Epodure Therapy of Anemia in End Stage Renal Disease on Dialysis With Epodure Skin Implant

Study Overview
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Brief Summary
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In this End Stage Renal Disease (ESRD) patients who need Erythropoietin (epo) hormone will get it by a small implant of skin using their own skin, the implant will be treated in the laboratory and programmed to secrete Epo. The implant secretes the patients own epo minimizing the need for injections for a period of up to 6 months.

Detailed Description
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This will be a Phase I-II, open-label, single-center, uncontrolled, tailored dose study. The trial will be conducted in Israel at the Tel Aviv Sourasky Medical Center. Subjects will undergo similar study procedures and evaluations; however each patient will receive his or her own individually targeted dose of EPO delivered via EPODURE Biopumps. The targeted dose may vary between 20IU/kg/d to 65IU/kg/d based on each patient's weight, the historical average EPO amount administered and historical Hb levels including at least the 3 months prior to inclusion in the study. The objective is maintaining Hb levels within the target range of 10-12 g/dl.

Official Title
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Safety and Efficacy of Sustained Erythropoietin Therapy of Anemia in End Stage Renal Disease (ESRD) Dialysis Patients Using EPODURE Biopump

Conditions
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Anemia, End Stage Renal Disease

Intervention / Treatment
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* Procedure: implantation of autologous skin graft after ex-vivo treatment
* Biological: Subcutan implantation of autologus skin graft after ex-vivo treatment


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria:1. Adult male or female subjects between 18 to 75 years of age at the time of screening visit. Subject diagnosed with Anemia due to Chronic Renal Failure CKD stage 5 on dialysis treatment for at least 3 months. Hb < 12g/dL on 2 consecutive measures Kt/V >1 INR not higher than 1.2 Subjects who are clinically stable. Serum albumin > 3.5 Subjects with adequate iron stores (transferrin saturation > 20.0% and/or ferritin > 100 ng/ml). Signed written informed consent to participate in the study. Exclusion Criteria: Uncontrolled hypertension (defined as diastolic blood pressure > 110 mmHg or systolic blood pressure > 180 mmHg during screening). Subjects who receive oral anti-coagulation treatment (warfarin) Subjects who receive Acetyl Salicylic Acid [(ASA), aspirin] above 325 mg/day or patients who receive ASA treatment between 100mg/d and 325 mg/d who cannot discontinue it for 1 week prior to each EPODURE procedure Patients currently receiving injections of long-acting ESA's (Aranesp, Mircera, etc.) Congestive heart failure (New York Heart Association functional class III or IV). Grand mal seizures within 2 years of the screening visit. Clinical evidence of severe hyperparathyroidism as defined by PTH levels of > 10 times the upper normal limits. Major surgery within 12 weeks of the screening visit. Systemic hematologic diseases (e.g., sickle cell anemia, myelodysplastic syndromes, hematologic malignancy, myeloma, hemolytic anemia). Current systemic infection, active inflammatory disease, or malignancy under treatment. Subjects known to have tested positive at any time in the past for antibodies to erythropoietic proteins. Subject has history of malignancy within the past 2 years prior to the screening visit, with the exception of basal cell carcinoma. Subjects with other concurrent severe and/or uncontrolled medical condition which could compromise participation in the study (i.e. active infection, uncontrolled diabetes, uncontrolled hypertension, congestive cardiac failure, unstable angina, ventricular arrhythmias, active ischemic heart disease, myocardial infarction within six months, uncompensated cirrhosis, active upper GI tract ulceration). Subject is currently enrolled in, or has not yet completed a period of at least 30 days since ending other investigational device or drug trial(s).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: EPODURE Low dose<br>EPODURE pump secreting hEPO 18-25 IU/kg/day | Procedure: implantation of autologous skin graft after ex-vivo treatment<br>* Subcutan implantation of autologous skin graft after ex-vivo treatment<br>Biological: Subcutan implantation of autologus skin graft after ex-vivo treatment<br>* Subcutan implantation of autologus skin graft after ex-vivo treatment<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hg maintenance with in the range of 10-12 gr/dl for the duration of 6 month | A Phase I-II, open-label. The trial will be conducted in Israel at the Tel Aviv Sourasky Medical Center. Subjects will undergo similar study procedures and evaluations; however each patient will receive his or her own individually targeted dose of EPO delivered via EPODURE Biopumps. The targeted dose may vary between 20IU/kg/d to 65IU/kg/d based on each patient's weight, the historical average EPO amount administered and historical Hb levels including at least the 3 months prior to inclusion in the study. The objective is maintaining Hb levels within the target range of 10-12 g/dl. | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| REDUCING THE AMOUNT OF EXOGENOUS EPO ADMINISTRATION | The biopumps are expected to secret sufficient Epo to support the Hb lebel in the desired range of 10-12 gr/dl | During the first 6 months of evaluation |