Randomized, Controlled, Double-blind Multicenter Safety Study to Evaluate the Safety and Immunogenicity of Subcutaneous EPO HEXAL vs. ERYPO® in the Treatment of Anemia Associated With Chronic Renal Insufficiency in Predialysis Patients

Anemia Clinical Trial

Official title:

Randomized, Controlled, Double-blind Multicenter Safety Study to Evaluate the Safety and Immunogenicity of Subcutaneous EPO HEXAL vs. ERYPO® in the Treatment of Anemia Associated With Chronic Renal Insufficiency in Predialysis Patients

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00701714
• Other study ID #: 2007-22-INJ-17
• Status: Terminated
• Phase: Phase 3
• First received: June 17, 2008
• Last updated: July 13, 2017
• Start date: September 2007
• Est. completion date: January 2010

Study information

• Verified date: July 2017
• Source: Sandoz
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a randomized, controlled, double-blind, multicenter multinational safety study involving about 300 predialysis patients aged 18 years or above suffering from anemia.

Symptomatic anemia will be corrected by s.c. application of EPO HEXAL or ERYPO® in order to achieve a hemoglobin target range of 10.0 -12.0 g/dL.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 337
• Est. completion date: January 2010
• Est. primary completion date: July 2009
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Known chronic renal insufficiency of at least 4 weeks duration; CKD stage at least 3 or higher

• Male and female patients, age: >=18

• Patients who are naïve to ESA treatment or previously ESA treated after 3 months of ESA-free period (i.v. or s.c.)

• Patients with symptomatic anemia, defined as Hb level below 11.0 g/dL and not lower than or equal to 7.5 g/dL on at least 2 visits during the screening period

• Adequate iron status, serum ferritin >= 100 µg/L or transferrin saturation >= 20%

• Ability to follow study instructions and likely to complete all required visits and compliant with subcutaneous administration

• Written informed consent of the patient.

Exclusion Criteria:

• Anemia of non-renal causes

• Therapy with immunosuppressants (other than corticosteroids for chronic treatment) within 3 months before screening and during the study for patients with renal allograft in place or other chronic conditions (e.g. lupus erythematosus, rheumatic arthritis)

• Patients previously treated with chronic dialysis within the last 6 months (exception:

one session of acute dialysis)

• Patients with acute deterioration of renal function during the screening phase according to the investigator's judgment

• Patients receiving any RBC/whole blood transfusion during the screening period

• Primary hematological disorder (e.g. myeloma, myelodysplastic syndrome, sickle cell anemia, hematological malignancy, hemolytic anemia)

• Evidence of uncontrolled diabetes mellitus (HbA1c > 10 % at visit -2)

• Evidence of severe hepatic dysfunction (e.g. ALT and/or AST above 2x upper limit of normal range; or gamma-GT above 3x upper limit of normal range)

• Clinical evidence of current uncontrolled or symptomatic hyperparathyroidism, defined as parathyroid hormone > 500 ng/L at visit -2.

• Uncontrolled hypertension, defined as a systolic blood pressure of >= 160 mmHg and a diastolic blood pressure measurement >= 100 mmHg (average of two values with at least one day between measurements)

• Congestive heart failure and/or angina pectoris [New York Heart Association (NYHA) class III and IV]

• History of stroke or myocardial infarction during the last 6 months prior to visit -2

• Ongoing treatment with phenprocoumon or other cumarin derivates

• Thrombocytopenia (platelet count <100.000/µL) or leucopenia (white blood cell count < 2.000/µL)

• Gastrointestinal bleeding within the last 6 months prior to visit -2 or hemolysis

• Evidence of acute or chronic infection by a C-reactive protein value of > 30 mg/L

• Suspicion or known PRCA (pure red cell aplasia)

• Previously diagnosed HIV or acute hepatitis infection

• History of epilepsy or epileptic seizures or treatment for epilepsy within the past 6 months prior to screening

• Planned major surgery (with expected high blood loss) during the next 3 months or major surgery within the previous 3 months (except laser photocoagulation, access surgery)

• Clinical evidence of active malignant diseases within the last 5 years (except non-melanoma skin cancer)

• Pregnancy, breastfeeding women or women not using a highly effective birth control method (e.g. implants, injectables, combined oral contraceptives, IUD, sexual abstinence, vasectomised partner)

• Known history of severe drug related allergies (e.g. anaphylactic shock)

• Known allergy to one of the ingredients of the test product or hypersensitivity to mammalian-derived products

• Known or suspicion of any non-compliance with respect to subcutaneous treatment

• Simultaneous participation in another clinical study or participation in a study in the month preceding visit-2 or previously randomized in this study

• Participation in another ESA study in the 3 months preceding visit -2

• Any other condition which at the investigator's discretion may put the patient at risk or which may confound the study results.

Related Conditions & MeSH terms

• Anemia
• Chronic Renal Insufficiency
• Renal Insufficiency
• Renal Insufficiency, Chronic

Intervention

Drug:
• HX575 recombinant human erythropoietin alfa
Solution for injection (s.c.)
• ERYPO
Solution for injection (s.c.)

Locations

Country	Name	City	State
Austria	Diakonissen KH Salzburg	Salzburg
Austria	LKH Steyr	Steyr
Austria	AKH Wien	Wien
Austria	Krankenanstalt der Stadt Wien	Wien
Austria	Sozialmedizinisches Zentrum Ost Donauspital	Wien
Bulgaria	MHAT Pazardijk	Pazardzhik
Bulgaria	MHAT Sveti Ivan Rilski	Sofia
Bulgaria	MHAT Stara Zagora	Stara Zagora
Bulgaria	MHAT "Sv. Anna"	Varna
Czechia	Nemocnice Šternberk	Šternberk
Czechia	Nefrologická a interní amb.	Žïár n. Sázavou
Czechia	Ambulance vnitrního lékarstvi	Brno
Czechia	Nemocnice Kladno	Kladno
Czechia	Litomyslska nemocnice, a.s.	Litomyšl
Czechia	Nemocnice s poliklinikou v Novem Jicine	Novi Jicin
Czechia	IKEM	Praha 4
Czechia	Dialcorp, s.r.o.	Praha 4 - Michle
Czechia	FN Motol	Praha 5
Czechia	Nemocnice Prostìjov	Prostìjov
France	CHU d'Amiens - Hopital Sud	Amiens
France	CHU de Rouen - Hopital de Bois Guillaume	Bois-Guillaume
Germany	Gesundheitszentrum Alzey	Alzey
Germany	Gemeinschaftspraxis Dr. med. Gert-Peter Dragoun, Dr. med Günther Hevendehl	Aschaffenburg
Germany	Studienzentrum Hämatologie / Onkologie / Diabetes	Aschaffenburg
Germany	Nephrologische Praxis Bad Münder	Bad Münder
Germany	Praxis Dr. Scharla	Bad Reichenhall
Germany	Nephrologisches Zentrum an Stadtkrankenhaus	Bad Wildungen
Germany	Dialyse-Centrum	Bad Windsheim
Germany	KfH Kuratorium f. Dialyse und Nierentransplantation e.V.	Bergisch Gladbach
Germany	Schwerpunktpraxis für Diabetologie und Nephrologie	Bernkastel-Kues
Germany	KfH Kuratorium für Dialyse und Nierentransplantation e.V.	Bischofswerda
Germany	Nephrologische Gemeinschaftspraxis Dr. Rensinghoff & Dr. Becker	Bochum-Wattenscheid
Germany	Dialysepraxis drs. Riedasch/Schreiber	Coesfeld
Germany	Praxis Dr. Kraatz	Demmin
Germany	Gemeinschaftspraxis Dr. Steffen & Dr. Perino	Dinkelsbühl
Germany	Diabetes- und Dialysezentrum Merker, Vogt	Dormagen
Germany	Dialysepraxis Häger, Schanze, Brause	Düsseldorf
Germany	Gemeinschaftspraxis Karlstraße	Düsseldorf
Germany	KfH Kuratorium f. Dialyse und Nierentransplantation e.V.	Eberswalde
Germany	Gemeinschaftspraxis Dr. Spitthöver, Dr. Knee, Dr. Gröschel	Essen
Germany	Praxis Dr. Zimmermann	Essen
Germany	Praxis Dr. Lüdemann	Falkensee
Germany	Dialysepraxis	Friedrichroda
Germany	KfH Kuratorium für Dialyse und Nierentransplantation e.V.	Fürstenzell
Germany	Dialysepraxis Barmbek	Hamburg
Germany	KfH Kuratorium für Dialyse und Nierentransplantation e.V.	Haßfurt
Germany	KfH Kuratorium für Dialyse und Nierentransplantation e.V.	Heringen
Germany	Dialysezentrum	Homberg/Efze
Germany	Gemeinschaftspraxis und Dialyse	Hürth
Germany	Dialyseplaxis DR. Rieck, DR. Göbel, DR. Wagner	Krefeld
Germany	Leipziger Institut für Präventivmedizin	Leipzig
Germany	Med Center Leipzig	Leipzig
Germany	GDG Gemeinnützige Dialyse Gesellschaft	Leverkusen
Germany	KfH Kuratorium für Dialyse und Nierentransplantation e.V.	Ludwigshafen
Germany	Gemeinschaftspraxis Dres. Leistikow, Hafezi und Sandner	Mannheim
Germany	Praxis Dr. Schütterle	Marburg
Germany	Praxis Dr. Vogel-Wagner	Mittweida
Germany	Praxis Dr. Rose, Pohlmeier und Dr. Lammers	Münster
Germany	Dialyse Nettetal	Nettetal
Germany	KfH Kuratorium für dialyse und Nierentransplantation e.V.	Nördlingen
Germany	KfH Kuratorium für Dialyse und Nierentransplantation e.V.	Passau
Germany	Praxis Dipl. med. Kosch	Pirna
Germany	Dialysepraxis Dipl. med. Gierak & Dipl. med. Rettig	Quedlinburg
Germany	Klinik für Nephrologie und Allgemeine Innere Medizin	Solingen
Germany	Gemeinschaftspraxis Dr. Kirchner und Dr. Menge	Sömmerda
Germany	KfH Kuratorium für Dialyse und Nierentransplantation e.V.	Straubing
Germany	Praxis Dr. med. Mauersberger	Villingen-Schwenningen
India	Kamineni Hospitals Ltd.	Hyderabaad
India	NIZAM Institute of Medical Sciences	Hyderabaad
India	Bombay Hospital	Indore
India	Monilek Hospital and Research Center	Jaipur
India	Vinaya Hospital & Research Centre	Mangalore
India	Pulse Diagnostix Cardiac and Medical Center	Pune
India	Kerala Institute of Medical Sciences	Trivandrum
Poland	SP ZOZ Miejski Szpital Zespolony	Czestochowa
Poland	Specjalistyczna Przychodnia Lekarska Medikard	Plock
Poland	Specjalistyczne Centrum Diagnostyczno-Lecznicze Bamberski Dwor (Solumed SC)	Poznan
Poland	Szpital Wojewódzki w Poznaniu	Poznan
Poland	NZOZ NEFROLUX Sp. J. Lucjan Sobieraj, Wojciech Kaminski	Siemianowice Slaskie
Poland	Wojewodzki Szpital Specjalistyczny nr. 1 im. Jozefa Gasinskiego	Tychy
Poland	Szpital Praski p.w. Przemienienia Panskiego II Oddzia Chorob Wewnetrznych	Warszawa
Poland	NZOZ Centrum Badan Klinicznych	Wroclaw
Romania	Centrul Medical de Diagnostic si Tratament Ambulator si Medicina Preventiva Bucuresti	Bucuresti
Romania	Institutul Clinic Fundeni	Bucuresti
Romania	Institutul National de DiabetNutritie si Boli Metabolice Paulescu	Bucuresti
Romania	Spitalul Universitar Bucuresti	Bucuresti
Romania	Spitalul Clinic Judetean Cluj	Cluj
Romania	County Hospital Deva	Deva
Romania	Spitalul Clinic CI Parhon Iasi	Iasi
Romania	Dr. Gavril Curteanu Clinical Hospital	Oradea
Romania	County Hospital Tg Mures	Tg Mures
Romania	Emergency Clinical County Hospital	Timisoara
Romania	Policlinica Dr. Citu	Timisoara
Romania	SC Medicali's SRL	Timisoara
Romania	Spitalul Judetean Timisoara	Timisoara
Russian Federation	Municipal medical Institution "City Hospital #1"	Barnaul
Russian Federation	Municipal Institution "City Clinical Hospital #40"	Ekaterinburg
Russian Federation	State Healthcare Institution "Sverdlovsk Regional Clinical Hospital #1"	Ekaterinburg
Russian Federation	State Healthcare Institution "Kemerova Regional Clinical Hospital"	Kemerovo
Russian Federation	Federal State Institution "National Medical Surgery center named after NI Pirogov of Federal Agency of Health Care and Social Development"	Moscow
Russian Federation	Russian University of Peoples Frienship (clinical base: City clinical hospital #53)	Moscow
Russian Federation	State Educational Institution of Higher Professional Education "Moscow State University of Medicine and dentistry of Federal Agency of health Care and Social Development", City Clinical Hospital #23	Moscow
Russian Federation	State Health Care Institution City Clinical Hospital named after SP Botkin	Moscow
Russian Federation	State healthcare Institution "Nizhegorodsky Regional Clinical Hospital named after NA Semashko"	Nizhniy Novgorod
Russian Federation	State Healthcare Institution "Reoublic Hospital named after VA Baranov"	Petrozavodsk
Russian Federation	Municipal healthcare Institution "City Clinical Hospital #2"	Pyatigorsk
Russian Federation	State Healthcare Institution "Ryazan Regional Cardiological Dispensary"	Ryazan
Russian Federation	State Educational Institution of High Professional Education Saratov State Medical University of Roszdrav	Saratov
Russian Federation	State Educational Institution of Higher Professional Education "Smolensk State Medical Academy of Federal Agency of Health Care and Social Development"	Smolensk
Russian Federation	St. Petersburg State Healthcare Institution "City Mariinsky Hospital"	St. Petersburg
Russian Federation	St. Petersburg State Healthcare Institution "City Outpatient Clinic #17"	St. petersburg
Russian Federation	State Educational Institution of Higher Professional Education "St. Petersburg State Medical Academy for Postgraduate studies of Roszdrav"	St. Petersburg
Russian Federation	State Educational Institution of Higher Professional Education "St. Petersburg State Medical Academy named after I.I. Mechnikov of Roszdrav"	St. Petersburg
Russian Federation	State Educational Institution of Higher Professional Education "St. Petersburg State Medical Institute named after IP Pavlov of Roszdrav"	St. Petersburg
Russian Federation	State Institute St. Petersburg	St. Petersburg
Russian Federation	State Institution "St. petersburg Clinical research Institute of Emergency Medical Care named after I.I. Dzhanelidze"	St. petersburg
Russian Federation	SibMedCenter LLC	Tomsk
Russian Federation	State Institution Scientific Research Institute of Cardiology of Tomsk Research Center of Siberian Branch of Russian Academy of Medical Sciences	Tomsk
Russian Federation	Municipal Healthcare Institution "City Clinical Hospital #2"	Yaroslavl
Russian Federation	State Healthcare Institution of Yaroslavl region "Regional Clinical Hosptal"	Yaroslavl
Slovakia	MEDIKOL s.r.o.	Košice
Slovakia	SMOLKO s.r.o.	Kosice
Slovakia	FN Trnava	Trnava

Sponsors (1)

Lead Sponsor	Collaborator
Sandoz

Countries where clinical trial is conducted

Austria,  Bulgaria,  Czechia,  France,  Germany,  India,  Poland,  Romania,  Russian Federation,  Slovakia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Hemoglobin Level	Mean absolute change in hemoglobin (baseline to end of study week 13)	13 weeks
Primary	Weekly Epoetin Dose	Mean weekly epoetin dose [IU/kg] in study weeks 11-13	weeks 11-13
Secondary	Immunogenicity	Number of participants with antibody formation against Epoetin during treatment period (safety set)	13 weeks