Trial Assessing the Efficacy of Human Placental Membrane Products and Standard of Care Versus Standard of Care Alone in the Management of Nonhealing Diabetic Foot Ulcers and Venous Leg Ulcers

This study is a multi-center, prospective, randomized controlled clinical study consisting of 650 subjects from up to 30 centers. The subjects are randomized to receive 1 of 4 treatments, either with Tri-Membrane Wrap™ (HPM-1); Membrane Wrap™ (HPM-2); Membrane Wrap-Lite™ (HPM-3); Membrane Wrap-Hydro™ (HPM-4); and SOC. The target ulcers are evaluated weekly by the investigator. The subject is treated once a week, to receive weekly applications of HPM-1 - HPM - 4 + SOC or SOC alone until or up to 12 weeks or until the study ulcer has completely closed (i.e. 100% closure as assessed by the investigator and confirmed 2 weeks later at the closure confirmation visit (CCV). One additional visit per week is optional for both arms, for the purpose of changing only (1) the secondary dressing in the HPM arm or (2) change the standard of care dressing in the control arm. A trial design diagram is found in Figure 3.

Inclusion criteria

• The potential subject must be at least 18 years of age or older.
• The potential subject must have a diagnosis of type 1 or 2 Diabetes mellitus.
• At enrollment, the potential subject must have a target ulcer with a minimum surface area of 1.0 cm2 and a maximum surface area of 20 cm2 measured post debridement with the eKare inSight® imaging device.
• The potential subject must have a target ulcer that has been present for a minimum of 4 weeks of standard of care, prior to the initial screening visit.
• The potential subject must have a target ulcer located on the foot with at least 50% of the ulcer below the malleolus.
• The potential subject must have a target ulcer that is Wagner 1 or 2 grade, extending at least through the dermis or subcutaneous tissue and may involve the muscle provided it is below the medial aspect of the malleolus. The ulcer may not include exposed tendon or bone.
• The potential subject's affected limb must have adequate perfusion confirmed by vascular assessment. Any of the following methods performed within 3 months of the first screening visit are acceptable:

• ABI between 0.7 and ≤ 1.3;
• TBI ≥ 0.6;
• TCOM ≥ 40 mmHg;
• PVR: biphasic.
• If the potential subject has two or more ulcers, they must be separated by at least 2 cm. The largest ulcer satisfying the inclusion and exclusion criteria will be designated as the target ulcer.
• The potential subject must consent to using the prescribed offloading method for the duration of the study.
• The potential subject must agree to attend the weekly study visits required by the protocol.
• The potential subject must be willing and able to participate in the informed consent process.

Exclusion criteria

DFU

• The potential subject is known to have a life expectancy of < 6 months.
• The potential subject's target ulcer is not secondary to diabetes.
• The target ulcer is infected or there is cellulitis in the surrounding skin.
• The target ulcer exposes tendon or bone.
• There is evidence of osteomyelitis complicating the target ulcer.
• There is an infection in the target ulcer or in a remote location that requires systemic antibiotic therapy.
• The potential subject is receiving immunosuppressants (including systemic corticosteroids at doses greater than 10 mg of prednisone per day or equivalent) or cytotoxic chemotherapy or is taking medications that the PI believes will interfere with wound healing (e.g., biologics).
• The potential subject is taking hydroxyurea.
• The potential subject has applied topical steroids to the ulcer surface within one month of initial screening.
• The potential subject with a previous partial amputation on the affected foot that results in a deformity that impedes proper offloading of the target ulcer.
• The potential subject has glycated hemoglobin (HbA1c) greater than or equal to 12% within 3 months of the initial screening visit.
• The surface area of the potential subject's target ulcer has reduced in size by more than 40% in the 4 weeks prior to Treatment Visit 1 ("historical" run-in period*). OR The surface area of the potential subject's target ulcer has reduced in size by more than 20% in the 2 weeks prior to the initial screening visit AND The surface area measurement of the potential subject's target ulcer decreases by 25% or more during the active 2-week screening phase: the 2 weeks from the initial screening visit (SV1) to the TV-1 visit.

a. eKare inSight® imaging device is not required for measurements taken during the historical run-in period (e.g., calculating surface area using length X width is acceptable)

• The potential subject has an acute Charcot foot, or an inactive Charcot foot, which impedes proper offloading of the target ulcer.
• The potential subject is a woman who is pregnant or considering becoming pregnant within the next 6 months.
• The potential subject has end stage renal disease requiring dialysis.
• The potential subject has participated in a clinical trial involving treatment with an investigational product within the previous 30 days.
• The potential subject, in the opinion of the investigator, has a medical or psychological condition that may interfere with study assessments.
• The potential subject was treated with hyperbaric oxygen therapy (HBOT) or a Cellular, Acellular, Matrix-like Product (CAMP) in the 30 days prior to the initial screening visit.
• The potential subject has a malnutrition indicator score <17 as measured on the Mini Nutritional Assessment.

Inclusion criteria

VLU

• The potential subject must be at least 21 years of age or older.
• At enrollment, the potential subjects must have a target ulcer with a minimum surface area of 1 cm2 and a maximum surface area of 20 cm2 measured post-debridement.
• The potential subject must have a target ulcer that has been present for a minimum of 4 weeks of standard of care prior to the initial screening visit.
• The potential subject's affected limb must have adequate perfusion confirmed by vascular assessment. Any of the following methods performed within 3 months of the first screening visit are acceptable:

• ABI between 0.7 and ≤ 1.3;
• TBI ≥ 0.6;
• TCOM ≥ 40 mmHg;
• PVR: biphasic.
• If the potential subject has two or more ulcers, they must be separated by at least 2 cm post-debridement. The largest ulcer satisfying the inclusion and exclusion criteria will be designated as the target ulcer.
• The potential subject must agree to attend the weekly study visits required by the protocol.
• The potential subject must be willing and able to participate in the informed consent process.

Exclusion criteria

• The potential subject is known to have a life expectancy of < 6 months.
• The potential subject's target ulcer is infected, requires systemic antibiotic therapy, or there is cellulitis in the surrounding skin.
• The potential subject's target ulcer exposes tendon or bone.
• There is evidence of osteomyelitis complicating the potential subject's target ulcer.
• The potential subject is receiving immunosuppressants (including systemic corticosteroids at doses greater than 10 mg of prednisone per day or equivalent) or cytotoxic chemotherapy or is taking medications that the PI believes will interfere with wound healing (e.g., biologics).
• The potential subject has applied topical steroids to the ulcer surface within one month of initial screening.
• The potential subject has glycated hemoglobin (HbA1c) greater than or equal to 12% within 3 months of the initial screening visit.
• The surface area of the potential subject's target ulcer has reduced in size by more than 40% in the 4 weeks prior to Treatment Visit 1 ("historical" run-in period*). OR The surface area of the potential subject's target ulcer has reduced in size by more than 20% in the 2 weeks prior to the initial screening visit AND The surface area measurement of the potential subject's target ulcer decreases by 25% or more during the active 2-week screening phase: the 2 weeks from the initial screening visit (SV1) to the TV-1 visit.

a. *eKare inSight® imaging device is not required for measurements taken during the historical run-in period (e.g., calculating surface area using length X width is acceptable)

• The potential subject is a woman who is pregnant or considering becoming pregnant within the next 6 months.
• The potential subject has end stage renal disease requiring dialysis.
• The potential subject has participated in a clinical trial involving treatment with an investigational product within the previous 30 days.
• A potential subject who, in the opinion of the investigator, has a medical or psychological condition that may interfere with study assessments.
• The potential subject was treated with hyperbaric oxygen therapy (HBOT) or a Cellular, Acellular, Matrix-like Product (CAMP) in the 30 days prior to the initial screening visit.
• The potential subject has a malnutrition indicator score <17 as measured on the Mini Nutritional Assessment.
• The potential subject has a wound with active or latent infection.
• The subject has a disorder that would create unacceptable risk of post-operative complication.