ExpressGraft-C9T1 Skin Tissue as a Treatment of Diabetic Foot Ulcers

An Open-Label, Prospective, Safety, and Tolerability Study of ExpressGraft-C9T1 Skin Tissue in the Treatment of Diabetic Foot Ulcers

This study is designed as a prospective, open-label trial focused on assessing the safety and tolerability of ExpressGraft-C9T1 skin tissue in the treatment of diabetic foot ulcers (DFU). Because the focus is on safety rather than efficacy, a standard of care comparator is not included in this first-in-human study. Targeted enrollment for this study is up to 6 subjects with a confirmed diagnosis of diabetes and who have foot ulcers. Subjects will each receive a single application of ExpressGraft-C9T1 skin tissue on a single identified study DFU following a 10-14 day run-in period. Any subjects requiring additional treatment will receive protocol-defined dressings through Study Treatment Week 12 as necessary. Enrollment will occur with a minimum of one week between each subject.

Study Overview

• Status: Completed
• Conditions: Diabetes; Diabetic Foot Ulcer; Non-healing Wound
• Intervention / Treatment: Biological: ExpressGraft-C9T1 Skin Tissue

• Study Type: Interventional
• Enrollment (Actual): 5
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15222
      • SerenaGroup Research Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

SUBJECT-SPECIFIC CRITERIA

1. Men and women 18 - 80 years of age, inclusive
2. Female subjects of childbearing potential must agree to practice birth control for the duration of the study
3. Documented Type 1 or Type 2 Diabetes Mellitus
4. HgbA1C ≤ 10.0%

5. Ankle:brachial blood pressure index (ABI) of 0.7 to 1.3

   • If ABI is > 1.3 (i.e., non-compressible ankle vessels) or cannot be measured, then Toe brachial index (TBI) of ≥ 0.5, or
   • Doppler arterial waveforms that are triphasic or biphasic at the ankle of affected leg
   • If ABI and TBI cannot be measured, then Transcutaneous pressure (TcpO2) of ≥ 40 around ulcer site, or
   • Skin perfusion pressure > 30 if neither ABI, TBI, nor TcpO2 can be measured near ulcer

6. Stable medications for 2 weeks prior to Study Treatment Day 0

   • Sliding scale insulin permitted
   • Select antimicrobial therapies can be used as needed
7. Capable and willing to attend the scheduled visits and comply with study procedures

8. Signed informed consent form (ICF) for study enrollment

   WOUND-SPECIFIC CRITERIA

9. Full-thickness ulcer on the foot of 1.0 cm^2 - 5.0 cm^2 at Screening Visit after debridement with no clinical signs and symptoms of infection. Full thickness is defined as penetrating the dermis, but not extending beyond the subcutaneous tissue.
10. Study ulcer has been present for at least 4 weeks but not more than 1 year

Exclusion criteria:

MEDICAL HISTORY/CURRENT MEDICAL CONDITION

1. Pregnant or nursing women
2. Prisoners
3. Abnormal laboratory value(s) for routine blood work that the Clinical Investigator deems would not be in the subject's best interest to participate
4. Osteomyelitis in the study ulcer foot in the last 30 days
5. Grade 3 or 4 lower extremity edema
6. Unable to tolerate off-loading
7. Active Charcot's foot
8. History of malignancy in previous 5 years, except for basal cell carcinoma that has been treated with local excision and is no longer present
9. Patients with unstable chronic renal disease or requiring dialysis
10. Gangrene in any part of study ulcer foot

11. Patients with a history of above- or below-knee amputation in the contralateral leg related to underlying chronic disease.

    • History of toe amputation in either leg would not be exclusionary.
12. Patients with history of poor compliance

13. Patients with baseline panel reactive antibody (PRA) of ≥ 20%

    MEDICATIONS/THERAPIES

14. Oral or parenteral corticosteroids, immunosuppressants, radiation therapy or chemotherapy within 30 days prior to study enrollment

15. Use of an investigational product within the preceding 60 days

    STUDY ULCER

16. Signs and symptoms of clinical infection at study ulcer site
17. Study ulcer requiring antimicrobial therapy at Screening Visit or Study Treatment Day 0 due to clinical suspicion of infection
18. Treatment of study ulcer with Regranex® or hyperbaric oxygen within preceding 30 days
19. Previous treatment of study ulcer with any cell and/or tissue product (CTP) therapy
20. Change in wound size (increase/decrease) greater than 25% from Screening Visit to Study Treatment Day 0
21. Other ulcers within 3 cm of study ulcer
22. Ulcers with tendon, muscle, joint capsule, or bone exposure

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: ExpressGraft-C9T1 Skin Tissue; Enrolled participants receive one application of ExpressGraft-C9T1 skin tissue	Biological: ExpressGraft-C9T1 Skin Tissue; ExpressGraft-C9T1 skin tissue is provided as a suturable, biologically-active, circular skin tissue with a fully-stratified epithelial compartment comprised of human keratinocytes (NIKSC9T1) and a dermal compartment containing fibroblasts

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with adverse events through study completion	Clinically significant vital signs, infection, blood chemistry, hematology and immunological evaluations are recorded as adverse events during the study. The safety of ExpressGraft-C9T1 skin tissue will be evaluated by adverse events through the 12 month study session.	Through study completion, at approximately 12 months

Collaborators and Investigators

• Sponsor: Stratatech, a Mallinckrodt Company
• Collaborators: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Study record dates

Study Major Dates

• Study Start (ACTUAL): January 31, 2018
• Primary Completion (ACTUAL): May 28, 2019
• Study Completion (ACTUAL): May 28, 2019

Study Registration Dates

• First Submitted: January 6, 2016
• First Submitted That Met QC Criteria: January 13, 2016
• First Posted (ESTIMATE): January 18, 2016

Study Record Updates

• Last Update Posted (ACTUAL): October 15, 2019
• Last Update Submitted That Met QC Criteria: October 11, 2019
• Last Verified: October 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Skin Diseases; Endocrine System Diseases; Diabetic Angiopathies; Leg Ulcer; Skin Ulcer; Diabetes Complications; Diabetes Mellitus; Diabetic Neuropathies; Foot Diseases; Diabetic Foot; Foot Ulcer; Ulcer
• Other Study ID Numbers: C9T12015; R44DK069924-08 (NIH)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No