Back to resultsCryopreserved Human Umbilical Cord (TTAX01) for Late Stage, Complex Non-healing Diabetic Foot Ulcers (AMBULATE DFU)
Primary Purpose
Diabetic Foot Infection, Non-healing Wound, Non-healing Diabetic Foot Ulcer
Status
Active
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
TTAX01
Standard Care
Sponsored by
About this trial
This is an interventional treatment trial for Diabetic Foot Infection
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, 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
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 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
- 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, i.e., life-threatening organ dysfunction caused by a dysregulated host response to infection
Sites / Locations
- BayArea Foot Care
- UCLA Olive View
- University of Miami
- Paley Orthopedic & Spine Institute
- Rosalind Franklin University
- Ochsner Medical Center
- Mount Sinai West
- University of North Carolina
- University Hospitals Richmond Medical Center
- Oregon Health & Science University
- Vanderbilt University Medical Center
- JPS
- Futuro Clinical Trials, LLC
- Bio-X-Cell Research
- Foot & Ankle Institute
- Carilion Clinic
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Other
Arm Label
TTAX01
Control
Arm Description
TTAX01 plus standard care
Standard Care alone
Outcomes
Primary Outcome Measures
Complete wound healing
Time from baseline to initial observation of healing, where healing has been confirmed at two consecutive visits each two weeks apart.
Secondary Outcome Measures
Complete wound healing
Proportion of wound healed
Wound durability
Proportion of wounds that re-ulcerate
Limb preservation
proportion of minor and major amputations following the initial procedure
Patient-reported mobility
compare total score on PROMIS Health Organization Neuro-QoL 'lower extremity function'; scale from 1-5; higher scores indicate better self-reported health
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04176120
Brief Title
Cryopreserved Human Umbilical Cord (TTAX01) for Late Stage, Complex Non-healing Diabetic Foot Ulcers (AMBULATE DFU)
Official Title
A Multicenter Phase 3 Trial of Biotherapy Using Cryopreserved Human Umbilical Cord (TTAX01) for Late Stage, Complex Non-healing Diabetic Foot Ulcers (AMBULATE DFU)
Study Type
Interventional
2. Study Status
Record Verification Date
September 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
July 1, 2020 (Actual)
Primary Completion Date
July 11, 2024 (Anticipated)
Study Completion Date
July 11, 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Tissue Tech Inc.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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.
Detailed Description
This trial is designed as a confirmatory study of the benefits and risks of TTAX01 when used in the treatment of Wagner Grades 3 and 4 DFU. Experience with the use of a cryopreserved umbilical cord (UC) product in treating such wounds, both prior to this Investigational New Drug application (IND) and under this IND, has indicated that a frequency of application of no shorter than every 4 weeks is associated with better than expected outcomes. Although treatment cannot be blinded, a "standard care only" arm is included to control for the benefits of aggressive baseline debridement combined with aggressive (6 weeks systemic) antibiotics. Current treatment guidelines indicate that aggressive debridement plus 1-2 weeks of antibiotics, or, minor debridement plus 6 weeks of antibiotics, would produce equivalent outcomes, although the evidence is not strong. By utilizing both maximum debridement and maximum antimicrobial therapy, the standard care described in this protocol may result in healing rates somewhat superior to current standard practice.
The design of this confirmatory study is matched to the design of the Phase 2 efficacy study TTCRNE-1501, with the exception of extending the primary endpoint from 16 to 26 weeks, and utilizing a proportional risk analysis rather than a landmark analysis. This design consideration is based on analysis of previous studies, and a desire to fold data from every visit into the primary analysis, rather than generating an excessive number of secondary endpoints.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Diabetic Foot Infection, Non-healing Wound, Non-healing Diabetic Foot Ulcer
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
Outcomes Assessor
Masking Description
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.
Allocation
Randomized
Enrollment
220 (Actual)
8. Arms, Groups, and Interventions
Arm Title
TTAX01
Arm Type
Experimental
Arm Description
TTAX01 plus standard care
Arm Title
Control
Arm Type
Other
Arm Description
Standard Care alone
Intervention Type
Biological
Intervention Name(s)
TTAX01
Intervention Description
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).
Intervention Type
Other
Intervention Name(s)
Standard Care
Intervention Description
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.
Primary Outcome Measure Information:
Title
Complete wound healing
Description
Time from baseline to initial observation of healing, where healing has been confirmed at two consecutive visits each two weeks apart.
Time Frame
over 26 weeks
Secondary Outcome Measure Information:
Title
Complete wound healing
Description
Proportion of wound healed
Time Frame
by Week 50
Title
Wound durability
Description
Proportion of wounds that re-ulcerate
Time Frame
by Week 50
Title
Limb preservation
Description
proportion of minor and major amputations following the initial procedure
Time Frame
by Week 50
Title
Patient-reported mobility
Description
compare total score on PROMIS Health Organization Neuro-QoL 'lower extremity function'; scale from 1-5; higher scores indicate better self-reported health
Time Frame
Baseline to End of Study (approximately 50 weeks)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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, 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
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 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
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, i.e., life-threatening organ dysfunction caused by a dysregulated host response to infection
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Herbert Slade, MD
Organizational Affiliation
Chief Medical Officer
Official's Role
Study Chair
Facility Information:
Facility Name
BayArea Foot Care
City
San Francisco
State/Province
California
ZIP/Postal Code
94117
Country
United States
Facility Name
UCLA Olive View
City
Sylmar
State/Province
California
ZIP/Postal Code
91342
Country
United States
Facility Name
University of Miami
City
Miami
State/Province
Florida
ZIP/Postal Code
33125
Country
United States
Facility Name
Paley Orthopedic & Spine Institute
City
West Palm Beach
State/Province
Florida
ZIP/Postal Code
33407
Country
United States
Facility Name
Rosalind Franklin University
City
North Chicago
State/Province
Illinois
ZIP/Postal Code
60064
Country
United States
Facility Name
Ochsner Medical Center
City
New Orleans
State/Province
Louisiana
ZIP/Postal Code
70121
Country
United States
Facility Name
Mount Sinai West
City
New York
State/Province
New York
ZIP/Postal Code
10019
Country
United States
Facility Name
University of North Carolina
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
27599
Country
United States
Facility Name
University Hospitals Richmond Medical Center
City
Richmond Heights
State/Province
Ohio
ZIP/Postal Code
44143
Country
United States
Facility Name
Oregon Health & Science University
City
Portland
State/Province
Oregon
ZIP/Postal Code
97239
Country
United States
Facility Name
Vanderbilt University Medical Center
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37212
Country
United States
Facility Name
JPS
City
Fort Worth
State/Province
Texas
ZIP/Postal Code
76104
Country
United States
Facility Name
Futuro Clinical Trials, LLC
City
McAllen
State/Province
Texas
ZIP/Postal Code
78501
Country
United States
Facility Name
Bio-X-Cell Research
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78224
Country
United States
Facility Name
Foot & Ankle Institute
City
Saint George
State/Province
Utah
ZIP/Postal Code
84470
Country
United States
Facility Name
Carilion Clinic
City
Roanoke
State/Province
Virginia
ZIP/Postal Code
24013
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Cryopreserved Human Umbilical Cord (TTAX01) for Late Stage, Complex Non-healing Diabetic Foot Ulcers (AMBULATE DFU)
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