TARGTEPO Treatment for Anemia in PD US Trial

Study Overview
=================
Brief Summary
-----------------
The objectives of this study are to assess safety and to evaluate the biologic activity of TARGTEPO treatment in Peritoneal Dialysis patients

Detailed Description
-----------------
This is a Phase II, open-label study. Each patient will be administered with a targeted dose of EPO delivered via TARGTEPO. The targeted doses will be determined according to 2 cohorts as follows: Group A (18-25 IU/Kg/day), Group B (35-45 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
-----------------
Safety & Efficacy of Prolonged Physiologic EPO Level Treatment of Anemia in ESRD Patients Undergoing Peritoneal Dialysis Using MDGN201 TARGTEPO

Conditions
-----------------
Anemia of End Stage Renal Disease

Intervention / Treatment
-----------------
* Biological: MDGN201 TARGTEPO
* Biological: MDGN201 TARGTEPO


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Adult male or female subjects between 18 to 80 years of age at the time of screening visit. Subject diagnosed with anemia due to Chronic Kidney Disease (CKD) Stage 5 on peritoneal dialysis treatment for at least 6 months. Average Hgb during last month between 9 to 12g/dL. Stable dose of ESAs over the past month prior to enrollment. Hypertensive subjects are stable on anti HTN treatment for the past one month prior to enrollment and has Systolic blood pressure (BP) below 150 and Diastolic BP below 90 upon enrollment. Kt/V > 1. INR ≤ 1.2. Serum albumin > 3.2. Subjects with adequate iron stores (transferrin saturation > 20.0% and/or ferritin >100 ng/ml). Capable of providing 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 (e.g. warfarin). Subjects who receive acetylsalicylic 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 Harvest or Implantation Procedure. 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 parathyroid hormone (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 (excluding thalassemia minor), 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 that 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 gastrointestinal (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 or 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 gentamicin and amphotericin. History of chronic or active hepatitis B and/or C infection or positive serology at screening, and known positive Human Immunodeficiency Virus (HIV) or positive serology at screening. Subject had a blood transfusion within 84 days prior to Screening Visit. Subject has a date for renal transplantation. Refer to the United States Product Insert (USPI) - Depo-Medrol (DM) - Methylprednisolone Acetate - Injectable (Appendix A) for any concomitant drug taken by the patient, which its interactions with DM will warrant exclusion from this protocol.

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

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MDGN201 TARGTEPO secreting EPO<br>MDGN201 TARGTEPO secreting EPO | Biological: MDGN201 TARGTEPO<br>* MDGN201 TARGTEPO secreting EPO (18-25 IU/Kg/day)<br>Biological: MDGN201 TARGTEPO<br>* MDGN201 TARGTEPO secreting EPO (35-45 IU/Kg/day)<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Patients Who Achieved Biological Activity of MDGN201 TARGTEPO Secretion as Measured by Serum EPO Levels Above Baseline. |  | 52 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Peritoneal Dialysis, End Stage Renal Disease, Anemia