Donor Site Complication
Conditions
Keywords
Donor Site Wounds
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follow-up evaluation at least 14 days after the first dose or (2) he/she who received at least one dose and had early withdrawn due to safety reasons before Day 28.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.
Interventions
DRUGTWB-103 Group
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.
DRUGPlacebo Group
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.
Sponsors
A2 Healthcare Taiwan Corporation
Transwell Biotech Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
20 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
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%. 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. 6. Willing to comply with the study protocol and to sign the Informed Consent Form
Exclusion criteria
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 take 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 study entry are excluded from the study: 1. systemic or inhaled corticosteroids or immunosuppressant agents; or 2. 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. 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 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: (Hemoglobin \< 10.0 g/dL, ANC \< 1,500/μL, platelets \< 75,000 /μL) 15. Any of the following serum chemistry abnormalities: (Total bilirubin \> 1.5 × ULN, AST or ALT \> 3 × ULN, gamma-GT \> 2.5 x ULN, Alk-P \> 2.5 x ULN, serum albumin \< 2.7 g/dL, creatinine \>1.5 x ULN, 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment-related AEs and SAEs (Including Infections and Bleeding) | Day 0~Day 28 | The number of participants with treatment-related AEs and SAEs (including infections and bleeding) will be observed for the 7 patients in Phase I |
| The Healing Time From DSW Creation to the First 100% Re-epithelialization With Confirmation for at Least 10 Days Apart Assessed by the Investigator | Days 42 or earlier | The healing time from DSW creation to the first 100% re-epithelialization with confirmation for at least 10 days apart assessed by the investigator for all patients in Phase I and II. |
| Number of Participants Reached Confirmed Healing Within 28 Days. | Days 42 or earlier | The number of participants in Phase I and II reached confirmed healing by the investigator within 28 days. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The Healing Percentage of Wounds (Ratio of Healing Area and Original Area) at Days 7, 10 and 14 After DSW Creation | Day 7, 10 and 14 | The healing percentage of wounds will be calculated based on the healing area measured on Day 7, 10 and 14, comparing to the original area measured on Day 0 for all patients in Phase I and II. |
| The Pain Change From Baseline to Post-wound Creation Visits Based on Short-form McGill Pain Questionnaire Score | Days 3, 7, 10, 14, 28, 42, Day 90/180/270/360 from Day 28 or 42 | All patients in Phase I and II will evaluate the pain based on Short-form McGill pain questionnaire at each visit. The visual analogue scale (VAS) for pain is a continuous scale comprised of a horizontal line, usually, 10 cm (= 100 mm) in length, scored from 0 (none) to 10 (extreme). On this scale, a higher score in VAS indicates the worse pain. |
| Number of Participants With AEs and SAEs | Screening~ Day 360 from Day 28 or 42 | The number of participants with AEs and SAEs will be analyzed for all patients in Phase I and II. |
| Changes in Post-treatment Vital Signs-pulse Rate Compared to Baseline | Days 3, 7, 10, 14, 28, 42 | Changes in post-treatment vital signs-pulse rate will be analyzed for all patients in Phase I and II. |
| Changes in Post-treatment Vital Signs-body Temperature Compared to Baseline | Days 3, 7, 10, 14, 28, 42 | Changes in post-treatment vital signs-body temperature will be analyzed for all patients in Phase I and II. |
| Changes in Post-treatment Vital Signs-systolic Blood Pressure Compared to Baseline | Days 3, 7, 10, 14, 28, 42 | Changes in post-treatment vital signs-systolic blood pressure will be analyzed for all patients in Phase I and II. |
| Changes in Post-treatment Vital Signs-diastolic Blood Pressure Compared to Baseline | Days 3, 7, 10, 14, 28, 42 | Changes in post-treatment vital signs-diastolic blood pressure will be analyzed for all patients in Phase I and II. |
| Changes in Post-treatment General Laboratory Assessment-hematology-white Blood Cells Compared to Baseline | Days 3, 7, 10, 14, 28, 42 | Changes in post-treatment general laboratory assessment-hematology-white blood cells will be analyzed for all patients in Phase I and II. |
| Changes in Post-treatment General Laboratory Assessment-hematology-neutrophils Compared to Baseline | Days 3, 7, 10, 14, 28, 42 | Changes in post-treatment general laboratory assessment-hematology-neutrophils will be analyzed for all patients in Phase I and II. |
| Changes in Post-treatment General Laboratory Assessment-hematology-Hemoglobin Compared to Baseline | Days 3, 7, 10, 14, 28, 42 | Changes in post-treatment general laboratory assessment-hematology-hemoglobin will be analyzed for all patients in Phase I and II. |
| Changes in Post-treatment General Laboratory Assessment-hematology-Hematocrit Compared to Baseline | Days 3, 7, 10, 14, 28, 42 | Changes in post-treatment general laboratory assessment-hematology-hematocrit will be analyzed for all patients in Phase I and II. |
| Changes in Post-treatment Physical Examination Compared to Baseline | Days 3, 7, 10, 14, 28, 42 | Changes in post-treatment physical examination will be analyzed for all patients in Phase I and II. |
| Changes in Post-treatment General Laboratory Assessment-hematology-red Blood Cells Compared to Baseline | Days 3, 7, 10, 14, 28, 42 | Changes in post-treatment general laboratory assessment-hematology-red blood cells will be analyzed for all patients in Phase I and II. |
| Changes in Post-treatment General Laboratory Assessment-biochemistry-aspartate Aminotransferase Compared to Baseline | Days 3, 7, 10, 14, 28, 42 | Changes in post-treatment general laboratory assessment-biochemistry-aspartate aminotransferase will be analyzed for all patients in Phase I and II. |
| Changes in Post-treatment General Laboratory Assessment-biochemistry-alanine Aminotransferase Compared to Baseline | Days 3, 7, 10, 14, 28, 42 | Changes in post-treatment general laboratory assessment-biochemistry-alanine aminotransferase will be analyzed for all patients in Phase I and II. |
| Changes in Post-treatment General Laboratory Assessment-biochemistry-serum Creatinine Compared to Baseline | Days 3, 7, 10, 14, 28, 42 | Changes in post-treatment general laboratory assessment-biochemistry-serum creatinine will be analyzed for all patients in Phase I and II. |
| Changes in Post-treatment General Laboratory Assessment-biochemistry-blood Urea Nitrogen Compared to Baseline | Days 3, 7, 10, 14, 28, 42 | Changes in post-treatment general laboratory assessment-biochemistry-blood urea nitrogen will be analyzed for all patients in Phase I and II. |
| Changes in Post-treatment General Laboratory Assessment-biochemistry-Albumin Compared to Baseline | Days 3, 7, 10, 14, 28, 42 | Changes in post-treatment general laboratory assessment-biochemistry-albumin will be analyzed for all patients in Phase I and II. |
| Changes in Post-treatment General Laboratory Assessment-biochemistry-bilirubin Compared to Baseline | Days 3, 7, 10, 14, 28, 42 | Changes in post-treatment general laboratory assessment-biochemistry-bilirubin will be analyzed for all patients in Phase I and II. |
| Changes in Post-treatment General Laboratory Assessment-biochemistry-gamma-glutamyl Transferase Compared to Baseline | Days 3, 7, 10, 14, 28, 42 | Changes in post-treatment general laboratory assessment-biochemistry-gamma-glutamyl transferase will be analyzed for all patients in Phase I and II. |
| Changes in Post-treatment General Laboratory Assessment-biochemistry-alkaline Phosphatase Compared to Baseline | Days 3, 7, 10, 14, 28, 42 | Changes in post-treatment general laboratory assessment-biochemistry-alkaline phosphatase will be analyzed for all patients in Phase I and II. |
| Number of Participants With Treatment-related AEs and SAEs (Including Infections and Bleeding) | Screening~ Day 360 from Day 28 or 42 | The number of participants with treatment-related AEs and SAEs (including infections and bleeding) will be observed for all patients in Phase I and II |
| The Number of Censored Subjects Assessed by the Investigator and the First Additional Evaluator | Days 42 or earlier | The number of censored subjects in Phase I and II assessed by the investigator and the first additional evaluator. The first additional evaluator judged the healing status by looking at the photos of DSW. If the 100% re-epithelialization was not observed by Day 28 visit, the healing time was censored on the day of the last visit up to Day 28 visit. If the 100% re-epithelialization was observed by Day 28 visit but no confirmation was made, the healing time was censored on day of the last visit up to Day 28 visit. |
| Changes in Post-treatment General Laboratory Assessment-hematology-platelets Compared to Baseline | Days 3, 7, 10, 14, 28, 42 | Changes in post-treatment general laboratory assessment-hematology-platelets will be analyzed for all patients in Phase I and II. |
| 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 | Days 42 or earlier | The healing time from DSW creation to the first 100% re-epithelialization with confirmation for at least 10 days apart assessed by the investigator for all patients in Phase I and II. The first additional evaluator judged the healing status by looking at the photos of DSW. |
| Number of Participants With Complete Wound Closure at Day 7, 10 and 14 After DSW Creation. | Day 7, 10 and 14 | Complete wound closure is defined as skin 100% re-epithelialization without drainage or dressing requirements. This endpoint will be in all patients in Phase I and II. |
Countries
Japan, Taiwan
Participant flow
Recruitment details
This was a multicenter study enrolling subjects from one site in Taiwan and two sites in Japan, between July 06, 2017 and May 07, 2021.
Pre-assignment details
48 subjects were screened in this study; 8 subjects were screen failures, resulting in 40 randomized subjects.
Participants by arm
| Arm | Count |
|---|---|
| TWB-103 Group 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. The baseline was defined as the most recently available data before the administration of 1st dose treatment. | 20 |
| Placebo Group 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. The baseline was defined as the most recently available data before the administration of 1st dose treatment. | 20 |
| Total | 40 |
Baseline characteristics
| Characteristic | TWB-103 Group | Placebo Group | Total |
|---|---|---|---|
| Age, Continuous | 44.8 years STANDARD_DEVIATION 14.53 | 42.2 years STANDARD_DEVIATION 14.56 | 43.5 years STANDARD_DEVIATION 14.41 |
| Baseline Donor Site Wound (DSW) Size | 53.37 cm^2 STANDARD_DEVIATION 18.726 | 40.91 cm^2 STANDARD_DEVIATION 19.427 | 47.14 cm^2 STANDARD_DEVIATION 19.863 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 20 Participants | 20 Participants | 40 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment Japan | 5 participants | 5 participants | 10 participants |
| Region of Enrollment Taiwan | 15 participants | 15 participants | 30 participants |
| Sex: Female, Male Female | 7 Participants | 9 Participants | 16 Participants |
| Sex: Female, Male Male | 13 Participants | 11 Participants | 24 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 20 | 0 / 20 |
| other Total, other adverse events | 7 / 20 | 10 / 20 |
| serious Total, serious adverse events | 0 / 20 | 0 / 20 |
Outcome results
Primary
Number of Participants Reached Confirmed Healing Within 28 Days.
The number of participants in Phase I and II reached confirmed healing by the investigator within 28 days.
Time frame: Days 42 or earlier
Population: Case first 100% re-epithelialization at any visit till Visit 7 (Day 28 Visit) with confirmation for at least 10 days apart:~Healing Time \[days\] = date of first 100% re-epithelialization - date of DSW creation (Visit 2).~Case else: Censored Healing Time \[days\] = date of last assessment up to Visit 7 - date of DSW creation (Visit 2).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| TWB-103 Group | Number of Participants Reached Confirmed Healing Within 28 Days. | 19 Participants |
| Placebo Group | Number of Participants Reached Confirmed Healing Within 28 Days. | 14 Participants |
p-value: 0.0324Cochran-Mantel-Haenszel
Primary
Number of Participants With Treatment-related AEs and SAEs (Including Infections and Bleeding)
The number of participants with treatment-related AEs and SAEs (including infections and bleeding) will be observed for the 7 patients in Phase I
Time frame: Day 0~Day 28
Population: 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.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| TWB-103 Group | Number of Participants With Treatment-related AEs and SAEs (Including Infections and Bleeding) | Treatment-Related AEs | 0 Participants |
| TWB-103 Group | Number of Participants With Treatment-related AEs and SAEs (Including Infections and Bleeding) | SAEs | 0 Participants |
| Placebo Group | Number of Participants With Treatment-related AEs and SAEs (Including Infections and Bleeding) | Treatment-Related AEs | 0 Participants |
| Placebo Group | Number of Participants With Treatment-related AEs and SAEs (Including Infections and Bleeding) | SAEs | 0 Participants |
Primary
The Healing Time From DSW Creation to the First 100% Re-epithelialization With Confirmation for at Least 10 Days Apart Assessed by the Investigator
The healing time from DSW creation to the first 100% re-epithelialization with confirmation for at least 10 days apart assessed by the investigator for all patients in Phase I and II.
Time frame: Days 42 or earlier
Population: Case first 100% re-epithelialization at any visit till Visit 7 (Day 28 Visit) with confirmation for at least 10 days apart:~Healing Time \[days\] = date of first 100% re-epithelialization - date of DSW creation (Visit 2).~Case else: Censored Healing Time \[days\] = date of last assessment up to Visit 7 - date of DSW creation (Visit 2).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| TWB-103 Group | The Healing Time From DSW Creation to the First 100% Re-epithelialization With Confirmation for at Least 10 Days Apart Assessed by the Investigator | 9 Healing Time [days] |
| Placebo Group | The Healing Time From DSW Creation to the First 100% Re-epithelialization With Confirmation for at Least 10 Days Apart Assessed by the Investigator | 10 Healing Time [days] |
p-value: 0.2217Cochran-Mantel-Haenszel
Secondary
Changes in Post-treatment General Laboratory Assessment-biochemistry-alanine Aminotransferase Compared to Baseline
Changes in post-treatment general laboratory assessment-biochemistry-alanine aminotransferase will be analyzed for all patients in Phase I and II.
Time frame: Days 3, 7, 10, 14, 28, 42
Population: The general laboratory assessment-biochemistry-alanine aminotransferase of each subject was examined at all scheduled visits.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| TWB-103 Group | Changes in Post-treatment General Laboratory Assessment-biochemistry-alanine Aminotransferase Compared to Baseline | Adjusted Visit 4 (Day 7) | 29.25 Alanine Aminotransferase [U/L] | Standard Deviation 24.512 |
| TWB-103 Group | Changes in Post-treatment General Laboratory Assessment-biochemistry-alanine Aminotransferase Compared to Baseline | Adjusted Visit 6 (Day 14) | 62.20 Alanine Aminotransferase [U/L] | Standard Deviation 54.509 |
| TWB-103 Group | Changes in Post-treatment General Laboratory Assessment-biochemistry-alanine Aminotransferase Compared to Baseline | Adjusted Visit 3 (Day 3) | 32.79 Alanine Aminotransferase [U/L] | Standard Deviation 42.926 |
| TWB-103 Group | Changes in Post-treatment General Laboratory Assessment-biochemistry-alanine Aminotransferase Compared to Baseline | Adjusted Visit 7 (Day 28) | 21.63 Alanine Aminotransferase [U/L] | Standard Deviation 16.78 |
| TWB-103 Group | Changes in Post-treatment General Laboratory Assessment-biochemistry-alanine Aminotransferase Compared to Baseline | Adjusted Visit 5 (Day 10) | 31.89 Alanine Aminotransferase [U/L] | Standard Deviation 29.57 |
| TWB-103 Group | Changes in Post-treatment General Laboratory Assessment-biochemistry-alanine Aminotransferase Compared to Baseline | Visit 8 (Day 42) | 54.50 Alanine Aminotransferase [U/L] | Standard Deviation 62.933 |
| TWB-103 Group | Changes in Post-treatment General Laboratory Assessment-biochemistry-alanine Aminotransferase Compared to Baseline | Baseline | 25.30 Alanine Aminotransferase [U/L] | Standard Deviation 18.374 |
| Placebo Group | Changes in Post-treatment General Laboratory Assessment-biochemistry-alanine Aminotransferase Compared to Baseline | Visit 8 (Day 42) | 28.00 Alanine Aminotransferase [U/L] | Standard Deviation 2.828 |
| Placebo Group | Changes in Post-treatment General Laboratory Assessment-biochemistry-alanine Aminotransferase Compared to Baseline | Baseline | 28.20 Alanine Aminotransferase [U/L] | Standard Deviation 16.776 |
| Placebo Group | Changes in Post-treatment General Laboratory Assessment-biochemistry-alanine Aminotransferase Compared to Baseline | Adjusted Visit 3 (Day 3) | 22.95 Alanine Aminotransferase [U/L] | Standard Deviation 14.125 |
| Placebo Group | Changes in Post-treatment General Laboratory Assessment-biochemistry-alanine Aminotransferase Compared to Baseline | Adjusted Visit 4 (Day 7) | 27.15 Alanine Aminotransferase [U/L] | Standard Deviation 15.301 |
| Placebo Group | Changes in Post-treatment General Laboratory Assessment-biochemistry-alanine Aminotransferase Compared to Baseline | Adjusted Visit 5 (Day 10) | 26.22 Alanine Aminotransferase [U/L] | Standard Deviation 15.619 |
| Placebo Group | Changes in Post-treatment General Laboratory Assessment-biochemistry-alanine Aminotransferase Compared to Baseline | Adjusted Visit 6 (Day 14) | 25.20 Alanine Aminotransferase [U/L] | Standard Deviation 23.868 |
| Placebo Group | Changes in Post-treatment General Laboratory Assessment-biochemistry-alanine Aminotransferase Compared to Baseline | Adjusted Visit 7 (Day 28) | 28.28 Alanine Aminotransferase [U/L] | Standard Deviation 24.826 |
Secondary
Changes in Post-treatment General Laboratory Assessment-biochemistry-Albumin Compared to Baseline
Changes in post-treatment general laboratory assessment-biochemistry-albumin will be analyzed for all patients in Phase I and II.
Time frame: Days 3, 7, 10, 14, 28, 42
Population: The general laboratory assessment-biochemistry-albumin of each subject was examined at all scheduled visits.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| TWB-103 Group | Changes in Post-treatment General Laboratory Assessment-biochemistry-Albumin Compared to Baseline | Adjusted Visit 6 (Day 14) | 4.02 Albumin [g/dL] | Standard Deviation 0.585 |
| TWB-103 Group | Changes in Post-treatment General Laboratory Assessment-biochemistry-Albumin Compared to Baseline | Baseline | 4.24 Albumin [g/dL] | Standard Deviation 0.411 |
| TWB-103 Group | Changes in Post-treatment General Laboratory Assessment-biochemistry-Albumin Compared to Baseline | Adjusted Visit 3 (Day 3) | 3.99 Albumin [g/dL] | Standard Deviation 0.54 |
| TWB-103 Group | Changes in Post-treatment General Laboratory Assessment-biochemistry-Albumin Compared to Baseline | Adjusted Visit 4 (Day 7) | 4.12 Albumin [g/dL] | Standard Deviation 0.586 |
| TWB-103 Group | Changes in Post-treatment General Laboratory Assessment-biochemistry-Albumin Compared to Baseline | Adjusted Visit 5 (Day 10) | 3.86 Albumin [g/dL] | Standard Deviation 0.529 |
| TWB-103 Group | Changes in Post-treatment General Laboratory Assessment-biochemistry-Albumin Compared to Baseline | Adjusted Visit 7 (Day 28) | 4.31 Albumin [g/dL] | Standard Deviation 0.401 |
| TWB-103 Group | Changes in Post-treatment General Laboratory Assessment-biochemistry-Albumin Compared to Baseline | Visit 8 (Day 42) | 4.45 Albumin [g/dL] | Standard Deviation 0.212 |
| Placebo Group | Changes in Post-treatment General Laboratory Assessment-biochemistry-Albumin Compared to Baseline | Adjusted Visit 7 (Day 28) | 4.33 Albumin [g/dL] | Standard Deviation 0.387 |
| Placebo Group | Changes in Post-treatment General Laboratory Assessment-biochemistry-Albumin Compared to Baseline | Adjusted Visit 5 (Day 10) | 3.98 Albumin [g/dL] | Standard Deviation 0.377 |
| Placebo Group | Changes in Post-treatment General Laboratory Assessment-biochemistry-Albumin Compared to Baseline | Baseline | 4.08 Albumin [g/dL] | Standard Deviation 0.492 |
| Placebo Group | Changes in Post-treatment General Laboratory Assessment-biochemistry-Albumin Compared to Baseline | Adjusted Visit 6 (Day 14) | 4.30 Albumin [g/dL] | Standard Deviation 0.2 |
| Placebo Group | Changes in Post-treatment General Laboratory Assessment-biochemistry-Albumin Compared to Baseline | Adjusted Visit 3 (Day 3) | 3.87 Albumin [g/dL] | Standard Deviation 0.526 |
| Placebo Group | Changes in Post-treatment General Laboratory Assessment-biochemistry-Albumin Compared to Baseline | Visit 8 (Day 42) | 4.50 Albumin [g/dL] | Standard Deviation 0.283 |
| Placebo Group | Changes in Post-treatment General Laboratory Assessment-biochemistry-Albumin Compared to Baseline | Adjusted Visit 4 (Day 7) | 4.09 Albumin [g/dL] | Standard Deviation 0.528 |
Secondary
Changes in Post-treatment General Laboratory Assessment-biochemistry-alkaline Phosphatase Compared to Baseline
Changes in post-treatment general laboratory assessment-biochemistry-alkaline phosphatase will be analyzed for all patients in Phase I and II.
Time frame: Days 3, 7, 10, 14, 28, 42
Population: The general laboratory assessment-biochemistry-alkaline phosphatase of each subject was examined at all scheduled visits.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| TWB-103 Group | Changes in Post-treatment General Laboratory Assessment-biochemistry-alkaline Phosphatase Compared to Baseline | Adjusted Visit 6 (Day 14) | 138.80 Alkaline Phosphatase [U/L] | Standard Deviation 101.935 |
| TWB-103 Group | Changes in Post-treatment General Laboratory Assessment-biochemistry-alkaline Phosphatase Compared to Baseline | Baseline | 102.65 Alkaline Phosphatase [U/L] | Standard Deviation 74.944 |
| TWB-103 Group | Changes in Post-treatment General Laboratory Assessment-biochemistry-alkaline Phosphatase Compared to Baseline | Adjusted Visit 3 (Day 3) | 97.95 Alkaline Phosphatase [U/L] | Standard Deviation 63.847 |
| TWB-103 Group | Changes in Post-treatment General Laboratory Assessment-biochemistry-alkaline Phosphatase Compared to Baseline | Adjusted Visit 4 (Day 7) | 104.63 Alkaline Phosphatase [U/L] | Standard Deviation 70.811 |
| TWB-103 Group | Changes in Post-treatment General Laboratory Assessment-biochemistry-alkaline Phosphatase Compared to Baseline | Adjusted Visit 5 (Day 10) | 156.22 Alkaline Phosphatase [U/L] | Standard Deviation 74.933 |
| TWB-103 Group | Changes in Post-treatment General Laboratory Assessment-biochemistry-alkaline Phosphatase Compared to Baseline | Adjusted Visit 7 (Day 28) | 108.16 Alkaline Phosphatase [U/L] | Standard Deviation 84.534 |
| TWB-103 Group | Changes in Post-treatment General Laboratory Assessment-biochemistry-alkaline Phosphatase Compared to Baseline | Visit 8 (Day 42) | 156.50 Alkaline Phosphatase [U/L] | Standard Deviation 118.087 |
| Placebo Group | Changes in Post-treatment General Laboratory Assessment-biochemistry-alkaline Phosphatase Compared to Baseline | Adjusted Visit 7 (Day 28) | 114.00 Alkaline Phosphatase [U/L] | Standard Deviation 82.523 |
| Placebo Group | Changes in Post-treatment General Laboratory Assessment-biochemistry-alkaline Phosphatase Compared to Baseline | Adjusted Visit 5 (Day 10) | 158.89 Alkaline Phosphatase [U/L] | Standard Deviation 79.899 |
| Placebo Group | Changes in Post-treatment General Laboratory Assessment-biochemistry-alkaline Phosphatase Compared to Baseline | Baseline | 107.65 Alkaline Phosphatase [U/L] | Standard Deviation 79.693 |
| Placebo Group | Changes in Post-treatment General Laboratory Assessment-biochemistry-alkaline Phosphatase Compared to Baseline | Adjusted Visit 6 (Day 14) | 196.40 Alkaline Phosphatase [U/L] | Standard Deviation 91.694 |
| Placebo Group | Changes in Post-treatment General Laboratory Assessment-biochemistry-alkaline Phosphatase Compared to Baseline | Adjusted Visit 3 (Day 3) | 101.35 Alkaline Phosphatase [U/L] | Standard Deviation 73.382 |
| Placebo Group | Changes in Post-treatment General Laboratory Assessment-biochemistry-alkaline Phosphatase Compared to Baseline | Visit 8 (Day 42) | 73.50 Alkaline Phosphatase [U/L] | Standard Deviation 7.778 |
| Placebo Group | Changes in Post-treatment General Laboratory Assessment-biochemistry-alkaline Phosphatase Compared to Baseline | Adjusted Visit 4 (Day 7) | 102.85 Alkaline Phosphatase [U/L] | Standard Deviation 71.589 |
Secondary
Changes in Post-treatment General Laboratory Assessment-biochemistry-aspartate Aminotransferase Compared to Baseline
Changes in post-treatment general laboratory assessment-biochemistry-aspartate aminotransferase will be analyzed for all patients in Phase I and II.
Time frame: Days 3, 7, 10, 14, 28, 42
Population: The general laboratory assessment-biochemistry-aspartate aminotransferase of each subject was examined at all scheduled visits.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| TWB-103 Group | Changes in Post-treatment General Laboratory Assessment-biochemistry-aspartate Aminotransferase Compared to Baseline | Adjusted Visit 4 (Day 7) | 24.75 Aspartate Aminotransferase [U/L] | Standard Deviation 15.21 |
| TWB-103 Group | Changes in Post-treatment General Laboratory Assessment-biochemistry-aspartate Aminotransferase Compared to Baseline | Baseline | 22.55 Aspartate Aminotransferase [U/L] | Standard Deviation 10.773 |
| TWB-103 Group | Changes in Post-treatment General Laboratory Assessment-biochemistry-aspartate Aminotransferase Compared to Baseline | Visit 8 (Day 42) | 32.50 Aspartate Aminotransferase [U/L] | Standard Deviation 23.335 |
| TWB-103 Group | Changes in Post-treatment General Laboratory Assessment-biochemistry-aspartate Aminotransferase Compared to Baseline | Adjusted Visit 6 (Day 14) | 45.00 Aspartate Aminotransferase [U/L] | Standard Deviation 43.052 |
| TWB-103 Group | Changes in Post-treatment General Laboratory Assessment-biochemistry-aspartate Aminotransferase Compared to Baseline | Adjusted Visit 3 (Day 3) | 33.37 Aspartate Aminotransferase [U/L] | Standard Deviation 46.94 |
| TWB-103 Group | Changes in Post-treatment General Laboratory Assessment-biochemistry-aspartate Aminotransferase Compared to Baseline | Adjusted Visit 7 (Day 28) | 19.05 Aspartate Aminotransferase [U/L] | Standard Deviation 6.06 |
| TWB-103 Group | Changes in Post-treatment General Laboratory Assessment-biochemistry-aspartate Aminotransferase Compared to Baseline | Adjusted Visit 5 (Day 10) | 26.44 Aspartate Aminotransferase [U/L] | Standard Deviation 16.883 |
| Placebo Group | Changes in Post-treatment General Laboratory Assessment-biochemistry-aspartate Aminotransferase Compared to Baseline | Visit 8 (Day 42) | 19.50 Aspartate Aminotransferase [U/L] | Standard Deviation 3.536 |
| Placebo Group | Changes in Post-treatment General Laboratory Assessment-biochemistry-aspartate Aminotransferase Compared to Baseline | Baseline | 21.85 Aspartate Aminotransferase [U/L] | Standard Deviation 8.177 |
| Placebo Group | Changes in Post-treatment General Laboratory Assessment-biochemistry-aspartate Aminotransferase Compared to Baseline | Adjusted Visit 3 (Day 3) | 20.00 Aspartate Aminotransferase [U/L] | Standard Deviation 5.648 |
| Placebo Group | Changes in Post-treatment General Laboratory Assessment-biochemistry-aspartate Aminotransferase Compared to Baseline | Adjusted Visit 4 (Day 7) | 24.40 Aspartate Aminotransferase [U/L] | Standard Deviation 9.762 |
| Placebo Group | Changes in Post-treatment General Laboratory Assessment-biochemistry-aspartate Aminotransferase Compared to Baseline | Adjusted Visit 5 (Day 10) | 21.33 Aspartate Aminotransferase [U/L] | Standard Deviation 6.837 |
| Placebo Group | Changes in Post-treatment General Laboratory Assessment-biochemistry-aspartate Aminotransferase Compared to Baseline | Adjusted Visit 6 (Day 14) | 22.40 Aspartate Aminotransferase [U/L] | Standard Deviation 12.876 |
| Placebo Group | Changes in Post-treatment General Laboratory Assessment-biochemistry-aspartate Aminotransferase Compared to Baseline | Adjusted Visit 7 (Day 28) | 22.00 Aspartate Aminotransferase [U/L] | Standard Deviation 8.931 |
Secondary
Changes in Post-treatment General Laboratory Assessment-biochemistry-bilirubin Compared to Baseline
Changes in post-treatment general laboratory assessment-biochemistry-bilirubin will be analyzed for all patients in Phase I and II.
Time frame: Days 3, 7, 10, 14, 28, 42
Population: The general laboratory assessment-biochemistry-bilirubin of each subject was examined at all scheduled visits.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| TWB-103 Group | Changes in Post-treatment General Laboratory Assessment-biochemistry-bilirubin Compared to Baseline | Adjusted Visit 4 (Day 7) | 8.39 Bilirubin [umol/L] | Standard Deviation 5.095 |
| TWB-103 Group | Changes in Post-treatment General Laboratory Assessment-biochemistry-bilirubin Compared to Baseline | Adjusted Visit 6 (Day 14) | 14.30 Bilirubin [umol/L] | Standard Deviation 10.487 |
| TWB-103 Group | Changes in Post-treatment General Laboratory Assessment-biochemistry-bilirubin Compared to Baseline | Adjusted Visit 3 (Day 3) | 7.44 Bilirubin [umol/L] | Standard Deviation 3.842 |
| TWB-103 Group | Changes in Post-treatment General Laboratory Assessment-biochemistry-bilirubin Compared to Baseline | Adjusted Visit 7 (Day 28) | 9.40 Bilirubin [umol/L] | Standard Deviation 6.565 |
| TWB-103 Group | Changes in Post-treatment General Laboratory Assessment-biochemistry-bilirubin Compared to Baseline | Adjusted Visit 5 (Day 10) | 9.20 Bilirubin [umol/L] | Standard Deviation 5.59 |
| TWB-103 Group | Changes in Post-treatment General Laboratory Assessment-biochemistry-bilirubin Compared to Baseline | Visit 8 (Day 42) | 18.22 Bilirubin [umol/L] | Standard Deviation 8.829 |
| TWB-103 Group | Changes in Post-treatment General Laboratory Assessment-biochemistry-bilirubin Compared to Baseline | Baseline | 9.63 Bilirubin [umol/L] | Standard Deviation 4.824 |
| Placebo Group | Changes in Post-treatment General Laboratory Assessment-biochemistry-bilirubin Compared to Baseline | Visit 8 (Day 42) | 6.84 Bilirubin [umol/L] | Standard Deviation 2.419 |
| Placebo Group | Changes in Post-treatment General Laboratory Assessment-biochemistry-bilirubin Compared to Baseline | Baseline | 8.10 Bilirubin [umol/L] | Standard Deviation 4.975 |
| Placebo Group | Changes in Post-treatment General Laboratory Assessment-biochemistry-bilirubin Compared to Baseline | Adjusted Visit 3 (Day 3) | 8.92 Bilirubin [umol/L] | Standard Deviation 6.039 |
| Placebo Group | Changes in Post-treatment General Laboratory Assessment-biochemistry-bilirubin Compared to Baseline | Adjusted Visit 4 (Day 7) | 8.73 Bilirubin [umol/L] | Standard Deviation 4.876 |
| Placebo Group | Changes in Post-treatment General Laboratory Assessment-biochemistry-bilirubin Compared to Baseline | Adjusted Visit 5 (Day 10) | 9.64 Bilirubin [umol/L] | Standard Deviation 4.47 |
| Placebo Group | Changes in Post-treatment General Laboratory Assessment-biochemistry-bilirubin Compared to Baseline | Adjusted Visit 6 (Day 14) | 9.03 Bilirubin [umol/L] | Standard Deviation 3.058 |
| Placebo Group | Changes in Post-treatment General Laboratory Assessment-biochemistry-bilirubin Compared to Baseline | Adjusted Visit 7 (Day 28) | 9.10 Bilirubin [umol/L] | Standard Deviation 2.873 |
Secondary
Changes in Post-treatment General Laboratory Assessment-biochemistry-blood Urea Nitrogen Compared to Baseline
Changes in post-treatment general laboratory assessment-biochemistry-blood urea nitrogen will be analyzed for all patients in Phase I and II.
Time frame: Days 3, 7, 10, 14, 28, 42
Population: The general laboratory assessment-biochemistry-blood urea nitrogen of each subject was examined at all scheduled visits.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| TWB-103 Group | Changes in Post-treatment General Laboratory Assessment-biochemistry-blood Urea Nitrogen Compared to Baseline | Adjusted Visit 4 (Day 7) | 14.46 Blood Urea Nitrogen [mg/dL] | Standard Deviation 3.956 |
| TWB-103 Group | Changes in Post-treatment General Laboratory Assessment-biochemistry-blood Urea Nitrogen Compared to Baseline | Adjusted Visit 6 (Day 14) | 14.12 Blood Urea Nitrogen [mg/dL] | Standard Deviation 5.304 |
| TWB-103 Group | Changes in Post-treatment General Laboratory Assessment-biochemistry-blood Urea Nitrogen Compared to Baseline | Adjusted Visit 3 (Day 3) | 11.58 Blood Urea Nitrogen [mg/dL] | Standard Deviation 2.234 |
| TWB-103 Group | Changes in Post-treatment General Laboratory Assessment-biochemistry-blood Urea Nitrogen Compared to Baseline | Adjusted Visit 7 (Day 28) | 12.82 Blood Urea Nitrogen [mg/dL] | Standard Deviation 3.873 |
| TWB-103 Group | Changes in Post-treatment General Laboratory Assessment-biochemistry-blood Urea Nitrogen Compared to Baseline | Adjusted Visit 5 (Day 10) | 13.02 Blood Urea Nitrogen [mg/dL] | Standard Deviation 3.938 |
| TWB-103 Group | Changes in Post-treatment General Laboratory Assessment-biochemistry-blood Urea Nitrogen Compared to Baseline | Visit 8 (Day 42) | 11.90 Blood Urea Nitrogen [mg/dL] | Standard Deviation 2.97 |
| TWB-103 Group | Changes in Post-treatment General Laboratory Assessment-biochemistry-blood Urea Nitrogen Compared to Baseline | Baseline | 13.59 Blood Urea Nitrogen [mg/dL] | Standard Deviation 4.838 |
| Placebo Group | Changes in Post-treatment General Laboratory Assessment-biochemistry-blood Urea Nitrogen Compared to Baseline | Visit 8 (Day 42) | 16.50 Blood Urea Nitrogen [mg/dL] | Standard Deviation 3.536 |
| Placebo Group | Changes in Post-treatment General Laboratory Assessment-biochemistry-blood Urea Nitrogen Compared to Baseline | Baseline | 14.06 Blood Urea Nitrogen [mg/dL] | Standard Deviation 4.271 |
| Placebo Group | Changes in Post-treatment General Laboratory Assessment-biochemistry-blood Urea Nitrogen Compared to Baseline | Adjusted Visit 3 (Day 3) | 13.23 Blood Urea Nitrogen [mg/dL] | Standard Deviation 3.779 |
| Placebo Group | Changes in Post-treatment General Laboratory Assessment-biochemistry-blood Urea Nitrogen Compared to Baseline | Adjusted Visit 4 (Day 7) | 14.72 Blood Urea Nitrogen [mg/dL] | Standard Deviation 5.427 |
| Placebo Group | Changes in Post-treatment General Laboratory Assessment-biochemistry-blood Urea Nitrogen Compared to Baseline | Adjusted Visit 5 (Day 10) | 13.54 Blood Urea Nitrogen [mg/dL] | Standard Deviation 2.967 |
| Placebo Group | Changes in Post-treatment General Laboratory Assessment-biochemistry-blood Urea Nitrogen Compared to Baseline | Adjusted Visit 6 (Day 14) | 14.48 Blood Urea Nitrogen [mg/dL] | Standard Deviation 3.189 |
| Placebo Group | Changes in Post-treatment General Laboratory Assessment-biochemistry-blood Urea Nitrogen Compared to Baseline | Adjusted Visit 7 (Day 28) | 13.13 Blood Urea Nitrogen [mg/dL] | Standard Deviation 2.537 |
Secondary
Changes in Post-treatment General Laboratory Assessment-biochemistry-gamma-glutamyl Transferase Compared to Baseline
Changes in post-treatment general laboratory assessment-biochemistry-gamma-glutamyl transferase will be analyzed for all patients in Phase I and II.
Time frame: Days 3, 7, 10, 14, 28, 42
Population: The general laboratory assessment-biochemistry-gamma-glutamyl transferase of each subject was examined at all scheduled visits.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| TWB-103 Group | Changes in Post-treatment General Laboratory Assessment-biochemistry-gamma-glutamyl Transferase Compared to Baseline | Adjusted Visit 3 (Day 3) | 37.16 Gamma-Glutamyl Transferase [U/L] | Standard Deviation 31.597 |
| TWB-103 Group | Changes in Post-treatment General Laboratory Assessment-biochemistry-gamma-glutamyl Transferase Compared to Baseline | Adjusted Visit 6 (Day 14) | 56.20 Gamma-Glutamyl Transferase [U/L] | Standard Deviation 36.072 |
| TWB-103 Group | Changes in Post-treatment General Laboratory Assessment-biochemistry-gamma-glutamyl Transferase Compared to Baseline | Adjusted Visit 4 (Day 7) | 37.60 Gamma-Glutamyl Transferase [U/L] | Standard Deviation 29.674 |
| TWB-103 Group | Changes in Post-treatment General Laboratory Assessment-biochemistry-gamma-glutamyl Transferase Compared to Baseline | Adjusted Visit 7 (Day 28) | 28.47 Gamma-Glutamyl Transferase [U/L] | Standard Deviation 19.234 |
| TWB-103 Group | Changes in Post-treatment General Laboratory Assessment-biochemistry-gamma-glutamyl Transferase Compared to Baseline | Baseline | 37.65 Gamma-Glutamyl Transferase [U/L] | Standard Deviation 36.863 |
| TWB-103 Group | Changes in Post-treatment General Laboratory Assessment-biochemistry-gamma-glutamyl Transferase Compared to Baseline | Visit 8 (Day 42) | 32.50 Gamma-Glutamyl Transferase [U/L] | Standard Deviation 24.749 |
| TWB-103 Group | Changes in Post-treatment General Laboratory Assessment-biochemistry-gamma-glutamyl Transferase Compared to Baseline | Adjusted Visit 5 (Day 10) | 44.11 Gamma-Glutamyl Transferase [U/L] | Standard Deviation 33.572 |
| Placebo Group | Changes in Post-treatment General Laboratory Assessment-biochemistry-gamma-glutamyl Transferase Compared to Baseline | Visit 8 (Day 42) | 21.50 Gamma-Glutamyl Transferase [U/L] | Standard Deviation 0.707 |
| Placebo Group | Changes in Post-treatment General Laboratory Assessment-biochemistry-gamma-glutamyl Transferase Compared to Baseline | Adjusted Visit 3 (Day 3) | 37.25 Gamma-Glutamyl Transferase [U/L] | Standard Deviation 26.479 |
| Placebo Group | Changes in Post-treatment General Laboratory Assessment-biochemistry-gamma-glutamyl Transferase Compared to Baseline | Adjusted Visit 4 (Day 7) | 39.65 Gamma-Glutamyl Transferase [U/L] | Standard Deviation 30.275 |
| Placebo Group | Changes in Post-treatment General Laboratory Assessment-biochemistry-gamma-glutamyl Transferase Compared to Baseline | Adjusted Visit 5 (Day 10) | 49.44 Gamma-Glutamyl Transferase [U/L] | Standard Deviation 39.17 |
| Placebo Group | Changes in Post-treatment General Laboratory Assessment-biochemistry-gamma-glutamyl Transferase Compared to Baseline | Adjusted Visit 6 (Day 14) | 47.80 Gamma-Glutamyl Transferase [U/L] | Standard Deviation 43.2 |
| Placebo Group | Changes in Post-treatment General Laboratory Assessment-biochemistry-gamma-glutamyl Transferase Compared to Baseline | Adjusted Visit 7 (Day 28) | 38.22 Gamma-Glutamyl Transferase [U/L] | Standard Deviation 33.676 |
| Placebo Group | Changes in Post-treatment General Laboratory Assessment-biochemistry-gamma-glutamyl Transferase Compared to Baseline | Baseline | 38.75 Gamma-Glutamyl Transferase [U/L] | Standard Deviation 26.754 |
Secondary
Changes in Post-treatment General Laboratory Assessment-biochemistry-serum Creatinine Compared to Baseline
Changes in post-treatment general laboratory assessment-biochemistry-serum creatinine will be analyzed for all patients in Phase I and II.
Time frame: Days 3, 7, 10, 14, 28, 42
Population: The general laboratory assessment-biochemistry-serum creatinine of each subject was examined at all scheduled visits.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| TWB-103 Group | Changes in Post-treatment General Laboratory Assessment-biochemistry-serum Creatinine Compared to Baseline | Baseline | 62.68 Serum Creatinine [umol/L] | Standard Deviation 14.386 |
| TWB-103 Group | Changes in Post-treatment General Laboratory Assessment-biochemistry-serum Creatinine Compared to Baseline | Adjusted Visit 6 (Day 14) | 57.64 Serum Creatinine [umol/L] | Standard Deviation 19.016 |
| TWB-103 Group | Changes in Post-treatment General Laboratory Assessment-biochemistry-serum Creatinine Compared to Baseline | Adjusted Visit 4 (Day 7) | 60.51 Serum Creatinine [umol/L] | Standard Deviation 15.129 |
| TWB-103 Group | Changes in Post-treatment General Laboratory Assessment-biochemistry-serum Creatinine Compared to Baseline | Adjusted Visit 7 (Day 28) | 62.44 Serum Creatinine [umol/L] | Standard Deviation 12.363 |
| TWB-103 Group | Changes in Post-treatment General Laboratory Assessment-biochemistry-serum Creatinine Compared to Baseline | Adjusted Visit 3 (Day 3) | 58.39 Serum Creatinine [umol/L] | Standard Deviation 14.422 |
| TWB-103 Group | Changes in Post-treatment General Laboratory Assessment-biochemistry-serum Creatinine Compared to Baseline | Visit 8 (Day 42) | 56.58 Serum Creatinine [umol/L] | Standard Deviation 5.001 |
| TWB-103 Group | Changes in Post-treatment General Laboratory Assessment-biochemistry-serum Creatinine Compared to Baseline | Adjusted Visit 5 (Day 10) | 54.42 Serum Creatinine [umol/L] | Standard Deviation 17.045 |
| Placebo Group | Changes in Post-treatment General Laboratory Assessment-biochemistry-serum Creatinine Compared to Baseline | Visit 8 (Day 42) | 66.30 Serum Creatinine [umol/L] | Standard Deviation 6.251 |
| Placebo Group | Changes in Post-treatment General Laboratory Assessment-biochemistry-serum Creatinine Compared to Baseline | Adjusted Visit 3 (Day 3) | 61.75 Serum Creatinine [umol/L] | Standard Deviation 18.31 |
| Placebo Group | Changes in Post-treatment General Laboratory Assessment-biochemistry-serum Creatinine Compared to Baseline | Adjusted Visit 4 (Day 7) | 63.78 Serum Creatinine [umol/L] | Standard Deviation 19.811 |
| Placebo Group | Changes in Post-treatment General Laboratory Assessment-biochemistry-serum Creatinine Compared to Baseline | Adjusted Visit 5 (Day 10) | 60.21 Serum Creatinine [umol/L] | Standard Deviation 17.133 |
| Placebo Group | Changes in Post-treatment General Laboratory Assessment-biochemistry-serum Creatinine Compared to Baseline | Adjusted Visit 6 (Day 14) | 63.12 Serum Creatinine [umol/L] | Standard Deviation 37.742 |
| Placebo Group | Changes in Post-treatment General Laboratory Assessment-biochemistry-serum Creatinine Compared to Baseline | Adjusted Visit 7 (Day 28) | 64.63 Serum Creatinine [umol/L] | Standard Deviation 18.637 |
| Placebo Group | Changes in Post-treatment General Laboratory Assessment-biochemistry-serum Creatinine Compared to Baseline | Baseline | 62.01 Serum Creatinine [umol/L] | Standard Deviation 17.022 |
Secondary
Changes in Post-treatment General Laboratory Assessment-hematology-Hematocrit Compared to Baseline
Changes in post-treatment general laboratory assessment-hematology-hematocrit will be analyzed for all patients in Phase I and II.
Time frame: Days 3, 7, 10, 14, 28, 42
Population: The general laboratory assessment-hematology-hematocrit of each subject was examined at all scheduled visits.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| TWB-103 Group | Changes in Post-treatment General Laboratory Assessment-hematology-Hematocrit Compared to Baseline | Adjusted Visit 4 (Day 7) | 40.35 Hematocrit [%] | Standard Deviation 5.706 |
| TWB-103 Group | Changes in Post-treatment General Laboratory Assessment-hematology-Hematocrit Compared to Baseline | Adjusted Visit 6 (Day 14) | 39.84 Hematocrit [%] | Standard Deviation 6.529 |
| TWB-103 Group | Changes in Post-treatment General Laboratory Assessment-hematology-Hematocrit Compared to Baseline | Adjusted Visit 3 (Day 3) | 40.01 Hematocrit [%] | Standard Deviation 5.41 |
| TWB-103 Group | Changes in Post-treatment General Laboratory Assessment-hematology-Hematocrit Compared to Baseline | Adjusted Visit 7 (Day 28) | 40.43 Hematocrit [%] | Standard Deviation 4.206 |
| TWB-103 Group | Changes in Post-treatment General Laboratory Assessment-hematology-Hematocrit Compared to Baseline | Adjusted Visit 5 (Day 10) | 38.07 Hematocrit [%] | Standard Deviation 4.537 |
| TWB-103 Group | Changes in Post-treatment General Laboratory Assessment-hematology-Hematocrit Compared to Baseline | Visit 8 (Day 42) | 41.45 Hematocrit [%] | Standard Deviation 1.768 |
| TWB-103 Group | Changes in Post-treatment General Laboratory Assessment-hematology-Hematocrit Compared to Baseline | Baseline | 40.60 Hematocrit [%] | Standard Deviation 3.886 |
| Placebo Group | Changes in Post-treatment General Laboratory Assessment-hematology-Hematocrit Compared to Baseline | Visit 8 (Day 42) | 42.05 Hematocrit [%] | Standard Deviation 2.192 |
| Placebo Group | Changes in Post-treatment General Laboratory Assessment-hematology-Hematocrit Compared to Baseline | Baseline | 42.00 Hematocrit [%] | Standard Deviation 4.92 |
| Placebo Group | Changes in Post-treatment General Laboratory Assessment-hematology-Hematocrit Compared to Baseline | Adjusted Visit 3 (Day 3) | 41.57 Hematocrit [%] | Standard Deviation 6.565 |
| Placebo Group | Changes in Post-treatment General Laboratory Assessment-hematology-Hematocrit Compared to Baseline | Adjusted Visit 4 (Day 7) | 41.34 Hematocrit [%] | Standard Deviation 5.591 |
| Placebo Group | Changes in Post-treatment General Laboratory Assessment-hematology-Hematocrit Compared to Baseline | Adjusted Visit 5 (Day 10) | 40.07 Hematocrit [%] | Standard Deviation 5.525 |
| Placebo Group | Changes in Post-treatment General Laboratory Assessment-hematology-Hematocrit Compared to Baseline | Adjusted Visit 6 (Day 14) | 40.80 Hematocrit [%] | Standard Deviation 7.005 |
| Placebo Group | Changes in Post-treatment General Laboratory Assessment-hematology-Hematocrit Compared to Baseline | Adjusted Visit 7 (Day 28) | 41.33 Hematocrit [%] | Standard Deviation 4.312 |
Secondary
Changes in Post-treatment General Laboratory Assessment-hematology-Hemoglobin Compared to Baseline
Changes in post-treatment general laboratory assessment-hematology-hemoglobin will be analyzed for all patients in Phase I and II.
Time frame: Days 3, 7, 10, 14, 28, 42
Population: The general laboratory assessment-hematology-hemoglobin of each subject was examined at all scheduled visits.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| TWB-103 Group | Changes in Post-treatment General Laboratory Assessment-hematology-Hemoglobin Compared to Baseline | Adjusted Visit 4 (Day 7) | 13.38 Hemoglobin [g/dL] | Standard Deviation 2.033 |
| TWB-103 Group | Changes in Post-treatment General Laboratory Assessment-hematology-Hemoglobin Compared to Baseline | Adjusted Visit 6 (Day 14) | 13.22 Hemoglobin [g/dL] | Standard Deviation 2.565 |
| TWB-103 Group | Changes in Post-treatment General Laboratory Assessment-hematology-Hemoglobin Compared to Baseline | Adjusted Visit 3 (Day 3) | 13.28 Hemoglobin [g/dL] | Standard Deviation 1.981 |
| TWB-103 Group | Changes in Post-treatment General Laboratory Assessment-hematology-Hemoglobin Compared to Baseline | Adjusted Visit 7 (Day 28) | 13.35 Hemoglobin [g/dL] | Standard Deviation 1.726 |
| TWB-103 Group | Changes in Post-treatment General Laboratory Assessment-hematology-Hemoglobin Compared to Baseline | Adjusted Visit 5 (Day 10) | 12.72 Hemoglobin [g/dL] | Standard Deviation 1.796 |
| TWB-103 Group | Changes in Post-treatment General Laboratory Assessment-hematology-Hemoglobin Compared to Baseline | Visit 8 (Day 42) | 14.05 Hemoglobin [g/dL] | Standard Deviation 1.344 |
| TWB-103 Group | Changes in Post-treatment General Laboratory Assessment-hematology-Hemoglobin Compared to Baseline | Baseline | 13.47 Hemoglobin [g/dL] | Standard Deviation 1.436 |
| Placebo Group | Changes in Post-treatment General Laboratory Assessment-hematology-Hemoglobin Compared to Baseline | Visit 8 (Day 42) | 13.30 Hemoglobin [g/dL] | Standard Deviation 1.697 |
| Placebo Group | Changes in Post-treatment General Laboratory Assessment-hematology-Hemoglobin Compared to Baseline | Baseline | 13.84 Hemoglobin [g/dL] | Standard Deviation 1.741 |
| Placebo Group | Changes in Post-treatment General Laboratory Assessment-hematology-Hemoglobin Compared to Baseline | Adjusted Visit 3 (Day 3) | 13.79 Hemoglobin [g/dL] | Standard Deviation 2.22 |
| Placebo Group | Changes in Post-treatment General Laboratory Assessment-hematology-Hemoglobin Compared to Baseline | Adjusted Visit 4 (Day 7) | 13.69 Hemoglobin [g/dL] | Standard Deviation 2.002 |
| Placebo Group | Changes in Post-treatment General Laboratory Assessment-hematology-Hemoglobin Compared to Baseline | Adjusted Visit 5 (Day 10) | 13.56 Hemoglobin [g/dL] | Standard Deviation 1.89 |
| Placebo Group | Changes in Post-treatment General Laboratory Assessment-hematology-Hemoglobin Compared to Baseline | Adjusted Visit 6 (Day 14) | 13.82 Hemoglobin [g/dL] | Standard Deviation 2.572 |
| Placebo Group | Changes in Post-treatment General Laboratory Assessment-hematology-Hemoglobin Compared to Baseline | Adjusted Visit 7 (Day 28) | 13.73 Hemoglobin [g/dL] | Standard Deviation 1.665 |
Secondary
Changes in Post-treatment General Laboratory Assessment-hematology-neutrophils Compared to Baseline
Changes in post-treatment general laboratory assessment-hematology-neutrophils will be analyzed for all patients in Phase I and II.
Time frame: Days 3, 7, 10, 14, 28, 42
Population: The general laboratory assessment-hematology-neutrophils of each subject were examined at all scheduled visits.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| TWB-103 Group | Changes in Post-treatment General Laboratory Assessment-hematology-neutrophils Compared to Baseline | Adjusted Visit 4 (Day 7) | 4.54 10^9 cells /L | Standard Deviation 1.431 |
| TWB-103 Group | Changes in Post-treatment General Laboratory Assessment-hematology-neutrophils Compared to Baseline | Adjusted Visit 6 (Day 14) | 6.62 10^9 cells /L | Standard Deviation 4.944 |
| TWB-103 Group | Changes in Post-treatment General Laboratory Assessment-hematology-neutrophils Compared to Baseline | Adjusted Visit 3 (Day 3) | 4.61 10^9 cells /L | Standard Deviation 1.604 |
| TWB-103 Group | Changes in Post-treatment General Laboratory Assessment-hematology-neutrophils Compared to Baseline | Adjusted Visit 7 (Day 28) | 3.94 10^9 cells /L | Standard Deviation 1.733 |
| TWB-103 Group | Changes in Post-treatment General Laboratory Assessment-hematology-neutrophils Compared to Baseline | Adjusted Visit 5 (Day 10) | 3.93 10^9 cells /L | Standard Deviation 0.808 |
| TWB-103 Group | Changes in Post-treatment General Laboratory Assessment-hematology-neutrophils Compared to Baseline | Visit 8 (Day 42) | 2.17 10^9 cells /L | Standard Deviation 0.826 |
| TWB-103 Group | Changes in Post-treatment General Laboratory Assessment-hematology-neutrophils Compared to Baseline | Baseline | 5.36 10^9 cells /L | Standard Deviation 1.95 |
| Placebo Group | Changes in Post-treatment General Laboratory Assessment-hematology-neutrophils Compared to Baseline | Visit 8 (Day 42) | 3.44 10^9 cells /L | Standard Deviation 0.074 |
| Placebo Group | Changes in Post-treatment General Laboratory Assessment-hematology-neutrophils Compared to Baseline | Baseline | 4.65 10^9 cells /L | Standard Deviation 1.542 |
| Placebo Group | Changes in Post-treatment General Laboratory Assessment-hematology-neutrophils Compared to Baseline | Adjusted Visit 3 (Day 3) | 4.71 10^9 cells /L | Standard Deviation 1.577 |
| Placebo Group | Changes in Post-treatment General Laboratory Assessment-hematology-neutrophils Compared to Baseline | Adjusted Visit 4 (Day 7) | 4.37 10^9 cells /L | Standard Deviation 2.322 |
| Placebo Group | Changes in Post-treatment General Laboratory Assessment-hematology-neutrophils Compared to Baseline | Adjusted Visit 5 (Day 10) | 4.06 10^9 cells /L | Standard Deviation 0.747 |
| Placebo Group | Changes in Post-treatment General Laboratory Assessment-hematology-neutrophils Compared to Baseline | Adjusted Visit 6 (Day 14) | 4.71 10^9 cells /L | Standard Deviation 0.523 |
| Placebo Group | Changes in Post-treatment General Laboratory Assessment-hematology-neutrophils Compared to Baseline | Adjusted Visit 7 (Day 28) | 4.19 10^9 cells /L | Standard Deviation 1.128 |
Secondary
Changes in Post-treatment General Laboratory Assessment-hematology-platelets Compared to Baseline
Changes in post-treatment general laboratory assessment-hematology-platelets will be analyzed for all patients in Phase I and II.
Time frame: Days 3, 7, 10, 14, 28, 42
Population: The general laboratory assessment-hematology-platelets of each subject were examined at all scheduled visits.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| TWB-103 Group | Changes in Post-treatment General Laboratory Assessment-hematology-platelets Compared to Baseline | Adjusted Visit 7 (Day 28) | 268.42 10^9 platelets/L | Standard Deviation 68.664 |
| TWB-103 Group | Changes in Post-treatment General Laboratory Assessment-hematology-platelets Compared to Baseline | Visit 8 (Day 42) | 248.50 10^9 platelets/L | Standard Deviation 88.388 |
| TWB-103 Group | Changes in Post-treatment General Laboratory Assessment-hematology-platelets Compared to Baseline | Baseline | 298.95 10^9 platelets/L | Standard Deviation 69.549 |
| TWB-103 Group | Changes in Post-treatment General Laboratory Assessment-hematology-platelets Compared to Baseline | Adjusted Visit 3 (Day 3) | 290.95 10^9 platelets/L | Standard Deviation 63.692 |
| TWB-103 Group | Changes in Post-treatment General Laboratory Assessment-hematology-platelets Compared to Baseline | Adjusted Visit 4 (Day 7) | 308.50 10^9 platelets/L | Standard Deviation 50.055 |
| TWB-103 Group | Changes in Post-treatment General Laboratory Assessment-hematology-platelets Compared to Baseline | Adjusted Visit 5 (Day 10) | 311.44 10^9 platelets/L | Standard Deviation 67.93 |
| TWB-103 Group | Changes in Post-treatment General Laboratory Assessment-hematology-platelets Compared to Baseline | Adjusted Visit 6 (Day 14) | 314.80 10^9 platelets/L | Standard Deviation 81.174 |
| Placebo Group | Changes in Post-treatment General Laboratory Assessment-hematology-platelets Compared to Baseline | Visit 8 (Day 42) | 290.50 10^9 platelets/L | Standard Deviation 19.092 |
| Placebo Group | Changes in Post-treatment General Laboratory Assessment-hematology-platelets Compared to Baseline | Adjusted Visit 7 (Day 28) | 260.11 10^9 platelets/L | Standard Deviation 50.326 |
| Placebo Group | Changes in Post-treatment General Laboratory Assessment-hematology-platelets Compared to Baseline | Adjusted Visit 4 (Day 7) | 279.10 10^9 platelets/L | Standard Deviation 67.043 |
| Placebo Group | Changes in Post-treatment General Laboratory Assessment-hematology-platelets Compared to Baseline | Adjusted Visit 6 (Day 14) | 225.60 10^9 platelets/L | Standard Deviation 26.885 |
| Placebo Group | Changes in Post-treatment General Laboratory Assessment-hematology-platelets Compared to Baseline | Baseline | 284.60 10^9 platelets/L | Standard Deviation 63.444 |
| Placebo Group | Changes in Post-treatment General Laboratory Assessment-hematology-platelets Compared to Baseline | Adjusted Visit 5 (Day 10) | 247.22 10^9 platelets/L | Standard Deviation 51.575 |
| Placebo Group | Changes in Post-treatment General Laboratory Assessment-hematology-platelets Compared to Baseline | Adjusted Visit 3 (Day 3) | 278.70 10^9 platelets/L | Standard Deviation 79.961 |
Secondary
Changes in Post-treatment General Laboratory Assessment-hematology-red Blood Cells Compared to Baseline
Changes in post-treatment general laboratory assessment-hematology-red blood cells will be analyzed for all patients in Phase I and II.
Time frame: Days 3, 7, 10, 14, 28, 42
Population: The general laboratory assessment-hematology-red blood cells of each subject were examined at all scheduled visits.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| TWB-103 Group | Changes in Post-treatment General Laboratory Assessment-hematology-red Blood Cells Compared to Baseline | Baseline | 4.61 10^12 cells/L | Standard Deviation 0.558 |
| TWB-103 Group | Changes in Post-treatment General Laboratory Assessment-hematology-red Blood Cells Compared to Baseline | Adjusted Visit 6 (Day 14) | 4.30 10^12 cells/L | Standard Deviation 0.842 |
| TWB-103 Group | Changes in Post-treatment General Laboratory Assessment-hematology-red Blood Cells Compared to Baseline | Adjusted Visit 4 (Day 7) | 4.59 10^12 cells/L | Standard Deviation 0.763 |
| TWB-103 Group | Changes in Post-treatment General Laboratory Assessment-hematology-red Blood Cells Compared to Baseline | Adjusted Visit 7 (Day 28) | 4.60 10^12 cells/L | Standard Deviation 0.586 |
| TWB-103 Group | Changes in Post-treatment General Laboratory Assessment-hematology-red Blood Cells Compared to Baseline | Adjusted Visit 3 (Day 3) | 4.54 10^12 cells/L | Standard Deviation 0.729 |
| TWB-103 Group | Changes in Post-treatment General Laboratory Assessment-hematology-red Blood Cells Compared to Baseline | Visit 8 (Day 42) | 4.41 10^12 cells/L | Standard Deviation 0.198 |
| TWB-103 Group | Changes in Post-treatment General Laboratory Assessment-hematology-red Blood Cells Compared to Baseline | Adjusted Visit 5 (Day 10) | 4.19 10^12 cells/L | Standard Deviation 0.476 |
| Placebo Group | Changes in Post-treatment General Laboratory Assessment-hematology-red Blood Cells Compared to Baseline | Visit 8 (Day 42) | 5.21 10^12 cells/L | Standard Deviation 0.488 |
| Placebo Group | Changes in Post-treatment General Laboratory Assessment-hematology-red Blood Cells Compared to Baseline | Baseline | 4.86 10^12 cells/L | Standard Deviation 0.674 |
| Placebo Group | Changes in Post-treatment General Laboratory Assessment-hematology-red Blood Cells Compared to Baseline | Adjusted Visit 3 (Day 3) | 4.82 10^12 cells/L | Standard Deviation 0.824 |
| Placebo Group | Changes in Post-treatment General Laboratory Assessment-hematology-red Blood Cells Compared to Baseline | Adjusted Visit 4 (Day 7) | 4.83 10^12 cells/L | Standard Deviation 0.811 |
| Placebo Group | Changes in Post-treatment General Laboratory Assessment-hematology-red Blood Cells Compared to Baseline | Adjusted Visit 5 (Day 10) | 4.58 10^12 cells/L | Standard Deviation 0.892 |
| Placebo Group | Changes in Post-treatment General Laboratory Assessment-hematology-red Blood Cells Compared to Baseline | Adjusted Visit 6 (Day 14) | 4.48 10^12 cells/L | Standard Deviation 0.832 |
| Placebo Group | Changes in Post-treatment General Laboratory Assessment-hematology-red Blood Cells Compared to Baseline | Adjusted Visit 7 (Day 28) | 4.83 10^12 cells/L | Standard Deviation 0.639 |
Secondary
Changes in Post-treatment General Laboratory Assessment-hematology-white Blood Cells Compared to Baseline
Changes in post-treatment general laboratory assessment-hematology-white blood cells will be analyzed for all patients in Phase I and II.
Time frame: Days 3, 7, 10, 14, 28, 42
Population: The general laboratory assessment-hematology-white blood cells of each subject were examined at all scheduled visits.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| TWB-103 Group | Changes in Post-treatment General Laboratory Assessment-hematology-white Blood Cells Compared to Baseline | Adjusted Visit 4 (Day 7) | 7.20 10^9 cells /L | Standard Deviation 1.638 |
| TWB-103 Group | Changes in Post-treatment General Laboratory Assessment-hematology-white Blood Cells Compared to Baseline | Adjusted Visit 6 (Day 14) | 9.27 10^9 cells /L | Standard Deviation 4.634 |
| TWB-103 Group | Changes in Post-treatment General Laboratory Assessment-hematology-white Blood Cells Compared to Baseline | Adjusted Visit 3 (Day 3) | 7.00 10^9 cells /L | Standard Deviation 1.84 |
| TWB-103 Group | Changes in Post-treatment General Laboratory Assessment-hematology-white Blood Cells Compared to Baseline | Adjusted Visit 7 (Day 28) | 6.52 10^9 cells /L | Standard Deviation 2.11 |
| TWB-103 Group | Changes in Post-treatment General Laboratory Assessment-hematology-white Blood Cells Compared to Baseline | Adjusted Visit 5 (Day 10) | 6.27 10^9 cells /L | Standard Deviation 0.877 |
| TWB-103 Group | Changes in Post-treatment General Laboratory Assessment-hematology-white Blood Cells Compared to Baseline | Visit 8 (Day 42) | 4.63 10^9 cells /L | Standard Deviation 1.025 |
| TWB-103 Group | Changes in Post-treatment General Laboratory Assessment-hematology-white Blood Cells Compared to Baseline | Baseline | 7.93 10^9 cells /L | Standard Deviation 2.107 |
| Placebo Group | Changes in Post-treatment General Laboratory Assessment-hematology-white Blood Cells Compared to Baseline | Visit 8 (Day 42) | 6.63 10^9 cells /L | Standard Deviation 1.605 |
| Placebo Group | Changes in Post-treatment General Laboratory Assessment-hematology-white Blood Cells Compared to Baseline | Baseline | 7.40 10^9 cells /L | Standard Deviation 1.785 |
| Placebo Group | Changes in Post-treatment General Laboratory Assessment-hematology-white Blood Cells Compared to Baseline | Adjusted Visit 3 (Day 3) | 7.44 10^9 cells /L | Standard Deviation 2.064 |
| Placebo Group | Changes in Post-treatment General Laboratory Assessment-hematology-white Blood Cells Compared to Baseline | Adjusted Visit 4 (Day 7) | 7.26 10^9 cells /L | Standard Deviation 2.835 |
| Placebo Group | Changes in Post-treatment General Laboratory Assessment-hematology-white Blood Cells Compared to Baseline | Adjusted Visit 5 (Day 10) | 7.19 10^9 cells /L | Standard Deviation 1.425 |
| Placebo Group | Changes in Post-treatment General Laboratory Assessment-hematology-white Blood Cells Compared to Baseline | Adjusted Visit 6 (Day 14) | 7.30 10^9 cells /L | Standard Deviation 0.78 |
| Placebo Group | Changes in Post-treatment General Laboratory Assessment-hematology-white Blood Cells Compared to Baseline | Adjusted Visit 7 (Day 28) | 6.99 10^9 cells /L | Standard Deviation 1.76 |
Secondary
Changes in Post-treatment Physical Examination Compared to Baseline
Changes in post-treatment physical examination will be analyzed for all patients in Phase I and II.
Time frame: Days 3, 7, 10, 14, 28, 42
Population: The physical examination of each subject was examined at all scheduled visits.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| TWB-103 Group | Changes in Post-treatment Physical Examination Compared to Baseline | Adjusted Visit 3 (Day 3) (Multi-Selection by Body System) | 1 Participant with Physical Abnormality |
| TWB-103 Group | Changes in Post-treatment Physical Examination Compared to Baseline | Adjusted Visit 4 (Day 7) (Multi-Selection by Body System) | 1 Participant with Physical Abnormality |
| TWB-103 Group | Changes in Post-treatment Physical Examination Compared to Baseline | Adjusted Visit 5 (Day 10) (Multi-Selection by Body System) | 0 Participant with Physical Abnormality |
| TWB-103 Group | Changes in Post-treatment Physical Examination Compared to Baseline | Adjusted Visit 6 (Day 14) (Multi-Selection by Body System) | 0 Participant with Physical Abnormality |
| TWB-103 Group | Changes in Post-treatment Physical Examination Compared to Baseline | Adjusted Visit 7 (Day 28) (Multi-Selection by Body System) | 1 Participant with Physical Abnormality |
| TWB-103 Group | Changes in Post-treatment Physical Examination Compared to Baseline | Visit 8 (Day 42) (Multi-Selection by Body System) | 0 Participant with Physical Abnormality |
| Placebo Group | Changes in Post-treatment Physical Examination Compared to Baseline | Adjusted Visit 7 (Day 28) (Multi-Selection by Body System) | 0 Participant with Physical Abnormality |
| Placebo Group | Changes in Post-treatment Physical Examination Compared to Baseline | Adjusted Visit 3 (Day 3) (Multi-Selection by Body System) | 0 Participant with Physical Abnormality |
| Placebo Group | Changes in Post-treatment Physical Examination Compared to Baseline | Adjusted Visit 6 (Day 14) (Multi-Selection by Body System) | 0 Participant with Physical Abnormality |
| Placebo Group | Changes in Post-treatment Physical Examination Compared to Baseline | Adjusted Visit 4 (Day 7) (Multi-Selection by Body System) | 0 Participant with Physical Abnormality |
| Placebo Group | Changes in Post-treatment Physical Examination Compared to Baseline | Visit 8 (Day 42) (Multi-Selection by Body System) | 0 Participant with Physical Abnormality |
| Placebo Group | Changes in Post-treatment Physical Examination Compared to Baseline | Adjusted Visit 5 (Day 10) (Multi-Selection by Body System) | 0 Participant with Physical Abnormality |
Secondary
Changes in Post-treatment Vital Signs-body Temperature Compared to Baseline
Changes in post-treatment vital signs-body temperature will be analyzed for all patients in Phase I and II.
Time frame: Days 3, 7, 10, 14, 28, 42
Population: The vital signs-body temperature of each subject was examined at all scheduled visits.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| TWB-103 Group | Changes in Post-treatment Vital Signs-body Temperature Compared to Baseline | Adjusted Visit 4 (Day 7) | 36.47 Body Temperature [degree C] | Standard Deviation 0.455 |
| TWB-103 Group | Changes in Post-treatment Vital Signs-body Temperature Compared to Baseline | Adjusted Visit 6 (Day 14) | 36.44 Body Temperature [degree C] | Standard Deviation 0.358 |
| TWB-103 Group | Changes in Post-treatment Vital Signs-body Temperature Compared to Baseline | Adjusted Visit 3 (Day 3) | 36.54 Body Temperature [degree C] | Standard Deviation 0.463 |
| TWB-103 Group | Changes in Post-treatment Vital Signs-body Temperature Compared to Baseline | Adjusted Visit 7 (Day 28) | 36.35 Body Temperature [degree C] | Standard Deviation 0.363 |
| TWB-103 Group | Changes in Post-treatment Vital Signs-body Temperature Compared to Baseline | Adjusted Visit 5 (Day 10) | 36.72 Body Temperature [degree C] | Standard Deviation 0.529 |
| TWB-103 Group | Changes in Post-treatment Vital Signs-body Temperature Compared to Baseline | Visit 8 (Day 42) | 36.30 Body Temperature [degree C] | Standard Deviation 0.141 |
| TWB-103 Group | Changes in Post-treatment Vital Signs-body Temperature Compared to Baseline | Baseline | 36.29 Body Temperature [degree C] | Standard Deviation 0.315 |
| Placebo Group | Changes in Post-treatment Vital Signs-body Temperature Compared to Baseline | Visit 8 (Day 42) | 36.35 Body Temperature [degree C] | Standard Deviation 0.212 |
| Placebo Group | Changes in Post-treatment Vital Signs-body Temperature Compared to Baseline | Baseline | 36.21 Body Temperature [degree C] | Standard Deviation 0.415 |
| Placebo Group | Changes in Post-treatment Vital Signs-body Temperature Compared to Baseline | Adjusted Visit 3 (Day 3) | 36.33 Body Temperature [degree C] | Standard Deviation 0.412 |
| Placebo Group | Changes in Post-treatment Vital Signs-body Temperature Compared to Baseline | Adjusted Visit 4 (Day 7) | 36.52 Body Temperature [degree C] | Standard Deviation 0.465 |
| Placebo Group | Changes in Post-treatment Vital Signs-body Temperature Compared to Baseline | Adjusted Visit 5 (Day 10) | 36.29 Body Temperature [degree C] | Standard Deviation 0.289 |
| Placebo Group | Changes in Post-treatment Vital Signs-body Temperature Compared to Baseline | Adjusted Visit 6 (Day 14) | 36.36 Body Temperature [degree C] | Standard Deviation 0.207 |
| Placebo Group | Changes in Post-treatment Vital Signs-body Temperature Compared to Baseline | Adjusted Visit 7 (Day 28) | 36.33 Body Temperature [degree C] | Standard Deviation 0.333 |
Secondary
Changes in Post-treatment Vital Signs-diastolic Blood Pressure Compared to Baseline
Changes in post-treatment vital signs-diastolic blood pressure will be analyzed for all patients in Phase I and II.
Time frame: Days 3, 7, 10, 14, 28, 42
Population: The vital signs-diastolic blood pressure of each subject was examined at all scheduled visits.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| TWB-103 Group | Changes in Post-treatment Vital Signs-diastolic Blood Pressure Compared to Baseline | Adjusted Visit 4 (Day 7) | 69.10 Diastolic Blood Pressure [mmHg] | Standard Deviation 6.439 |
| TWB-103 Group | Changes in Post-treatment Vital Signs-diastolic Blood Pressure Compared to Baseline | Adjusted Visit 6 (Day 14) | 77.60 Diastolic Blood Pressure [mmHg] | Standard Deviation 7.893 |
| TWB-103 Group | Changes in Post-treatment Vital Signs-diastolic Blood Pressure Compared to Baseline | Adjusted Visit 3 (Day 3) | 71.50 Diastolic Blood Pressure [mmHg] | Standard Deviation 12.705 |
| TWB-103 Group | Changes in Post-treatment Vital Signs-diastolic Blood Pressure Compared to Baseline | Adjusted Visit 7 (Day 28) | 71.35 Diastolic Blood Pressure [mmHg] | Standard Deviation 11.82 |
| TWB-103 Group | Changes in Post-treatment Vital Signs-diastolic Blood Pressure Compared to Baseline | Adjusted Visit 5 (Day 10) | 68.22 Diastolic Blood Pressure [mmHg] | Standard Deviation 11.745 |
| TWB-103 Group | Changes in Post-treatment Vital Signs-diastolic Blood Pressure Compared to Baseline | Visit 8 (Day 42) | 89.50 Diastolic Blood Pressure [mmHg] | Standard Deviation 24.749 |
| TWB-103 Group | Changes in Post-treatment Vital Signs-diastolic Blood Pressure Compared to Baseline | Baseline | 71.25 Diastolic Blood Pressure [mmHg] | Standard Deviation 13.325 |
| Placebo Group | Changes in Post-treatment Vital Signs-diastolic Blood Pressure Compared to Baseline | Visit 8 (Day 42) | 95.00 Diastolic Blood Pressure [mmHg] | Standard Deviation 2.828 |
| Placebo Group | Changes in Post-treatment Vital Signs-diastolic Blood Pressure Compared to Baseline | Baseline | 69.90 Diastolic Blood Pressure [mmHg] | Standard Deviation 9.91 |
| Placebo Group | Changes in Post-treatment Vital Signs-diastolic Blood Pressure Compared to Baseline | Adjusted Visit 3 (Day 3) | 69.15 Diastolic Blood Pressure [mmHg] | Standard Deviation 10.282 |
| Placebo Group | Changes in Post-treatment Vital Signs-diastolic Blood Pressure Compared to Baseline | Adjusted Visit 4 (Day 7) | 76.15 Diastolic Blood Pressure [mmHg] | Standard Deviation 13.374 |
| Placebo Group | Changes in Post-treatment Vital Signs-diastolic Blood Pressure Compared to Baseline | Adjusted Visit 5 (Day 10) | 70.00 Diastolic Blood Pressure [mmHg] | Standard Deviation 13.739 |
| Placebo Group | Changes in Post-treatment Vital Signs-diastolic Blood Pressure Compared to Baseline | Adjusted Visit 6 (Day 14) | 78.40 Diastolic Blood Pressure [mmHg] | Standard Deviation 11.014 |
| Placebo Group | Changes in Post-treatment Vital Signs-diastolic Blood Pressure Compared to Baseline | Adjusted Visit 7 (Day 28) | 77.95 Diastolic Blood Pressure [mmHg] | Standard Deviation 13.323 |
Secondary
Changes in Post-treatment Vital Signs-pulse Rate Compared to Baseline
Changes in post-treatment vital signs-pulse rate will be analyzed for all patients in Phase I and II.
Time frame: Days 3, 7, 10, 14, 28, 42
Population: The vital signs-pulse rate of each subject was examined at all scheduled visits.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| TWB-103 Group | Changes in Post-treatment Vital Signs-pulse Rate Compared to Baseline | Adjusted Visit 4 (Day 7) | 74.70 Pulse Rate [beats/min] | Standard Deviation 9.314 |
| TWB-103 Group | Changes in Post-treatment Vital Signs-pulse Rate Compared to Baseline | Adjusted Visit 6 (Day 14) | 84.20 Pulse Rate [beats/min] | Standard Deviation 17.021 |
| TWB-103 Group | Changes in Post-treatment Vital Signs-pulse Rate Compared to Baseline | Adjusted Visit 3 (Day 3) | 74.25 Pulse Rate [beats/min] | Standard Deviation 11.964 |
| TWB-103 Group | Changes in Post-treatment Vital Signs-pulse Rate Compared to Baseline | Adjusted Visit 7 (Day 28) | 75.15 Pulse Rate [beats/min] | Standard Deviation 12.119 |
| TWB-103 Group | Changes in Post-treatment Vital Signs-pulse Rate Compared to Baseline | Adjusted Visit 5 (Day 10) | 77.67 Pulse Rate [beats/min] | Standard Deviation 11.554 |
| TWB-103 Group | Changes in Post-treatment Vital Signs-pulse Rate Compared to Baseline | Visit 8 (Day 42) | 71.00 Pulse Rate [beats/min] | Standard Deviation 2.828 |
| TWB-103 Group | Changes in Post-treatment Vital Signs-pulse Rate Compared to Baseline | Baseline | 71.95 Pulse Rate [beats/min] | Standard Deviation 10.359 |
| Placebo Group | Changes in Post-treatment Vital Signs-pulse Rate Compared to Baseline | Visit 8 (Day 42) | 76.00 Pulse Rate [beats/min] | Standard Deviation 2.828 |
| Placebo Group | Changes in Post-treatment Vital Signs-pulse Rate Compared to Baseline | Baseline | 73.90 Pulse Rate [beats/min] | Standard Deviation 15.001 |
| Placebo Group | Changes in Post-treatment Vital Signs-pulse Rate Compared to Baseline | Adjusted Visit 3 (Day 3) | 78.20 Pulse Rate [beats/min] | Standard Deviation 13.332 |
| Placebo Group | Changes in Post-treatment Vital Signs-pulse Rate Compared to Baseline | Adjusted Visit 4 (Day 7) | 73.55 Pulse Rate [beats/min] | Standard Deviation 11.821 |
| Placebo Group | Changes in Post-treatment Vital Signs-pulse Rate Compared to Baseline | Adjusted Visit 5 (Day 10) | 72.33 Pulse Rate [beats/min] | Standard Deviation 8.732 |
| Placebo Group | Changes in Post-treatment Vital Signs-pulse Rate Compared to Baseline | Adjusted Visit 6 (Day 14) | 82.40 Pulse Rate [beats/min] | Standard Deviation 7.092 |
| Placebo Group | Changes in Post-treatment Vital Signs-pulse Rate Compared to Baseline | Adjusted Visit 7 (Day 28) | 74.79 Pulse Rate [beats/min] | Standard Deviation 12.376 |
Secondary
Changes in Post-treatment Vital Signs-systolic Blood Pressure Compared to Baseline
Changes in post-treatment vital signs-systolic blood pressure will be analyzed for all patients in Phase I and II.
Time frame: Days 3, 7, 10, 14, 28, 42
Population: The vital signs-systolic blood pressure of each subject was examined at all scheduled visits.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| TWB-103 Group | Changes in Post-treatment Vital Signs-systolic Blood Pressure Compared to Baseline | Adjusted Visit 4 (Day 7) | 118.85 Systolic Blood Pressure [mmHg] | Standard Deviation 12.783 |
| TWB-103 Group | Changes in Post-treatment Vital Signs-systolic Blood Pressure Compared to Baseline | Adjusted Visit 6 (Day 14) | 119.80 Systolic Blood Pressure [mmHg] | Standard Deviation 17.584 |
| TWB-103 Group | Changes in Post-treatment Vital Signs-systolic Blood Pressure Compared to Baseline | Adjusted Visit 3 (Day 3) | 123.45 Systolic Blood Pressure [mmHg] | Standard Deviation 16.794 |
| TWB-103 Group | Changes in Post-treatment Vital Signs-systolic Blood Pressure Compared to Baseline | Adjusted Visit 7 (Day 28) | 124.60 Systolic Blood Pressure [mmHg] | Standard Deviation 10.928 |
| TWB-103 Group | Changes in Post-treatment Vital Signs-systolic Blood Pressure Compared to Baseline | Adjusted Visit 5 (Day 10) | 117.44 Systolic Blood Pressure [mmHg] | Standard Deviation 13.436 |
| TWB-103 Group | Changes in Post-treatment Vital Signs-systolic Blood Pressure Compared to Baseline | Visit 8 (Day 42) | 140.00 Systolic Blood Pressure [mmHg] | Standard Deviation 12.728 |
| TWB-103 Group | Changes in Post-treatment Vital Signs-systolic Blood Pressure Compared to Baseline | Baseline | 116.80 Systolic Blood Pressure [mmHg] | Standard Deviation 17.665 |
| Placebo Group | Changes in Post-treatment Vital Signs-systolic Blood Pressure Compared to Baseline | Visit 8 (Day 42) | 122.00 Systolic Blood Pressure [mmHg] | Standard Deviation 5.657 |
| Placebo Group | Changes in Post-treatment Vital Signs-systolic Blood Pressure Compared to Baseline | Baseline | 116.65 Systolic Blood Pressure [mmHg] | Standard Deviation 15.792 |
| Placebo Group | Changes in Post-treatment Vital Signs-systolic Blood Pressure Compared to Baseline | Adjusted Visit 3 (Day 3) | 120.30 Systolic Blood Pressure [mmHg] | Standard Deviation 21.293 |
| Placebo Group | Changes in Post-treatment Vital Signs-systolic Blood Pressure Compared to Baseline | Adjusted Visit 4 (Day 7) | 121.95 Systolic Blood Pressure [mmHg] | Standard Deviation 15.278 |
| Placebo Group | Changes in Post-treatment Vital Signs-systolic Blood Pressure Compared to Baseline | Adjusted Visit 5 (Day 10) | 117.11 Systolic Blood Pressure [mmHg] | Standard Deviation 15.584 |
| Placebo Group | Changes in Post-treatment Vital Signs-systolic Blood Pressure Compared to Baseline | Adjusted Visit 6 (Day 14) | 120.00 Systolic Blood Pressure [mmHg] | Standard Deviation 13.304 |
| Placebo Group | Changes in Post-treatment Vital Signs-systolic Blood Pressure Compared to Baseline | Adjusted Visit 7 (Day 28) | 121.21 Systolic Blood Pressure [mmHg] | Standard Deviation 11.622 |
Secondary
Number of Participants With AEs and SAEs
The number of participants with AEs and SAEs will be analyzed for all patients in Phase I and II.
Time frame: Screening~ Day 360 from Day 28 or 42
Population: 40 subjects (20 in TWB-103 group and 20 in Placebo group) were included in the population for safety analysis. Treatment-emergent adverse events (TEAE) were classified as treatment-related AE, Grade 3 or greater AE, AE that required to take special actions, SAE, or SUSAR during the study.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| TWB-103 Group | Number of Participants With AEs and SAEs | Grade≥3 AE | 0 Participants |
| TWB-103 Group | Number of Participants With AEs and SAEs | AE Leading to Drug withdrawn | 0 Participants |
| TWB-103 Group | Number of Participants With AEs and SAEs | Treatment-Related AE | 0 Participants |
| TWB-103 Group | Number of Participants With AEs and SAEs | Grade ≥ 3 Treatment-Related AE | 0 Participants |
| TWB-103 Group | Number of Participants With AEs and SAEs | Death SAE | 0 Participants |
| TWB-103 Group | Number of Participants With AEs and SAEs | AE | 7 Participants |
| TWB-103 Group | Number of Participants With AEs and SAEs | SUSAR | 0 Participants |
| TWB-103 Group | Number of Participants With AEs and SAEs | AE Leading to Action Taken | 0 Participants |
| TWB-103 Group | Number of Participants With AEs and SAEs | Death SUSAR | 0 Participants |
| TWB-103 Group | Number of Participants With AEs and SAEs | SAE | 0 Participants |
| Placebo Group | Number of Participants With AEs and SAEs | Death SUSAR | 0 Participants |
| Placebo Group | Number of Participants With AEs and SAEs | AE | 10 Participants |
| Placebo Group | Number of Participants With AEs and SAEs | Treatment-Related AE | 0 Participants |
| Placebo Group | Number of Participants With AEs and SAEs | Grade≥3 AE | 0 Participants |
| Placebo Group | Number of Participants With AEs and SAEs | Grade ≥ 3 Treatment-Related AE | 0 Participants |
| Placebo Group | Number of Participants With AEs and SAEs | AE Leading to Action Taken | 0 Participants |
| Placebo Group | Number of Participants With AEs and SAEs | AE Leading to Drug withdrawn | 0 Participants |
| Placebo Group | Number of Participants With AEs and SAEs | SAE | 0 Participants |
| Placebo Group | Number of Participants With AEs and SAEs | Death SAE | 0 Participants |
| Placebo Group | Number of Participants With AEs and SAEs | SUSAR | 0 Participants |
Secondary
Number of Participants With Complete Wound Closure at Day 7, 10 and 14 After DSW Creation.
Complete wound closure is defined as skin 100% re-epithelialization without drainage or dressing requirements. This endpoint will be in all patients in Phase I and II.
Time frame: Day 7, 10 and 14
Population: Healing rates (complete wound closure) of subjects at Days 7, 10, and 14 after DSW creation were analyzed. Due to the study design, subjects would skip the following treatment visits when their wound was completely closed, resulting in the smaller subject numbers at Visit 5 (N=18) and Visit 6 (N=10). To rectify this issue, post-hoc LOCF analysis was performed.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| TWB-103 Group | Number of Participants With Complete Wound Closure at Day 7, 10 and 14 After DSW Creation. | Adjusted Visit 4 (Day 7) with LOCF | 9 Participants |
| TWB-103 Group | Number of Participants With Complete Wound Closure at Day 7, 10 and 14 After DSW Creation. | Adjusted Visit 5 (Day 10) with LOCF | 15 Participants |
| TWB-103 Group | Number of Participants With Complete Wound Closure at Day 7, 10 and 14 After DSW Creation. | Adjusted Visit 6 (Day 14) with LOCF | 18 Participants |
| Placebo Group | Number of Participants With Complete Wound Closure at Day 7, 10 and 14 After DSW Creation. | Adjusted Visit 4 (Day 7) with LOCF | 11 Participants |
| Placebo Group | Number of Participants With Complete Wound Closure at Day 7, 10 and 14 After DSW Creation. | Adjusted Visit 5 (Day 10) with LOCF | 15 Participants |
| Placebo Group | Number of Participants With Complete Wound Closure at Day 7, 10 and 14 After DSW Creation. | Adjusted Visit 6 (Day 14) with LOCF | 18 Participants |
Secondary
Number of Participants With Treatment-related AEs and SAEs (Including Infections and Bleeding)
The number of participants with treatment-related AEs and SAEs (including infections and bleeding) will be observed for all patients in Phase I and II
Time frame: Screening~ Day 360 from Day 28 or 42
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| TWB-103 Group | Number of Participants With Treatment-related AEs and SAEs (Including Infections and Bleeding) | Treatment-Related AEs | 0 Participants |
| TWB-103 Group | Number of Participants With Treatment-related AEs and SAEs (Including Infections and Bleeding) | SAEs | 0 Participants |
| Placebo Group | Number of Participants With Treatment-related AEs and SAEs (Including Infections and Bleeding) | Treatment-Related AEs | 0 Participants |
| Placebo Group | Number of Participants With Treatment-related AEs and SAEs (Including Infections and Bleeding) | SAEs | 0 Participants |
Secondary
The Healing Percentage of Wounds (Ratio of Healing Area and Original Area) at Days 7, 10 and 14 After DSW Creation
The healing percentage of wounds will be calculated based on the healing area measured on Day 7, 10 and 14, comparing to the original area measured on Day 0 for all patients in Phase I and II.
Time frame: Day 7, 10 and 14
Population: Healing percentage was measured by the study investigator. Due to the study design, subjects would skip the following treatment visits when their wound was completely closed, resulting in the smaller subject numbers at Visit 5 (N=18) and Visit 6 (N=10). To rectify this issue, post-hoc LOCF analysis was performed.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| TWB-103 Group | The Healing Percentage of Wounds (Ratio of Healing Area and Original Area) at Days 7, 10 and 14 After DSW Creation | Adjusted Visit 4 (Day 7) with LOCF | 65.36 Healing Percentage (%) | Standard Error 8.676 |
| TWB-103 Group | The Healing Percentage of Wounds (Ratio of Healing Area and Original Area) at Days 7, 10 and 14 After DSW Creation | Adjusted Visit 5 (Day 10) with LOCF | 89.20 Healing Percentage (%) | Standard Error 5.111 |
| TWB-103 Group | The Healing Percentage of Wounds (Ratio of Healing Area and Original Area) at Days 7, 10 and 14 After DSW Creation | Adjusted Visit 6 (Day 14) with LOCF | 88.56 Healing Percentage (%) | Standard Error 5.159 |
| Placebo Group | The Healing Percentage of Wounds (Ratio of Healing Area and Original Area) at Days 7, 10 and 14 After DSW Creation | Adjusted Visit 5 (Day 10) with LOCF | 83.74 Healing Percentage (%) | Standard Error 5.111 |
| Placebo Group | The Healing Percentage of Wounds (Ratio of Healing Area and Original Area) at Days 7, 10 and 14 After DSW Creation | Adjusted Visit 4 (Day 7) with LOCF | 62.60 Healing Percentage (%) | Standard Error 8.676 |
| Placebo Group | The Healing Percentage of Wounds (Ratio of Healing Area and Original Area) at Days 7, 10 and 14 After DSW Creation | Adjusted Visit 6 (Day 14) with LOCF | 83.51 Healing Percentage (%) | Standard Error 5.159 |
Secondary
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
The healing time from DSW creation to the first 100% re-epithelialization with confirmation for at least 10 days apart assessed by the investigator for all patients in Phase I and II. The first additional evaluator judged the healing status by looking at the photos of DSW.
Time frame: Days 42 or earlier
Population: The additional evaluator who was not aware of the treatment groups would assess the wound based on the photos.~Case first 100% re-epithelialization at any visit till Visit 7 (Day 28 Visit) with confirmation for at least 10 days apart:~Healing Time \[days\] = date of first 100% re-epithelialization - date of DSW creation (Visit 2).~Case else: Censored Healing Time \[days\] = date of last assessment up to Visit 7 - date of DSW creation (Visit 2).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| TWB-103 Group | 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 | 20 Healing Time [days] | Standard Error 2.2 |
| Placebo Group | 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 | 13 Healing Time [days] | Standard Error 0.7 |
p-value: 0.3975Log Rank
Secondary
The Number of Censored Subjects Assessed by the Investigator and the First Additional Evaluator
The number of censored subjects in Phase I and II assessed by the investigator and the first additional evaluator. The first additional evaluator judged the healing status by looking at the photos of DSW. If the 100% re-epithelialization was not observed by Day 28 visit, the healing time was censored on the day of the last visit up to Day 28 visit. If the 100% re-epithelialization was observed by Day 28 visit but no confirmation was made, the healing time was censored on day of the last visit up to Day 28 visit.
Time frame: Days 42 or earlier
Population: The additional evaluator who was not aware of the treatment groups would assess the wound based on the photos.~Case first 100% re-epithelialization at any visit till Visit 7 (Day 28 Visit) with confirmation for at least 10 days apart:~Healing Time \[days\] = date of first 100% re-epithelialization - date of DSW creation (Visit 2).~Case else: Censored Healing Time \[days\] = date of last assessment up to Visit 7 - date of DSW creation (Visit 2).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| TWB-103 Group | The Number of Censored Subjects Assessed by the Investigator and the First Additional Evaluator | Investigator | 1 Participants |
| TWB-103 Group | The Number of Censored Subjects Assessed by the Investigator and the First Additional Evaluator | First Additional Evaluator | 10 Participants |
| Placebo Group | The Number of Censored Subjects Assessed by the Investigator and the First Additional Evaluator | Investigator | 6 Participants |
| Placebo Group | The Number of Censored Subjects Assessed by the Investigator and the First Additional Evaluator | First Additional Evaluator | 13 Participants |
Secondary
The Pain Change From Baseline to Post-wound Creation Visits Based on Short-form McGill Pain Questionnaire Score
All patients in Phase I and II will evaluate the pain based on Short-form McGill pain questionnaire at each visit. The visual analogue scale (VAS) for pain is a continuous scale comprised of a horizontal line, usually, 10 cm (= 100 mm) in length, scored from 0 (none) to 10 (extreme). On this scale, a higher score in VAS indicates the worse pain.
Time frame: Days 3, 7, 10, 14, 28, 42, Day 90/180/270/360 from Day 28 or 42
Population: The pain assessment was measured by employing short-form McGill pain questionnaire at all scheduled visits, except Visit 2 (Day 0). The visual analogue scale (VAS) for pain is a continuous scale comprised of a horizontal line, usually, 10 cm (= 100 mm) in length, scored from 0 (none) to 10 (extreme). On this scale, a higher score in VAS indicates the worse pain.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| TWB-103 Group | The Pain Change From Baseline to Post-wound Creation Visits Based on Short-form McGill Pain Questionnaire Score | Adjusted Visit 5 (Day 10) | 0.80 VAS (0~10 cm) | Standard Deviation 0.763 |
| TWB-103 Group | The Pain Change From Baseline to Post-wound Creation Visits Based on Short-form McGill Pain Questionnaire Score | Adjusted Visit 8 (Day 42) | 0.45 VAS (0~10 cm) | Standard Deviation 0.636 |
| TWB-103 Group | The Pain Change From Baseline to Post-wound Creation Visits Based on Short-form McGill Pain Questionnaire Score | Adjusted Visit 4 (Day 7) | 0.82 VAS (0~10 cm) | Standard Deviation 1.313 |
| TWB-103 Group | The Pain Change From Baseline to Post-wound Creation Visits Based on Short-form McGill Pain Questionnaire Score | Visit 9 (FU 3 Months) | 0.40 VAS (0~10 cm) | Standard Deviation 1.588 |
| TWB-103 Group | The Pain Change From Baseline to Post-wound Creation Visits Based on Short-form McGill Pain Questionnaire Score | Adjusted Visit 6 (Day 14) | 0.38 VAS (0~10 cm) | Standard Deviation 0.522 |
| TWB-103 Group | The Pain Change From Baseline to Post-wound Creation Visits Based on Short-form McGill Pain Questionnaire Score | Visit 10 (FU 6 Months) | 0.00 VAS (0~10 cm) | Standard Deviation 0 |
| TWB-103 Group | The Pain Change From Baseline to Post-wound Creation Visits Based on Short-form McGill Pain Questionnaire Score | Adjusted Visit 3 (Day 3) | 1.79 VAS (0~10 cm) | Standard Deviation 2.137 |
| TWB-103 Group | The Pain Change From Baseline to Post-wound Creation Visits Based on Short-form McGill Pain Questionnaire Score | Visit 11 (FU 9 Months) | 0.05 VAS (0~10 cm) | Standard Deviation 0.212 |
| TWB-103 Group | The Pain Change From Baseline to Post-wound Creation Visits Based on Short-form McGill Pain Questionnaire Score | Adjusted Visit 7 (Day 28) | 0.37 VAS (0~10 cm) | Standard Deviation 0.713 |
| TWB-103 Group | The Pain Change From Baseline to Post-wound Creation Visits Based on Short-form McGill Pain Questionnaire Score | Visit 12 (FU 12 Months) | 0.04 VAS (0~10 cm) | Standard Deviation 0.161 |
| TWB-103 Group | The Pain Change From Baseline to Post-wound Creation Visits Based on Short-form McGill Pain Questionnaire Score | Baseline | 1.89 VAS (0~10 cm) | Standard Deviation 2.833 |
| Placebo Group | The Pain Change From Baseline to Post-wound Creation Visits Based on Short-form McGill Pain Questionnaire Score | Visit 12 (FU 12 Months) | 0.00 VAS (0~10 cm) | Standard Deviation 0 |
| Placebo Group | The Pain Change From Baseline to Post-wound Creation Visits Based on Short-form McGill Pain Questionnaire Score | Baseline | 1.06 VAS (0~10 cm) | Standard Deviation 2.399 |
| Placebo Group | The Pain Change From Baseline to Post-wound Creation Visits Based on Short-form McGill Pain Questionnaire Score | Adjusted Visit 3 (Day 3) | 1.58 VAS (0~10 cm) | Standard Deviation 2.091 |
| Placebo Group | The Pain Change From Baseline to Post-wound Creation Visits Based on Short-form McGill Pain Questionnaire Score | Adjusted Visit 4 (Day 7) | 0.40 VAS (0~10 cm) | Standard Deviation 0.701 |
| Placebo Group | The Pain Change From Baseline to Post-wound Creation Visits Based on Short-form McGill Pain Questionnaire Score | Adjusted Visit 5 (Day 10) | 1.02 VAS (0~10 cm) | Standard Deviation 1.731 |
| Placebo Group | The Pain Change From Baseline to Post-wound Creation Visits Based on Short-form McGill Pain Questionnaire Score | Adjusted Visit 6 (Day 14) | 1.48 VAS (0~10 cm) | Standard Deviation 2.062 |
| Placebo Group | The Pain Change From Baseline to Post-wound Creation Visits Based on Short-form McGill Pain Questionnaire Score | Adjusted Visit 7 (Day 28) | 0.35 VAS (0~10 cm) | Standard Deviation 0.943 |
| Placebo Group | The Pain Change From Baseline to Post-wound Creation Visits Based on Short-form McGill Pain Questionnaire Score | Adjusted Visit 8 (Day 42) | 0.00 VAS (0~10 cm) | Standard Deviation 0 |
| Placebo Group | The Pain Change From Baseline to Post-wound Creation Visits Based on Short-form McGill Pain Questionnaire Score | Visit 9 (FU 3 Months) | 0.06 VAS (0~10 cm) | Standard Deviation 0.236 |
| Placebo Group | The Pain Change From Baseline to Post-wound Creation Visits Based on Short-form McGill Pain Questionnaire Score | Visit 10 (FU 6 Months) | 0.000 VAS (0~10 cm) | Standard Deviation 0 |
| Placebo Group | The Pain Change From Baseline to Post-wound Creation Visits Based on Short-form McGill Pain Questionnaire Score | Visit 11 (FU 9 Months) | 0.00 VAS (0~10 cm) | Standard Deviation 0 |