Biosimilar Erythropoietin in Anaemia Treatment (Maintenance Phase Study)

Study Overview
=================
Brief Summary
-----------------
This study is aimed to comprehensively establish the bio-similarity/bioequivalence in EPIAO® and EPREX® in terms of 52-week comparisons in efficacy, safety and immunogenicity. The targeted population is anaemia patients with end-stage chronic renal disease who previously received epoetin treatment and on haemodialysis.

Detailed Description
-----------------
This is a prospective, randomized, double blind, parallel group two arm study to establish the therapeutic equivalence, safety and tolerability of EPIAO® as compared to EPREX® in the treatment of CKD related anaemia in subjects who are on haemodialysis. A total of 264 subjects will be randomized into two groups in a 1:1 ratio. Treatment arm A will receive EPIAO® 1-3 times a week, intravenously for period of 52 weeks and treatment arm B will receive EPREX, 1-3 times a week, intravenously for period of 52 weeks.

Official Title
-----------------
A Prospective, Randomized, Double Blind, Parallel Group Study to Evaluate a 1:1 Dose Conversion From EPREX to EPIAO in Term of Clinical Efficacy and Safety in Subjects With End-Stage Renal Disease on Haemodialysis

Conditions
-----------------
Renal Anemia

Intervention / Treatment
-----------------
* Drug: EPREX®
* Drug: EPIAO®


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Male and female subjects between the age of 18 to 75 years Subjects with end stage renal disease (CKD stage 5) on hemodialysis and on epoetin treatment for at least 3 months prior to screening Subjects with haemoglobin between 10 g/dl to 12 g/dl Subjects who are on clinically stable haemodialysis (defined as no clinically relevant changes of dialysis regimen and/or dialyzer) for at least 3 months prior to screening Subjects willing to provide a written informed consent Subjects with serum ferritin ≥ 200 μg/L and/or transferrin saturation ≥ 20% Subjects with a life expectancy of more than at least study period in clinical judgment of the investigator Exclusion Criteria: Subjects with anaemia due to other reasons (that is not renal anaemia) Subjects who have undergone blood transfusion within the last 3 months Subjects with major complication such as severe/chronic infections or bleeding or aluminum toxicity Subjects with suspected or known pure red cell aplasia (PRCA) Subjects with a history of aplastic anaemia Subjects with uncontrolled diabetes (fasting blood glucose > 240 mg/dl) or uncontrolled hypertension (systolic blood pressure > 180 mm Hg, diastolic blood pressure > 110 mm Hg) Subjects with known hypersensitivity to any of the ingredients of the investigational products, the mammalian cell-derived product or human albumin products Subjects with history of seizure disorder Subjects with hematological disorder Subjects with hyperparathyroidism Subjects with congestive heart failure and/or angina (NYHA class III and IV) Subjects with myocardial infarction or stroke in the preceding 6 months of screening Subjects with active malignancy in the previous 5 years Subjects with gastrointestinal bleeding in the past 6 months Subjects with immunosuppressive therapy in the previous 3 months Subjects with active hepatitis B virus (HBsAg) (positive for HBsAg and IgM anti-HBc) and hepatitis C virus (HCV) (positive for Anti-HCV antibody) and human immunodeficiency virus (HIV) Female subjects who are pregnant, breast-feeding, planning to be pregnant during the study, or women of child-bearing potential (any woman who is not surgically sterile i.e. bilateral tubal ligation, total hysterectomy or < 2 years post menopause) not using a reliable method of double contraception (e.g. condom plus diaphragm, condom or diaphragm plus spermicidal gel/foam, tubal ligation, or stable dose of hormonal contraception) throughout the study period Subjects participating in trials involving erythropoietin in the past 6 months before screening.Subjects currently participating or participation in an investigational study within 30 days prior screening

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 75 Years

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

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

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

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Reference group<br>Generic name: recombinant human erythropoetin injection which is indicated for the treatment of anaemia caused by chronic renal disease. Dosage form:Injection Strength: 2000IU, 3000IU, 4000IU Frequency and Dosage: Intravenously injection 1-3 times a week for a period of 52 weeks. | Drug: EPREX®<br>* Recombinant human erythropoietin falls under the pharmacological class of haematopoietic / anti anaemic agents. It has been developed for the treatment of anaemia in subjects with chronic kidney disease. Erythropoietin, also known as EPO, is a glycoprotein hormone that controls erythropoiesis, or RBC production. It is a cytokine (protein signalling molecule) for erythrocyte precursors in the bone marrow. Human EPO has a molecular weight of 34,000.<br>* Other names: Recombinant human erythropoietin;|
| Experimental: Experimental group<br>Generic name: recombinant human erythropoetin injection which is indicated for the treatment of anaemia caused by chronic renal disease. Dosage form: Injection Strength: 2000IU, 3000IU, 4000IU Frequency and Dosage: Intravenously injection 1-3 times a week for a period of 52 weeks. | Drug: EPIAO®<br>* Recombinant human erythropoietin falls under the pharmacological class of haematopoietic / anti anaemic agents. It has been developed for the treatment of anaemia in subjects with chronic kidney disease. Erythropoietin, also known as EPO, is a glycoprotein hormone that controls erythropoiesis, or RBC production. It is a cytokine (protein signalling molecule) for erythrocyte precursors in the bone marrow. Human EPO has a molecular weight of 34,000.<br>* Other names: Recombinant human erythropoietin;|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean absolute change in haemoglobin level from baseline to 6 months | Mean absolute change in haemoglobin level from baseline to 6 months after treatment with EPIAO/EPREX in parallel groups (g/dl). | from baseline to 6 months | 
| Mean absolute change in weekly epoetin dosage per kg body weight from baseline to 6 months | Mean absolute change in weekly epoetin dosage per kg body weight from baseline to 6 months after treatment with EPIAO/EPREX in parallel groups (IU/kg/week). | from baseline to 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean absolute change in haemoglobin level from baseline to 9 months | Mean absolute change in haemoglobin level from baseline to 9 months after treatment with EPIAO/EPREX in parallel groups (g/dl). | from baseline to 9 months | 
| Mean absolute change in weekly epoetin dosage per kg body weight from baseline to 9 months | Mean absolute change in weekly epoetin dosage per kg body weight from baseline to 9 months after treatment with EPIAO/EPREX in parallel groups (IU/kg/week). | from baseline to 9 months | 
| Proportion of subjects with hemoglobin values are within 10 - 12 g/dl | Proportion of subjects with hemoglobin values are within 10 - 12 g/dl for the last 4 weeks of the period for assessment of treatment of efficacy and safety (weeks 32-36) | weeks 32-36 | 
| Incidence of blood transfusions | Incidence of blood transfusions | 52 weak | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Renal anemia, Haemodialysis, Maintenance phase