A Study of Methoxy Polyethylene Glycol-epoetin Beta (Mircera) in Participants With Chronic Kidney Disease (PRIMAVERA)

Phase 2

Completed

• Conditions: Kidney Disease, Chronic
• Interventions: Drug: Placebo; Drug: Methoxy polyethylene glycol-epoetin beta

• Registration Number: NCT01194154
• Lead Sponsor: Hoffmann-La Roche

Brief Summary

This randomized, single-blind, proof-of-concept study will investigate the protective effects of early treatment with Mircera in participants with chronic kidney disease on renal disease progression. Participants will be randomly assigned to receive 30 microgram (mcg) Mircera as subcutaneous injection once monthly or matching placebo. Depending on change of hemoglobin values, the dose of Mircera can be adjusted to 50 mcg or 75 mcg once monthly. The anticipated time on study treatment is 24 months.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2010-08-25
• Study First Submitted QC: 2010-09-01
• Study First Posted: 2010-09-02
• Study Start: 2010-09-30
• Primary Completion: 2015-03-31
• Study Completion: 2015-03-31
• Results First Submitted: 2016-03-16
• Results First Submitted QC: 2016-05-05
• Results First Posted: 2016-06-14
• Status Verified: 2017-04
• Last Update Submitted: 2017-04-03
• Last Update Posted: 2017-05-10

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 241

Inclusion Criteria

• For diabetic participants: Type 2 diabetes mellitus with glycated hemoglobin (HbA1c) greater than (>) 7% or anti-diabetic treatment
• For renal allograft recipients: Status at least 6 months post transplantation
• Chronic kidney disease stage III
• Urinary albumin-to-creatinine ratio less than (<) 3000 milligram (mg)/gram (g) or total protein <3000 mg/ 24 hour urine sample where applicable

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Exclusion Criteria

• Hemoglobin-level < 11 or > 14 g/deciliter (dL)
• Average systolic blood pressure (SBP) > 140 millimeter of mercury (mm Hg) or average diastolic blood pressure (DBP) > 90 mm Hg
• Initiation of angiotensin converting enzyme inhibitor, angiotensin 2 receptor blocker or aliskiren treatment less than 3 months before enrolment
• Present and known iron deficiency
• HbA1c >9%

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	-
Mircera	Methoxy polyethylene glycol-epoetin beta	-

Primary Outcome Measures

Name	Time	Method
Yearly Reduction Rate of Estimated Glomerular Filtration Rate (eGFR) Calculated by Modification of Diet in Renal Disease With 4 Variables (MDRD-4)	24 months	The yearly reduction in eGFR was calculated using the MDRD-4 formula. This formula is based on age, sex, and serum creatinine and eGFR values are calculated as follows: GFR in milliliter per minute (mL/min) per 1.73 meter square (m\^2) = 175 x Serum Cr\^-1.154 x age\^-0.203 x 0.742 (if female). The yearly reduction rate (mL/min/1.73m\^2 / Year) is defined as -365.25 multiplied by Beta, where Beta is the slope parameter derived for each participants separately by simple linear regression of the change from baseline in participant's eGFR measurements (from Baseline to Visit 24) on the actual day of measurement.

Secondary Outcome Measures

Name	Time	Method
Change From Baseline in Urinary Albumin Creatinine Ratio (UACR) at Month 24	Baseline, Month 24	UACR is defined as the ratio: milligram of albumin per gram of creatinine. The presence of albumin in the urine (macroalbuminuria) is a marker of kidney disease. Albumin and creatinine concentrations were obtained from spot urine samples.
Change From Baseline in Serum Cystatin C Concentration at Month 24	Baseline, Month 24	Cystatin C is a protein which is mainly used as a biomarker of kidney function. If kidney function and GFR decline, the blood levels of cystatin C rise.
Yearly Reduction Rate of Estimated Glomerular Filtration Rate (eGFR) Calculated by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)	24 months	The eGFR value calculated using the CKD-EPI equation. The formula used is based on age, sex, ethnicity, and serum creatinine and eGFR values are calculated as follows: GFR in mL/min per 1.73 m\^2 = 141 x min (SerumCr/k; 1)\^a x max(SerumCr/k; 1)\^(-1.209) x 0.993\^age x F x B, where k=0.7 for female (else=0.9); a=-0.329 for female (else=-0.411), F=1.018 for female (else=1), B=1.159 for black (else=1), min/max=minimum/maximum of listed values. The Yearly Reduction Rate (mL/min/1.73m\^2 / Year) is defined as -365.25 x Beta, where Beta is the slope parameter derived for each participant separately by simple linear regression of the change from baseline in participant's eGFR measurements (from Baseline to Visit 24) on the actual day of measurement.
Change From Baseline in Calculated Creatinine Clearance (Cockcroft-Gault Equation) at Month 24	Baseline, Month 24	Creatinine clearance was calculated according to the Cockcroft and Gault Formula. It measures rate creatinine (substance formed from metabolism of creatine) is cleared from blood by kidneys. Normal adult creatinine clearance is greater than or equal to (\>=) 90 mL/min. Change from baseline=CC at Week X minus CC at baseline where higher scores represented improved renal function.
Change From Baseline in Serum Creatinine Concentration at Month 24	Baseline, Month 24	Serum creatinine is an indicator of kidney function. Creatinine is a substance formed from the metabolism of creatine, commonly found in blood, urine, and muscle tissue. It is removed from the blood by the kidneys and excreted in urine. Normal adult blood levels of creatinine=45 to 90 micromoles per liter (mcmol/L) for females, 60 to 110 mcmol/L for males, however normal values are age-dependent.
Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)	24 months	An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability or incapacity; and congenital anomaly. Percentage of participants with AEs included participants affected with both SAEs and non-SAEs.

Trial Locations

Locations (33)

Klinikum d.Universität München Campus Großhadern; 🇩🇪 München, Germany

Nierenzentrum Bogenhausen/Perlach; Praxis für Nierenheilkunde; 🇩🇪 München-Bogenhausen, Germany

Charité - Klinikum Mitte; Medizinische Klinik Für Nephrologie; 🇩🇪 Berlin, Germany

Uniklinik RWTH Aachen; Med. Klinik II; Klinik für Nephrologie und klinische Immunologie; 🇩🇪 Aachen, Germany

Dialysepraxis Dr. Stallforth, Dr. Kirschner, Dr. Al-Sarraf und Dr. Pawlik; 🇩🇪 Augsburg, Germany

Gemeinschaftspraxis Dres. Erika Eger, Frank Seibt, Oliver Eike u.w. - Dialysezentrum Treptower Park; 🇩🇪 Berlin, Germany

KfH Kuratorium für Dialyse und Nierentransplantation e.V. im Kurhaus; 🇩🇪 Bad König, Germany

Charité - Campus Benjamin Franklin; Zentrum fuer Innere Medizin, Med. Klinik I; 🇩🇪 Berlin, Germany

DaVita Clinical Research Deutschland GmbH; 🇩🇪 Düsseldorf, Germany

Universitätsklinikum "Carl Gustav Carus"; Medizinische Klinik III; 🇩🇪 Dresden, Germany

Uniklinikum Heidelberg; 🇩🇪 Heidelberg, Germany

Dialyse-Institut Bovenden; 🇩🇪 Bovenden, Germany

Universitätsklinikum Essen Zentrum f.Innere Medizin Abt.Nephrologie; 🇩🇪 Essen, Germany

Klinik Johann Wolfgang von Goethe Uni; Zentrum der Inneren Medizin; Medizinische Klinik III; 🇩🇪 Frankfurt, Germany

Dialysepraxis Prof.Dr.med. Michael Rambausek Dres. Stephan Matthias und Gabriele Kunowski - Dialysz.; 🇩🇪 Heilbronn, Germany

Nephrologisches Zentrum Hilden am St. Josefs-Krankenhaus; 🇩🇪 Hilden, Germany

Universitaetsklinikum des Saarlandes; Klinik f. Innere Medizin IV; 🇩🇪 Homburg/Saar, Germany

Dres. Jan Nawka und Frank Pistrosch; 🇩🇪 Hoyerswerda, Germany

Westpfalz-Klinikum Gmbh; Nephrologie/Transplantationsmedizin; 🇩🇪 Kaiserslautern, Germany

PHV Patienten-Heimversorgung Dialyse-Station; 🇩🇪 Kiel, Germany

Kliniken der Stadt Köln gGmbH Krankenhaus Merheim; 🇩🇪 Köln, Germany

Gemienschaftspraxis Dres. Leistikow, Rachti & Sandner; 🇩🇪 Mannheim, Germany

Universitätsklinikum Schleswig-Holstein / Campus Lübeck, Med. Klinik I, Transplantationszentrum; 🇩🇪 Lübeck, Germany

Klinikum Innenstadt Medizinische Klinik; Abt.Endokrinologie und Diabetologie; 🇩🇪 Muenchen, Germany

Dres. Michael Koch Hannelore Klimke Wolfgang Kulas u.w.; 🇩🇪 Mettmann, Germany

Universitätsklinikum Münster Innere Medizin D; 🇩🇪 Münster, Germany

Dres. Georg Fuchs und Nexhat Miftari; 🇩🇪 Neckarsulm, Germany

Nephrologische Praxis Neunkirchen - Dr.med. Klemens Dorr und Artem Goldmann; 🇩🇪 Neunkirchen/Saar, Germany

Dialysezentrum Saarlouis; 🇩🇪 Saarlouis, Germany

Gemeinschaftspraxis Rosemarie Krämer und Lars Rothermund; 🇩🇪 Ulm, Germany

Nephrologisches Zentrum; 🇩🇪 Velbert, Germany

Nephrologisches Zentrum Dialyse-Institut; 🇩🇪 Villingen-Schwenningen, Germany

KfH Kuratiorium für Dialyse und Nierentransplantation e.V.; 🇩🇪 Wiesbaden, Germany