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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT00559273
First received: November 15, 2007
Last updated: September 13, 2016
Last verified: September 2016
  Purpose
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.

Condition Intervention Phase
Renal Anemia, Chronic
Drug: Methoxy polyethylene glycol-epoetin beta
Drug: Darbepoetin alfa
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • Percentage of Participants With Hemoglobin (Hb) Response [ Time Frame: Baseline up to Week 28 ] [ Designated as safety issue: No ]
    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.

  • Change in Hemoglobin (Hb) Concentration Between Baseline and Evaluation Period [ Time Frame: Baseline (measurements at Week -2, Week -1 and Day 1) and Evaluation Period (Week 22, Week 24, Week 26, Week 28) ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Hemoglobin (Hb) Concentration Over the Time [ Time Frame: Baseline, Weeks 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, and final visit (Week 29) ] [ Designated as safety issue: No ]
    The hemoglobin concentration was measured in g/dL every 2 weeks and at final visit.

  • Time to Hemoglobin Response [ Time Frame: Baseline up to Week 28 ] [ Designated as safety issue: No ]
    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.

  • Percentage of Participants With Red Blood Cell (RBC) Transfusions [ Time Frame: Baseline up to Week 28 ] [ Designated as safety issue: No ]
    The percentage of participants who received RBC transfusions during the titration and evaluation periods were reported.

  • Percentage of Participants Who Had at Least 1 Hemoglobin Value Exceeding 12.0 g/dL [ Time Frame: Baseline to Week 8 ] [ Designated as safety issue: No ]
    Percentage of participants having at least one Hb value greater than (>) 12 g/dL during the first 8 weeks of the study was reported.

  • Percentage of Participants With Stable Hemoglobin Response [ Time Frame: Baseline to Week 28 ] [ Designated as safety issue: No ]
    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.

  • Percentage of Participants Who Required Dose Adjustments to Achieve a Stabilized Response [ Time Frame: Baseline to Week 28 ] [ Designated as safety issue: No ]
    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.


Enrollment: 307
Study Start Date: December 2007
Study Completion Date: October 2009
Primary Completion Date: October 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

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

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
  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: NCT00559273

  Show 76 Study Locations
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Study Director: Clinical Trials Hoffmann-La Roche
  More Information

Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT00559273     History of Changes
Other Study ID Numbers: NH20052 
Study First Received: November 15, 2007
Results First Received: September 13, 2016
Last Updated: September 13, 2016
Health Authority: USA: WIRB

Additional relevant MeSH terms:
Anemia
Kidney Diseases
Renal Insufficiency, Chronic
Hematologic Diseases
Urologic Diseases
Renal Insufficiency
Epoetin Alfa
Darbepoetin alfa
Hematinics

ClinicalTrials.gov processed this record on December 09, 2016