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

NCT ID: NCT03230175

Last Updated: 2021-06-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 32 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-10-04
• Study Completion Date: 2019-04-01

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.

Conditions

Non-healing Wound; Non-healing Diabetic Foot Ulcer; Diabetic Foot Infection

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

TTAX01 plus standard care

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.

Group Type: EXPERIMENTAL

TTAX01

Intervention Type: BIOLOGICAL

TTAX01 will be applied directly to the wound surface and retained with non-absorbable sutures. A single layer of the test article should cover the entire open surface of the wound. The material is 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

Intervention Type: PROCEDURE

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

Intervention Type: DRUG

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

Intervention Type: DEVICE

Provide off-loading device appropriate to the location of wound with full length boot or total contact cast

Interventions

TTAX01

TTAX01 will be applied directly to the wound surface and retained with non-absorbable sutures. A single layer of the test article should cover the entire open surface of the wound. The material is 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.

Intervention Type: BIOLOGICAL

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.

Intervention Type: PROCEDURE

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.

Intervention Type: DRUG

Off-loading

Provide off-loading device appropriate to the location of wound with full length boot or total contact cast

Intervention Type: DEVICE

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

BioTissue Holdings, Inc

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Scheffer Tseng, MD

Role: STUDY_CHAIR

Chief Technology Officer

Locations

Banner University Medical Center

Phoenix, Arizona, United States

UCLA Olive View

Sylmar, California, United States

University of Miami

Miami, Florida, United States

Village Podiatry Centers

Smyrna, Georgia, United States

Rosalind Franklin University

North Chicago, Illinois, United States

Ochsner Medical Center

New Orleans, Louisiana, United States

St Luke's-Roosevelt Hospital Center

New York, New York, United States

University of North Carolina

Chapel Hill, North Carolina, United States

Vanderbilt University Medical Center

Nashville, Tennessee, United States

Futuro Clinical Trials, LLC

McAllen, Texas, United States

Carilion Clinic

Roanoke, Virginia, United States

Countries

United States

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

TTCRNE-1501

Identifier Type: -

Identifier Source: org_study_id