Study to Evaluate the Safety and Efficacy of CHAM* for the Treatment of Diabetic Foot Ulcers

Study Overview
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Brief Summary
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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

Official Title
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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

Conditions
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Chronic Diabetic Foot Ulcers

Intervention / Treatment
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* Biological: CHAM
* Other: Control


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Between 18 years and 80 years of age inclusive, as of the date of screening Confirmed diagnosis of Type I or Type II Diabetes An Index Ulcer defined as chronic (presence of wound for > 4 weeks), but not present for more than 52 weeks at the Screening Visit Index Ulcer is located below the malleoli on the plantar or dorsal surface of the foot The Index Ulcer is between 1 cm2 and 15 cm2, inclusive, at the Screening Visit The Index Ulcer extends into the dermis or subcutaneous tissue without evidence of exposed muscle, tendon, bone, or joint capsule Wound is free of necrotic debris 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: Index Ulcer is of non-diabetic pathophysiology Gangrene is present on any part of the affected foot Index Ulcer is over an active Charcot deformity The longest dimension of the Index Ulcer exceeds 5 cm at the Baseline Visit Patient is currently receiving dialysis or planning to go on dialysis Patient has had 2 or more previous disease-related amputations of the lower extremities Patient has a glycated hemoglobin A1c (HbA1c) level of >10% Chronic oral steroid use >7.5 mg daily for longer than 3 months at the time of screening Patient is receiving IV corticosteroids, immunosuppressive or cytotoxic agents at the time of screening Requiring intravenous (IV) antibiotics to treat the index wound infection at the time of screening Patient has an ulcer within 5 cm of the Index Ulcer identified for study consideration Patient is Human Immunodeficiency Virus (HIV) positive or has Acquired Immune Deficiency Syndrome (AIDS) Current evidence of cellulitis, or other evidence of infection including fever or pus drainage from the wound site Current evidence of osteomyelitis or history of osteomyelitis within 30 days of screening Patient has active malignancy other than non-melanoma skin cancer Patient's Index Ulcer has decreased by ≥20% during 1-week screening period Patient's random blood sugar is >350 mg/dl at screening Patient has untreated alcohol or substance abuse at the time of screening Pregnant women and women who are breastfeeding Patient is currently enrolled or participated in another investigational device, drug, or biological trial within 30 days of screening 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 Patient is an employee, or an immediate family member of an employee, of the sponsor company or site research staff conducting the study 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 Patients with a history of poor compliance, or an unwillingness or inability to adhere to the requirements of the protocol.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: CHAM<br>Cryopreserved Human Amniotic Membrane | Biological: CHAM<br>* The treatment indication is for chronic diabetic foot ulcers that can accommodate up to one 5cm x 5cm piece of CHAM<br>|
| Placebo Comparator: Control<br>Standard of Care | Other: Control<br>* Standard of Care<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 |  | Up to 112 days after Baseline Visit | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete index wound closure by the End of Single-Blind Treatment Visit as defined by 100% re-epithelialization, as determined by the Investigator. |  | Up to 84 days after Baseline Visit | 
| Time to initial wound closure among patients that receive CHAM versus those that receive control as measured by Kaplan-Meier analysis. |  | Up to 84 days after Baseline Visit | 
| 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. |  | Up to 28 days after Baseline | 
| Number of applications of CHAM versus control |  | Up to 77 days after Baseline | 
| 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 |  | Up to 91 days after Single-Blind Treatment Phase |