Study of safety, efficacy, pharmacokinetics and pharmacodynamics of APO-EPO versus Epogen®/Procrit® in patients with anemia and chronic kidney disease not yet on hemodialysis

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 196

Inclusion Criteria

1. Written informed consent of the patient;
2. Hb level <10 g/dl;
3. Age: = 18 years, male or female patients;
4. Patients suffering from chronic renal failure (CRF) not yet undergoing dialysis, with glomerular filtration rate (GFR) below 30 ml/min calculated from the plasma creatinine using the Cockroft-Gault formula;
5. Epoetin-naïve patients;
6. CRF patients with estimated time to progression to ESRF (end stage renal failure) of 8-12 months as estimated by the Reciprocal creatinine vs time plot” method;
7. Serum ferritin level = 100 ng/ml and transferrin saturation = 20% prior to entry into the correction phase of the study;
8. Ability to comply with study medication use, study visits, and study procedures as judged by the investigator;
9. Females of childbearing potential agree to practice an acceptable method of birth control (e.g. abstinence, hormonal or barrier methods, partner sterilization, or IUD) for the duration of the study.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 180
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 16

Exclusion Criteria

1. Patients on regular hemodialysis or peritoneal dialysis;
2. C-Reactive protein (CRP) > 10 mg/l, as measured with a standard method;
3. Uncontrolled hypertension (defined as diastolic blood pressure = 100 mmHg or systolic blood pressure = 180 mmHg);
4. Primary hematological disorder (e.g. myelodysplastic syndrome, multiple myeloma, sickle cell anemia, hematological malignancy, hemolytic anemia);
5. Decompensated liver failure;
6. Clinical evidence of concurrent uncontrolled hyperparathyroidism defined as serum parathyroid hormone (PTH) > 1000 pg/ml;
7. Previous stroke or evident disturbances of brain blood flow, e.g. transient ischemic attack (TIA);
8. Hypothyroidism without adequate replacement therapy (adequate defined as stable dose with stable thyroid hormone levels for at least 3 months prior to Screening);
9. Any red blood cell transfusion during the last 3 months (measured at the time of eligibility verification);
10. Heart failure [New York Heart Association (NYHA) class III and IV]
11. Unstable angina pectoris, active cardiac disease, stroke and/or myocardial infarction within the last six months prior to screening;
12. History of or active blood coagulation disease;
13. Thrombocytosis (platelet count > 500,000/µl);
14. Thrombocytopenia (platelet count < 100,000/µl);
15. Leukopenia (white blood cell count < 2,000/µl);
16. History of phenylketonuria;
17. Deficiency in vitamin B12 (if not corrected during the 6-week-anemia-work-up period);
18. Deficiency in folic acid (if not corrected during the 6-week-anemia- work-up period);
19. Overt bleeding (acute or chronic bleeding within the last two months prior to screening);
20. Suspicion of or confirmed occult bleeding (increased reticulocyte count);
21. Clinical evidence of concurrent systemic infection or inflammatory disease;
22. Presence of neutralizing antibodies or suspicion of or known pure red cell aplasia (PRCA);
23. Currently receiving treatment for epilepsy;
24. Major surgery within the last six months prior to Screening and during the conduct of the trial;
25. Proven HIV, HBV or HCV infection (to be tested if no test was performed within four weeks prior to the screening);
26. Any androgen therapy within the last two months prior to screening and during the study;
27. Concomitant immunosuppressive therapy; patients on a short course of steroids (e.g. treatment of a gout attack), topical or intranasal steroids are allowed in the study;
28. History of malignant disease within the last 5 years prior to Screening;
29. Pregnant or breastfeeding women;
30. Known history of severe drug-related allergies;
31. Known allergy to one of the ingredients of the test or reference product (including the preservative used for the multi-dose IP) or Venofer or hypersensitivity to mammalian-derived products;
32. Transplant received within 48 weeks prior to study entry;
33. Simultaneous participation in another clinical study or participation in a study within 3 months before randomization;
34. Psychiatric, addictive (drugs or alcohol), or any other disorder that compromises the ability to give an informed consent;
35. Any other condition which at the investigator’s opinion may put the patient at risk or may confound the study results.