Clinical trial NCT02571738: Study to Evaluate the Safety and Efficacy of CHAM* for the Treatment of Diabetic Foot Ulcers
Official title: A Multicenter, Randomized, Single-Blind Study With an Open-Label Extension Option to Further Evaluate the Safety and Efficacy of Cryopreserved Human Amniotic Membrane for the Treatment of Chronic Diabetic Foot Ulcers
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Chronic Diabetic Foot Ulcers
Lead sponsor: Osiris Therapeutics
Sponsor class: INDUSTRY
First posted: 2015-10-08
Enrollment: 108
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: A Multicenter, Randomized, Single-Blind Study with an Open-Label Extension Option to Further Evaluate the Safety and Efficacy of Cryopreserved Human Amniotic Membrane for the Treatment of Chronic Diabetic Foot Ulcers


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 1 cm2 and 15 cm2, inclusive, 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, or
   * 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 or planning to go on dialysis
6. Patient has had 2 or more previous disease-related amputations of the lower extremities
7. Patient has a glycated hemoglobin A1c (HbA1c) level of \>10%
8. Chronic oral steroid use \>7.5 mg daily for longer than 3 months at the time of screening
9. Patient is receiving IV corticosteroids, immunosuppressive or cytotoxic agents at the time of screening
10. Requiring intravenous (IV) antibiotics to treat the index wound infection at the time of screening
11. Patient has an ulcer within 5 cm of the Index Ulcer identified for study consideration
12. Patient is Human Immunodeficiency Virus (HIV) positive or has Acquired Immune Deficiency Syndrome (AIDS)
13. Current evidence of cellulitis, or other evidence of infection including fever or pus drainage from the wound site
14. Current evidence of osteomyelitis or history of osteomyelitis within 30 days of screening
15. Patient has active malignancy other than non-melanoma skin cancer
16. Patient's Index Ulcer has decreased by ≥20% during 1-week screening period
17. Patient's random blood sugar is \>350 mg/dl at screening
18. Patient has untreated alcohol or substance abuse at the time of screening
19. Pregnant women and women who are breastfeeding
20. Patient is currently enrolled or participated in another investigational device, drug, or biological trial within 30 days of screening
21. Patient has had within the last 30 days, or is currently undergoing, or is planning for wound treatments with growth factors, living skin, dermal substitutes or other advanced biological therapies
22. Patient is an employee, or an immediate family member of an employee, of the sponsor company or site research staff conducting the study
23. Patients who have already been randomized in Protocol 303 at any center may not be considered for screening or for re-entry into the trial at any center, even after the end of their follow-up period
24. Patients with a history of poor compliance, or an unwillingness or inability to adhere to the requirements of the protocol.

Primary outcomes:
measure: Complete closure of the index wound, defined as 100% re-epithelialization as determined by the Investigator, by the End of Single-Blind Treatment Visit with follow-up confirmation of continued closure at 2 consecutive study visits 2 weeks apart
timeFrame: Up to 112 days after Baseline Visit
Secondary outcomes:
measure: Complete index wound closure by the End of Single-Blind Treatment Visit as defined by 100% re-epithelialization, as determined by the Investigator.
timeFrame: Up to 84 days after Baseline Visit
measure: Time to initial wound closure among patients that receive CHAM versus those that receive control as measured by Kaplan-Meier analysis.
timeFrame: Up to 84 days after Baseline Visit
measure: Proportion of patients receiving CHAM that achieve a 50% reduction or greater in wound size by Day 28 (± 3 days) versus those that receive control.
timeFrame: Up to 28 days after Baseline
measure: Number of applications of CHAM versus control
timeFrame: Up to 77 days after Baseline
measure: Percentage of patients who achieve complete wound closure, defined as 100% re-epithelialization as determined by the Investigator, who participate in the Open-Label Treatment Phase
timeFrame: Up to 91 days after Single-Blind Treatment Phase
Other outcomes:
measure: Wound re-occurrence for up to 3 months after initial wound closure in patients receiving CHAM versus control.
timeFrame: Up to 84 days after Single-Blind Treatment Phase
measure: Number and types of Adverse Events (AE) and Serious Adverse Events (SAE)
timeFrame: Up to 84 days after Single-Blind Treatment Phase
measure: Number of patients with worsening of wound defined by a 50% increase in wound size
timeFrame: Up to 84 days after Baseline
measure: Change in Quality of Life from Baseline, as determined by the Cardiff Wound Impact Schedule (CWIS)
timeFrame: Up to 84 days after Baseline
Locations:
city: Tucson
country: United States
facility: SAVAHCS
state: Arizona
city: Carlsbad
country: United States
facility: ILD Research Center
state: California
city: Castro Valley
country: United States
facility: Center for Clinical Research
state: California
city: San Francisco
country: United States
facility: Center for Clinical Research
state: California
city: Stanford
country: United States
facility: Stanford University
state: California
city: Washington, D.C.
country: United States
facility: MedStar Georgetown University Hospital
state: District of Columbia
city: North Miami Beach
country: United States
facility: Barry University Clinical Research
state: Florida
city: South Weymouth
country: United States
facility: SSH
state: Massachusetts
city: Toms River
country: United States
facility: Ocean County Foot & Ankle Surgical Associates
state: New Jersey
city: Lake Success
country: United States
facility: NSLIJHS
state: New York
city: Chapel Hill
country: United States
facility: UNC
state: North Carolina
city: Durham
country: United States
facility: Duke University
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Altoona
country: United States
facility: University Orthopedics
state: Pennsylvania
city: Philadelphia
country: United States
facility: Temple University
state: Pennsylvania
city: Spartanburg
country: United States
facility: Spartanburg Regional Healthcare System
state: South Carolina
city: Dallas
country: United States
facility: North Texas Podiatric Medicine and Surgery Associates
state: Texas
city: Webster
country: United States
facility: Texas Gulf Coast Medical Group
state: Texas
Study officials:
References: