Clinical trial NCT02947438: Biosimilar Erythropoietin in Anaemia Treatment (Maintenance Phase Study)
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Renal Anemia
Keywords: Renal anemia
Haemodialysis
Maintenance phase
Lead sponsor: Shenyang Sunshine Pharmaceutical Co., LTD.
Sponsor class: INDUSTRY
Collaborators: name: Navitas Life Sciences GmbH
First posted: 2016-10-27
Enrollment: 207
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Mean absolute change in haemoglobin level from baseline to 6 months
timeFrame: from baseline to 6 months
measure: Mean absolute change in weekly epoetin dosage per kg body weight from baseline to 6 months
timeFrame: from baseline to 6 months
Secondary outcomes:
measure: Mean absolute change in haemoglobin level from baseline to 9 months
timeFrame: from baseline to 9 months
measure: Mean absolute change in weekly epoetin dosage per kg body weight from baseline to 9 months
timeFrame: from baseline to 9 months
measure: Proportion of subjects with hemoglobin values are within 10 - 12 g/dl
timeFrame: weeks 32-36
measure: Incidence of blood transfusions
timeFrame: 52 weak
Other outcomes:
measure: Incidence and nature of adverse events
timeFrame: 52 weak
measure: Incidence of drug related adverse events
timeFrame: 52 weak
measure: Number of subjects who prematurely withdrew from the study due to AE and SAE
timeFrame: 52 weak
measure: Number of subjects with presence of anti-erythropoietin antibodies (anti-EPO Ab)
timeFrame: 52 weak
Locations:
city: Volzhskiy
country: Russian Federation
facility: State Budgetary Healthcare Institution "Volgogradskiy Regional Center of Urology and Nephrology"
state: Volgogradskaya Region
city: Moscow
country: Russian Federation
facility: 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
city: Moscow
country: Russian Federation
facility: State Budgetary Healthcare Institution of the Republic of Karelia "V.A. Baranov Republican Hospital"
city: Orenburg
country: Russian Federation
facility: State budgetary healthcare institution "City Clinical Hospital № 1" of Orenburg
city: Saint Petersburg
country: Russian Federation
facility: State Budgetary Educational Institution of Higher Professional Education "North-Western State Medical University named after I.I. Mechnikov " Ministry of Health of Russian Federation
city: Saint Petersburg
country: Russian Federation
facility: 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
city: Saint Petersburg
country: Russian Federation
facility: St- Petersburg state budgetary healthcare institution "City Mariinsky Hospital", department of hemodialysis
city: Saint Petersburg
country: Russian Federation
facility: State budgetary institution "St-Petersburg' scientific-research institution of emergency n.a Dzanelidze)"
city: Saint Petersburg
country: Russian Federation
facility: St-Peterburg State healthcare institution "Municipal hospital of "Elizabethan Hospital
city: Saint Petersburg
country: Russian Federation
facility: Saint-Petersburg State Budgetary Healthcare Institution "City Hospital No. 15"
city: Samara
country: Russian Federation
facility: Federal State Institution of Higher Education "Samara State Medical University" of the Ministry of Health of the Russian Federation
city: Bangkok
country: Thailand
facility: Bamrasnaradura Infectious Disease Institute
city: Bangkok
country: Thailand
facility: Bhumibol Adulyadej hospital
city: Bangkok
country: Thailand
facility: BMA hospital
city: Bangkok
country: Thailand
facility: Chulalongkorn King Memorial hospital
city: Bangkok
country: Thailand
facility: Klongton Hospital
city: Bangkok
country: Thailand
facility: Phramongkutklao hospital
city: Bangkok
country: Thailand
facility: Rajavithi hospital
city: Bangkok
country: Thailand
facility: Siriraj Hospital
Study officials:
affiliation: Shenyang Sunshine Pharmaceutical Co., LTD.
name: Bolong Miao, Doctoral
role: STUDY_DIRECTOR
References: