Cryopreserved Human Umbilical Cord (TTAX01) for Late Stage, Complex Non-healing Diabetic Foot Ulcers (AMBULATE DFU)

NCT04176120 | Completed Phase 3 DMC FDA Drug

• 1 other identifier: TTAX01-CR003
• Study Type: interventional
• Target: 220
• Locations: 1 country
• Sites: 16

Brief Summary

It is hypothesized that application at 4-week or greater intervals of the human placental umbilical cord tissue TTAX01 to the surface of a well debrided, complex diabetic foot ulcer (DFU) will, with concomitant management of infection, will result in a higher rate of wounds showing complete healing within 26 weeks of initiating therapy, compared with standard care alone. This confirmatory Phase 3 study examines a population of diabetic foot ulcer patients having adequate perfusion, with or without neuropathy, and a high suspicion of associated osteomyelitis in a complex, high grade wound.

Conditions

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

Outcome Measures

Primary Outcomes (1)

• Complete wound healing

  Time from baseline to initial observation of healing, where healing has been confirmed at two consecutive visits each two weeks apart.

  over 26 weeks

Secondary Outcomes (4)

• Complete wound healing

  by Week 50

• Wound durability

  by Week 50

• Limb preservation

  by Week 50

• Patient-reported mobility

  Baseline to End of Study (approximately 50 weeks)

Study Arms (2)

TTAX01

EXPERIMENTAL

TTAX01 plus standard care

Biological: TTAX01; Other: Standard Care

Control

OTHER

Standard Care alone

Other: Standard Care

Interventions

TTAX01 BIOLOGICAL

TTAX01 is a cryopreserved human umbilical cord product derived from donated human placental tissue following healthy, live, caesarian section, full-term births after determination of donor eligibility and placenta suitability. TTAX01 is manufactured by TissueTech Inc. utilizing a proprietary CRYOTEK® process, which devitalizes the living cells but retains the natural structural and biological characteristics relevant to this tissue. TTAX01 is aseptically processed in compliance with current Good Tissue Practices (cGTP). TTAX01 will be manufactured in various sizes, stored in a medium of lactated Ringer's/glycerol (1:1).

TTAX01

Standard Care OTHER

Standard care is defined in this protocol to consist of the following: * Debridement; * Wound cleansing, using sterile saline, a non-ionic cleanser or a hypochlorous solution. Antiseptic agents including hydrogen peroxide, acetic acid, chlorhexidine, povidone/iodine, and cetrimide should not be used. Topical antimicrobials and silver dressings are also prohibited; * Primary wound dressings including a non-adherent, standard foam pad with or without a hydrogel beneath the dressing, or and alginate dressing, as is appropriate to maintain a moist wound environment while managing exudate; * A secondary retention bandage appropriate to the amount of wound exudate, so as to avoid maceration of the peri-wound skin; * Off-loading device appropriate to the location of wound with full length boot or total contact cast (unless not appropriate where a substitute off-loading device can be made with sponsor approval); and, * Appropriate use of systemic antibiotics.

Control; TTAX01

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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, lateral or medial surface of the foot
• The subject has an index ulcer with visible margins having an area ≤ 12.0 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 ABI ≥ 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
• The subject is willing to return for all mandatory visits as defined in the protocol
• The subject is willing to follow the instructions of the trial Investigator

You may not qualify if:

• 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 contralateral major amputation of the lower extremity
• The subject has a glycated hemoglobin A1c (HbA1c) level of \> 12%
• The subject has been on oral steroid use of \> 7.5 mg daily for greater than seven (7) consecutive days in 30 days before Screening
• The subject has been on parenteral corticosteroids, or any cytotoxic agents for seven consecutive days in the period of 30 days before Screening
• The subject is currently taking the type 2 diabetes medicine canagliflozin (Invokana™, Invokamet™, Invokamet XR™)
• 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 is a woman of child-bearing potential who is unwilling to avoid pregnancy or use an appropriate form of birth control (adequate birth control methods are defined as: topical, oral, implantable, or injectable contraceptives; spermicide in conjunction with a barrier such as a condom or diaphragm; intrauterine device (IUD); or surgical sterilization of partner).
• The subject is unable to sustain off-loading as defined by the protocol
• The subject has an allergy to primary or secondary dressing materials used in this trial
• The subject has an allergy to glycerol
• The subject's index ulcer is over an acute Charcot deformity

Sponsors & Collaborators

• BioTissue Holdings, Inc: lead

Study Sites (16)

Center for Clinical Research, Inc

San Francisco, California, 94117, United States

Location

UCLA Olive View

Sylmar, California, 91342, United States

Location

University of Miami

Miami, Florida, 33125, United States

Location

Paley Orthopedic & Spine Institute

West Palm Beach, Florida, 33407, United States

Location

Rosalind Franklin University

North Chicago, Illinois, 60064, United States

Location

Ochsner Medical Center

New Orleans, Louisiana, 70121, United States

Location

Mount Sinai West

New York, New York, 10019, United States

Location

University of North Carolina

Chapel Hill, North Carolina, 27599, United States

Location

University Hospitals Richmond Medical Center

Richmond Heights, Ohio, 44143, United States

Location

Oregon Health & Science University

Portland, Oregon, 97239, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37212, United States

Location

JPS

Fort Worth, Texas, 76104, United States

Location

Futuro Clinical Trials, LLC

McAllen, Texas, 78501, United States

Location

Bio-X-Cell Research

San Antonio, Texas, 78224, United States

Location

Foot & Ankle Institute

St. George, Utah, 84470, United States

Location

Carilion Clinic

Roanoke, Virginia, 24013, United States

Location

MeSH Terms

Interventions

Standard of Care

Intervention Hierarchy (Ancestors)

Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Study Officials

• Herbert Slade, MD

  Chief Medical Officer

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: Due to the nature of the test article, the trial is open label, with no blinding of the site staff. The determination of wound closure will be made by the Investigator based on visual and tactile assessment of the wound. To reduce bias in the ascertainment of closure, one independent blinded reviewer will review the image obtained from a wound measurement device in each case where the Investigator makes a determination of closure. Discordant opinions will be adjudicated by a second independent blinded reviewer who will examine multiple additional images taken at various angles to the wound surface.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 20, 2019
• First Posted: November 25, 2019
• Study Start: July 1, 2020
• Primary Completion: January 25, 2024
• Study Completion: June 12, 2024
• Last Updated: June 14, 2024

Record last verified: 2024-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (16)