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IRCT201601156135N6 IRCT 2016-01-17 CinnaGen Pharmaceutical Company CinnaPoietin® versus Eprex® on treatment of anemia in End stage renal disease (ESRD ) hemodialysis patients A Phase III, randomized, two armed, multicenter, parallel, double blind (patient and assessor blinded), active controlled non inferiority clinical trial to determine the non inferior therapeutic efficacy and safety between Beta erythropoietin ®(CinnaPoietin) and Eprex® (epoetin alpha) on treatment of anemia in End stage renal disease (ESRD) hemodialysis patients 2016-03-01 anticipated 156 Complete https://irct.ir/trial/6572 interventional Randomization: Randomized, Blinding: Double blinded, Placebo: Not used, Assignment: Parallel, Purpose: Treatment. 3 Chronic kidney disease. Intervention 1: In Cinnapoeitin group, the starting dose is 60 (50-100) IU/kg body weight/week for naïve patients. Administration dose for patients who are treated with erythropetin is similar dose of previously administered amount (IV or SC without any change). After then, dose adjustment will be done based on patients’ response. Intervention 2: In Eprex group, the starting dose is 60 (50-100) IU/kg body weight/week for naïve patients. Administration dose for patients who are treated with erythropetin is similar dose of previously administered amount (IV or SC without any change). After then, dose adjustment will be done based on patients’ response.
public Dr.somayeh Amini
No.2 , 7thSt., Simaye Iran St., Shahrak Gharb, Tehran, IRAN
Tehran 146699874 00982188088821 amini.s@orchidpharmed.com Orchidpharmed company scientific Somayeh Amini
No.2 , 7thSt., Simaye Iran St., Shahrak Gharb, Tehran, IRAN
Tehran Iran (Islamic Republic of) 146699874 +98 21 8808 8821 amini@orchidpharmed.com Orchidpharmed company Iran (Islamic Republic of) Iran (Islamic Republic of) Iran (Islamic Republic of) Iran (Islamic Republic of) Iran (Islamic Republic of) Iran (Islamic Republic of) Iran (Islamic Republic of) Iran (Islamic Republic of) • 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); • who present iron stores according to the KDIGO guidelines; • 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 myoloma, 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 six months; • History of or active blood coagulation disorders including DVT, PTE, native access Thrombosis during last six 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) • 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,…) • 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. 18 years 70 years Both N18 Chronic kidney disease Treatment - Drugs Treatment - Drugs In Cinnapoeitin group, the starting dose is 60 (50-100) IU/kg body weight/week for naïve patients. Administration dose for patients who are treated with erythropetin is similar dose of previously administered amount (IV or SC without any change). After then, dose adjustment will be done based on patients’ response. In Eprex group, the starting dose is 60 (50-100) IU/kg body weight/week for naïve patients. Administration dose for patients who are treated with erythropetin is similar dose of previously administered amount (IV or SC without any change). After then, dose adjustment will be done based on patients’ response. • mean Hb change level during the last 4 weeks of treatment. Timepoint: during 26 weeks every 2 week. Method of measurement: CBC test. Mean weekly epoetin dosage per kg body weight during the last 4 weeks of treatment. Timepoint: during 26 weeks every 2 week. Method of measurement: Total dose administered. Proportion of patients with any permanent or transient dose change during main study phase. Timepoint: during 26 weeks every 2 week. Method of measurement: any dose change. Proportion of patients with any Hb measurement outside the target range. Timepoint: during 26 weeks every 2 week. Method of measurement: CBC test. Incidence of blood transfusions. Timepoint: during 26 weeks follow up. Method of measurement: count of blood transfusion event. Proportion of patients with treatment success. Timepoint: during 26 weeks every 2 week. Method of measurement: Hb concentration≥11.0 g/dl or two consecutive weeks without any blood transfusion within the preceding 3 months. The incidence of Hb levels above 13 g/dL. Timepoint: during 26 weeks every 2 week. Method of measurement: CBC test. Proportion of patients with an increase in Hb concentration of > 1.0 g/dL for 4 weeks. Timepoint: during 26 weeks every 2 week. Method of measurement: CBC test. CinnaGen Pharmaceutical Company Approved 2015-10-17 Tehran University of Medical Sciences TUMS Ethic Committee, 6th floor, Central Building, Ghods st, Keshavarz Blvd, Teahran, Iran Tehran Iran (Islamic Republic of) Approved 2015-12-05 Shiraz University of Medical Sciences Shiraz, Iran. Shiraz Iran (Islamic Republic of)