Biosimilar Erythropoietin in Anaemia Treatment (Correction Phase Study) (BEAT_001)

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

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.

Study Overview

• Status: Terminated
• Conditions: Renal Anaemia
• Intervention / Treatment: Drug: EPIAO®; Drug: EPREX®

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 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.

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 4

Contacts and Locations

Study Locations

• 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:

1. Male and female subjects between the age of 18 to 75 years
2. Subjects with renal anaemia (haemoglobin 7.5 g/dl to 10 g/dl)
3. Subjects who are treatment naïve to epoetin
4. Subjects with chronic kidney disease (CKD) stages* 3 and 4 not yet on dialysis (predialysis)
5. Subjects willing to provide a written informed consent

6. 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:

1. Subjects with anaemia due to other reasons (that is not renal anaemia)
2. Subjects on dialysis
3. Subjects who have undergone blood transfusion within the last 3 months
4. Subjects with major complication such as severe/chronic infections or bleeding, or aluminum toxicity
5. Subjects with suspected or known PRCA
6. Subjects with a history of aplastic anaemia
7. 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)
8. Subjects with known hypersensitivity to any of the ingredients of the investigational products, the mammalian cell-derived product or human albumin products
9. Subjects with history of seizure disorder
10. Subjects with hematological disorder (thrombocytopenia, neutropenia, or hemolysis)
11. Subjects with hyperparathyroidism (intact parathyroid hormone > 1000 pg/ml)
12. Subjects with severe liver dysfunction
13. Subjects with congestive heart failure and/or angina (NYHA class III and IV)
14. Subjects with myocardial infarction or stroke in the preceding 6 months of screening
15. Subjects with active malignancy in the previous 5 years
16. Subjects with gastrointestinal bleeding in the past 6 months
17. Subjects with immunosuppressive therapy in the previous 3 months
18. Subjects with Hepatitis B virus (HbsAg), Hepatitis C virus (HCV), Human Immunodeficiency Virus (HIV) and syphilis
19. 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
20. Subjects participating in trials involving erythropoietin in the past 6 months before screening
21. 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 Assignment
• 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: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®; 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: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®; 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(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

Collaborators and Investigators

• Sponsor: Shenyang Sunshine Pharmaceutical Co., LTD.
• Collaborators: Navitas Life Sciences GmbH
• Investigators: Study Director: BOLONG MIAO, Ph.D, Shenyang Sunshine Pharmaceutical Co., LTD.

Study record dates

Study Major Dates

• Study Start: August 1, 2015
• Primary Completion (Actual): June 1, 2019
• Study Completion (Actual): August 1, 2019

Study Registration Dates

• First Submitted: August 10, 2015
• First Submitted That Met QC Criteria: August 12, 2015
• First Posted (Estimate): August 14, 2015

Study Record Updates

• Last Update Posted (Actual): October 22, 2020
• Last Update Submitted That Met QC Criteria: October 19, 2020
• Last Verified: October 1, 2020

More Information

Terms related to this study

• Keywords: safety; efficacy; immunogenicity; renal anaemia; biosimilar epoetin
• Additional Relevant MeSH Terms: Hematologic Diseases; Anemia; Hematinics; Epoetin Alfa
• Other Study ID Numbers: SSS_EP_001