Back to resultsA Study of Mircera in Anemic Patients With Chronic Kidney Disease Not Yet on Dialysis.
Primary Purpose
Anemia
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
methoxy polyethylene glycol-epoetin beta [Mircera]
Sponsored by
About this trial
This is an interventional treatment trial for Anemia
Eligibility Criteria
Inclusion Criteria: adult patients >=18 years of age; chronic renal anemia; not receiving renal replacement therapy. Exclusion Criteria: women who are pregnant, breastfeeding or using unreliable birth control methods; administration of any investigational drug within 30 days preceding the screening visit and during the run-in period.
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm 6
Arm 7
Arm 8
Arm 9
Arm Type
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Arm Label
Cohort 1 (RO0503821, 0.15 mcg/kg 1x/Week)
Cohort 2 (RO0503821, 0.3 mcg/kg 1x/Week)
Cohort 3 (RO0503821, 0.6 mcg/kg 1x/Week)
Cohort 4 (RO0503821, 0.3 mcg/kg 1x/2 Week)
Cohort 5 (RO0503821, 0.6 mcg/kg 1x/2Week)
Cohort 6 (RO0503821, 1.2 mcg/kg 1x/2 Week)
Cohort 7 (RO0503821, 0.45 mcg/kg 1x/3 Week)
Cohort 8 (RO0503821, 0.9 mcg/kg 1x/3Week)
Cohort 9 (RO0503821,1.8 mcg/kg 1x/3 Week)
Arm Description
Eligible participants will be receiving RO0503821 (methoxy polyethylene glycol-epoetin beta [Mircera]) at a dose of 0.15 microgram per kilogram (mcg/kg) subcutaneously (SC) once every week to complete the dosage of 0.9 mcg/kg up to 6 weeks (Week 1 to Week 6). Participants will be followed-up for one week post the treatment period. During extension Years 1 and 2, the participants will remain at the same frequency of administration as that of core treatment period.
Eligible participants will be receiving RO0503821 at a dose of 0.3 mcg/kg SC once every week to complete the dosage of 1.8 mcg/kg up to 6 weeks (Week 7 to Week 12). Participants will be followed-up for one week post the treatment period. During extension Years 1 and 2, the participants will remain at the same frequency of administration as that of core treatment period.
Eligible participants will be receiving RO0503821 at a dose of 0.6 mcg/kg SC once every week, to complete the dosage of 3.6 mcg/kg up to 6 weeks (Week 13 to Week 18). Participants will be followed-up for one week post the treatment period. During extension Years 1 and 2, the participants will remain at the same frequency of administration as that of core treatment period.
Eligible participants will be receiving RO0503821 at a dose of 0.3 mcg/kg SC once every two week, to complete the dosage of 0.9 mcg/kg up to 6 weeks (Week 1 to Week 6). Participants will be followed-up for one week post the treatment period. During extension Years 1 and 2, the participants will remain at the same frequency of administration as that of core treatment period.
Eligible participants will be receiving RO0503821 at a dose of 0.6 mcg/kg SC once every two week, to complete the dosage of 1.8 mcg/kg up to 6 weeks (Week 7 to Week 12). Participants will be followed-up for one week post the treatment period. During extension Years 1 and 2, the participants will remain at the same frequency of administration as that of core treatment period.
Eligible participants will be receiving RO0503821 at a dose of 1.2 mcg/kg SC once every two week, to complete the dosage of 3.6 mcg/kg up to 6 weeks (Week 13 to Week 18). Participants will be followed-up for one week post the treatment period. During extension Years 1 and 2, the participants will remain at the same frequency of administration as that of core treatment period.
Eligible participants will be receiving RO0503821 at a dose of 0.45 mcg/kg SC once every three week, to complete the dosage of 0.9 mcg/kg up to 6 weeks (Week 1 to Week 6). Participants will be followed-up for one week post the treatment period. During extension Years 1 and 2, the participants will remain at the same frequency of administration as that of core treatment period.
Eligible participants will be receiving RO0503821 at a dose of 0.9 mcg/kg SC once every three week, to complete the dosage of 1.8 mcg/kg up to 6 weeks (Week 7 to Week 12). Participants will be followed-up for one week post the treatment period. During extension Years 1 and 2, the participants will remain at the same frequency of administration as that of core treatment period.
Eligible participants will be receiving RO0503821 at a dose of 1.8 mcg/kg SC once every three week, to complete the dosage of 3.6 mcg/kg up to 6 weeks (Week 13 to Week 18). Participants will be followed-up for one week post the treatment period. During extension Years 1 and 2, the participants will remain at the same frequency of administration as that of core treatment period.
Outcomes
Primary Outcome Measures
The Change in Hemoglobin Over Time Between Baseline and End of Initial Treatment Based on Individual Regression Slopes
The primary efficacy variable was blood Hb level and its changes from Baseline (defined as the mean Hb of Screening assessment (SA) (Week -3), Weeks -2 and -1 of the Run-in period) over time during the core treatment period. For each participant, the primary efficacy parameter was the change in hemoglobin level over time based on regression slopes. All values until end-of-initial treatment (EOIT), defined as the last observed value before a dose change or blood transfusion, were included in the calculation of this endpoint. For participants without any dose adjustments, the EOIT value was identical to the value for Week 19.
Secondary Outcome Measures
Hematocrit Levels at End of Initial Treatment Under Constant Dosing Regimen
Hematocrit (Hct) levels at end of initial treatment under constant dosing regimen were reported. Baseline (Day -28 to Day 1) Hct values was calculated as the mean of the SA (Week -3) and Run-in period (Weeks -2 and -1). For all participants, an EOIT value was calculated as the last observed Hct value before a dose change or blood transfusion. For participants without any dose adjustments, the EOIT value was identical to the value for Week 19.
Reticulocyte Count at End of Initial Treatment Under Constant Dosing Regimen
Reticulocyte levels at EOIT under constant dosing regimen was analysed and reported. Baseline (Day -28 to Day 1) reticulocyte values were calculated as the mean of the SA (Week -3) and Run-in period (Weeks -2 and -1). For all participants, an EOIT value was calculated as the last observed reticulocyte count before a dose change or blood transfusion. For participants without any dose adjustments, the EOIT value was identical to the value for Week 19.
Number of Participants With Any Serious Adverse Events and Any Adverse Events
An Adverse Events (AEs) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Serious Adverse Events (SAEs) is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or is a significant medical event in the investigator's judgment or requires intervention to prevent one or other of these outcomes. The study design tested 3 different starting dose conversion factors at 3 different dosing schedules during the core study period. As study drug doses can be modified continually over time all results for the two long term safety periods were displayed by dose schedule group only.
Number of Participants With Marked Laboratory Abnormalities for Blood Chemistry and Electrolytes Over Time
Marked abnormality was defined as above and/or below a value (according to the Roche specified limits) which was considered to be potentially clinically relevant. The Roche reference range are: white blood cells (WBC) (3.0-18.0 10^9 cells/L), platelets (100-550 10^9 cells/L), alanine aminotransferase (ALT) [0-110 units per litre (U/L)], alkaline phosphatase (ALP) (0-220 U/L), aspartate aminotransferase (AST) (0-80 U/L), albumin >= 30 g/L, phosphate [0.75 - 1.60 millimoles per liter (mmol/L)], potassium (2.9 - 5.8 mmol/L), total bilirubin (0-17 µmol/L), lymphocytes (1- 4.80 10^9 cells/L), eosinophils (0 - 0.45 10^9 cells/L), monocytes (0 - 0.8 10^9 cells/L), and neutrophils (1.80 - 7.70 10^9 cells/L). The study design tested 3 different starting dose conversion factors at 3 different dosing schedules during the core study period. As study drug doses can be modified continually over time, all results for the two long term safety periods were displayed by dose schedule group only.
Heart Rate Over Time
Heart rate was defined as the measure of heart beats per minute (bpm). The study design tested 3 different starting dose conversion factors at 3 different dosing schedules during the core study period. As study drug doses can be modified continually over time all results for the two long term safety periods were displayed by dose schedule group only.
Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure
Change from Baseline in systolic blood pressure (SBP) and diastolic blood pressure (DBP) is calculated as the end of treatment values minus the Baseline value. Baseline (Day -28 to Day 1) values were calculated as the mean of the SA (Week -3) and Run-in period (Week -2 and Week -1).
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00048048
Brief Title
A Study of Mircera in Anemic Patients With Chronic Kidney Disease Not Yet on Dialysis.
Official Title
An Open-label, Randomized, Multi-centre, Multiple Dose Trial to Investigate the Efficacy and Safety of Subcutaneous Injections of RO0503821 at Different Dosing Intervals in Patients With Chronic Renal Anemia Who Are Not on Renal Replacement Therapy
Study Type
Interventional
2. Study Status
Record Verification Date
May 2017
Overall Recruitment Status
Completed
Study Start Date
March 2002 (undefined)
Primary Completion Date
October 2003 (Actual)
Study Completion Date
November 2004 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hoffmann-La Roche
4. Oversight
5. Study Description
Brief Summary
This study will evaluate the efficacy and safety of different subcutaneous starting doses and dosing frequencies of Mircera in anemic patients with chronic kidney disease not yet on dialysis. The anticipated time on study treatment is 3-12 months and the target sample size is <100 individuals.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Anemia
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
65 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Cohort 1 (RO0503821, 0.15 mcg/kg 1x/Week)
Arm Type
Experimental
Arm Description
Eligible participants will be receiving RO0503821 (methoxy polyethylene glycol-epoetin beta [Mircera]) at a dose of 0.15 microgram per kilogram (mcg/kg) subcutaneously (SC) once every week to complete the dosage of 0.9 mcg/kg up to 6 weeks (Week 1 to Week 6). Participants will be followed-up for one week post the treatment period. During extension Years 1 and 2, the participants will remain at the same frequency of administration as that of core treatment period.
Arm Title
Cohort 2 (RO0503821, 0.3 mcg/kg 1x/Week)
Arm Type
Experimental
Arm Description
Eligible participants will be receiving RO0503821 at a dose of 0.3 mcg/kg SC once every week to complete the dosage of 1.8 mcg/kg up to 6 weeks (Week 7 to Week 12). Participants will be followed-up for one week post the treatment period. During extension Years 1 and 2, the participants will remain at the same frequency of administration as that of core treatment period.
Arm Title
Cohort 3 (RO0503821, 0.6 mcg/kg 1x/Week)
Arm Type
Experimental
Arm Description
Eligible participants will be receiving RO0503821 at a dose of 0.6 mcg/kg SC once every week, to complete the dosage of 3.6 mcg/kg up to 6 weeks (Week 13 to Week 18). Participants will be followed-up for one week post the treatment period. During extension Years 1 and 2, the participants will remain at the same frequency of administration as that of core treatment period.
Arm Title
Cohort 4 (RO0503821, 0.3 mcg/kg 1x/2 Week)
Arm Type
Experimental
Arm Description
Eligible participants will be receiving RO0503821 at a dose of 0.3 mcg/kg SC once every two week, to complete the dosage of 0.9 mcg/kg up to 6 weeks (Week 1 to Week 6). Participants will be followed-up for one week post the treatment period. During extension Years 1 and 2, the participants will remain at the same frequency of administration as that of core treatment period.
Arm Title
Cohort 5 (RO0503821, 0.6 mcg/kg 1x/2Week)
Arm Type
Experimental
Arm Description
Eligible participants will be receiving RO0503821 at a dose of 0.6 mcg/kg SC once every two week, to complete the dosage of 1.8 mcg/kg up to 6 weeks (Week 7 to Week 12). Participants will be followed-up for one week post the treatment period. During extension Years 1 and 2, the participants will remain at the same frequency of administration as that of core treatment period.
Arm Title
Cohort 6 (RO0503821, 1.2 mcg/kg 1x/2 Week)
Arm Type
Experimental
Arm Description
Eligible participants will be receiving RO0503821 at a dose of 1.2 mcg/kg SC once every two week, to complete the dosage of 3.6 mcg/kg up to 6 weeks (Week 13 to Week 18). Participants will be followed-up for one week post the treatment period. During extension Years 1 and 2, the participants will remain at the same frequency of administration as that of core treatment period.
Arm Title
Cohort 7 (RO0503821, 0.45 mcg/kg 1x/3 Week)
Arm Type
Experimental
Arm Description
Eligible participants will be receiving RO0503821 at a dose of 0.45 mcg/kg SC once every three week, to complete the dosage of 0.9 mcg/kg up to 6 weeks (Week 1 to Week 6). Participants will be followed-up for one week post the treatment period. During extension Years 1 and 2, the participants will remain at the same frequency of administration as that of core treatment period.
Arm Title
Cohort 8 (RO0503821, 0.9 mcg/kg 1x/3Week)
Arm Type
Experimental
Arm Description
Eligible participants will be receiving RO0503821 at a dose of 0.9 mcg/kg SC once every three week, to complete the dosage of 1.8 mcg/kg up to 6 weeks (Week 7 to Week 12). Participants will be followed-up for one week post the treatment period. During extension Years 1 and 2, the participants will remain at the same frequency of administration as that of core treatment period.
Arm Title
Cohort 9 (RO0503821,1.8 mcg/kg 1x/3 Week)
Arm Type
Experimental
Arm Description
Eligible participants will be receiving RO0503821 at a dose of 1.8 mcg/kg SC once every three week, to complete the dosage of 3.6 mcg/kg up to 6 weeks (Week 13 to Week 18). Participants will be followed-up for one week post the treatment period. During extension Years 1 and 2, the participants will remain at the same frequency of administration as that of core treatment period.
Intervention Type
Drug
Intervention Name(s)
methoxy polyethylene glycol-epoetin beta [Mircera]
Intervention Description
Differing doses and frequencies of sc administration
Primary Outcome Measure Information:
Title
The Change in Hemoglobin Over Time Between Baseline and End of Initial Treatment Based on Individual Regression Slopes
Description
The primary efficacy variable was blood Hb level and its changes from Baseline (defined as the mean Hb of Screening assessment (SA) (Week -3), Weeks -2 and -1 of the Run-in period) over time during the core treatment period. For each participant, the primary efficacy parameter was the change in hemoglobin level over time based on regression slopes. All values until end-of-initial treatment (EOIT), defined as the last observed value before a dose change or blood transfusion, were included in the calculation of this endpoint. For participants without any dose adjustments, the EOIT value was identical to the value for Week 19.
Time Frame
From Baseline (Day -28 to Day 1) to EOIT (Week 19)
Secondary Outcome Measure Information:
Title
Hematocrit Levels at End of Initial Treatment Under Constant Dosing Regimen
Description
Hematocrit (Hct) levels at end of initial treatment under constant dosing regimen were reported. Baseline (Day -28 to Day 1) Hct values was calculated as the mean of the SA (Week -3) and Run-in period (Weeks -2 and -1). For all participants, an EOIT value was calculated as the last observed Hct value before a dose change or blood transfusion. For participants without any dose adjustments, the EOIT value was identical to the value for Week 19.
Time Frame
From Baseline (Day -28 to Day 1) to EOIT (Week 19)
Title
Reticulocyte Count at End of Initial Treatment Under Constant Dosing Regimen
Description
Reticulocyte levels at EOIT under constant dosing regimen was analysed and reported. Baseline (Day -28 to Day 1) reticulocyte values were calculated as the mean of the SA (Week -3) and Run-in period (Weeks -2 and -1). For all participants, an EOIT value was calculated as the last observed reticulocyte count before a dose change or blood transfusion. For participants without any dose adjustments, the EOIT value was identical to the value for Week 19.
Time Frame
From Baseline (Day -28 to Day 1) to EOIT (Week 19)
Title
Number of Participants With Any Serious Adverse Events and Any Adverse Events
Description
An Adverse Events (AEs) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Serious Adverse Events (SAEs) is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or is a significant medical event in the investigator's judgment or requires intervention to prevent one or other of these outcomes. The study design tested 3 different starting dose conversion factors at 3 different dosing schedules during the core study period. As study drug doses can be modified continually over time all results for the two long term safety periods were displayed by dose schedule group only.
Time Frame
Up to Week 125
Title
Number of Participants With Marked Laboratory Abnormalities for Blood Chemistry and Electrolytes Over Time
Description
Marked abnormality was defined as above and/or below a value (according to the Roche specified limits) which was considered to be potentially clinically relevant. The Roche reference range are: white blood cells (WBC) (3.0-18.0 10^9 cells/L), platelets (100-550 10^9 cells/L), alanine aminotransferase (ALT) [0-110 units per litre (U/L)], alkaline phosphatase (ALP) (0-220 U/L), aspartate aminotransferase (AST) (0-80 U/L), albumin >= 30 g/L, phosphate [0.75 - 1.60 millimoles per liter (mmol/L)], potassium (2.9 - 5.8 mmol/L), total bilirubin (0-17 µmol/L), lymphocytes (1- 4.80 10^9 cells/L), eosinophils (0 - 0.45 10^9 cells/L), monocytes (0 - 0.8 10^9 cells/L), and neutrophils (1.80 - 7.70 10^9 cells/L). The study design tested 3 different starting dose conversion factors at 3 different dosing schedules during the core study period. As study drug doses can be modified continually over time, all results for the two long term safety periods were displayed by dose schedule group only.
Time Frame
Up to Week 125
Title
Heart Rate Over Time
Description
Heart rate was defined as the measure of heart beats per minute (bpm). The study design tested 3 different starting dose conversion factors at 3 different dosing schedules during the core study period. As study drug doses can be modified continually over time all results for the two long term safety periods were displayed by dose schedule group only.
Time Frame
Up to Week 125
Title
Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure
Description
Change from Baseline in systolic blood pressure (SBP) and diastolic blood pressure (DBP) is calculated as the end of treatment values minus the Baseline value. Baseline (Day -28 to Day 1) values were calculated as the mean of the SA (Week -3) and Run-in period (Week -2 and Week -1).
Time Frame
From Baseline (Day -28 to Day 1) to Week 125
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
adult patients >=18 years of age;
chronic renal anemia;
not receiving renal replacement therapy.
Exclusion Criteria:
women who are pregnant, breastfeeding or using unreliable birth control methods;
administration of any investigational drug within 30 days preceding the screening visit and during the run-in period.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Trials
Organizational Affiliation
Hoffmann-La Roche
Official's Role
Study Director
Facility Information:
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35211
Country
United States
City
San Diego
State/Province
California
ZIP/Postal Code
92103-8342
Country
United States
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48202-2689
Country
United States
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48236
Country
United States
City
Las Vegas
State/Province
Nevada
ZIP/Postal Code
89106
Country
United States
City
Portland
State/Province
Oregon
ZIP/Postal Code
97201-2940
Country
United States
City
Edmonton
State/Province
Alberta
ZIP/Postal Code
T6G 2B7
Country
Canada
City
Vancouver
State/Province
British Columbia
ZIP/Postal Code
V6Z 1Y6
Country
Canada
City
Mexico City
ZIP/Postal Code
14000
Country
Mexico
City
Monterrey
ZIP/Postal Code
64710
Country
Mexico
City
Gdansk
ZIP/Postal Code
80-211
Country
Poland
City
Krakow
ZIP/Postal Code
31-501
Country
Poland
City
Wroclaw
ZIP/Postal Code
50-417
Country
Poland
City
Belfast
ZIP/Postal Code
BT9 7LJ
Country
United Kingdom
City
London
ZIP/Postal Code
SE22 8PT
Country
United Kingdom
12. IPD Sharing Statement
Learn more about this trial
A Study of Mircera in Anemic Patients With Chronic Kidney Disease Not Yet on Dialysis.
We'll reach out to this number within 24 hrs