Grafix® DFU: Open-Label Extension Option to Evaluate Safety & Efficacy of Grafix® for Chronic Diabetic Foot Ulcers (DFU)

A Multicenter, Adaptive Design, Randomized, Single-Blind Study With an Open-Label Extension Option to Further Evaluate the Safety and Efficacy of Grafix® for the Treatment of Chronic Diabetic Foot Ulcers

The primary objective of the present study is to further establish in a randomized controlled trial, the safety and efficacy of weekly Grafix® administration versus control in patients with chronic diabetic foot ulcers. The primary endpoint is complete wound closure of the index wound, defined as 100% re-epithelialization as determined by the Investigator.

Grafix® is a product regulated for use in the US by the FDA as a Human Cellular and Tissue Based Product (HCT/P) under Title 21 CFR Part 1271.

Study Overview

• Status: Completed
• Conditions: Diabetic Foot Ulcers
• Intervention / Treatment: Other: Tissue; Other: Control

Detailed Description

The treatment indication is for chronic, diabetic foot ulcers (DFUs) between 1cm2 and 15cm2 located below the malleoli on the plantar or dorsal surface of the foot. Patients must have confirmed Type I or Type II Diabetes.

Patients will receive treatment every week for 12 weeks duration in the Single-Blind Treatment phase of the trial.

Patients who receive Grafix® or control will be evaluated for primary efficacy up to 84 days, and for safety and wound re-occurrence for 84 days after wound closure. Patients in the control group whose wounds are not closed at the end of treatment may be offered Grafix® in an Open-Label Treatment phase. The Open-Label Treatment phase can last up to an additional 84 days.

• Study Type: Interventional
• Enrollment (Actual): 97
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Montgomery, Alabama, United States, 36111
      • Institute for Advanced Wound Care at Baptist Medical
  • Arizona
    • Glendale, Arizona, United States, 85306
      • Clinical Trials of Arizona, Inc.
  • California
    • Encinitas, California, United States, 92024
      • ILD Laser and Research Center
  • Florida
    • Inverness, Florida, United States, 34452
      • Nature Coast Clinical Research
    • Jacksonville, Florida, United States, 32207
      • River City Clinical Research
  • Georgia
    • Evans, Georgia, United States, 30809
      • Aiyan Diabetes Center
  • New Jersey
    • Toms River, New Jersey, United States, 08753
      • Ocean County Foot and Ankle Surgical Associates
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • UNC at Chapel Hill
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic
    • Columbus, Ohio, United States, 43214
      • Ohio Health Research Institute
  • Pennsylvania
    • Altoona, Pennsylvania, United States, 16602
      • Blair Orthopedics Associates, Inc
  • Rhode Island
    • Warwick, Rhode Island, United States, 02886
      • Omega Medical Research
  • Texas
    • Dallas, Texas, United States, 75235
      • UT Southwestern Medical Center at Dallas
    • San Antonio, Texas, United States, 78229
      • Clincal Trials of Texas, Inc.

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

Inclusion Criteria:

1. Between 18 years and 80 years of age inclusive, as of the date of screening
2. Confirmed diagnosis of Type I or Type II Diabetes
3. An Index Ulcer defined as chronic (presence of wound for > 4 weeks) but not present for more than 52 weeks at the Screening Visit
4. Index Ulcer is located below the malleoli on the plantar or dorsal surface of the foot
5. The Index Ulcer is between 1cm2 and 15 cm2 at the Screening Visit
6. The Index Ulcer extends into the dermis or subcutaneous tissue without evidence of exposed muscle, tendon, bone, or joint capsule
7. Wound is free of necrotic debris

8. Patient has adequate circulation to the foot as documented by either:

   • Ankle Brachial Index (ABI) > 0.70 and < 1.30, or
   • In patients with non-compressible ankle vessels defined as an ABI ≥ 1.30, a Toe Brachial Index (TBI) ≥ 0.50
   • In patients with non-compressible ankle vessels defined as an ABI ≥ 1.30 and TBI cannot be performed (e.g., toe is absent, wounds are present, or site cannot perform a TBI), a Doppler waveform in the posterior tibial or dorsalis pedis arteries at the ankle consistent with adequate flow in the foot (biphasic or triphasic) and other diagnostic confirmation of adequate flow (e.g., duplex imaging, normal pulse volume recording [PVR] testing).

Exclusion Criteria:

1. Index Ulcer is of non-diabetic pathophysiology
2. Gangrene is present on any part of the affected foot
3. Index Ulcer is over an active Charcot deformity
4. The longest dimension of the Index Ulcer exceeds 5 cm at the Baseline Visit
5. Patient is currently receiving dialysis
6. Patient has a glycated hemoglobin A1c (HbA1c) level of > 12%
7. Chronic oral steroid use > 7.5 mg daily
8. Requiring intravenous (IV) antibiotics to treat the index wound infection
9. Patient has an ulcer within 15cm of the Index Ulcer identified for study consideration
10. Patient is receiving oral or parenteral corticosteroids, immunosuppressive or cytotoxic agents
11. Patient is Human Immunodeficiency Virus (HIV) positive or has Acquired Immune Deficiency Syndrome (AIDS)
12. Current evidence of osteomyelitis, cellulitis, or other evidence of infection including fever or pus drainage from the wound site
13. Patient has active malignancy other than non-melanoma skin cancer
14. Patient's Index Ulcer has decreased by ≥ 30% during 1-week screening period as determined by criteria provided by the Wound Core Lab
15. Patient's random blood sugar is > 450 mg/dl at screening
16. Patient has untreated alcohol or substance abuse at the time of screening
17. Pregnant women
18. Patient is currently enrolled or participated in another investigational device, drug, or biological trial within 60 days of screening
19. Patient has allergy to primary or secondary dressing materials used in this trial
20. Patient has had within the last 30 days, or is currently undergoing, or is planning for wound treatments with enzymes, growth factors, living skin, dermal substitutes or other advanced biological therapies

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Grafix®	Other: Tissue; Allograft Tissue Cellular Repair Matrix
Placebo Comparator: Control (non-adherent dressing)	Other: Control; Non-adherent Dressing

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Complete closure of the index wound, defined as 100% re-epithelialization as determined by the Investigator, anytime up to the Day 84 Visit	Up to 84 days

Secondary Outcome Measures

Outcome Measure	Time Frame
Time to initial wound closure	Up to 84 days after the Single-Blind Treatment Visits
number of patients with >50% reduction in wound size by Day 28	Up to 84 days after the Single-Blind Treatment Visits
number of applications of Grafix® versus control	Up to 84 days after the Single-Blind Treatment Visits
number of re-occurrences of index wound post-healing	Up to 84 days after the Single-Blind Treatment Visits
percent of wounds achieving complete closure	Up to 84 days after the Single-Blind Treatment Visits

Collaborators and Investigators

• Sponsor: Osiris Therapeutics
• Investigators: Study Director: Sharron E McCulloch, Osiris Therapeutics, Inc

Study record dates

Study Major Dates

• Study Start: April 1, 2012
• Primary Completion (Actual): August 1, 2013
• Study Completion (Actual): March 1, 2014

Study Registration Dates

• First Submitted: March 14, 2012
• First Submitted That Met QC Criteria: May 10, 2012
• First Posted (Estimate): May 11, 2012

Study Record Updates

• Last Update Posted (Estimate): April 9, 2014
• Last Update Submitted That Met QC Criteria: April 7, 2014
• Last Verified: April 1, 2014

More Information

Terms related to this study

• Keywords: Diabetic Foot Ulcers; Chronic DFUs
• 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: Osiris 302