PHASE 1, OPEN-LABEL SAFETY STUDY OF UMBILICAL CORD LINING MESENCHYMAL STEM CELLS (CORLICYTE®) TO HEAL CHRONIC DIABETIC FOOT ULCERS

Study Overview
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Brief Summary
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Study Objective: The objective of this Phase 1 open-label study is to establish the safety and tolerability of Corlicyte mesenchymal stem cells (MSCs) in the treatment of patients with chronic diabetic foot ulcers (DFUs).

Official Title
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PHASE 1, OPEN-LABEL SAFETY STUDY OF UMBILICAL CORD LINING MESENCHYMAL STEM CELLS (CORLICYTE®) TO HEAL CHRONIC DIABETIC FOOT ULCERS

Conditions
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Diabetic Foot Ulcer

Intervention / Treatment
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* Drug: Corlicyte


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Inclusion Criteria: Males or non-pregnant, non-lactating females. Age 18 or greater at the time of informed consent. Able and willing to provide written informed consent. Type 1 or Type 2 diabetes. Chronic DFU as the index ulcer meeting all of the following criteria: present for at least 4 weeks at the time of Screening Visit 1 located below the malleoli of the foot extends to the dermis or subcutaneous tissue, surrounded by healthy skin, without evidence of exposed muscle, tendon, bone, or joint capsule area measures 1 to 10 cm2 inclusive, at Screening Visit 1, and non-healing (defined as ≤50% reduction in ulcer size by the Baseline Visit, as compared to Screening Visit 1). Negative for antibodies to HLA Class I molecules expressed on Corlicyte MSCs, as measured by Luminex HLA single antigen beads, within 3 months prior to start of Treatment Phase without interval sensitizing events. For an index ulcer on the plantar surface of the foot, willingness to offload the foot per study protocol. In women of childbearing potential, willingness to use effective means of birth control during the course of the study; if using systemic birth control, this must have been used for 6 months or longer prior to Screening Visit 1. Exclusion Criteria: Exclusion Criteria: Planned DFU treatment to the index ulcer that includes enzymatic agents, cytotoxic agents or any substance(s) that would affect MSC survival during the study period. Women planning to become pregnant during the course of the study. Significant history of, or current evidence of a severe comorbid medical or psychiatric condition such as liver disease, end-stage renal disease, untreated proliferative retinopathy, bleeding diathesis, schizophrenia, or laboratory abnormality that, in the opinion of the Investigator, would preclude enrollment because of unacceptable risk. Presence of any skin condition or skin disorder around the index ulcer that might interfere with the diagnosis of or assessment of study-related endpoints, such as atopic dermatitis, eczema, psoriasis, or seborrheic dermatitis. Presence of actinic keratosis or skin cancer within 2 cm of the index ulcer. Cellulitis or other active infection of the index ulcer or any non-index ulcer at Screening. Use of an investigational agent for ulcer care within 30 days prior to Screening Visit 1. Receipt of an investigational agent or device not approved by the US FDA for marketed use in any indication within 30 days prior to Screening Visit 1. Planned participation in another therapeutic study for any indication prior to completion of study participation. Unwillingness or inability to comply with study visits and study procedures for the entire duration of study participation. Known positivity for Human Immunodeficiency Virus (HIV). Active osteomyelitis or gangrene of either foot at Screening. Known Methicillin-resistant Staphylococcus aureus (MRSA) infection within 30 days prior to Screening Visit 1. Poorly-controlled diabetes mellitus, defined as hemoglobin A1c (HbA1c) >12%. Unsuitable for cellular therapy for any reason, in the opinion of the Investigator. Planned use of cell therapy or amniotic membrane treatment for the index ulcer during study participation. Significant titer of antibodies to HLA Class I molecules expressed on Corlicyte MSCs, as measured by Luminex HLA single antigen beads. Presence of severe peripheral artery disease (PAD) defined as clinical evidence of critical limb ischemia (CLI) during Screening.

Ages Eligible for Study
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Minimum Age: 18 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: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dose 1<br> | Drug: Corlicyte<br>* expanded umbilical cord lining mesenchymal stem cells<br>|
| Experimental: Dose 2<br> | Drug: Corlicyte<br>* expanded umbilical cord lining mesenchymal stem cells<br>|
| Experimental: Dose 3<br> | Drug: Corlicyte<br>* expanded umbilical cord lining mesenchymal stem cells<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| SAE | Number and percent of subjects in each dosing cohort and overall with a serious adverse reaction to Corlicyte®. | throughout study completion, an average of 4 months per subject | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Antibodies to HLA Class I - number and percent | 1. Number and percent of subjects who develop a high titer of antibodies to human leukocyte antigen (HLA) Class I molecules expressed on Corlicyte® | throughout study completion, an average of 4 months per subject | 
| Antibodies to HLA Class I - Time To Development | 2. Time to development of high titer of antibodies to HLA Class I molecules expressed on Corlicyte® | throughout study completion, an average of 4 months per subject | 
| Increase Ulcer Size | 3. Number and percent of subjects with an increase in ulcer size by the end of the Treatment Phase as reviewed by the Wound Core Laboratory (WCL). | throughout study completion, an average of 4 months per subject | 
| Adverse Reaction | 4. Number and percent of subjects with an adverse reaction to Corlicyte® in each cohort and overall. | throughout study completion, an average of 4 months per subject | 
| Suspected Adverse Reaction | 5. Number and percent of subjects with a suspected adverse reaction to Corlicyte® in each cohort and overall. | throughout study completion, an average of 4 months per subject | 
| Suspected Serious Adverse Reaction | 6. Number and percent of subjects with a suspected serious adverse reaction to Corlicyte® in each cohort and overall. | throughout study completion, an average of 4 months per subject | 
| Change in A1c | 7. Change in hemoglobin A1c from Screening to End-of-Study/Early Termination | throughout study completion, an average of 4 months per subject |