Biosimilar Erythropoietin in Anaemia Treatment (Correction Phase Study)

Study Overview
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Brief Summary
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This study is aimed to comprehensively establish the biosimilarity/bioquivalence in EPIAO® and EPREX® in terms of 52-week comparisons in efficacy,safety and immunogenicity.The targeted population is anaemia patients with chronic renal disease who are naive to epoetin treatment and not yet on haemodialysis.

Detailed Description
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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 not yet on dialysis (pre-dialysis). A total of 96 subjects will be randomized into two groups in a 1:1ratio. Treatment arm A will receive EPIAO® once a week, subcutaneously for period of 52 weeks and treatment arm B will receive EPREX, weight once a week, subcutaneously for period of 52 weeks.

Official Title
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A Prospective, Randomized, Double Blind, Parallel Group Study to Establish the Therapeutic Equivalence of EPIAO® With the Standard Treatment EPREX® in Subjects With Chronic Kidney Disease (CKD) Related Anaemia Not Yet on Dialysis

Conditions
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Renal Anaemia

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female subjects between the age of 18 to 75 years Subjects with renal anaemia (haemoglobin 7.5 g/dl to 10 g/dl) Subjects who are treatment naïve to epoetin Subjects with chronic kidney disease (CKD) stages* 3 and 4 not yet on dialysis (predialysis) Subjects willing to provide a written informed consent Subjects with serum ferritin ≥ 100 μg/L and/or transferrin saturation ≥ 20% CKD staging will be based on the five-stage system for classification of CKD based on KDIGO guidelines. Exclusion Criteria: Subjects with anaemia due to other reasons (that is not renal anaemia) Subjects on dialysis 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 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 (thrombocytopenia, neutropenia, or hemolysis) Subjects with hyperparathyroidism (intact parathyroid hormone > 1000 pg/ml) Subjects with severe liver dysfunction 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 Hepatitis B virus (HbsAg), Hepatitis C virus (HCV), Human Immunodeficiency Virus (HIV) and syphilis 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
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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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:subcutaneously injection once a week for a period of 52 weeks. The initial dose of EPREX® will be 60 IU/kg body weight. | 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:subcutaneously injection once a week for a period of 52 weeks. The initial dose of EPIAO® will be 60 IU/kg body weight. | 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?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean absolute change in haemoglobin(Hb) | Mean absolute change in haemoglobin(Hb) level from baseline to 24 weeks after treatment with EPIAO®/EPREX® in parallel groups (g/dl),respectively. | 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean absolute change in weekly epoetin dosage | Mean absolute change in weekly epoetin dosage per kg body weight from baseline to 24 weeks after treatment with EPIAO®/EPREX® in parallel groups (IU/kg/week). | 24 weeks | 
| Frequency of adverse events | To observe the frequency of adverse events following EPIAO® and EPREX® administration. | 52 weeks | 
| Occurence of anti-epoetin antibodies | To monitor the occurrence of anti-epoetin antibodies among subjects following at least 52 weeks of therapy. | 52 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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biosimilar epoetin, efficacy, safety, immunogenicity, renal anaemia