Surveillance Study to Estimate the Incidence of Pure Red Blood Cell Aplasia Among Patients With Chronic Kidney Failure

NCT ID: NCT00391287

Last Updated: 2014-10-03

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 15334 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2006-06-30
• Study Completion Date: 2010-12-31

Brief Summary

The purpose of this study is to estimate the incidence rate of pure red cell aplasia (PRCA; aplastic anemia) mediated by erythropoietin (EPO) antibodies in patients who are receiving subcutaneous (s.c.) epoetin alfa (polysorbate 80 formulation) for the treatment of anemia associated with chronic renal failure (CRF), and to compare this incidence rate to the incidence rate with s.c. exposure to other currently marketed recombinant erythropoietin products (epoetin alfa, epoetin beta, darbepoetin alfa), with adjustment of duration for which the drug is given to the patient. The study will also examine the impact of the pattern of using mixed s.c. exposure to multiple erythropoietin products occurring in this patients, and the impact of the time from which the treatment is started to the onset of PRCA.

Detailed Description

In 1998, prompted by concern that human serum albumin (HAS- the stabilizer in the epoetin alfa formulation) could theoretically transmit Creutzfeldt-Jakob disease and bovine spongiform encephalopathy, an alternative epoetin alfa formulation using polysorbate 80 as a stabilizer was introduced. The polysorbate 80 epoetin alfa formulation became available in a variety of product presentations (i.e., single-use vials and prefilled syringes with both coated and uncoated stoppers) to provide for prescribing flexibility, patient convenience, and choice of route of administration. Soon after the introduction of the polysorbate 80 epoetin alfa formulation in prefilled syringes, an increasing number of cases of EPO antibody-mediated pure red cell aplasia (PRCA) were reported in patients with chronic renal failure (CRF) exposed to epoetin alfa by the s.c. route. This led to contraindication of the s.c. route for epoetin alfa in the European Union (E.U.) and Switzerland in December 2002. It was subsequently shown that the increased risk for PRCA was associated with one specific polysorbate 80 epoetin alfa presentation - prefilled syringes with uncoated rubber stoppers. It appeared that uncoated rubber stoppers, when exposed to polysorbate 80, released organic compounds (leachates) into the epoetin alfa formulation, and that these leachates were the most probable product-specific cause for the increase in EPO antibody-mediated PRCA. A worldwide recall of the polysorbate 80 epoetin formulation in prefilled syringes with uncoated stoppers was completed in March 2004. FluroTec-coated stoppers are now used in all prefilled syringes containing the polysorbate 80 epoetin alfa formulation, to prevent leachates from entering the formulation. Following these actions, the incidence rate of EPO antibody-mediated PRCA in CRF patients receiving s.c. epoetin alfa fell to a level similar to that for the HSA-containing epoetin formulation, which has a long-standing and well-characterized safety profile. As of 30 November 2005, s.c. exposure in CRF patients to the polysorbate 80 epoetin alfa formulation in prefilled syringes with coated stoppers was 71,880 patient-years, with 4 cases of EPO antibody-mediated PRCA reported. In 2006, E.U. Health Authorities reauthorized s.c. epoetin alfa use in CRF patients for whom intravenous access is not readily available. As part of the reauthorization, the sponsor agreed to conduct this registry in order to demonstrate that the polysorbate 80 epoetin alfa formulation using a coated stopper has an acceptable immunogenic safety profile and to define the incidence of EPO antibody-mediated PRCA associated with recombinant erythropoietin use among patients with anemia associated with CRF. This is a multicenter, multinational, immunogenicity surveillance registry using a prospective cohort design (patients identified by a common characteristic), with enrollment of parallel groups that are exposed to the polysorbate 80 formulation of epeotin alfa or other marketed erythropoietin products administered by the s.c. route of administration for the treatment of anemia associated with CRF. The registry is designed to address the following question: Is the current rate of PRCA with the s.c. polysorbate 80 epoetin alfa formulation using coated stoppers similar to the current rate with other marketed erythropoietin products administered by the s.c. route, adjusted for duration of exposure? Each patient will be observed for development of PRCA for up to 3 years. Information on exposure to erythropoietin products, stage of CRF, treatment modality for CRF, erythropoietin handling and storage information, and most recent hemoglobin level will be collected quarterly. Cases of unexplained loss or lack of effect (LOE) with an administered erythropoietin product, including cases of suspected PRCA, will be reported to the sponsor as serious adverse events. Cases of EPO antibody-mediated PRCA will be determined by the clinical presence of suspected PRCA, an unexplained LOE with administered erythropoietin product, and the presence of EPO antibody. An Independent Case Adjudication Committee will review blinded case data for patients with unexplained LOE and identify cases of EPO antibody-mediated PRCA. A separate Independent Safety Advisory Committee will be responsible for periodically reviewing unblinded patient data and summary data and will make recommendations related to the incidence rate of PRCA associated with s.c. epoetin alfa use. The sponsor will actively monitor registry enrollment and erythropoietin brand usage to ensure that the registry accrues 20,000 person-years of s.c. exposure to epoetin alfa and 20,000 person-years of s.c. exposure to all other erythropoietin products combined. If it appears that one registry arm will meet this accrual goal before the other, the sponsor may elect to selectively close those investigational sites with predominant use of the erythropoietin product(s) in the arm approaching full accrual. The registry will provide no inducement to change therapy and will be non-interventional.

Conditions

Pure Red-Cell Aplasia; Chronic Kidney Failure

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

erythropoietin treatment in CRF

Patients exposed to EPREX or other marketed erythropoietin products administered by the subcutaneous route of administration for the treatment of anemia of Chronic Renal Failure

No interventions assigned to this group

Eligibility Criteria

Inclusion Criteria

• Patients with established CRF as an indication for the treatment of anemia
• Patients who are receiving or are about to receive (within 1 month) a marketed erythropoietin (i.e., epoetin alfa [EPREX/ERYPO/GLOBUREN], epoetin beta [NEORECORMON®], or darbepoetin alfa [ARANESP®]) by the s.c. route of administration
• Patients who are likely to continue to receive s.c. erythropoietin product(s) for at least 1 year.

Exclusion Criteria

• Patients with a history of pure red cell aplasia or aplastic anemia
• Patients who are experiencing unexplained loss or lack of effect to a recombinant erythropoietin product ongoing at the time of enrollment
• Patients who have had prior recombinant erythropoietin treatment whose anemia had never responded (primary lack of efficacy)
• Patients with a history of EPO antibodies prior to enrollment
• Subjects who are currently receiving immunosuppressive medication (e.g., cyclosporine, tacrolimus, sirolimus, mycophenolic mofetil, azathioprine, or monoclonal antibodies) or corticosteroids at a dose corresponding to >15 mg/day prednisolone
• Subjects whose first s.c. exposure to any erythropoietin product was >1 year prior to enrollment.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Janssen-Cilag International NV

INDUSTRY

Sponsor Role: collaborator

Johnson & Johnson Pharmaceutical Research & Development, L.L.C.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Johnson & Johnson Pharmaceutical Research & Development, L.L. C. Clinical Trial

Role: STUDY_DIRECTOR

Johnson & Johnson Pharmaceutical Research & Development, L.L.C.

Locations

Adelaide, , Australia

Central Queensland M C, , Australia

Fremantle, , Australia

Hobart, , Australia

Launceston, , Australia

Liverpool, , Australia

Newcastle, , Australia

Parkville, , Australia

Perth, , Australia

Randwick, , Australia

Wollongong, , Australia

Woodville, , Australia

Aalst, , Belgium

Antwerp, , Belgium

Arlon, , Belgium

Assebroek, , Belgium

Ath, , Belgium

Bonheiden, , Belgium

Bruges, , Belgium

Brussels, , Belgium

Charleroi, , Belgium

Deinze, , Belgium

Edegem, , Belgium

Eeklo, , Belgium

Frameries, , Belgium

Genk, , Belgium

Ghent, , Belgium

Gilly, , Belgium

Huy, , Belgium

Ieper, , Belgium

La Louvière, , Belgium

Leuven, , Belgium

Liège, , Belgium

Mons, , Belgium

Namur, , Belgium

Roeselare, , Belgium

Sint-Gillis-Dendermonde, , Belgium

Sint-Niklaas, , Belgium

St-Truiden, , Belgium

Tournai, , Belgium

Turnhout, , Belgium

Westmalle, , Belgium

Wilrijk, , Belgium

Århus N N/A, , Denmark

Holstebro, , Denmark

Sønderborg, , Denmark

Viborg, , Denmark

Helsinki, , Finland

Tampere, , Finland

Turku, , Finland

Aachen, , Germany

Aalen, , Germany

Altötting, , Germany

Alzey, , Germany

Annaberg-Buchholz, , Germany

Ansbach, , Germany

Arnstadt, , Germany

Aschersleben, , Germany

Augsburg, , Germany

Aurich, , Germany

Bad Bevensen, , Germany

Bad Ems, , Germany

Bad Homburg, , Germany

Bad König, , Germany

Bad Krozingen, , Germany

Bad Mergentheim, , Germany

Bad Nenndorf, , Germany

Bad Oeynhausen, , Germany

Bad Tölz, , Germany

Bassum, , Germany

Bergisch Gladbach, , Germany

Berlin, , Germany

Bernburg, , Germany

Betzdorf, , Germany

Biberach, , Germany

Bielefeld, , Germany

Bischofswerda, , Germany

Bonn, , Germany

Braunschweig, , Germany

Bremen, , Germany

Bremerhaven, , Germany

Coburg, , Germany

Cochem, , Germany

Coesfeld, , Germany

Cologne, , Germany

Cottbus, , Germany

Darmstadt, , Germany

Deggendorf, , Germany

Dillingen, , Germany

Dinkelsbühl, , Germany

Dormagen, , Germany

Düsseldorf, , Germany

Eberswalde, , Germany

Eisenach, , Germany

Elmshorn, , Germany

Elsenfeld, , Germany

Emmering, , Germany

Emsdetten, , Germany

Erftstadt, , Germany

Erfurt, , Germany

Erkelenz, , Germany

Essen, , Germany

Finsterwalde, , Germany

Flensburg, , Germany

Frankfurt, , Germany

Freiberg, , Germany

Freiburg im Breisgau, , Germany

Fürstenwalde, , Germany

Fürstenzell, , Germany

Fürth, , Germany

Gera, , Germany

Göppingen, , Germany

Greifswald, , Germany

Gütersloh, , Germany

Hagenow, , Germany

Halberstadt, , Germany

Hamburg, , Germany

Hamelin, , Germany

Hanover, , Germany

Haßfurt, , Germany

Heidenau, , Germany

Heilbronn, , Germany

Helmstedt, , Germany

Herford, , Germany

Herzberg, , Germany

Hilden, , Germany

Hildesheim, , Germany

Hoyerswerda, , Germany

Hürth, , Germany

Ibbenbueren, , Germany

Immenstadt im Allgäu, , Germany

Ingolstadt, , Germany

Jena, , Germany

Kaiserslautern, , Germany

Kamen, , Germany

Kelheim, , Germany

Kempten, , Germany

Kerpen, , Germany

Kiel, , Germany

Kleve, , Germany

Kronach, , Germany

Kulmbach, , Germany

Lahr, , Germany

Landshut, , Germany

Landstuhl, , Germany

Langenfeld, , Germany

Langenhagen, , Germany

Langenselbold, , Germany

Lehrte, , Germany

Leipzig, , Germany

Leverkusen, , Germany

Lichtenfels, , Germany

Lindau, , Germany

Linnich, , Germany

Lohr, , Germany

Lübeck, , Germany

Lüdenscheid, , Germany

Lüneburg, , Germany

Magdeburg, , Germany

Malente, , Germany

Mannheim, , Germany

Marburg, , Germany

Markkleeberg, , Germany

Marl, , Germany

Mayen, , Germany

Meiningen, , Germany

Moers, , Germany

Mönchengladbach, , Germany

Mühlhausen, , Germany

München, , Germany

Münster, , Germany

Neubrandenburg, , Germany

Neunkirchen, , Germany

Neuruppin, , Germany

Nuremberg, , Germany

Nürtingen, , Germany

Oberschleißheim, , Germany

Offenburg, , Germany

Olpe, , Germany

Passau, , Germany

Peine, , Germany

Pfaffenhofen, , Germany

Pforzheim, , Germany

Potsdam, , Germany

Quedlinburg, , Germany

Regensburg, , Germany

Remagen, , Germany

Rosenheim, , Germany

Rostock, , Germany

Rüsselsheim am Main, , Germany

Saarlouis, , Germany

Sachsen, , Germany

Saint Martin, , Germany

Saint Wendel, , Germany

Salzgitter, , Germany

Schönebeck, , Germany

Schwabach, , Germany

Schwedt, , Germany

Schweinfurt, , Germany

Schwerin, , Germany

Seehausen, , Germany

Seelow, , Germany

Siegen, , Germany

Sigmaringen, , Germany

Sindelfingen, , Germany

Singen, , Germany

Sinsheim, , Germany

Sonneberg, , Germany

Spremberg, , Germany

Stade, , Germany

Straubing, , Germany

Stuttgart, , Germany

Suhl, , Germany

Tangermünde, , Germany

Traunstein, , Germany

Uelzen, , Germany

Viersen, , Germany

Villingen-Schwenningen, , Germany

Waiblingen, , Germany

Waldshut-Tiengen, , Germany

Weinheim, , Germany

Weißenburg, , Germany

Weißenfels, , Germany

Weißwasser, , Germany

Wesseling, , Germany

Weyhausen, , Germany

Wiesbaden, , Germany

Wittenberg, , Germany

Wolfenbüttel, , Germany

Worms, , Germany

Wuppertal, , Germany

Würzburg, , Germany

Zirndorf, , Germany

Zwickau, , Germany

Alexandroupoli, , Greece

Athens, , Greece

Chalcis, , Greece

Didimoteicho, , Greece

Edessa, , Greece

Grevená, , Greece

Heraklion, , Greece

Ioannina, , Greece

Larissa, , Greece

Piraias, , Greece

Rhodes, , Greece

Serres, , Greece

Thessaloniki, , Greece

Thessalonikis, , Greece

Véroia, , Greece

Cork, , Ireland

Galway, , Ireland

's-Hertogenbosch, , Netherlands

Apeldoorn, , Netherlands

Rotterdam, , Netherlands

Weert, , Netherlands

Oslo, , Norway

Trondheim, , Norway

Tvnsberg, , Norway

Bialystok, , Poland

Bytom, , Poland

Chojnice, , Poland

Ciechanów, , Poland

Działdowo, , Poland

Gdansk, , Poland

Gdansk-Zaspa, , Poland

Koszalin, , Poland

Lodz, , Poland

Lublin, , Poland

Oława, , Poland

Poznan, , Poland

Proszowice, , Poland

Radomsko, , Poland

Rybnik, , Poland

Stalowa Wola, , Poland

Torun, , Poland

Warsaw, , Poland

Wroclaw, , Poland

Łomża, , Poland

Aveiro, , Portugal

Barcelos, , Portugal

Braga, , Portugal

Coimbra, , Portugal

Evora, , Portugal

Faro, , Portugal

Leiria, , Portugal

P-1100 Lisboa N/A, , Portugal

Portalegre, , Portugal

Porto, , Portugal

S. Joao Da Madeira, , Portugal

Setúbal, , Portugal

Viana do Castelo, , Portugal

Vila Nova de Gaia, , Portugal

Alcorcón, , Spain

Barcelona, , Spain

Burgos, , Spain

Castellon, , Spain

Girona, , Spain

Leganés, , Spain

León, , Spain

Madrid, , Spain

Manresa, , Spain

Marañón, , Spain

Mollet del Vallès, , Spain

Oviedo, , Spain

Palma de Mallorca, , Spain

Sabadell, , Spain

Santa Cruz de Tenerife, , Spain

Santander, , Spain

Teruel, , Spain

Valencia, , Spain

Valladolid, , Spain

Zaragoza, , Spain

Avesta, , Sweden

Bollnäs, , Sweden

Borås, , Sweden

Eksjö, , Sweden

Eskilstuna, , Sweden

Gällivare, , Sweden

Gävle, , Sweden

Gothenburg, , Sweden

Halmstad, , Sweden

Karlshamn, , Sweden

Karlskoga, , Sweden

Karlskrona, , Sweden

Köping, , Sweden

Linköping, , Sweden

Luleå, , Sweden

Malmo, , Sweden

Norrköping, , Sweden

Nyköping, , Sweden

Örebro, , Sweden

Örnsköldsvik, , Sweden

Östersund, , Sweden

Skellefteå, , Sweden

Skene, , Sweden

Skövde, , Sweden

Stockholm, , Sweden

Sundsvall, , Sweden

Trollhättan, , Sweden

Umeå, , Sweden

Uppsala, , Sweden

Varberg, , Sweden

Värnamo, , Sweden

Västerås, , Sweden

Västervik, , Sweden

Aarau, , Switzerland

Baden, , Switzerland

Bellinzona, , Switzerland

Chur, , Switzerland

Lausanne, , Switzerland

Nyon, , Switzerland

Schwyz, , Switzerland

Sierre, , Switzerland

Sion, , Switzerland

Wil, , Switzerland

Zurich, , Switzerland

Antrim, , United Kingdom

Basildon, , United Kingdom

Bradford, , United Kingdom

Brighton, , United Kingdom

Cambridge, , United Kingdom

Cardiff, , United Kingdom

Carshalton, , United Kingdom

Derby, , United Kingdom

Doncaster, , United Kingdom

Dundee, , United Kingdom

Edinburgh, , United Kingdom

Exeter, , United Kingdom

Great Yarmouth, , United Kingdom

Inverness, , United Kingdom

Kilmarnock, , United Kingdom

Leicester, , United Kingdom

London, , United Kingdom

Londonderry, , United Kingdom

Manchester, , United Kingdom

Merseyside, , United Kingdom

Merthyr Tydfil, , United Kingdom

Norwich, , United Kingdom

Nottingham, , United Kingdom

Oxford, , United Kingdom

Plymouth, , United Kingdom

Portsmouth, , United Kingdom

Reading, , United Kingdom

Sheffield, , United Kingdom

Shrewsbury, , United Kingdom

Stevenage, , United Kingdom

Suffolk, , United Kingdom

Countries

Australia; Belgium; Denmark; Finland; Germany; Greece; Ireland; Netherlands; Norway; Poland; Portugal; Spain; Sweden; Switzerland; United Kingdom

Related Links

http://filehosting.pharmacm.com/DownloadService.ashx?client=CTR_JNJ_6051&studyid=736&filename=CR011587_CSR.pdf

Prospective, Immunogenicity Surveillance Registry (PRIMS) to Estimate the Incidence of Erythropoietin Antibody-Mediated Pure Red Cell Aplasia Among Subjects With Chronic Renal Failure and Subcutaneous Exposure to Recombinant Erythropoietin Products

Other Identifiers

EPOANE4014

Identifier Type: OTHER

Identifier Source: secondary_id

001992-001

Identifier Type: OTHER

Identifier Source: secondary_id

CR011587

Identifier Type: -

Identifier Source: org_study_id