Comparing Efficacy and Safety of CinnaGen Beta Erythropoietin (CinnaPoietin®) Versus Eprex® on the Treatment of Anemia in ESRD Hemodialysis Patients
Condition: Anemia in End-Stage Renal Disease
MeSH terms: Kidney Diseases; Kidney Failure, Chronic; Anemia
Intervention: CinnaPoietin®; Eprex®; Nephrovit; Vitamin B12 Injection
Intervention description: The starting dose of Erythropoietin is 60 (50-100) IU/kg body weight/week for naïve patients. Administration dose for patients who are treated with erythropoietin is similar dose of previously administered amount (IV or SC without any change). After then, dose adjustment will be done based on patients' response.; The starting dose of Erythropoietin is 60 (50-100) IU/kg body weight/week for naïve patients. Administration dose for patients who are treated with erythropoietin is similar dose of previously administered amount (IV or SC without any change). After then, dose adjustment will be done based on patients' response.; Nephrovit tablet is daily administered to all the patients.; Vitamin B12 is monthly injected to all the patients.
Intervention MeSH terms: Vitamin B 12; Hydroxocobalamin; Epoetin Alfa
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 156.0
Sex: All
Minimum age: 18 Years
Maximum age: 70 Years
Healthy volunteers: No
Keywords: End-Stage Renal Disease, Anemia, Erythropoietin, Hemoglobin

Summary:

      This Phase III, randomized, two-armed, parallel, double-blind, active-controlled clinical
      trial is designed to compare efficacy and safety of CinnaPoietin® (Beta erythropoietin) and
      Eprex® (epoetin alpha) on the treatment of anemia in 156 End-Stage Renal Disease hemodialysis
      patients. 156 patients have been planned to randomize and assign to receive CinnaPoietin® or
      Eprex® for a 26-week period. Administration dose for patients who are treated with
      erythropoietin is the similar dose of the previously administered amount (IV or SC without
      any change). After then, dose adjustment will be made based on patients' response. The
      primary objective of this study is to compare the efficacy of CinnaPoietin® with Eprex®. The
      secondary objectives of this study are further comparison and evaluation of efficacy along
      with safety between CinnaPoietin® and Eprex®.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Aged between 18 and 70

          -  ESRD patients who are on hemodialysis for ≥3 months.

          -  Hb level 8- 11.5 g/dl

          -  Patients are on adequate hemodialysis: the minimally adequate dose of hemodialysis
             given 3 times per week should be a spKt/V (single-pool delivered Kt/V; clearance of
             urea x dialysis time/volume of distribution) of 1.2 per dialysis. For treatment
             periods of less than 5 hours, an alternative minimum dose is a urea reduction rate
             (URR) of 65%. All types of hemodialysis systems and hemodiafiltration, including
             high-flux membranes are allowed as long as there is no plan to change the patient's
             regimen during the study.

          -  Sufficient iron stores, defined as serum ferritin ≥ 200 ng/ml and transferrin
             saturation ≥20%. (Patients not meeting these criteria may receive iron supplementation
             therapy during the Screening and stabilization period to appropriately correct their
             iron store deficiency to meet the criterion required for randomization);

          -  Ability to comply with study medication use, study visits, and study procedures as
             judged by the investigator;

          -  Females of childbearing potential agree to use an acceptable method of birth control
             (e.g., abstinence, hormonal or barrier methods, partner sterilization, or IUD) for the
             duration of the study.

          -  Qualified and willing to sign the informed consent form with the commitment of
             complying with all the scheduled visits, and study procedures as judged by the
             investigator;

          -  In any circumstances that potential participants are not able to give consent, it may
             be given by responsible parents or guardian.

        Exclusion Criteria:

          -  Uncontrolled hypertension (defined as pre-dialysis diastolic blood pressure ≥ 100 mmHg
             or systolic blood pressure ≥180 mmHg);

          -  Anemia secondary to other causes different to the CKD (e.g. multiple myeloma, aplastic
             anemia, leukemia;….)

          -  Decompensated liver failure;

          -  Clinical evidence of concurrent uncontrolled hyperparathyroidism (defined as serum
             parathyroid hormone (iPTH) > 800 pg/ml);

          -  Heart failure [New York Heart Association (NYHA) class III and IV];

          -  Unstable angina pectoris, active cardiac disease, stroke and/or cardiac infarction
             within the last 6 months;

          -  History of or active blood coagulation disorders including DVT, PTE, native access
             Thrombosis during last 6 months.

          -  Thrombocytosis (platelet count > 500,000/µl);

          -  Thrombocytopenia (platelet count < 100,000/µl);

          -  White blood cell count < 3,000/µl);

          -  White blood cell count >15,000/µl)

          -  Recent Bleeding (acute or chronic bleeding within three months prior to screening);

          -  Suspicion of or confirmed occult bleeding (increased reticulocyte count);

          -  Clinical evidence of concurrent systemic infection, or inflammatory disease (e.g;
             diabetic foot, bed sore, access infection, CRP> 30 mg/l,…)

          -  Currently receiving treatment for epilepsy;

          -  Major surgery within 3 months prior to randomization and during the conduct of the
             trial (except vascular access surgery);

          -  Concomitant immunosuppressive therapy; patients on a short course of steroids (up to 7
             days), topical or intranasal steroids are allowed in the study;

          -  History of any malignant disease within the last 5 years (except excised non-melanoma
             skin cancer);

          -  Women who are pregnant or breastfeeding;

          -  Known history of severe drug-related allergies;

          -  Known history of drug related allergy to Erythropoietin or one of the ingredients of
             the test or the reference products or hypersensitivity to mammalian-derived products;

          -  Transplant received within one year prior to the start of the study;

          -  Simultaneous participation in another clinical study or having received an
             Investigational Medicinal Product within three months before randomization in this
             study.

          -  Psychiatric, addictive (drugs or alcohol) or any other disorder that compromises the
             ability to give an informed consent;

          -  Any red blood cell transfusion during the last 3 months (measured at the time of
             eligibility verification);

          -  Primary hematological disorder (e.g. myelodysplastic syndrome, myeloma, sickle cell
             anemia, hematological malignancy, multiple myeloma hemolytic anemia);

          -  known resistance to the rHuEPO defined by a requirement > 450 IU/kg/week by IV or 300
             IU/kg/week by SC, equivalent to approximately 20.000 IU/week SC and in absence of iron
             deficiency;

          -  who have suffered an event of active bleeding in the 30 days prior to the beginning of
             the study;

          -  Morbid obesity, defined by a Body Mass Index (BMI) > 37 kg/m2 in women and > 40 kg/m2
             in men.