A Study of Subcutaneous Mircera Once Monthly in the Treatment of Anemia in Participants With Chronic Kidney Disease Not on Dialysis

An Open-label, Randomized, Multicenter, Parallel-group Study to Demonstrate Correction of Anemia Using Once Every 4 Weeks Subcutaneous Injections of RO0503821 in Patients With Chronic Kidney Disease Who Are Not on Dialysis

This study will compare the efficacy and safety of subcutaneous Mircera and subcutaneous darbepoetin in the treatment of renal anemia in participants with chronic kidney disease who are not on dialysis and not receiving erythropoiesis-stimulating agents (ESA). Participants will be randomized to receive either Mircera once every 4 weeks, at a starting dose of 1.2 micrograms/kilogram (mcg/kg), or darbepoetin alfa once weekly, at a starting dose of 0.45 mcg/kg (or once every two weeks, 0.75 mcg/kg). The anticipated time on study treatment is 3-12 months.

Study Overview

• Status: Completed
• Conditions: Renal Anemia, Chronic
• Intervention / Treatment: Drug: Methoxy polyethylene glycol-epoetin beta; Drug: Darbepoetin alfa

• Study Type: Interventional
• Enrollment (Actual): 307
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • Adelaide, Australia, 5011
  • Clayton, Australia, 3186
  • Gosford, Australia, 2250
  • Parkville, Australia, 3052
  • Reservoir, Australia, 3073
• Belgium
  • Aalst, Belgium, 9300
  • Roeselare, Belgium, 8800
• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 2B7
  • Ontario
    • London, Ontario, Canada, N6A 5A5
    • Toronto, Ontario, Canada, M4N 3M5
  • Quebec
    • Montreal, Quebec, Canada, H1T 2M4
• France
  • Cahors, France, 46005
  • Clermont-ferrand, France, 63000
  • Limoges, France, 87042
  • Lyon, France, 69437
  • Nice, France, 06002
  • Paris, France, 75651
• Germany
  • Berlin, Germany, 13353
  • Bonn, Germany, 53127
  • Heilbronn, Germany, 74076
  • Homburg/saar, Germany, 66424
• Greece
  • Alexandroupolis, Greece, 68100
  • Larissa, Greece, 41 110
  • Thessaloniki, Greece, 54636
  • Volos, Greece, 38222
• Hong Kong
  • Hong Kong, Hong Kong
• Hungary
  • Baja, Hungary, 6500
  • Budapest, Hungary, 1071
  • Esztergom, Hungary, 2500
  • Hatvan, Hungary, 3000
  • Szigetvar, Hungary, 7390
• Israel
  • Haifa, Israel, 34362
  • Kfar Saba, Israel, 44281
  • Petach Tikva, Israel, 49100
• Italy
  • Como, Italy, 22100
  • Lecco, Italy, 23900
  • Lodi, Italy, 26900
  • Mestre, Italy, 30174
  • Modena, Italy, 41100
  • Pavia, Italy, 27100
• Korea, Republic of
  • Seoul, Korea, Republic of
  • Seoul, Korea, Republic of, 120-752
  • Seoul, Korea, Republic of, 133-792
• Poland
  • Gdansk, Poland, 80-211
  • Katowice, Poland, 40-027
  • Krakow, Poland, 31-501
  • Lodz, Poland, 90-153
  • Radom, Poland, 26-610
  • Rzeszow, Poland, 35-055
  • Sieradz, Poland, 98-200
  • Szczecin, Poland, 70-111
  • Warszawa, Poland, 02-006
  • Wroclaw, Poland, 50-417
• Russian Federation
  • Moscow, Russian Federation, 125101
  • Moscow, Russian Federation, 129110
  • Moscow, Russian Federation, 117036
  • Saratov, Russian Federation, 410053
  • St Petersburg, Russian Federation, 195067
  • St Petersburg, Russian Federation, 197089
  • St Petersburg, Russian Federation, 191015
  • St Petersburg, Russian Federation, 197110
• Spain
  • Barcelona, Spain, 08907
  • Barcelona, Spain, 08025
  • Madrid, Spain, 28046
  • Madrid, Spain, 28922
  • Palma de Mallorca, Spain, 07014
  • Sevilla, Spain, 41013
  • Sevilla, Spain, 41009
  • Valencia, Spain, 46017
• Taiwan
  • Taichung, Taiwan, 407
  • Taipei, Taiwan, 100
• Thailand
  • Bangkok, Thailand
  • Bangkok, Thailand, 10400
  • Bangkok, Thailand, 10700
  • Nakhon Ratchasima, Thailand, 30000
  • Pathumthani, Thailand, 12120

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Participants with chronic kidney disease (CKD) stage 3 (creatinine clearance [CrCl]/ glomerular filtration rate [GFR] 30 to 59 milliliter per minutes per 1.73 meter square [mL/min/1.73m^2]) or Stage 4 (CrCl/GFR 15-29 mL/min/1.73m^2) who did not require dialysis. CrCl/GFR was estimated with the Cockcroft-Gault equation or the abbreviated Modification of Diet in Renal Disease (MDRD) equation
• Anemia defined as baseline Hb concentration less than (<) 10.5 gram per deciliter (g/dL)

Exclusion Criteria:

• Previous therapy with any ESA within 12 weeks prior to screening
• Renal allograft in place
• Immunosuppressive therapy in the 12 weeks prior to screening
• Overt gastrointestinal bleeding and red blood cells (RBC) transfusions within 8 weeks before screening

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Mircera; Participants will receive Mircera (Methoxy polyethylene glycol-epoetin beta), administered subcutaneously (SC) at a starting dose of 1.2 mcg/kg once every 4 weeks for 28 weeks.	Drug: Methoxy polyethylene glycol-epoetin beta; 1.2 mcg/kg SC monthly, starting dose; Other Names: Mircera; RO0503821
Active Comparator: Darbepoetin Alfa; Participants will receive darbepoetin alfa, administered SC once weekly or once every 2 weeks according to local labeling specifications for 28 weeks.	Drug: Darbepoetin alfa; 0.45 mcg/kg SC weekly or 0.75 mcg/kg every 2 weeks, starting dose

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Hemoglobin (Hb) Response	Hb response was an observed increase in Hb greater than or equal to (>=) 1.0 gram per deciliter (g/dL) from baseline and an Hb concentration >= 10.0 g/dL before the end of the study without red blood cells (RBC) transfusion before response.	Baseline up to Week 28
Change in Hemoglobin (Hb) Concentration Between Baseline and Evaluation Period	A time adjusted average baseline Hb concentration was calculated using the trapezoid rule from all available Hb measurements taken during the baseline period. The average evaluation period Hb concentration for each individual was calculated using the same method, from all their available measurements taken during the 2 month evaluation period (Week 21 to 28). The change in Hb concentration between the baseline and evaluation period was calculated by subtracting the baseline Hb from the evaluation period Hb. All blood samples for Hb measurements were taken prior to study drug administration.	Baseline (measurements at Week -2, Week -1 and Day 1) and Evaluation Period (Week 22, Week 24, Week 26, Week 28)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hemoglobin (Hb) Concentration Over the Time	The hemoglobin concentration was measured in g/dL every 2 weeks and at final visit.	Baseline, Weeks 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, and final visit (Week 29)
Time to Hemoglobin Response	Time to Hb response is defined as the number of study days until the first occurrence of an Hb response. Participants without events were censored at the time of evaluation. Median and 95 percent (%) confidence interval (CI) were estimated using Kaplan-Meier Survival Analysis. Hb response was an observed increase in Hb >=1.0 g/dL from baseline and an Hb concentration >= 10.0 g/dL before the end of the study without RBC transfusion before response.	Baseline up to Week 28
Percentage of Participants With Red Blood Cell (RBC) Transfusions	The percentage of participants who received RBC transfusions during the titration and evaluation periods were reported.	Baseline up to Week 28
Percentage of Participants Who Had at Least 1 Hemoglobin Value Exceeding 12.0 g/dL	Percentage of participants having at least one Hb value greater than (>) 12 g/dL during the first 8 weeks of the study was reported.	Baseline to Week 8
Percentage of Participants With Stable Hemoglobin Response	A participant was defined as having achieved a stable Hb response, if at least 75 percent (%) of the scheduled Hb values were between 10.0 g/dL and 12.0 g/dL and >=1.0 g/dL from baseline for any 8-week time period, regardless of the requirement for dose adjustment for Hb maintenance. Achievement of stable response was determined using a moving 8-week time window, moving forward by 14 days in each iteration starting at Day 15, searching to see if the following conditions were met: 1) At least 3 scheduled Hb values (75% of the scheduled Hb values) in any 8-week time window were >=1.0 g/dL from baseline (as calculated above) and within the range of 10.0 g/dL to 12.0 g/dL. 2). There were at least 3 recorded Hb values within the time window.	Baseline to Week 28
Percentage of Participants Who Required Dose Adjustments to Achieve a Stabilized Response	The total number of dose adjustments needed to achieve stabilized response was calculated from Day 1 until the first 8-week time window in which response was achieved. A participant was defined as having achieved a stable Hb response, if at least 75% of the scheduled Hb values were between 10.0 g/dL and 12.0 g/dL and >=1.0 g/dL from baseline for any 8-week time period, regardless of the requirement for dose adjustment for Hb maintenance. Achievement of stable response was determined using a moving 8-week time window, moving forward by 14 days in each iteration starting at Day 15, searching to see if the following conditions were met: 1) At least 3 scheduled Hb values (75% of the scheduled Hb values) in any 8-week time window were >=1.0 g/dL from baseline (as calculated above) and within the range of 10.0 g/dL to 12.0 g/dL. 2) There were at least 3 recorded Hb values within the time window.	Baseline to Week 28

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche

Study record dates

Study Major Dates

• Study Start: December 1, 2007
• Primary Completion (Actual): October 1, 2009
• Study Completion (Actual): October 1, 2009

Study Registration Dates

• First Submitted: November 15, 2007
• First Submitted That Met QC Criteria: November 15, 2007
• First Posted (Estimate): November 16, 2007

Study Record Updates

• Last Update Posted (Estimate): November 1, 2016
• Last Update Submitted That Met QC Criteria: September 13, 2016
• Last Verified: September 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urologic Diseases; Hematologic Diseases; Renal Insufficiency; Kidney Diseases; Renal Insufficiency, Chronic; Anemia; Hematinics; Darbepoetin alfa
• Other Study ID Numbers: NH20052