Biosimilar Erythropoietin in Anaemia Treatment (Maintenance Phase Study) (BEAT_002)

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

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.

Study Overview

• Status: Completed
• Conditions: Renal Anemia
• Intervention / Treatment: Drug: EPREX®; Drug: EPIAO®

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.

• Study Type: Interventional
• Enrollment (Actual): 207
• Phase: Phase 3

Contacts and Locations

Study Locations

• Russian Federation
  • Moscow, Russian Federation, 129110
    • State budgetary healthcare institution of Moscow region "Moscow Regional Scientific Research and Clinical Institute named after M.F.Vladimirsky", Department of Transplantation, nephrology and surgical hemocorrection
  • Moscow, Russian Federation, 185019
    • State Budgetary Healthcare Institution of the Republic of Karelia "V.A. Baranov Republican Hospital"
  • Orenburg, Russian Federation, 460040
    • State budgetary healthcare institution "City Clinical Hospital № 1" of Orenburg
  • Saint Petersburg, Russian Federation, 191015
    • State Budgetary Educational Institution of Higher Professional Education "North-Western State Medical University named after I.I. Mechnikov " Ministry of Health of Russian Federation
  • Saint Petersburg, Russian Federation, 191015
    • The Federal State Budgetary Institute "The Nikiforov Russian Center of Emergency and Radiation Medicine" of the Ministry of Russian Federation for Civil Defense, Emergencies and Elimination of Consequences of Natural Disasters
  • Saint Petersburg, Russian Federation, 191104
    • St- Petersburg state budgetary healthcare institution "City Mariinsky Hospital", department of hemodialysis
  • Saint Petersburg, Russian Federation, 192242
    • State budgetary institution "St-Petersburg' scientific-research institution of emergency n.a Dzanelidze)"
  • Saint Petersburg, Russian Federation, 195427
    • St-Peterburg State healthcare institution "Municipal hospital of "Elizabethan Hospital
  • Saint Petersburg, Russian Federation, 198205
    • Saint-Petersburg State Budgetary Healthcare Institution "City Hospital No. 15"
  • Samara, Russian Federation, 443099
    • Federal State Institution of Higher Education "Samara State Medical University" of the Ministry of Health of the Russian Federation
  • Volgogradskaya Region
    • Volzhskiy, Volgogradskaya Region, Russian Federation, 404120
      • State Budgetary Healthcare Institution "Volgogradskiy Regional Center of Urology and Nephrology"
• Thailand
  • Bangkok, Thailand, 10700
    • Siriraj Hospital
  • Bangkok, Thailand, 10700
    • Bamrasnaradura Infectious Disease Institute
  • Bangkok, Thailand, 10700
    • Bhumibol Adulyadej Hospital
  • Bangkok, Thailand, 10700
    • BMA hospital
  • Bangkok, Thailand, 10700
    • Chulalongkorn King Memorial hospital
  • Bangkok, Thailand, 10700
    • Klongton Hospital
  • Bangkok, Thailand, 10700
    • Phramongkutklao Hospital
  • Bangkok, Thailand, 10700
    • Rajavithi Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Reference group; 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®; 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.; Other Names: Recombinant human erythropoietin
EXPERIMENTAL: Experimental group; 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®; 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.; 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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence and nature of adverse events	Incidence and nature of adverse events	52 weak
Incidence of drug related adverse events	Incidence of drug related adverse events	52 weak
Number of subjects who prematurely withdrew from the study due to AE and SAE	Number of subjects who prematurely withdrew from the study due to AE and SAE	52 weak
Number of subjects with presence of anti-erythropoietin antibodies (anti-EPO Ab)	Number of subjects with presence of anti-erythropoietin antibodies (anti-EPO Ab)	52 weak

Collaborators and Investigators

• Sponsor: Shenyang Sunshine Pharmaceutical Co., LTD.
• Collaborators: Navitas Life Sciences GmbH
• Investigators: Study Director: Bolong Miao, Doctoral, Shenyang Sunshine Pharmaceutical Co., LTD.

Study record dates

Study Major Dates

• Study Start: December 1, 2015
• Primary Completion (ACTUAL): October 9, 2021
• Study Completion (ACTUAL): October 9, 2021

Study Registration Dates

• First Submitted: October 26, 2016
• First Submitted That Met QC Criteria: October 26, 2016
• First Posted (ESTIMATE): October 27, 2016

Study Record Updates

• Last Update Posted (ACTUAL): November 23, 2022
• Last Update Submitted That Met QC Criteria: November 18, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Keywords: Haemodialysis; Renal anemia; Maintenance phase
• Additional Relevant MeSH Terms: Hematologic Diseases; Anemia; Hematinics; Epoetin Alfa
• Other Study ID Numbers: SSS_EP_002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO