Clinical trial NCT04176120: 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
Overall status: COMPLETED
Phase: PHASE3
Conditions: Diabetic Foot Infection
Non-healing Wound
Non-healing Diabetic Foot Ulcer
Lead sponsor: BioTissue Holdings, Inc
Sponsor class: INDUSTRY
First posted: 2019-11-25
Enrollment: 220
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Complete wound healing
timeFrame: over 26 weeks
Secondary outcomes:
measure: Complete wound healing
timeFrame: by Week 50
measure: Wound durability
timeFrame: by Week 50
measure: Limb preservation
timeFrame: by Week 50
measure: Patient-reported mobility
timeFrame: Baseline to End of Study (approximately 50 weeks)
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: Center for Clinical Research, Inc
state: California
city: Sylmar
country: United States
facility: UCLA Olive View
state: California
city: Miami
country: United States
facility: University of Miami
state: Florida
city: West Palm Beach
country: United States
facility: Paley Orthopedic & Spine Institute
state: Florida
city: North Chicago
country: United States
facility: Rosalind Franklin University
state: Illinois
city: New Orleans
country: United States
facility: Ochsner Medical Center
state: Louisiana
city: New York
country: United States
facility: Mount Sinai West
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina
state: North Carolina
city: Richmond Heights
country: United States
facility: University Hospitals Richmond Medical Center
state: Ohio
city: Portland
country: United States
facility: Oregon Health & Science University
state: Oregon
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Fort Worth
country: United States
facility: JPS
state: Texas
city: McAllen
country: United States
facility: Futuro Clinical Trials, LLC
state: Texas
city: San Antonio
country: United States
facility: Bio-X-Cell Research
state: Texas
city: Saint George
country: United States
facility: Foot & Ankle Institute
state: Utah
city: Roanoke
country: United States
facility: Carilion Clinic
state: Virginia
Study officials:
affiliation: Chief Medical Officer
name: Herbert Slade, MD
role: STUDY_CHAIR
References: