheduled when the wound closure is not completed by Day14 but is observed 
on Day 28) 
 
Perform physical examinations 
 
Obtain vital signs 


Study Protocol 
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Version: 3.0 
Date: 11APR2019 
 
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 
Obtain blood samples for hemogram and biochemical tests 
 
Pain questionnaire  
 
Wound assessment 
 
Return unused TegadermTM, Vaseline Gauze or Non-Stick Gauze 
 
Record adverse events 
 
Record concomitant treatments 
7.5.3   Visit 9~12 (90, 180, 270, 360 days  14 days after Visit 7 (if no visit 8) or Visit 
8) 
 
Perform physical examinations 
 
Obtain vital signs 
 
Pain questionnaire  
 
Wound assessment (scar assessment, skin texture and any altered sensations, see 
details in section 6.11) 
 
Record adverse events (only TWB-103/placebo-relative and DSWs-relative 
adverse events will be recorded) 
 
Exit of study (Visit 12) 


Study Protocol 
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8. 
ADVERSE EVENTS 
8.1 
Definitions 
- Adverse Event (AE): 
An AE is any untoward medical occurrence in a patient or clinical investigation 
participant administered a study medication and that does not necessarily have a 
causal relationship with this treatment. An AE can therefore be any unfavorable and 
unintended sign, symptom, or disease temporally associated with the use of a study 
medication, whether or not related to the study medication. Laboratory abnormalities 
should not be recorded as AEs unless determined to be clinically significant by the 
Investigator. 
- Expected AE: 
Expected AE are defined as any event, the specificity or severity of which is consistent 
with the current investigator brochure.  
- Unexpected AE: 
Unexpected AE is defined as any event, the specificity or severity of which is not 
consistent with the current investigator brochure. "Unexpected", as used in this 
definition, refers to an adverse drug experience that has not been previously observed 
(e.g., included in the investigator brochure) rather than from the perspective of such 
experience not being anticipated from the pharmacological properties of the 
pharmaceutical product. 
- Serious Adverse Event (SAE): 
Serious Adverse Event (SAE): A Serious Adverse Event is defined as an AE meeting 
one of the following conditions: 


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 
Death during the period of protocol defined surveillance 
 
Life Threatening Event (defined as a participant at immediate risk of death at 
the time of the event) 
 
An event requiring inpatient hospitalization or prolongation of existing 
hospitalization during the period of protocol defined surveillance  
 
Results in congenital anomaly or birth defect  
 
Results in a persistent or significant disability/incapacity 
 
Based upon appropriate medical judgment, the event may jeopardize the 
participant and may require medical or surgical intervention to prevent one of 
the outcomes listed above. 
8.2 
AE/SAE Intensity and Relationship Assignment 
- AE/SAE Intensity 
The investigator must rate the intensity for all AEs that occur during the study using 
the grades based on CTCAE (v4.03) provided below: 
 Grade 1 (Mild):  
Asymptomatic or mild symptoms; clinical or diagnostic observations only; 
intervention not indicated. 
 
Grade 2 (Moderate):  
Minimal, local or noninvasive intervention indicated; limiting age-appropriate 
instrumental ADL*. 


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 
Grade 3 (Severe or medically significant but not immediately life-threatening):  
Hospitalization or prolongation of hospitalization indicated; disabling; limiting 
self-care ADL**. 
 
Grade 4 (Life threatening consequences):  
Urgent intervention indicated. 
 
Grade 5 (Death related to AE) 
Note: Activities of Daily Living (ADL) 
*Instrumental ADL refer to preparing meals, shopping for groceries or clothes, 
using the telephone, managing money, etc. 
**Self-care ADL refer to bathing, dressing and undressing, feeding self, using 
the toilet, taking medications, and not bedridden. 
Adverse events observed during the study will be coded using Medical Dictionary for 
Regulatory Activities (MedDRA) and will be reported by dose level and overall by 
System/Organ/Class (SOC) classified in MedDRA as appropriate. 
 
- AE/SAE Relationship Assessment 
The investigator will be asked to assess all AEs with respect to their causal 
relationship to the study drug according to the following classification:  
 
Definitely Related  
There is clear evidence to suggest a causal relationship, and other possible 
contributing factors can be ruled out. The clinical event, including an abnormal 
laboratory test result, occurs in a plausible time relationship to study 


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agent/intervention administration and cannot be explained by concurrent disease 
or other drugs or chemicals. The response to withdrawal of the study 
agent/intervention (dechallenge) should be clinically plausible. The event must 
be pharmacologically or phenomenologically definitive, with use of a 
satisfactory rechallenge procedure if necessary. 
 
Probably Related  
There is evidence to suggest a causal relationship, and the influence of other 
factors is unlikely. The clinical event, including an abnormal laboratory test 
result, occurs within a reasonable time sequence to administration of the study 
agent/intervention, is unlikely to be attributed to concurrent disease or other 
drugs or chemicals, and follows a clinically reasonable response on withdrawal 
(dechallenge). Rechallenge information is not required to fulfill this definition.  
 
Possibly Related 
There is some evidence to suggest a causal relationship (e.g., the event occurred 
within a reasonable time after administration of the trial medication). However, 
the influence of other factors may have contributed to the event (e.g., the 
subject’s clinical condition, other concomitant events). Although an adverse 
drug event may rate only as “possible” soon after discovery, it can be flagged as 
requiring more information and later be upgraded to probable or certain as 
appropriate. 
 
Unlikely  
A clinical event, including an abnormal laboratory test result, whose temporal 
relationship to study agent/intervention administration makes a causal 
relationship improbable (e.g., the event did not occur within a reasonable time 


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after administration of the trial medication) and in which other drugs or 
chemicals or underlying disease provides plausible explanations (e.g., the 
subject’s clinical condition, other concomitant treatments).  
 
Not related 
The AE is completely independent of study agent/intervention administration, 
and/or evidence exists that the event is definitely related to another etiology. 
There must be an alternative, definitive etiology documented by the clinician 
Expected Events Related to Disease Process: Provide explicit definitions of the 
type(s), grade(s), and duration(s) of adverse event(s) that will be considered 
disease related. 
8.3 
Collecting, Recording and Reporting of Adverse Events 
8.3.1 Collecting and Reporting of AE 
AEs may be volunteered spontaneously by the study subject, discovered as a 
result of general questioning by the study staff, or determined by physical 
examination. All AEs will be recorded on the CRF. For all AEs, the 
investigator must pursue and obtain adequate information both to determine the 
outcome of the AE and to assess whether it meets the criteria for classification 
as a serious AE requiring immediate notification. AEs should be reported 
starting from signing ICF to the end of study (Visit 12) or to the last visit 
patients finish before withdrawal. Follow-up of the AE, even after the date of 
study drug discontinuation, is required if the AE persists. The study subject 
will be followed until the event resolves or stabilizes at a level acceptable to 
the investigator. 
8.3.2 Reporting of SAE 


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Serious, alarming and/or unusual adverse events must be reported to the 
sponsor/CRO contact within 24 hours of the investigator's knowledge of the 
event. Any event requiring hospitalization (or prolongation of hospitalization) 
that occurs during the course of a subject’s participation in a clinical study 
must be reported as a serious adverse event, except hospitalizations for the 
following: 
•Social reasons in absence of an adverse event 
•Surgery or procedure planned before entry into the study (must be 
documented in the CRF) 
The investigator is responsible to communicate details of medical emergencies 
in trial subjects to the Ethics Committee. Reporting of adverse events will 
comply with US federal regulations, Japanese regulations and Taiwanese 
regulations for IND safety reporting. Sponsor/CRO is responsible to inform the 
events to FDA, PMDA and TFDA.  
Fatal or life-threatening, suspected unexpected ADRs should be notified to 
Local ADR Reporting Center by sponsor/CRO as soon as possible, but no later 
than 7 calendar days, after first acknowledged by the sponsor, and a complete 
report should be followed 8 additional calendar days. This report must include 
an assessment of the importance and implication of the findings and/or 
previous experience on the same or similar medical products. Serious, 
unexpected ADRs that are not fatal or life-threatening must be filed as soon as 
possible but no later than 15 calendar days after first acknowledged by the 
investigator that a case qualifies. 


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The information which sponsor/CRO evaluates as threatening the safety of the 
subject and having impact on the ongoing study should be urgently (as soon as 
possible and within 1 business day following the information receipt date) 
transmitted to the investigators/trial sites via e-mail, etc. from the study 
monitor or person responsible for monitoring out of the safety information to 
be reported to the regulatory authority. In unexpected serious adverse events to 
be reported to the regulatory authority, the information which sponsor/CRO 
considers to be highly emergent safety information (per case) should be 
transmitted to the investigators/trial sites within 30 days following the 
information receipt date. Other serious events to be reported to the regulatory 
authority should be transmitted to the investigators/trial sites as monthly 
periodic report or annual report within 30 days following the transmission 
request date via e-mail, etc. from the study monitor or person responsible for 
monitoring. 
 
8.3.3 Reporting of Pregnancy 
Any patient or patient’s partner who becomes pregnant during the treatment 
period should be recorded and the information regarding this pregnancy should 
be collected. Any pregnancy occurs during the 30 days following the last dose 
of investigational product should also be reported and accompanied 
information should also be collected. When female patient or male patient’s 
partner suspects a pregnancy during the treatment period or within 30 days of 
the last dose, a pregnancy test should be conducted. Once pregnancy is 
confirmed, the patient should stop the administration of investigation product 


Study Protocol 
TWB-103 for Donor Site Wounds 
(Project Number: 16-FDF-C001) 
Confidential  
Version: 3.0 
Date: 11APR2019 
 
Sponsor: TRANSWELL BIOTECH CO., LTD. 
Prepared by: A2 Healthcare Taiwan Corporation 
Page 69 of 82
immediately, if patient is still during the treatment period. The pregnancy 
should be reported to the sponsor using the pregnancy report form. The 
Obstetrician/Gynecologist of the female patient or male patient’s partner 
should be notified the trial information. Because information of specific tests 
regarding this investigational product is not clear yet, whenever possible, a 
pregnancy should be followed to term or to any premature terminations 
reported. Additionally, the status of the mother and child should be reported to 
the sponsor after delivery. Although pregnancy occurring during the trial is not 
considered as an adverse event, any pregnancy complications should be 
recorded as AEs or SAEs. 


Study Protocol 
TWB-103 for Donor Site Wounds 
(Project Number: 16-FDF-C001) 
Confidential  
Version: 3.0 
Date: 11APR2019 
 
Sponsor: TRANSWELL BIOTECH CO., LTD. 
Prepared by: A2 Healthcare Taiwan Corporation 
Page 70 of 82
9. 
DATA ANALYSIS 
9.1 
Data Quality Assurance 
The PI/CRO will provide paper CRFs or electronic CRFs (via EDC system) for the 
recording and collection of subject data and for the collection of data. All CRFs will 
be completed as soon as possible after the subject’s visit. Corrections to data on the 
CRFs will be documented or traced. The investigator will review CRFs to indicate 
that, to his/her knowledge, they are complete and accurate. If further changes are made 
after this, the investigator will need to again sign the investigator signature page or 
approve electronically. Designated source documents will be signed and dated by the 
appropriate study personnel. 
9.2 
Clinical Data Management 
The investigator must agree to complete and maintain source documents and CRFs for 
each subject participating in the study. 
The sponsor/CRO will be responsible for the processing and quality control of the 
data. Data management will be carried out as described in the sponsor/CRO’s standard 
operating procedures (SOPs) for clinical studies. 
The handling of data, including data quality control, will comply with regulatory 
guidelines and the sponsor/CRO’s SOPs as well as provisions of the study-specific 
Data Management Plan if any. 
 


Study Protocol 
TWB-103 for Donor Site Wounds 
(Project Number: 16-FDF-C001) 
Confidential  
Version: 3.0 
Date: 11APR2019 
 
Sponsor: TRANSWELL BIOTECH CO., LTD. 
Prepared by: A2 Healthcare Taiwan Corporation 
Page 71 of 82
10. 
SAMPLE SIZE AND STATISTICAL METHODS 
10.1 
Determination of Sample Size  
The target number will be up to 30 evaluable subjects. Approximately up to 36 
patients will be recruited and to complete a total of 30 evaluable patients. In this study, 
evaluable population will be per-protocol (PP) population defined in Section 10.2. The 
determination of sample size is arbitrary as there is no historical data can be referred.  
10.2 
Statistical and Analytical Plans 
10.2.1 Analysis Population 
Two populations will be introduced for statistical analysis: 
Intent-to-treat (ITT) population:  
• Patients randomized 
• Patients ever treated by at least one dose of trial medication 
• Patients with any post-treatment evaluation 
Per-protocol (PP) population: 
• Dosed with planned dosing regimen of investigational product 
• With efficacy endpoint measurement at wound assessment (with first 
100% re-epithelialization or complete Day 14 visit evaluation) 
• Fulfilling all inclusion and exclusion criteria 
• Without taking prohibited medication 
Since the dosing regimen designed in Phase I are exactly those designed for 
Phase II, and the procedures/schedules of assessment that patients receive are 


Study Protocol 
TWB-103 for Donor Site Wounds 
(Project Number: 16-FDF-C001) 
Confidential  
Version: 3.0 
Date: 11APR2019 
 
Sponsor: TRANSWELL BIOTECH CO., LTD. 
Prepared by: A2 Healthcare Taiwan Corporation 
Page 72 of 82
identical in both phases, the data collected in Phase I portion will be combined 
with those in the Phase II portion for statistical analysis. 
Primary endpoints and secondary efficacy endpoints in Phase I/II will be 
analyzed on ITT and PP population. Non-primary safety endpoints, 
demographics and baseline characteristics will be analyzed on ITT population. 
Conclusion of primary endpoint in Phase I will be made based on ITT 
population analysis results and that in Phase II will be made according to the 
result of ITT population analysis. 
10.2.2 Analysis methods 
For all assessments, the baseline will be defined as the most recently available 
data before the administration of 1st dose treatment. 
Descriptive statistics will be provided by treatment group/country and by all 
for all of the endpoints, including primary and secondary ones. Frequency table 
will be provided for categorical data, while mean, standard deviation, 
maximum, minimum, median, inter-quartile range (IQR), and 95% two-sided 
confidence interval will be calculated for continuous measurements. 
AEs and SAEs will be reported by treatment group/country and physiological 
systems as appropriate. The incidence of treatment-related AEs and SAEs 
between treatments will be analyzed by Cochran-Mantel-Haenszel test (CMH) 
test. 
Incidence of AEs and SAEs will be analyzed by CMH test. Changes in 
physical examinations will be displayed for each individual system. Net 
changes from pre-treatment laboratory test results and vital signs will be 
analyzed by descriptive statistics.  


Study Protocol 
TWB-103 for Donor Site Wounds 
(Project Number: 16-FDF-C001) 
Confidential  
Version: 3.0 
Date: 11APR2019 
 
Sponsor: TRANSWELL BIOTECH CO., LTD. 
Prepared by: A2 Healthcare Taiwan Corporation 
Page 73 of 82
Healing time from DSW creation to 100% re-epithelialization will be 
estimated by using Kaplan-Meier methods and compared between groups by 
using log-rank test. The healing time is defined as from DSW creation to the 
first 100% re-epithelialization with confirmation for at least 10 days apart, 
observed by the investigator and the first additional evaluator.  
If the first 100% re-epithelialization is observed at any visit by Day 28 with 
confirmation for at least 10 days apart, the healing time is noted as the duration 
from the Day of DSW creation to the day of the first 100% re-epithelialization. 
The fulfilling of the visits and/or follow-ups after the 100% re-epithelialization 
date will not be taken into account to determine the healing time. If the 100% 
re-epithelialization is not observed by Day 28 visit, the healing time will be 
censored on day of the last visit up to Day 28 visit. If the 100% re-
epithelialization is observed by Day 28 visit but no confirmation is made, the 
healing time will be censored on day of the last visit up to Day 28 visit. The 
censoring rules will be applied immediately once patients leave the study 
regardless the participation and/or completion of the long-term (360 days) 
follow-ups. 
If patient develops grade 2 or above SAEs and should exit the study 
prematurely before Day 14, he/she should be excluded from the primary 
efficacy analysis, because early censor will result in under estimation of the 
healing time while treatment group (TWB-103+TegadermTM) is prone to have 
higher risk of developing treatment related SAE.  


Study Protocol 
TWB-103 for Donor Site Wounds 
(Project Number: 16-FDF-C001) 
Confidential  
Version: 3.0 
Date: 11APR2019 
 
Sponsor: TRANSWELL BIOTECH CO., LTD. 
Prepared by: A2 Healthcare Taiwan Corporation 
Page 74 of 82
In the cases of TWB-103/placebo discontinuation due to allergic reaction or 
infection, wound assessments performed after onset of allergic reaction or 
infection will be excluded from statistical analysis. 
Healing rates (complete wound closure) of patients at Days 7, 10 and 14 after 
DSW creation will be analyzed by CMH test. Healing percentage of wounds 
(ratio of healing and original areas) at Days 7, 10 and 14 after DSW creation 
will be analyzed by Analysis of variance (ANOVA) model with treatment 
group and country as factor. Score on short-form McGill pain questionnaire 
will be analyzed by using Analysis of covariance (ANCOVA) model with 
treatment group and country as factor and baseline characteristics as covariate. 
Vancouver Scar Scale will be analyzed by Wilcoxon ranked sum test. The 
score in each category (pigmentation, vascularity, pliability and height) and the 
sum score of all category in Vancouver Scar Scale will be analyzed. 
All treatment group comparisons will be conducted with significance level of 
0.05, using 2-tailed tests. 
Demographics and baseline characteristics will be summarized for each 
group/country by using descriptive statistics.  
10.2.3 Interim analyses 
There is no planned interim analysis for this study. The statistical analysis and 
clinical study report writing will be done based on the collected data from the 
study. 
10.2.4 Data and safety monitoring board 
Independent Data and Safety Monitoring Board (DSMB) will not be held. 


Study Protocol 
TWB-103 for Donor Site Wounds 
(Project Number: 16-FDF-C001) 
Confidential  
Version: 3.0 
Date: 11APR2019 
 
Sponsor: TRANSWELL BIOTECH CO., LTD. 
Prepared by: A2 Healthcare Taiwan Corporation 
Page 75 of 82
10.2.5 Missing data estimation 
No missing data imputation will be applied for this study. 


Study Protocol 
TWB-103 for Donor Site Wounds 
(Project Number: 16-FDF-C001) 
Confidential  
Version: 3.0 
Date: 11APR2019 
 
Sponsor: TRANSWELL BIOTECH CO., LTD. 
Prepared by: A2 Healthcare Taiwan Corporation 
Page 76 of 82
11. 
ETHICAL CONSIDERATIONS 
11.1 
Informed Consent 
Informed consent is a process that is initiated prior to the individual’s agreeing to 
participate in the study and continuing throughout the individual’s study participation. 
Extensive discussion of risks and possible benefits of this therapy will be provided to 
the participants and their families.  
Consent forms will be IRB approved and the participant will be asked to read and 
review the document. Upon reviewing the document, the investigator will explain the 
research study to the participant and answer any questions that may arise. The 
participants will sign the informed consent document prior to any procedures being 
done specifically for the study. The participants should have sufficient opportunity to 
discuss the study and process the information in the consent process prior to agreeing 
to participate. The participants may withdraw consent at any time throughout the 
course of the trial. A copy of the informed consent document will be given to the 
participants for their records. The rights and welfare of the participants will be 
protected by emphasizing to them that the quality of their medical care will not be 
adversely affected if they decline to participate in this study. 
11.2 
IRB review 
This protocol and the associated informed consent documents must be submitted to the 
IRB for review and approval. The study will not be initiated until the IRB provides 
written approval of the aforementioned documents and until approval documents have 
been obtained by the Principal Investigator and CRO.  
No changes from the final approved protocol will be initiated without the IRB/IEC’s 
prior written approval or favorable opinion of a written amendment, except when 


Study Protocol 
TWB-103 for Donor Site Wounds 
(Project Number: 16-FDF-C001) 
Confidential  
Version: 3.0 
Date: 11APR2019 
 
Sponsor: TRANSWELL BIOTECH CO., LTD. 
Prepared by: A2 Healthcare Taiwan Corporation 
Page 77 of 82
necessary to eliminate immediate hazards to the study participants or when the change 
involves only logistics or administration. Any significant deviation from the protocol 
when no approved amendment exists will be regarded as a protocol violation, and will 
be addressed as such during the reporting of the study. 
11.3 
Confidentiality of Data and Patient Records 
Include procedures for maintaining participant confidentiality, any special data 
security requirements, and record retention per the sponsor’s requirements. 
Participant confidentiality is strictly held in trust by the participating investigators, and 
their staff. This confidentiality is extended to cover testing of biological samples and 
genetic tests in addition to the clinical information relating to participating patients. 
The study protocol, documentation, data and all other information generated will be 
held in strict confidence. No information concerning the study or the data will be 
released to any unauthorized third party, without prior written approval of the sponsor. 
If applicable, the study monitor or other authorized representatives may inspect all 
documents and records required to be maintained by the Investigator, including but 
not limited to, medical records (office, clinic or hospital) and pharmacy records for the 
participants in this study. The clinical study site will permit access to such records. 
The information provided by sponsor in this protocol and the associated Clinical 
Investigator's Brochure and the data generated by this clinical study is to be 
considered as confidential property of the sponsor. 


Study Protocol 
TWB-103 for Donor Site Wounds 
(Project Number: 16-FDF-C001) 
Confidential  
Version: 3.0 
Date: 11APR2019 
 
Sponsor: TRANSWELL BIOTECH CO., LTD. 
Prepared by: A2 Healthcare Taiwan Corporation 
Page 78 of 82
12. 
PUBLICATIONS 
The data and information associated with this study may be used by sponsor now and 
in the future for the purposes of presentation, publication at the discretion of the 
sponsor or for submission to regulatory agencies. In addition, relative to the release of 
any proprietary information, sponsor reserves the right of prior review of any 
publication or presentation of data from this study. 
In signing this protocol, the investigator agrees to the release of the data from this 
study and acknowledges the above publication policy. 
 


Study Protocol 
TWB-103 for Donor Site Wounds 
(Project Number: 16-FDF-C001) 
Confidential  
Version: 3.0 
Date: 11APR2019 
 
Sponsor: TRANSWELL BIOTECH CO., LTD. 
Prepared by: A2 Healthcare Taiwan Corporation 
Page 79 of 82
13. 
RETENTION OF TRIAL DOCUMENTS 
Records of all participants, including CRFs, all source documentation (containing 
evidence to study eligibility, history and physical findings, laboratory data, results of 
consultations, etc.) as well as IRB records and other regulatory documentation should 
be retained by the PI in a secure storage facility. The records should be accessible for 
inspection and copying by authorized authorities.  
All study documentation at the clinical site and PI records will be archived in 
accordance with ICH GCP, applicable regulations. Study records should not be 
destroyed without prior written agreement between sponsor/CRO and the study 
investigator. 
 


Study Protocol 
TWB-103 for Donor Site Wounds 
(Project Number: 16-FDF-C001) 
Confidential  
Version: 3.0 
Date: 11APR2019 
 
Sponsor: TRANSWELL BIOTECH CO., LTD. 
Prepared by: A2 Healthcare Taiwan Corporation 
Page 80 of 82
14. 
REFERENCES 
1  Beldon P. What you need to know about skin grafts and donor site wounds. Wound 
Essentials 2007; 2: 149–155. 
2  Eskes AM, Brölmann FE, Gerbens LA, Ubbink DT, Vermeulen H. Which dressing 
do donor site wounds need?: study protocol for a randomized controlled trial. Trials 
2011; 12: 229. 
3  Demirtas Y, Yagmur C, Soylemez F, Ozturk N, Demir A. Management of split-
thickness skin graft donor site: A prospective clinical trial for comparison of five 
different dressing materials. Burns 2010; 36: 999–1005. 
 
 
 


Study Protocol 
TWB-103 for Donor Site Wounds 
(Project Number: 16-FDF-C001) 
Confidential  
Version: 3.0 
Date: 11APR2019 
 
Sponsor: TRANSWELL BIOTECH CO., LTD. 
Prepared by: A2 Healthcare Taiwan Corporation 
Page 81 of 82
15. 
PROTOCOL AMENDMENT HISTORY 
The protocol amendment history is made after version 1.6. 
Version 
Date 
Description of Change  
Brief Rationale 
1.6 
25-Jan-2017 
 
 
1.8 
18-Apr-2017 
1. Correct the name of 
solution, the items in the label 
and typos. 
2. Add the rationale for the 
inclusion criteria and exclusion 
criteria. 
3. Include male patients to 
exclusion criteria #1 and add 
the human serum albumin to 
exclusion criteria #12. 
4. Revise the period of 
contraceptive use. 
5. Revise the wound photo 
guideline. 
6. Revise the source of AE 
definitions. 
7. Add the reporting procedure 
of SAE and pregnancy. 
1., 6. Changes are made to 
avoid confusion. 
2. Changes are made to assist 
the understanding of eligibility 
criteria. 
3-4. Changes are made to 
ensure safety of patients. 
5. Changes are made to ensure 
the quality of wound 
assessment. 
7. Changes are made to ensure 
the safety of patients and the 
quality of the study. 
2.0 
25-Sep-2017 
1. Revise the window days for 
Day 28 and Day 42 Visits. 
2. Revise inclusion/exclusion 
criteria including the thickness 
of DSW, tobacco use and the 
limitation of serum albumin. 
3. Define the prohibited 
medications (d) that are 
specific for DSW. 
4. Redefine the assessments for 
unscheduled visit. 
5. Revise the storage condition 
of trial products. 
6. Revise procedures after the 
creation of DSW but before the 
wound assessment, including 
the treatment of bleeding and 
the cleaning of wound. 
7. Revise the duration of 
tobacco use in this study. 
8. Define the window days for 
hematologic, biochemical and 
PRA tests of Visit 2. 
9. Revise the wound photo 
1., 6. Changes are made to 
accommodate clinical practice 
at three study sites. 
2-3., 7., 11., 14. Changes are 
made to ensure safety of 
patients and to minimize the 
complexity of efficacy 
evaluation. 
4., 8. Changes are made to 
reduce unnecessary blood 
samples. 
5. Changes are made to ensure 
the proper storage of the trail 
products. 
9. Changes are made to ensure 
the quality of wound 
assessment. 
10. Changes are made to 
ensure the accuracy of pain 
assessment. 
12-13. Changes are made for 
data analysis. 


Study Protocol 
TWB-103 for Donor Site Wounds 
(Project Number: 16-FDF-C001) 
Confidential  
Version: 3.0 
Date: 11APR2019 
 
Sponsor: TRANSWELL BIOTECH CO., LTD. 
Prepared by: A2 Healthcare Taiwan Corporation 
Page 82 of 82
guideline. 
10. Revise pain assessment, 
including required visits and 
evaluating body part. 
11. Revise the use of 
TegadermTM, including the 
visits of dispensing and two 
additional dressing options for 
Day 14 and later. 
12. Correct the AE grading 
guidelines and the use of 
MedDRA. 
13. Define the baseline for all 
assessments. 
14. Revise withdrawal 
procedures. 
3.0 
11-Apr-2019 
1. The number of evaluable 
subjects remains unchanged 
(30), but “(20 from Taiwan and 
10 from Japan)” is deleted. 
2. The number of recruited 
subjects remains unchanged 
(approx. 36), but “(24 from 
Taiwan, 12 from Japan)” is 
deleted. 
To facilitate patient 
recruitment.