Trial Outcomes & Findings for Phase 2 Pilot Trial of Subjects With Complex Non-healing Diabetic Foot Ulcers Treated With Standard Care Plus Cryopreserved Umbilical Cord Allograft (TTAX01) (NCT NCT03230175)

Last Updated: 2021-06-15

Results Overview

Proportion of subjects with complete wound healing observed over the 16-week treatment period. Complete wound healing was defined as an initial observation of closure, followed by two confirmatory visits two weeks apart.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

32 participants

Primary outcome timeframe

16-weeks

Results posted on

2021-06-15

Participant Flow

Participant milestones

Participant milestones
Measure	TTAX01 Plus Standard Care Eligible consenting subjects underwent a baseline aggressive debridement in the operating room to remove infected and devitalized bone and soft tissue. infection. TTAX01: TTAX01 was applied directly to the wound surface and retained with non-absorbable sutures. A single layer of the test article covered the entire open surface of the wound. The material was to be applied once every 4 weeks unless the wound shows evidence of healing, in which case dosing is suspended; or, if the test article has been accidentally dislodged, it may be replaced at any time. Surgical resection and debridement: Perform surgical sharp debridement in the OR, to remove: * infectious agents and biofilms (purulence), * all debris, eschar, callus and macerated non-viable tissue from the wound base, and * dead (suprabasal epidermis), scarred (elevated/edematous) and necrotic/macerated tissue from the wound edge. Surgical Resection will be performed to remove as much of the necrotic bone detected by the radiographic evidence as is appropriate. Systemic antibiotics: Six (6) weeks of systemic antibiotic therapy is required. A definitive therapy will be guided by the microbiological results based on bone biopsy. Off-loading: Provide off-loading device appropriate to the location of wound with full length boot or total contact cast
Overall Study STARTED	32
Overall Study COMPLETED	30
Overall Study NOT COMPLETED	2

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Phase 2 Pilot Trial of Subjects With Complex Non-healing Diabetic Foot Ulcers Treated With Standard Care Plus Cryopreserved Umbilical Cord Allograft (TTAX01)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	TTAX01 Plus Standard Care n=32 Participants Eligible consenting subjects underwent a baseline aggressive debridement in the operating room to remove infected and devitalized bone and soft tissue. TTAX01: TTAX01 was applied directly to the wound surface and retained with non-absorbable sutures. A single layer of the test article covered the entire open surface of the wound. The material was applied once every 4 weeks unless the wound shows evidence of healing, in which case dosing is suspended; or, if the test article has been accidentally dislodged, it may be replaced at any time. Surgical resection and debridement: Perform surgical sharp debridement in the OR, to remove: * infectious agents and biofilms (purulence), * all debris, eschar, callus and macerated non-viable tissue from the wound base, and * dead (suprabasal epidermis), scarred (elevated/edematous) and necrotic/macerated tissue from the wound edge. Surgical Resection will be performed to remove as much of the necrotic bone detected by the radiographic evidence as is appropriate. Systemic antibiotics: Six (6) weeks of systemic antibiotic therapy is required. A definitive therapy will be guided by the microbiological results based on bone biopsy. Off-loading: Provide off-loading device appropriate to the location of wound with full length boot or total contact cast
Age, Customized < 65 years	23 participants n=5 Participants
Age, Customized > or = to 65 years	9 participants n=5 Participants
Sex: Female, Male Female	1 Participants n=5 Participants
Sex: Female, Male Male	31 Participants n=5 Participants
Race/Ethnicity, Customized Alaskan Native/American Indian	1 Participants n=5 Participants
Race/Ethnicity, Customized Black/African American	8 Participants n=5 Participants
Race/Ethnicity, Customized White/Caucasian	22 Participants n=5 Participants
Race/Ethnicity, Customized Other, not specified	1 Participants n=5 Participants
Region of Enrollment United States	32 participants n=5 Participants
Subject presents with history, signs or symptoms leading to a clinical suspicion of osteomyelitis	32 Participants n=5 Participants

PRIMARY outcome

Timeframe: 16-weeks

Outcome measures

Outcome measures
Measure	TTAX01 Plus Standard Care n=32 Participants Eligible consenting subjects underwent a baseline aggressive debridement in the operating room to remove infected and devitalized bone and soft tissue. TTAX01: TTAX01 was applied directly to the wound surface and retained with non-absorbable sutures. A single layer of the test article covered the entire open surface of the wound. The material was applied once every 4 weeks unless the wound shows evidence of healing, in which case dosing is suspended; or, if the test article has been accidentally dislodged, it was replaced at any time. Surgical resection and debridement: Performed surgical sharp debridement in the OR, to remove: * infectious agents and biofilms (purulence), * all debris, eschar, callus and macerated non-viable tissue from the wound base, and * dead (suprabasal epidermis), scarred (elevated/edematous) and necrotic/macerated tissue from the wound edge. Surgical Resection performed to remove as much of the necrotic bone detected by the radiographic evidence as is appropriate. Systemic antibiotics: Six (6) weeks of systemic antibiotic therapy was required. A definitive therapy was guided by the microbiological results based on bone biopsy. Off-loading: Provided off-loading device appropriate to the location of wound with full length boot or total contact cast
Number of Subjects With Complete Wound Healing	16 participants

SECONDARY outcome

Timeframe: up to 16 weeks

Time in number of days to complete wound closure over the 16 week treatment period, starting from enrollment to the time of the initial observation of wound closure

Outcome measures

Outcome measures
Measure	TTAX01 Plus Standard Care n=32 Participants Eligible consenting subjects underwent a baseline aggressive debridement in the operating room to remove infected and devitalized bone and soft tissue. TTAX01: TTAX01 was applied directly to the wound surface and retained with non-absorbable sutures. A single layer of the test article covered the entire open surface of the wound. The material was applied once every 4 weeks unless the wound shows evidence of healing, in which case dosing is suspended; or, if the test article has been accidentally dislodged, it was replaced at any time. Surgical resection and debridement: Performed surgical sharp debridement in the OR, to remove: * infectious agents and biofilms (purulence), * all debris, eschar, callus and macerated non-viable tissue from the wound base, and * dead (suprabasal epidermis), scarred (elevated/edematous) and necrotic/macerated tissue from the wound edge. Surgical Resection performed to remove as much of the necrotic bone detected by the radiographic evidence as is appropriate. Systemic antibiotics: Six (6) weeks of systemic antibiotic therapy was required. A definitive therapy was guided by the microbiological results based on bone biopsy. Off-loading: Provided off-loading device appropriate to the location of wound with full length boot or total contact cast
Time to Complete Wound Healing	12.8 weeks Standard Deviation 4.3

SECONDARY outcome

Timeframe: at week 16

Rate of wound closure, specifically percent change in the wound surface area (cm2) at each visit from baseline for assessing the rate of wound closure in area. Only percent change in wound surface area at week 16 reported.

Outcome measures

Outcome measures
Measure	TTAX01 Plus Standard Care n=32 Participants Eligible consenting subjects underwent a baseline aggressive debridement in the operating room to remove infected and devitalized bone and soft tissue. TTAX01: TTAX01 was applied directly to the wound surface and retained with non-absorbable sutures. A single layer of the test article covered the entire open surface of the wound. The material was applied once every 4 weeks unless the wound shows evidence of healing, in which case dosing is suspended; or, if the test article has been accidentally dislodged, it was replaced at any time. Surgical resection and debridement: Performed surgical sharp debridement in the OR, to remove: * infectious agents and biofilms (purulence), * all debris, eschar, callus and macerated non-viable tissue from the wound base, and * dead (suprabasal epidermis), scarred (elevated/edematous) and necrotic/macerated tissue from the wound edge. Surgical Resection performed to remove as much of the necrotic bone detected by the radiographic evidence as is appropriate. Systemic antibiotics: Six (6) weeks of systemic antibiotic therapy was required. A definitive therapy was guided by the microbiological results based on bone biopsy. Off-loading: Provided off-loading device appropriate to the location of wound with full length boot or total contact cast
Percent Change in Wound Surface Area	90.93 Percent Change Interval 84.54 to 95.31

Adverse Events

TTAX01 Plus Standard Care

Serious events: 7 serious events

Other events: 19 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	TTAX01 Plus Standard Care n=32 participants at risk Eligible consenting subjects underwent a baseline aggressive debridement in the operating room to remove infected and devitalized bone and soft tissue. TTAX01: TTAX01 was applied directly to the wound surface and retained with non-absorbable sutures. A single layer of the test article covered the entire open surface of the wound. The material was applied once every 4 weeks unless the wound shows evidence of healing, in which case dosing is suspended; or, if the test article has been accidentally dislodged, it was replaced at any time. Surgical resection and debridement: Performed surgical sharp debridement in the OR, to remove: * infectious agents and biofilms (purulence), * all debris, eschar, callus and macerated non-viable tissue from the wound base, and * dead (suprabasal epidermis), scarred (elevated/edematous) and necrotic/macerated tissue from the wound edge. Surgical Resection performed to remove as much of the necrotic bone detected by the radiographic evidence as is appropriate. Systemic antibiotics: Six (6) weeks of systemic antibiotic therapy was required. A definitive therapy was guided by the microbiological results based on bone biopsy. Off-loading: Provided off-loading device appropriate to the location of wound with full length boot or total contact cast
Infections and infestations Osteomyelitis	9.4% 3/32 • Number of events 3 • The maximum time in the study for any subject was 21 weeks, with 1 week in screening and assuming wound healing occurs at week 16 followed by 2 weeks of observation for confirmation of closure, and a final exit visit 14 days later. An Adverse Event (AE) is any untoward medical occurrence temporally associated with the use of an investigational medicinal product, whether or not considered causally related to that product. An Serious Adverse Event is defined as any AE occurring at any dose that results in any of the following outcomes: death, life-threatening AE, requires hospitalization or prolongation of existing hospitalization, a persistent or significant disability/incapacity, or a congenital anomaly/birth defect.
General disorders non-cardiac chest pain	3.1% 1/32 • Number of events 1 • The maximum time in the study for any subject was 21 weeks, with 1 week in screening and assuming wound healing occurs at week 16 followed by 2 weeks of observation for confirmation of closure, and a final exit visit 14 days later. An Adverse Event (AE) is any untoward medical occurrence temporally associated with the use of an investigational medicinal product, whether or not considered causally related to that product. An Serious Adverse Event is defined as any AE occurring at any dose that results in any of the following outcomes: death, life-threatening AE, requires hospitalization or prolongation of existing hospitalization, a persistent or significant disability/incapacity, or a congenital anomaly/birth defect.
Endocrine disorders gastroparesis	3.1% 1/32 • Number of events 1 • The maximum time in the study for any subject was 21 weeks, with 1 week in screening and assuming wound healing occurs at week 16 followed by 2 weeks of observation for confirmation of closure, and a final exit visit 14 days later. An Adverse Event (AE) is any untoward medical occurrence temporally associated with the use of an investigational medicinal product, whether or not considered causally related to that product. An Serious Adverse Event is defined as any AE occurring at any dose that results in any of the following outcomes: death, life-threatening AE, requires hospitalization or prolongation of existing hospitalization, a persistent or significant disability/incapacity, or a congenital anomaly/birth defect.
Respiratory, thoracic and mediastinal disorders Bilateral Pleural Effusions	3.1% 1/32 • Number of events 1 • The maximum time in the study for any subject was 21 weeks, with 1 week in screening and assuming wound healing occurs at week 16 followed by 2 weeks of observation for confirmation of closure, and a final exit visit 14 days later. An Adverse Event (AE) is any untoward medical occurrence temporally associated with the use of an investigational medicinal product, whether or not considered causally related to that product. An Serious Adverse Event is defined as any AE occurring at any dose that results in any of the following outcomes: death, life-threatening AE, requires hospitalization or prolongation of existing hospitalization, a persistent or significant disability/incapacity, or a congenital anomaly/birth defect.
Vascular disorders recurrent transient ischemic attack	3.1% 1/32 • Number of events 1 • The maximum time in the study for any subject was 21 weeks, with 1 week in screening and assuming wound healing occurs at week 16 followed by 2 weeks of observation for confirmation of closure, and a final exit visit 14 days later. An Adverse Event (AE) is any untoward medical occurrence temporally associated with the use of an investigational medicinal product, whether or not considered causally related to that product. An Serious Adverse Event is defined as any AE occurring at any dose that results in any of the following outcomes: death, life-threatening AE, requires hospitalization or prolongation of existing hospitalization, a persistent or significant disability/incapacity, or a congenital anomaly/birth defect.

Other adverse events

Other adverse events
Measure	TTAX01 Plus Standard Care n=32 participants at risk Eligible consenting subjects underwent a baseline aggressive debridement in the operating room to remove infected and devitalized bone and soft tissue. TTAX01: TTAX01 was applied directly to the wound surface and retained with non-absorbable sutures. A single layer of the test article covered the entire open surface of the wound. The material was applied once every 4 weeks unless the wound shows evidence of healing, in which case dosing is suspended; or, if the test article has been accidentally dislodged, it was replaced at any time. Surgical resection and debridement: Performed surgical sharp debridement in the OR, to remove: * infectious agents and biofilms (purulence), * all debris, eschar, callus and macerated non-viable tissue from the wound base, and * dead (suprabasal epidermis), scarred (elevated/edematous) and necrotic/macerated tissue from the wound edge. Surgical Resection performed to remove as much of the necrotic bone detected by the radiographic evidence as is appropriate. Systemic antibiotics: Six (6) weeks of systemic antibiotic therapy was required. A definitive therapy was guided by the microbiological results based on bone biopsy. Off-loading: Provided off-loading device appropriate to the location of wound with full length boot or total contact cast
Blood and lymphatic system disorders Anaemia	6.2% 2/32 • Number of events 2 • The maximum time in the study for any subject was 21 weeks, with 1 week in screening and assuming wound healing occurs at week 16 followed by 2 weeks of observation for confirmation of closure, and a final exit visit 14 days later. An Adverse Event (AE) is any untoward medical occurrence temporally associated with the use of an investigational medicinal product, whether or not considered causally related to that product. An Serious Adverse Event is defined as any AE occurring at any dose that results in any of the following outcomes: death, life-threatening AE, requires hospitalization or prolongation of existing hospitalization, a persistent or significant disability/incapacity, or a congenital anomaly/birth defect.
Endocrine disorders Diabetes mellitus inadequate control	6.2% 2/32 • Number of events 2 • The maximum time in the study for any subject was 21 weeks, with 1 week in screening and assuming wound healing occurs at week 16 followed by 2 weeks of observation for confirmation of closure, and a final exit visit 14 days later. An Adverse Event (AE) is any untoward medical occurrence temporally associated with the use of an investigational medicinal product, whether or not considered causally related to that product. An Serious Adverse Event is defined as any AE occurring at any dose that results in any of the following outcomes: death, life-threatening AE, requires hospitalization or prolongation of existing hospitalization, a persistent or significant disability/incapacity, or a congenital anomaly/birth defect.
Endocrine disorders Diabetic Foot	6.2% 2/32 • Number of events 2 • The maximum time in the study for any subject was 21 weeks, with 1 week in screening and assuming wound healing occurs at week 16 followed by 2 weeks of observation for confirmation of closure, and a final exit visit 14 days later. An Adverse Event (AE) is any untoward medical occurrence temporally associated with the use of an investigational medicinal product, whether or not considered causally related to that product. An Serious Adverse Event is defined as any AE occurring at any dose that results in any of the following outcomes: death, life-threatening AE, requires hospitalization or prolongation of existing hospitalization, a persistent or significant disability/incapacity, or a congenital anomaly/birth defect.
Gastrointestinal disorders Diarrhoea	9.4% 3/32 • Number of events 3 • The maximum time in the study for any subject was 21 weeks, with 1 week in screening and assuming wound healing occurs at week 16 followed by 2 weeks of observation for confirmation of closure, and a final exit visit 14 days later. An Adverse Event (AE) is any untoward medical occurrence temporally associated with the use of an investigational medicinal product, whether or not considered causally related to that product. An Serious Adverse Event is defined as any AE occurring at any dose that results in any of the following outcomes: death, life-threatening AE, requires hospitalization or prolongation of existing hospitalization, a persistent or significant disability/incapacity, or a congenital anomaly/birth defect.
Infections and infestations Osteomyelitis acute	9.4% 3/32 • Number of events 3 • The maximum time in the study for any subject was 21 weeks, with 1 week in screening and assuming wound healing occurs at week 16 followed by 2 weeks of observation for confirmation of closure, and a final exit visit 14 days later. An Adverse Event (AE) is any untoward medical occurrence temporally associated with the use of an investigational medicinal product, whether or not considered causally related to that product. An Serious Adverse Event is defined as any AE occurring at any dose that results in any of the following outcomes: death, life-threatening AE, requires hospitalization or prolongation of existing hospitalization, a persistent or significant disability/incapacity, or a congenital anomaly/birth defect.
Injury, poisoning and procedural complications Limb injury	6.2% 2/32 • Number of events 3 • The maximum time in the study for any subject was 21 weeks, with 1 week in screening and assuming wound healing occurs at week 16 followed by 2 weeks of observation for confirmation of closure, and a final exit visit 14 days later. An Adverse Event (AE) is any untoward medical occurrence temporally associated with the use of an investigational medicinal product, whether or not considered causally related to that product. An Serious Adverse Event is defined as any AE occurring at any dose that results in any of the following outcomes: death, life-threatening AE, requires hospitalization or prolongation of existing hospitalization, a persistent or significant disability/incapacity, or a congenital anomaly/birth defect.
Skin and subcutaneous tissue disorders Blister	12.5% 4/32 • Number of events 6 • The maximum time in the study for any subject was 21 weeks, with 1 week in screening and assuming wound healing occurs at week 16 followed by 2 weeks of observation for confirmation of closure, and a final exit visit 14 days later. An Adverse Event (AE) is any untoward medical occurrence temporally associated with the use of an investigational medicinal product, whether or not considered causally related to that product. An Serious Adverse Event is defined as any AE occurring at any dose that results in any of the following outcomes: death, life-threatening AE, requires hospitalization or prolongation of existing hospitalization, a persistent or significant disability/incapacity, or a congenital anomaly/birth defect.
Skin and subcutaneous tissue disorders Skin ulcer	6.2% 2/32 • Number of events 7 • The maximum time in the study for any subject was 21 weeks, with 1 week in screening and assuming wound healing occurs at week 16 followed by 2 weeks of observation for confirmation of closure, and a final exit visit 14 days later. An Adverse Event (AE) is any untoward medical occurrence temporally associated with the use of an investigational medicinal product, whether or not considered causally related to that product. An Serious Adverse Event is defined as any AE occurring at any dose that results in any of the following outcomes: death, life-threatening AE, requires hospitalization or prolongation of existing hospitalization, a persistent or significant disability/incapacity, or a congenital anomaly/birth defect.
Skin and subcutaneous tissue disorders Skin maceration	6.2% 2/32 • Number of events 2 • The maximum time in the study for any subject was 21 weeks, with 1 week in screening and assuming wound healing occurs at week 16 followed by 2 weeks of observation for confirmation of closure, and a final exit visit 14 days later. An Adverse Event (AE) is any untoward medical occurrence temporally associated with the use of an investigational medicinal product, whether or not considered causally related to that product. An Serious Adverse Event is defined as any AE occurring at any dose that results in any of the following outcomes: death, life-threatening AE, requires hospitalization or prolongation of existing hospitalization, a persistent or significant disability/incapacity, or a congenital anomaly/birth defect.

Additional Information

Nick McCoy, Vice President Clinical Operations

TissueTech, Inc.

Phone: 7867340023

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place