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

• Sponsor: Osiris Therapeutics
• Information provided by (Responsible Party): Osiris Therapeutics

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Diabetic Foot Ulcers	Other: Tissue; Other: Control	Phase 4

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 Design

Layout table for study information

Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	97 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	Single (Participant)
Primary Purpose:	Treatment
Official Title:	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
Study Start Date :	April 2012
Actual Primary Completion Date :	August 2013
Actual Study Completion Date :	March 2014

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Complete closure of the index wound, defined as 100% re-epithelialization as determined by the Investigator, anytime up to the Day 84 Visit [ Time Frame: Up to 84 days ]

Secondary Outcome Measures :

1. Time to initial wound closure [ Time Frame: Up to 84 days after the Single-Blind Treatment Visits ]
2. number of patients with >50% reduction in wound size by Day 28 [ Time Frame: Up to 84 days after the Single-Blind Treatment Visits ]
3. number of applications of Grafix® versus control [ Time Frame: Up to 84 days after the Single-Blind Treatment Visits ]
4. number of re-occurrences of index wound post-healing [ Time Frame: Up to 84 days after the Single-Blind Treatment Visits ]
5. percent of wounds achieving complete closure [ Time Frame: Up to 84 days after the Single-Blind Treatment Visits ]

Eligibility Criteria

Layout table for eligibility information

Ages Eligible for Study:	18 Years to 80 Years (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

Locations

Layout table for location information

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

Sponsors and Collaborators

Osiris Therapeutics

Investigators

Layout table for investigator information

Study Director:	Sharron E McCulloch	Osiris Therapeutics, Inc

More Information

Layout table for additonal information

Responsible Party:	Osiris Therapeutics
ClinicalTrials.gov Identifier:	NCT01596920 History of Changes
Other Study ID Numbers:	Osiris 302
First Posted:	May 11, 2012
Last Update Posted:	April 9, 2014
Last Verified:	April 2014

Keywords provided by Osiris Therapeutics:

Chronic DFUs; Diabetic Foot Ulcers

Additional relevant MeSH terms:

Layout table for MeSH terms

Ulcer; Diabetic Foot; Foot Ulcer; Pathologic Processes; Diabetic Angiopathies; Vascular Diseases; Cardiovascular Diseases; Leg Ulcer	Skin Ulcer; Skin Diseases; Diabetes Complications; Diabetes Mellitus; Endocrine System Diseases; Diabetic Neuropathies; Foot Diseases