TARGTEPO Treatment for Anemia in Chronic Kidney Disease (CKD) Patients and End-Stage Renal Disease (ESRD)

Study Overview
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Brief Summary
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The objectives of this study are to assess safety and to evaluate the biologic activity of TARGTEPO treatment.

Detailed Description
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This is a Phase I-II, open-label study. Each patient will receive targeted dose of EPO delivered via TARGTEPO. The targeted doses will be determined according to 3 cohorts as follows: Group A (18-25 IU/Kg/day), Group B (35-45 IU/Kg/day), Group C (55-65 IU/Kg/day). The objective is to evaluate safety and biologic activity of TARGTEPO treatment when maintaining Hb levels within the target range of 9-12 g/dl. Biological activity assessments will include duration of TARGTEPO secretion as measured by serum EPO levels above baseline

Official Title
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Safety and Efficacy of Sustained Erythropoietin Therapy of Anemia in Chronic Kidney Disease (CKD) Patients and End-Stage Renal Disease (ESRD) Dialysis Patients Using MDGN201 TARGTEPO

Conditions
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Chronic Kidney Disease, End Stage Renal Disease

Intervention / Treatment
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* Biological: MDGN201 TARGTEPO


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: For ESRD patients: Subject diagnosed with Anemia due to Chronic Renal Failure CKD stage 5 on hemodialysis treatment for at least 6 months. Average Hb during last month between 9 to 12g/dL. Kt/V >1 INR not higher than 1.2 Serum albumin >3.5 Subjects with adequate iron stores (transferrin saturation > 20.0% and/or ferritin >100 ng/ml). 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 (e.g. warfarin) Subjects who receive Acetyl Salicylic Acid (ASA) 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 Erythropoiesis Stimulating Agents (ESA) (e.g. Aranesp, Mircera), a patient on long acting ESA can be switched to a short acting preparation (e.g Eprex) and enroll in the study after meeting the inclusion criteria and not meeting any other exclusion criteria. 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, thalassemia, myelodysplastic syndromes, hematologic malignancy, myeloma, hemolytic anemia). Current systemic infection, active inflammatory disease, or malignancy under active 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 heart 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 or five half-lives of the investigational drug whichever is longer, since ending other investigational device or drug trial(s) prior to Screening phase. Psychiatric, addictive, or any other disorder that compromises ability to provide informed consent for participation in this study. Female subjects of child-bearing potential and males that do not agree to use acceptable methods of contraception during the study. Pregnant and lactating female subjects. Chronic alcoholic or drug abuse subjects. Steroid or other immunosuppressive treatment (other than topical or inhaled steroids). Subjects unwilling or unable to comply with the study procedures. EPO Naïve subjects. Known sensitivity to Gentamycin and Amphotericin History of chronic or active Hepatitis B and/or C infection or positive serology at screening and known positive HIV or positive serology at screening. Subject had blood transfusion within 84 days prior to Screening visit. Subject has a date for renal transplantation. Subject has a temporary or permanent hemodialysis catheter, unless: Subject has a permanent hemodialysis catheter over 6 months without signs/events of line sepsis. Refer to the USPI - Depo-Medrol - Methylprednisolone Acetate - Injectable (Appendix A) for any concomitant drug taken by the patient which its interaction with Depo-Medrol will warrant exclusion from this 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: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group A<br>MDGN201 TARGTEPO secreting EPO (18-25 IU/Kg/day) | Biological: MDGN201 TARGTEPO<br>* Erythropoietin secreted by TARGTEPO transduced with MDGN201<br>|
| Experimental: Group B<br>MDGN201 TARGTEPO secreting EPO (35-45 IU/Kg/day) | Biological: MDGN201 TARGTEPO<br>* Erythropoietin secreted by TARGTEPO transduced with MDGN201<br>|
| Experimental: Group C<br>MDGN201 TARGTEPO secreting EPO (55-65 IU/Kg/day) | Biological: MDGN201 TARGTEPO<br>* Erythropoietin secreted by TARGTEPO transduced with MDGN201<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total EPO Secretion |  | up to 52 weeks | 
| Percent (%) of Hb Measurements After Implantation Within 9-11 g/dL |  | 52 weeks | 
| Percent (%) of Hb Measurements After Implantation Within 9-12 g/dL | Due to the small sample size and the dispersion of total EPO secretion, the efficacy analyses were performed on all of the patients as a single cohort of intended dose between 25 and 45 U/Kg/d. | 52 weeks |