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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT01194154
First received: August 25, 2010
Last updated: May 5, 2016
Last verified: May 2016
  Purpose
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.

Condition Intervention Phase
Kidney Disease, Chronic
Drug: Methoxy polyethylene glycol-epoetin beta
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Subject)
Primary Purpose: Treatment
Official Title: A Randomized Controlled, Single-blind, Proof-of-concept-study to Investigate the Protective Effects of Early Treatment With C.E.R.A. in Patients With Chronic Kidney Disease on Renal Disease Progression (PRIMAVERA-Study)

Resource links provided by NLM:


Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • Yearly Reduction Rate of Estimated Glomerular Filtration Rate (eGFR) Calculated by Modification of Diet in Renal Disease With 4 Variables (MDRD-4) [ Time Frame: 24 months ] [ Designated as safety issue: No ]
    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:
  • Yearly Reduction Rate of Estimated Glomerular Filtration Rate (eGFR) Calculated by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) [ Time Frame: 24 months ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline, Month 24 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline, Month 24 ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline in Urinary Albumin Creatinine Ratio (UACR) at Month 24 [ Time Frame: Baseline, Month 24 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline, Month 24 ] [ Designated as safety issue: No ]
    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.

  • Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: 24 months ] [ Designated as safety issue: Yes ]
    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.


Enrollment: 241
Study Start Date: September 2010
Study Completion Date: March 2015
Primary Completion Date: March 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Mircera Drug: Methoxy polyethylene glycol-epoetin beta
Methoxy polyethylene glycol-epoetin beta 30 microgram (mcg) subcutaneous injection once monthly up to 24 months with sequential dose adjustments to 50 mcg or 75 mcg depending on change of hemoglobin values of more than 1.0 gram (g)/ deciliter (dL).
Other Name: Mircera, C.E.R.A.
Placebo Comparator: Placebo Drug: Placebo
Placebo matching to Methoxy polyethylene glycol-epoetin beta subcutaneous injection once monthly up to 24 months.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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

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%
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01194154

Locations
Germany
Aachen, Germany, 52057
Augsburg, Germany, 86157
Bad König, Germany, 64732
Berlin, Germany, 10117
Berlin, Germany, 12203
Berlin, Germany, 12435
Bovenden, Germany, 37120
Dresden, Germany, 01307
Düsseldorf, Germany, 40210
Essen, Germany, 45122
Frankfurt, Germany, 60596
Heidelberg, Germany, 69120
Heilbronn, Germany, 74076
Hilden, Germany, 40724
Homburg/Saar, Germany, 66424
Hoyerswerda, Germany, 02977
Kaiserslautern, Germany, 67655
Kiel, Germany, 24106
Köln, Germany, 51109
Lübeck, Germany, 23562
Mannheim, Germany, 68309
Mettmann, Germany, 40822
Muenchen, Germany, 80336
München, Germany, 81377
München-Bogenhausen, Germany, 81925
Münster, Germany, 48149
Neckarsulm, Germany, 74172
Neunkirchen/Saar, Germany, 66538
Saarlouis, Germany, 66740
Ulm, Germany, 89077
Velbert, Germany, 42549
Villingen-Schwenningen, Germany, 78052
Wiesbaden, Germany, 65191
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Study Director: Clinical Trials Hoffmann-La Roche
  More Information

Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT01194154     History of Changes
Other Study ID Numbers: ML22916  2009-015114-22 
Study First Received: August 25, 2010
Results First Received: March 16, 2016
Last Updated: May 5, 2016
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

Additional relevant MeSH terms:
Kidney Diseases
Renal Insufficiency, Chronic
Chronic Disease
Urologic Diseases
Renal Insufficiency
Disease Attributes
Pathologic Processes
Epoetin Alfa
Hematinics

ClinicalTrials.gov processed this record on July 24, 2016