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

Phase 2

Completed

Conditions: Non-healing Wound
Non-healing Diabetic Foot Ulcer
Diabetic Foot Infection

Interventions: Biological: TTAX01
Procedure: Surgical resection and debridement
Drug: Systemic antibiotics
Device: Off-loading

Registration Number: NCT03230175

Lead Sponsor: Tissue Tech Inc.

Brief Summary: It is hypothesized that application of the human placental umbilical cord tissue TTAX01 to the surface of a well debrided, complex diabetic foot ulcer will, with concomitant management of infection, result in a higher proportion of wounds showing complete healing within 16 weeks of initiating therapy.

Detailed Description: The hypothesis under study is that one or more applications of TTAX01 to the wound surface of a well debrided, complex diabetic foot ulcer managed with appropriate antibiotic therapy will result in a higher probability of complete healing than would be expected from management with standard care alone. In this open label Phase 2 pilot trial, all subjects will receive the intervention over a maximum period of 16 weeks. Eligible consenting subjects will undergo a baseline aggressive debridement in the operating room to remove infected and devitalized bone and soft tissue. TTAX01 will be applied to the debrided wound bed at baseline, and if healing is not evident, it will be applied again at 4 week intervals. At each weekly visit the wound will be further debrided as necessary.

Consenting subjects who qualify for enrollment will undergo an aggressive surgical debridement at the baseline visit, including biopsies of bone for histology and microbiologic testing at the start and completion of debridement. Systemic antibiotics will be given empirically, with adjustments made on the basis of culture and sensitivity results. New or recurrent infections will be managed with additional debridement and adjustment or addition of appropriate systemic antibiotics. The test article, TTAX01, will be sutured to the debrided wound bed at baseline and again at 4 week intervals over the 16 week treatment period for wounds that do not show evidence of healing. For wounds that do show evidence of healing, additional applications of TTAX01 will be withheld, based on observations from retrospective case series.

Subjects whose wounds close prior to 16 weeks will move directly to a 2 week confirmation of closure period. Subjects whose wounds have not closed by the end of 16 weeks will exit the trial.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 32

Inclusion Criteria

The subject has signed the informed consent form
The subject is male or female, at least 18 years of age inclusive at the date of Screening
The subject has confirmed diagnosis of Type I or Type II diabetes
The subject's index ulcer is located on the plantar surface, inter digital, heel, or lateral or medial surface of the foot
The subject has an index ulcer with visible margins having an area ≥1.0 cm2 to ≤ 10.0 cm2 when measured by the electronic measuring device at Screening
The subject's index ulcer extends beyond the dermis, into subcutaneous tissue with evidence of exposed bone, tendon, muscle and/or joint capsule
The subject presents with history, signs or symptoms leading to a clinical suspicion of osteomyelitis in the opinion of the Investigator supported by positive Probe to Bone (PTB) and any of the following: radiographic (x-ray, Magnetic Resonance Imaging (MRI), or bone scan) or evidence of bone necrosis
The subject has an Ankle Brachial Index ≥ 0.7 to ≤ 1.3 or TcPO2 ≥ 40 mmHg on the dorsum of the affected foot, or Great Toe Pressure ≥ 50 mmHg
The subject is under the care of a physician for the management of Diabetes Mellitus

Exclusion Criteria

The subject's index ulcer is primarily located on the dorsal surface of the foot
The subject's index ulcer can be addressed by primary closure through the completion of the initial or staged surgical procedure
The subject has a glycated hemoglobin A1c (HbA1c) level of > 12%
The subject has a serum albumin level ≤ 2.0 g/dL
The subject has a white blood cell count < 2.0 x109/L, neutrophils < 1.0 x109/L, or platelets < 100 x109/L
The subject has malignancy or a history of cancer, other than non-melanoma skin cancer, in five years before Screening
The subject is pregnant
The subject is a nursing mother
The subject's index ulcer is over an active Charcot deformity
The subject has had previous use of NEOX®, CLARIX®, or TTAX01 applied to the index ulcer
Per Investigator's discretion the subject is not appropriate for inclusion in the trial, e.g., undergoing surgical treatments listed in the protocol or the subject currently has sepsis

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
TTAX01 plus standard care	TTAX01	Eligible consenting subjects will undergo a baseline aggressive debridement in the operating room to remove infected and devitalized bone and soft tissue. A six week course of systemic antibiotics will be used to resolve baseline infection. TTAX01 will be applied to the debrided wound bed at baseline, and if healing is not evident, it will be applied again at 4 week intervals. At each weekly visit the wound will be further debrided as necessary.
TTAX01 plus standard care	Surgical resection and debridement	Eligible consenting subjects will undergo a baseline aggressive debridement in the operating room to remove infected and devitalized bone and soft tissue. A six week course of systemic antibiotics will be used to resolve baseline infection. TTAX01 will be applied to the debrided wound bed at baseline, and if healing is not evident, it will be applied again at 4 week intervals. At each weekly visit the wound will be further debrided as necessary.
TTAX01 plus standard care	Systemic antibiotics	Eligible consenting subjects will undergo a baseline aggressive debridement in the operating room to remove infected and devitalized bone and soft tissue. A six week course of systemic antibiotics will be used to resolve baseline infection. TTAX01 will be applied to the debrided wound bed at baseline, and if healing is not evident, it will be applied again at 4 week intervals. At each weekly visit the wound will be further debrided as necessary.
TTAX01 plus standard care	Off-loading	Eligible consenting subjects will undergo a baseline aggressive debridement in the operating room to remove infected and devitalized bone and soft tissue. A six week course of systemic antibiotics will be used to resolve baseline infection. TTAX01 will be applied to the debrided wound bed at baseline, and if healing is not evident, it will be applied again at 4 week intervals. At each weekly visit the wound will be further debrided as necessary.

Primary Outcome Measures

Name	Time	Method
Number of Subjects With Complete Wound Healing	16-weeks	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.

Secondary Outcome Measures

Name	Time	Method
Time to Complete Wound Healing	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
Percent Change in Wound Surface Area	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.

Trial Locations

Locations (11): Carilion Clinic
🇺🇸
Roanoke, Virginia, United States
Futuro Clinical Trials, LLC
🇺🇸
McAllen, Texas, United States
UCLA Olive View
🇺🇸
Sylmar, California, United States
Rosalind Franklin University
🇺🇸
North Chicago, Illinois, United States
Village Podiatry Centers
🇺🇸
Smyrna, Georgia, United States
St Luke's-Roosevelt Hospital Center
🇺🇸
New York, New York, United States
Banner University Medical Center
🇺🇸
Phoenix, Arizona, United States
Ochsner Medical Center
🇺🇸
New Orleans, Louisiana, United States
University of Miami
🇺🇸
Miami, Florida, United States
University of North Carolina
🇺🇸
Chapel Hill, North Carolina, United States
Vanderbilt University Medical Center
🇺🇸
Nashville, Tennessee, United States