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

• ClinicalTrials.gov Identifier: NCT01596920
• Recruitment Status: Completed
• First Posted: May 11, 2012
• Last Update Posted: April 9, 2014
• Sponsor: Osiris Therapeutics
• Information provided by (Responsible Party): Osiris Therapeutics

Tracking Information

• First Submitted Date: March 14, 2012
• First Posted Date: May 11, 2012
• Last Update Posted Date: April 9, 2014
• Study Start Date: April 2012
• Actual Primary Completion Date: August 2013 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: May 10, 2012): 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 ]
• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: May 10, 2012)

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

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

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

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.

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
• Study Phase: Phase 4
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Single (Participant); Primary Purpose: Treatment
• Condition: Diabetic Foot Ulcers

Intervention

• Other: Tissue
  Allograft Tissue Cellular Repair Matrix
• Other: Control
  Non-adherent Dressing

Study Arms

• Active Comparator: Grafix®
  Intervention: Other: Tissue
• Placebo Comparator: Control (non-adherent dressing)
  Intervention: Other: Control

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: April 7, 2014): 97
• Original Estimated Enrollment (submitted: May 10, 2012): 266
• Actual Study Completion Date: March 2014
• Actual Primary Completion Date: August 2013 (Final data collection date for primary outcome measure)

Eligibility 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 80 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT01596920
• Other Study ID Numbers: Osiris 302
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Osiris Therapeutics
• Study Sponsor: Osiris Therapeutics
• Collaborators: Not Provided

Investigators

• Study Director: Sharron E McCulloch; Osiris Therapeutics, Inc

• PRS Account: Osiris Therapeutics
• Verification Date: April 2014