Clinical Trials Register

Summary
EudraCT Number:	2011-005057-31
Sponsor's Protocol Code Number:	APO-EPO-02
National Competent Authority:	Hungary - National Institute of Pharmacy
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2012-08-31
Trial results	View results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Hungary - National Institute of Pharmacy

A.2

EudraCT number

2011-005057-31

A.3

Full title of the trial

A phase III, randomized, assessor-blinded, active-controlled, multicenter study of the efficacy and safety of APO-EPO as compared to Procrit® when given subcutaneously to patients with anemia of chronic kidney disease stage 5D who are currently not on epoetin replacement therapy

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

Study of safety and efficacy of APO-EPO versus US licensed Procrit® in patients with anemia of chronic kidney disease stage 5D

A.4.1

Sponsor's protocol code number

APO-EPO-02

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	APOTEX Inc.
B.1.3.4	Country	Canada
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	APOTEX Inc.
B.4.2	Country	Canada
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Accelsiors CRO and Consultancy Services
B.5.2	Functional name of contact point	Clinical Trials Info
B.5.3	Address:
B.5.3.1	Street Address	50 Miskolci Ut
B.5.3.2	Town/ city	Budapest
B.5.3.3	Post code	1147
B.5.3.4	Country	Hungary
B.5.4	Telephone number	+3612990091
B.5.5	Fax number	+3612990096
B.5.6	E-mail	clinicaltrials@accelsiors.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	n/a
D.3.2	Product code	APO-EPO
D.3.4	Pharmaceutical form	Solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	EPOETIN ALFA
D.3.9.1	CAS number	113427-24-0
D.3.9.2	Current sponsor code	APO-EPO
D.3.9.3	Other descriptive name	n/a
D.3.9.4	EV Substance Code	SUB06575MIG
D.3.10	Strength
D.3.10.1	Concentration unit	IU/ml international unit(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	2000
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	Yes
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 2
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	n/a
D.3.2	Product code	APO-EPO
D.3.4	Pharmaceutical form	Solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	EPOETIN ALFA
D.3.9.1	CAS number	113427-24-0
D.3.9.2	Current sponsor code	APO-EPO
D.3.9.3	Other descriptive name	n/a
D.3.9.4	EV Substance Code	SUB06575MIG
D.3.10	Strength
D.3.10.1	Concentration unit	IU/ml international unit(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	3000
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	Yes
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 3
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	n/a
D.3.2	Product code	APO-EPO
D.3.4	Pharmaceutical form	Solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	EPOETIN ALFA
D.3.9.1	CAS number	113427-24-0
D.3.9.2	Current sponsor code	APO-EPO
D.3.9.3	Other descriptive name	n/a
D.3.9.4	EV Substance Code	SUB06575MIG
D.3.10	Strength
D.3.10.1	Concentration unit	IU/ml international unit(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	4000
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	Yes
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 4
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	n/a
D.3.2	Product code	APO-EPO
D.3.4	Pharmaceutical form	Solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	EPOETIN ALFA
D.3.9.1	CAS number	113427-24-0
D.3.9.2	Current sponsor code	APO-EPO
D.3.9.3	Other descriptive name	n/a
D.3.9.4	EV Substance Code	SUB06575MIG
D.3.10	Strength
D.3.10.1	Concentration unit	IU/ml international unit(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	10000
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	Yes
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 5
D.1.2 and D.1.3	IMP Role	Comparator
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Procrit®
D.2.1.1.2	Name of the Marketing Authorisation holder	Amgen Inc.
D.2.1.2	Country which granted the Marketing Authorisation	United States
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Procrit®
D.3.2	Product code	n/a
D.3.4	Pharmaceutical form	Solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	EPOETIN ALFA
D.3.9.1	CAS number	113427-24-0
D.3.9.2	Current sponsor code	n/a
D.3.9.3	Other descriptive name	n/a
D.3.9.4	EV Substance Code	SUB06575MIG
D.3.10	Strength
D.3.10.1	Concentration unit	IU/ml international unit(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	2000
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	Yes
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 6
D.1.2 and D.1.3	IMP Role	Comparator
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Procrit®
D.2.1.1.2	Name of the Marketing Authorisation holder	Amgen Inc.
D.2.1.2	Country which granted the Marketing Authorisation	United States
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Procrit®
D.3.2	Product code	n/a
D.3.4	Pharmaceutical form	Solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	EPOETIN ALFA
D.3.9.1	CAS number	113427-24-0
D.3.9.2	Current sponsor code	n/a
D.3.9.3	Other descriptive name	n/a
D.3.9.4	EV Substance Code	SUB06575MIG
D.3.10	Strength
D.3.10.1	Concentration unit	IU/ml international unit(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	3000
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	Yes
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 7
D.1.2 and D.1.3	IMP Role	Comparator
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Procrit®
D.2.1.1.2	Name of the Marketing Authorisation holder	Amgen Inc.
D.2.1.2	Country which granted the Marketing Authorisation	United States
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Procrit®
D.3.2	Product code	n/a
D.3.4	Pharmaceutical form	Solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	EPOETIN ALFA
D.3.9.1	CAS number	113427-24-0
D.3.9.2	Current sponsor code	n/a
D.3.9.3	Other descriptive name	n/a
D.3.9.4	EV Substance Code	SUB06575MIG
D.3.10	Strength
D.3.10.1	Concentration unit	IU/ml international unit(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	4000
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	Yes
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 8
D.1.2 and D.1.3	IMP Role	Comparator
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Procrit®
D.2.1.1.2	Name of the Marketing Authorisation holder	Amgen Inc.
D.2.1.2	Country which granted the Marketing Authorisation	United States
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Procrit®
D.3.2	Product code	n/a
D.3.4	Pharmaceutical form	Solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	EPOETIN ALFA
D.3.9.1	CAS number	113427-24-0
D.3.9.2	Current sponsor code	n/a
D.3.9.3	Other descriptive name	n/a
D.3.9.4	EV Substance Code	SUB06575MIG
D.3.10	Strength
D.3.10.1	Concentration unit	IU/ml international unit(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	10000
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	Yes
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Anemia and chronic kidney disease stage 5D (patients on stable hemodialysis)

E.1.1.1

Medical condition in easily understood language

Low hemoglobin level in patients with kidney failure on stable hemodialysis

E.1.1.2

Therapeutic area

Not possible to specify

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	14.1
E.1.2	Level	LLT
E.1.2	Classification code	10064848
E.1.2	Term	Chronic kidney disease
E.1.2	System Organ Class	100000004857

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

To assess the therapeutic equivalence of Apotex’s epoetin alfa (APO-EPO) versus US registered epoetin alfa (Procrit®) for correction of the hemoglobin (Hb) concentration in patients with anemia of chronic kidney disease (CKD) stage 5 maintained on stable hemodialysis (CKD stage 5D).

E.2.2

Secondary objectives of the trial

To assess the long-term safety and efficacy of APO-EPO in the 6-month maintenance phase of the study.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Written informed consent of the patient;
2. Hb level below 10 g/dl;
3. Age: ≥ 18 years, male or female patients;
4. Patients are on adequate hemodialysis: the minimally adequate dose of hemodialysis given 3 times per week should be an spKt/V (single-pool delivered Kt/V; clearance of urea x dialysis time/volume of distribution) of 1.2 per dialysis. For treatment periods of less than 5 hours, an alternative minimum dose is a urea reduction rate (URR) of 65%. All types of hemodialysis systems and hemodiafiltration, including high-flux membranes are allowed as long as there is no plan to change the patient’s
regimen during the study;
5. Patients suffering from CKD stage 5 and undergoing chronic hemodialysis (t.i.w) for a sufficient time so as to become stable (as per inclusion criterion No. 4) for at least 1 month prior to randomization;
6. Sufficient iron stores, defined as serum ferritin ≥ 100 ng/ml and transferrin saturation ≥ 20%. (Patients not meeting these criteria may receive iron supplementation therapy during the Screening and stabilization period to appropriately correct their iron store deficiency to meet the criterion required for randomization);
7. Ability to comply with study medication use, study visits, and study procedures as judged by the investigator;
8. Females of childbearing potential agree to use an acceptable method of birth control (e.g., abstinence, hormonal or barrier methods, partner sterilization, or IUD) for the duration of the study.

E.4

Principal exclusion criteria

1. Peritoneal dialysis;
2. CRP >10 mg/l, as measured with a standard method (if not
corrected during the Screening and stabilization period);
3. Previous use of any erythropoiesis stimulating agent (ESA);
4. Uncontrolled hypertension (defined as pre-dialysis diastolic
blood pressure ≥ 100 mmHg or systolic blood pressure ≥ 180
mmHg);
5. Primary hematological disorder (e.g. myelodysplastic
syndrome, myeloma, sickle cell anemia, hematological
malignancy, multiple myeloma hemolytic anemia);
6. Decompensated liver failure;
7. Clinical evidence of concurrent uncontrolled
hyperparathyroidism (defined as serum parathyroid hormone
(PTH) > 1000 pg/ml);
8. Previous stroke or evident disturbances of brain blood flow, e.g.
transient ischemic attack (TIA);
9. Hypothyroidism without adequate replacement therapy
(adequate defined as: stable dose of therapy with stable
thyroid hormone levels for at least 3 months prior to
screening);
10. Any red blood cell transfusion during the last 3 months
(measured at the time of eligibility verification);
11. Heart failure [New York Heart Association (NYHA) class III and
IV];
12. Unstable angina pectoris, active cardiac disease and/or cardiac
infarction within the last six months;
13. History of or active blood coagulation disease;
14. Thrombocytosis (platelet count > 500,000/μl);
15. Thrombocytopenia (platelet count < 100,000/μl);
16. Leukopenia (white blood cell count < 2,000/μl);
17. History of phenylketonuria;
18. Deficiency in vitamin B12 (if not corrected during the screening
and stabilization period);
19. Deficiency in folic acid (if not corrected during the screening
and stabilization period);
20. Overt bleeding (acute or chronic bleeding within two months
prior to screening);
21. Suspicion of or confirmed occult bleeding (increased
reticulocyte count);
22. Clinical evidence of concurrent systemic infection or
inflammatory disease;
23. Presence of neutralizing anti-erythropoietin antibodies or
suspicion of or known pure red cell aplasia (PRCA);
24. Currently receiving treatment for epilepsy;
25. Major surgery within six months prior to randomization and
during the conduct of the trial (except vascular access surgery);
26. Proven HIV, HBV or HCV infection (is to be tested if no test was
performed within four weeks prior to the screening);
27. Any androgen therapy within two months prior to screening
and during the study;
28. Concomitant immunosuppressive therapy; patients on a short
course of steroids (up to 7 days), topical or intranasal steroids
are allowed in the study;
29. History of any malignant disease within the last 5 years (except excised non-melanoma skin cancer);
30. Women who are pregnant or breastfeeding;
31. Known history of severe drug-related allergies;
32. Known allergy to one of the ingredients of the test or the
reference products or hypersensitivity to mammalian-derived
products;
33. Transplant received within 48 weeks prior to the start of the
study;
34. Simultaneous participation in another clinical study or having
received an Investigational Medicinal Product within three
months before randomization in this study.
35. Psychiatric, addictive (drugs or alcohol) or any other disorder
that compromises the ability to give an informed consent;
36. Any other condition which at the investigator’s discretion may
put the patient at risk or may confound the study results.

E.5 End points

E.5.1

Primary end point(s)

The primary efficacy variable will be the mean weekly dose of epoetin per kilogram of body weight necessary to maintain the Hb level within 10-11 g/dl during the last 4 weeks of treatment (evaluation phase).
Co-primary endpoint: Mean Hb concentration during the last 4 weeks of treatment (evaluation phase).

E.5.1.1

Timepoint(s) of evaluation of this end point

Last 4 weeks of the correction phase (evaluation phase): W21, W22, W23 and W24

E.5.2

Secondary end point(s)

Secondary and exploratory efficacy endpoints:
•proportion of patients with treatment success, i.e. Hb concentration between 10 - 11.0 g/dl for 2 consecutive weeks without any blood transfusion within the preceding 3 months (correction phase);
•number of transfusions and proportion of the patients needing blood transfusions during the treatment period (titration, evaluation and maintenance phase);
•increase in Hb concentration over time (titration, evaluation and maintenance phase);
•change in Hb concentration after initial 4 weeks of treatment;
•proportion of patients with maintenance success (maintenance of mean Hb concentration of 10-11 g/dl for at least 4 consecutive weeks in maintenance phase) ;
•percentage of Hb values outside the target range (<10, >11 g/dl) (titration, evaluation and maintenance phase);
•mean weekly dose of epoetin per kilogram of body weight;
•mean Hb concentration during each 4-week-interval;
•percentage of hematocrit measurements > 30% (in titration, evaluation and maintenance phase).
•EPO resistance index (ERI) - mean weekly dose of epoetin per
kilogram of body weight divided by mean Hb concentration
(titration, evaluation and maintenance phase);
• mean iron dose used;
•number of low TSAT and ferritin values requiring i.v. supplementation of iron (TSAT<20% and ferritin <100 ng/ml).

E.5.2.1

Timepoint(s) of evaluation of this end point

Titration phase: W4, W8, W12, W16 and W20
Evaluation phase: W24
Maintenance phase: W28, W32, W36, W40, W44, and W48

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

E.7.3

Therapeutic confirmatory (Phase III)

Yes

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

Yes

E.8.1.4

Double blind

E.8.1.5

Parallel group

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

Yes

E.8.2.2

Placebo

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

Serbia

Armenia

Bosnia and Herzegovina

Bulgaria

Czech Republic

Egypt

Georgia

Greece

Hungary

Poland

Romania

Russian Federation

Slovakia

Tunisia

Turkey

Ukraine

E.8.7

Trial has a data monitoring committee

Yes

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

LVLS

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

515

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

240

F.4.2.2

In the whole clinical trial

533

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

After participation in the trial, subject will continue with their standard treatment.

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2012-10-17

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2012-10-09

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2017-09-18

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Orphan Designation Number:
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