TWB-103 for Adult Patients With Split-Thickness Skin Graft Donor Site Wounds

A Phase I/II Study to Evaluate the Safety and Efficacy of TWB-103 in Adult Patients With Split-Thickness Skin Graft Donor Site Wounds (DSW)

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

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follow-up evaluation at least 14 days after the first dose or (2) he/she who received at least one dose and had early withdrawn due to safety reasons before Day 28.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.

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