Trial Outcomes & Findings for Study to Determine Optimum Intravenous Starting Dose of MIRCERA for Treatment of Pediatric Participants With Anemia and Chronic Kidney Disease on Hemodialysis (NCT NCT00717366)

Last Updated: 2017-09-08

Results Overview

A time adjusted average baseline Hb concentration for each individual was calculated using an area under the curve (AUC) approach from all available Hb measurements taken during the baseline period (Day -20 to Day 1). The average evaluation period Hb concentration for each individual was calculated using the same method, from all their available measurements taken during the evaluation period (Week 17 to Week 21). The change in Hb concentration between the baseline and evaluation periods was calculated by subtracting the baseline Hb concentration from the evaluation period Hb concentration.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

64 participants

Primary outcome timeframe

Baseline (Day -20 to Day 1), Evaluation Period (Week 17 to Week 21)

Results posted on

2017-09-08

Participant Flow

A total of 112 participants were screened at 28 sites in 10 countries, of which 64 participants were enrolled (16 initially in MIRCERA Group 1 and then 48 in MIRCERA Group 2, following a preliminary analysis of MIRCERA Group 1).

Participant milestones

Participant milestones
Measure	MIRCERA Group 1: Intermediate-Conversion-Factor Group Participants received methoxy polyethylene glycol-epoetin beta (MIRCERA) intravenous (IV) injection at a starting dose based on an intermediate conversion factor from their previous Erythropoiesis-Stimulating Agent (ESA) dose (4 \* previous weekly epoetin dose \[international units {IU}\]/250 or 4 \* previous weekly darbepoetin alfa dose \[micrograms {mcg}\]/1.1) once every 4 weeks for 20 weeks. Participants who completed the 20 weeks of treatment and had hemoglobin (Hb) level within ± 1 grams per deciliter (g/dL) of their baseline Hb level and within the target range of 10-12 g/dL, entered an optional 52-weeks safety extension period. During this period, the participants continued to receive MIRCERA IV injection once every 4 weeks.	MIRCERA Group 2: High-Conversion-Factor Group Participants received MIRCERA IV injection based on a high conversion factor from their previous ESA dose (4 \* previous weekly epoetin dose \[IU\]/125 or 4 \* previous weekly darbepoetin alfa dose \[mcg\]/0.55) once every 4 weeks for 20 weeks. Participants who completed the 20 weeks of treatment and had Hb level within ± 1 g/dL of their baseline Hb level and within the target range of 10-12 g/dL, entered an optional 52-weeks safety extension period. During this period, the participants continued to receive MIRCERA IV injection once every 4 weeks.
Core Study Period (20 Weeks) STARTED	16	48
Core Study Period (20 Weeks) COMPLETED	12	35
Core Study Period (20 Weeks) NOT COMPLETED	4	13
Extension Period (52 Weeks) STARTED	9	28
Extension Period (52 Weeks) Received Visit/Week 21 Dose	8	28
Extension Period (52 Weeks) COMPLETED	5	12
Extension Period (52 Weeks) NOT COMPLETED	4	16

Reasons for withdrawal

Reasons for withdrawal
Measure	MIRCERA Group 1: Intermediate-Conversion-Factor Group Participants received methoxy polyethylene glycol-epoetin beta (MIRCERA) intravenous (IV) injection at a starting dose based on an intermediate conversion factor from their previous Erythropoiesis-Stimulating Agent (ESA) dose (4 \* previous weekly epoetin dose \[international units {IU}\]/250 or 4 \* previous weekly darbepoetin alfa dose \[micrograms {mcg}\]/1.1) once every 4 weeks for 20 weeks. Participants who completed the 20 weeks of treatment and had hemoglobin (Hb) level within ± 1 grams per deciliter (g/dL) of their baseline Hb level and within the target range of 10-12 g/dL, entered an optional 52-weeks safety extension period. During this period, the participants continued to receive MIRCERA IV injection once every 4 weeks.	MIRCERA Group 2: High-Conversion-Factor Group Participants received MIRCERA IV injection based on a high conversion factor from their previous ESA dose (4 \* previous weekly epoetin dose \[IU\]/125 or 4 \* previous weekly darbepoetin alfa dose \[mcg\]/0.55) once every 4 weeks for 20 weeks. Participants who completed the 20 weeks of treatment and had Hb level within ± 1 g/dL of their baseline Hb level and within the target range of 10-12 g/dL, entered an optional 52-weeks safety extension period. During this period, the participants continued to receive MIRCERA IV injection once every 4 weeks.
Core Study Period (20 Weeks) Renal transplant	4	9
Core Study Period (20 Weeks) Admin/Other than specified	0	2
Core Study Period (20 Weeks) Death	0	1
Core Study Period (20 Weeks) Refused treatment/Did not cooperate	0	1
Extension Period (52 Weeks) Renal transplant	3	13
Extension Period (52 Weeks) Admin/Other than specified	0	2
Extension Period (52 Weeks) Withdrew consent	1	1

Baseline Characteristics

Study to Determine Optimum Intravenous Starting Dose of MIRCERA for Treatment of Pediatric Participants With Anemia and Chronic Kidney Disease on Hemodialysis

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	MIRCERA Group 1: Intermediate-Conversion-Factor Group n=16 Participants Participants received MIRCERA IV injection at a starting dose based on an intermediate conversion factor from their previous ESA dose (4 \* previous weekly epoetin dose \[IU\]/250 or 4 \* previous weekly darbepoetin alfa dose \[mcg\]/1.1) once every 4 weeks for 20 weeks. Participants who completed the 20 weeks of treatment and had Hb level within ± 1 g/dL of their baseline Hb level and within the target range of 10-12 g/dL, entered an optional 52-weeks safety extension period. During this period, the participants continued to receive MIRCERA IV injection once every 4 weeks.	MIRCERA Group 2: High-Conversion-Factor Group n=48 Participants Participants received MIRCERA IV injection based on a high conversion factor from their previous ESA dose (4 \* previous weekly epoetin dose \[IU\]/125 or 4 \* previous weekly darbepoetin alfa dose \[mcg\]/0.55) once every 4 weeks for 20 weeks. Participants who completed the 20 weeks of treatment and had Hb level within ± 1 g/dL of their baseline Hb level and within the target range of 10-12 g/dL, entered an optional 52-weeks safety extension period. During this period, the participants continued to receive MIRCERA IV injection once every 4 weeks.	Total n=64 Participants Total of all reporting groups
Age, Continuous	11.3 years STANDARD_DEVIATION 3.24 • n=5 Participants	13.0 years STANDARD_DEVIATION 3.06 • n=7 Participants	12.6 years STANDARD_DEVIATION 3.17 • n=5 Participants
Sex: Female, Male Female	5 Participants n=5 Participants	25 Participants n=7 Participants	30 Participants n=5 Participants
Sex: Female, Male Male	11 Participants n=5 Participants	23 Participants n=7 Participants	34 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline (Day -20 to Day 1), Evaluation Period (Week 17 to Week 21)

Population: ITT population. Hb values within 21 days after blood transfusion(s) were excluded from analysis.

Outcome measures

Outcome measures
Measure	MIRCERA Group 1: Intermediate-Conversion-Factor Group n=16 Participants Participants received MIRCERA IV injection at a starting dose based on an intermediate conversion factor from their previous ESA dose (4 \* previous weekly epoetin dose \[IU\]/250 or 4 \* previous weekly darbepoetin alfa dose \[mcg\]/1.1) once every 4 weeks for 20 weeks. Participants who completed the 20 weeks of treatment and had Hb level within ± 1 g/dL of their baseline Hb level and within the target range of 10-12 g/dL, entered an optional 52-weeks safety extension period. During this period, the participants continued to receive MIRCERA IV injection once every 4 weeks.	MIRCERA Group 2: High-Conversion-Factor Group n=48 Participants Participants received MIRCERA IV injection based on a high conversion factor from their previous ESA dose (4 \* previous weekly epoetin dose \[IU\]/125 or 4 \* previous weekly darbepoetin alfa dose \[mcg\]/0.55) once every 4 weeks for 20 weeks. Participants who completed the 20 weeks of treatment and had Hb level within ± 1 g/dL of their baseline Hb level and within the target range of 10-12 g/dL, entered an optional 52-weeks safety extension period. During this period, the participants continued to receive MIRCERA IV injection once every 4 weeks.
Change in Average Hb Concentration Between Baseline and Evaluation Period Baseline (n=16,48)	11.26 g/dL Standard Deviation 0.496	11.08 g/dL Standard Deviation 0.493
Change in Average Hb Concentration Between Baseline and Evaluation Period Change at Evaluation Period (n=12,36)	-0.78 g/dL Standard Deviation 1.237	-0.15 g/dL Standard Deviation 1.014

SECONDARY outcome

Timeframe: Evaluation Period (Week 17 to Week 21)

Population: ITT population. Hb values within 21 days after blood transfusion(s) were excluded from analysis. Number of participants analyzed = participants with Hb concentration assessment at specified time-points.

Baseline Hb value was defined as the average Hb concentration from all available Hb measurements taken during the baseline period (Day -20 to Day 1). The evaluation period Hb concentration was defined as the average Hb concentration from all available Hb measurements taken during the evaluation period (Week 17 to Week 21).

Outcome measures

Outcome measures
Measure	MIRCERA Group 1: Intermediate-Conversion-Factor Group n=12 Participants Participants received MIRCERA IV injection at a starting dose based on an intermediate conversion factor from their previous ESA dose (4 \* previous weekly epoetin dose \[IU\]/250 or 4 \* previous weekly darbepoetin alfa dose \[mcg\]/1.1) once every 4 weeks for 20 weeks. Participants who completed the 20 weeks of treatment and had Hb level within ± 1 g/dL of their baseline Hb level and within the target range of 10-12 g/dL, entered an optional 52-weeks safety extension period. During this period, the participants continued to receive MIRCERA IV injection once every 4 weeks.	MIRCERA Group 2: High-Conversion-Factor Group n=36 Participants Participants received MIRCERA IV injection based on a high conversion factor from their previous ESA dose (4 \* previous weekly epoetin dose \[IU\]/125 or 4 \* previous weekly darbepoetin alfa dose \[mcg\]/0.55) once every 4 weeks for 20 weeks. Participants who completed the 20 weeks of treatment and had Hb level within ± 1 g/dL of their baseline Hb level and within the target range of 10-12 g/dL, entered an optional 52-weeks safety extension period. During this period, the participants continued to receive MIRCERA IV injection once every 4 weeks.
Number of Participants With an Average Hb Concentration During the Evaluation Period Within ±1 g/dL of Their Baseline Hb	7 participants	27 participants

SECONDARY outcome

Timeframe: Evaluation Period (Week 17 to Week 21)

The evaluation period Hb concentration was defined as the average Hb concentration from all available Hb measurements taken during the evaluation period (Week 17 to Week 21).

Outcome measures

Outcome measures
Measure	MIRCERA Group 1: Intermediate-Conversion-Factor Group n=12 Participants Participants received MIRCERA IV injection at a starting dose based on an intermediate conversion factor from their previous ESA dose (4 \* previous weekly epoetin dose \[IU\]/250 or 4 \* previous weekly darbepoetin alfa dose \[mcg\]/1.1) once every 4 weeks for 20 weeks. Participants who completed the 20 weeks of treatment and had Hb level within ± 1 g/dL of their baseline Hb level and within the target range of 10-12 g/dL, entered an optional 52-weeks safety extension period. During this period, the participants continued to receive MIRCERA IV injection once every 4 weeks.	MIRCERA Group 2: High-Conversion-Factor Group n=36 Participants Participants received MIRCERA IV injection based on a high conversion factor from their previous ESA dose (4 \* previous weekly epoetin dose \[IU\]/125 or 4 \* previous weekly darbepoetin alfa dose \[mcg\]/0.55) once every 4 weeks for 20 weeks. Participants who completed the 20 weeks of treatment and had Hb level within ± 1 g/dL of their baseline Hb level and within the target range of 10-12 g/dL, entered an optional 52-weeks safety extension period. During this period, the participants continued to receive MIRCERA IV injection once every 4 weeks.
Number of Participants With an Average Hb Concentration During the Evaluation Period Above, Within or Below the Range of 10-12 g/dL Above 12 g/dL	0 participants	3 participants
Number of Participants With an Average Hb Concentration During the Evaluation Period Above, Within or Below the Range of 10-12 g/dL Within 10-12 g/dL	9 participants	29 participants
Number of Participants With an Average Hb Concentration During the Evaluation Period Above, Within or Below the Range of 10-12 g/dL Below 10 g/dL	3 participants	4 participants

SECONDARY outcome

Timeframe: Baseline to Week 20

Population: ITT population.

Outcome measures

Outcome measures
Measure	MIRCERA Group 1: Intermediate-Conversion-Factor Group n=16 Participants Participants received MIRCERA IV injection at a starting dose based on an intermediate conversion factor from their previous ESA dose (4 \* previous weekly epoetin dose \[IU\]/250 or 4 \* previous weekly darbepoetin alfa dose \[mcg\]/1.1) once every 4 weeks for 20 weeks. Participants who completed the 20 weeks of treatment and had Hb level within ± 1 g/dL of their baseline Hb level and within the target range of 10-12 g/dL, entered an optional 52-weeks safety extension period. During this period, the participants continued to receive MIRCERA IV injection once every 4 weeks.	MIRCERA Group 2: High-Conversion-Factor Group n=48 Participants Participants received MIRCERA IV injection based on a high conversion factor from their previous ESA dose (4 \* previous weekly epoetin dose \[IU\]/125 or 4 \* previous weekly darbepoetin alfa dose \[mcg\]/0.55) once every 4 weeks for 20 weeks. Participants who completed the 20 weeks of treatment and had Hb level within ± 1 g/dL of their baseline Hb level and within the target range of 10-12 g/dL, entered an optional 52-weeks safety extension period. During this period, the participants continued to receive MIRCERA IV injection once every 4 weeks.
Number of Participants With Blood Transfusions	1 participants	2 participants

SECONDARY outcome

Timeframe: Baseline (Day -20 to Day 1), Evaluation Period (Week 17 to Week 21)

Population: ITT population. Reticulocyte values within 21 days after blood transfusion(s) were excluded from analysis. Here, number of participants analyzed = participants evaluable for this outcome measure and 'n' signifies number of participants evaluable at specified time-points.

A time adjusted average baseline reticulocyte count for each individual was calculated using an AUC approach from all available reticulocyte counts taken during the baseline period (Day -20 to Day 1). The average evaluation period reticulocyte count for each individual was calculated using the same method, from all their available measurements taken during the evaluation period (Weeks 17 to 21). The change in reticulocyte count between the baseline and evaluation periods was calculated by subtracting the baseline reticulocyte count from the evaluation period reticulocyte count. Relative reticulocytes were recorded conversion to absolute values was performed.

Outcome measures

Outcome measures
Measure	MIRCERA Group 1: Intermediate-Conversion-Factor Group n=15 Participants Participants received MIRCERA IV injection at a starting dose based on an intermediate conversion factor from their previous ESA dose (4 \* previous weekly epoetin dose \[IU\]/250 or 4 \* previous weekly darbepoetin alfa dose \[mcg\]/1.1) once every 4 weeks for 20 weeks. Participants who completed the 20 weeks of treatment and had Hb level within ± 1 g/dL of their baseline Hb level and within the target range of 10-12 g/dL, entered an optional 52-weeks safety extension period. During this period, the participants continued to receive MIRCERA IV injection once every 4 weeks.	MIRCERA Group 2: High-Conversion-Factor Group n=48 Participants Participants received MIRCERA IV injection based on a high conversion factor from their previous ESA dose (4 \* previous weekly epoetin dose \[IU\]/125 or 4 \* previous weekly darbepoetin alfa dose \[mcg\]/0.55) once every 4 weeks for 20 weeks. Participants who completed the 20 weeks of treatment and had Hb level within ± 1 g/dL of their baseline Hb level and within the target range of 10-12 g/dL, entered an optional 52-weeks safety extension period. During this period, the participants continued to receive MIRCERA IV injection once every 4 weeks.
Change in Average Reticulocyte Count Between the Baseline and Evaluation Period Baseline (n=15,48)	46.08 10^3 cells/microliter Standard Deviation 26.472	43.70 10^3 cells/microliter Standard Deviation 25.984
Change in Average Reticulocyte Count Between the Baseline and Evaluation Period Change at Evaluation Period (n=11,36)	23.38 10^3 cells/microliter Standard Deviation 29.279	24.80 10^3 cells/microliter Standard Deviation 32.428

SECONDARY outcome

Timeframe: Pre-dose (with 1 hour before drug administration) and 2, 48 hours post dose on Week 9, at Weeks 10, 11, and 12, pre-dose (with 1 hour before drug administration) on Week 13

Population: Pharmacokinetic (PK) evaluable population included all enrolled participants who received at least one dose of study drug and had evaluable PK assessment. Here 'n' signifies number of participants evaluable at specified time-points.

Cmax was defined as the highest serum concentration observed from all sample collection timepoints (as provided in timeframe) and was averaged out among participants and reported.

Outcome measures

Outcome measures
Measure	MIRCERA Group 1: Intermediate-Conversion-Factor Group n=12 Participants Participants received MIRCERA IV injection at a starting dose based on an intermediate conversion factor from their previous ESA dose (4 \* previous weekly epoetin dose \[IU\]/250 or 4 \* previous weekly darbepoetin alfa dose \[mcg\]/1.1) once every 4 weeks for 20 weeks. Participants who completed the 20 weeks of treatment and had Hb level within ± 1 g/dL of their baseline Hb level and within the target range of 10-12 g/dL, entered an optional 52-weeks safety extension period. During this period, the participants continued to receive MIRCERA IV injection once every 4 weeks.	MIRCERA Group 2: High-Conversion-Factor Group n=34 Participants Participants received MIRCERA IV injection based on a high conversion factor from their previous ESA dose (4 \* previous weekly epoetin dose \[IU\]/125 or 4 \* previous weekly darbepoetin alfa dose \[mcg\]/0.55) once every 4 weeks for 20 weeks. Participants who completed the 20 weeks of treatment and had Hb level within ± 1 g/dL of their baseline Hb level and within the target range of 10-12 g/dL, entered an optional 52-weeks safety extension period. During this period, the participants continued to receive MIRCERA IV injection once every 4 weeks.
Maximum Observed Serum Concentration (Cmax) of MIRCERA	37700 picograms per milliliter (pg/mL) Geometric Coefficient of Variation 74.5	66100 picograms per milliliter (pg/mL) Geometric Coefficient of Variation 149.5

SECONDARY outcome

Timeframe: Pre-dose (with 1 hour before drug administration) and 2, 48 hours post dose on Week 9, at Weeks 10, 11, and 12, pre-dose (with 1 hour before drug administration) on Week 13

Population: PK evaluable population. Number of participants analyzed = participants with AUC0-672h assessment at specified time-points.

Area under the serum concentration versus time curve over 672 hours. AUC0-672h represents area under the serum concentration versus time curve from time zero to end of dosing interval (AUC0-tau).

Outcome measures

Outcome measures
Measure	MIRCERA Group 1: Intermediate-Conversion-Factor Group n=11 Participants Participants received MIRCERA IV injection at a starting dose based on an intermediate conversion factor from their previous ESA dose (4 \* previous weekly epoetin dose \[IU\]/250 or 4 \* previous weekly darbepoetin alfa dose \[mcg\]/1.1) once every 4 weeks for 20 weeks. Participants who completed the 20 weeks of treatment and had Hb level within ± 1 g/dL of their baseline Hb level and within the target range of 10-12 g/dL, entered an optional 52-weeks safety extension period. During this period, the participants continued to receive MIRCERA IV injection once every 4 weeks.	MIRCERA Group 2: High-Conversion-Factor Group n=32 Participants Participants received MIRCERA IV injection based on a high conversion factor from their previous ESA dose (4 \* previous weekly epoetin dose \[IU\]/125 or 4 \* previous weekly darbepoetin alfa dose \[mcg\]/0.55) once every 4 weeks for 20 weeks. Participants who completed the 20 weeks of treatment and had Hb level within ± 1 g/dL of their baseline Hb level and within the target range of 10-12 g/dL, entered an optional 52-weeks safety extension period. During this period, the participants continued to receive MIRCERA IV injection once every 4 weeks.
Area Under the Serum Concentration-Time Curve From 0 to 672 Hours (AUC0-672h) of MIRCERA	3630000 picogramshour/milliliter (pgh/mL) Geometric Coefficient of Variation 91.8	7170000 picogramshour/milliliter (pgh/mL) Geometric Coefficient of Variation 140.0

SECONDARY outcome

Timeframe: Pre-dose (with 1 hour before drug administration) and 2, 48 hours post dose on Week 9, at Weeks 10, 11, and 12, pre-dose (with 1 hour before drug administration) on Week 13

Population: PK evaluable population.

Tmax was defined as the time (in hours) to achieve Cmax (Cmax was defined as the highest serum concentration observed over all sample collection timepoints \[as provided in timeframe\]). The median time, among all participants, was reported.

Outcome measures

Outcome measures
Measure	MIRCERA Group 1: Intermediate-Conversion-Factor Group n=12 Participants Participants received MIRCERA IV injection at a starting dose based on an intermediate conversion factor from their previous ESA dose (4 \* previous weekly epoetin dose \[IU\]/250 or 4 \* previous weekly darbepoetin alfa dose \[mcg\]/1.1) once every 4 weeks for 20 weeks. Participants who completed the 20 weeks of treatment and had Hb level within ± 1 g/dL of their baseline Hb level and within the target range of 10-12 g/dL, entered an optional 52-weeks safety extension period. During this period, the participants continued to receive MIRCERA IV injection once every 4 weeks.	MIRCERA Group 2: High-Conversion-Factor Group n=34 Participants Participants received MIRCERA IV injection based on a high conversion factor from their previous ESA dose (4 \* previous weekly epoetin dose \[IU\]/125 or 4 \* previous weekly darbepoetin alfa dose \[mcg\]/0.55) once every 4 weeks for 20 weeks. Participants who completed the 20 weeks of treatment and had Hb level within ± 1 g/dL of their baseline Hb level and within the target range of 10-12 g/dL, entered an optional 52-weeks safety extension period. During this period, the participants continued to receive MIRCERA IV injection once every 4 weeks.
Time to Reach Cmax (Tmax) of MIRCERA	2.00 hours Interval 1.98 to 2.17	2.00 hours Interval 1.83 to 164.0

SECONDARY outcome

Timeframe: Pre-dose (with 1 hour before drug administration) and 2, 48 hours post dose on Week 9, at Weeks 10, 11, and 12, pre-dose (with 1 hour before drug administration) on Week 13

Population: PK evaluable population. Number of participants analyzed = participants evaluable for t1/2 assessments.

t1/2 was defined as the time (in hours) measured (from all sample collection timepoints \[as provided in timeframe\]) for the serum concentration to decrease by one half. The t1/2 was calculated as natural logarithm of 2 divided by λz; where λz = terminal elimination rate constant.

Outcome measures

Outcome measures
Measure	MIRCERA Group 1: Intermediate-Conversion-Factor Group n=11 Participants Participants received MIRCERA IV injection at a starting dose based on an intermediate conversion factor from their previous ESA dose (4 \* previous weekly epoetin dose \[IU\]/250 or 4 \* previous weekly darbepoetin alfa dose \[mcg\]/1.1) once every 4 weeks for 20 weeks. Participants who completed the 20 weeks of treatment and had Hb level within ± 1 g/dL of their baseline Hb level and within the target range of 10-12 g/dL, entered an optional 52-weeks safety extension period. During this period, the participants continued to receive MIRCERA IV injection once every 4 weeks.	MIRCERA Group 2: High-Conversion-Factor Group n=32 Participants Participants received MIRCERA IV injection based on a high conversion factor from their previous ESA dose (4 \* previous weekly epoetin dose \[IU\]/125 or 4 \* previous weekly darbepoetin alfa dose \[mcg\]/0.55) once every 4 weeks for 20 weeks. Participants who completed the 20 weeks of treatment and had Hb level within ± 1 g/dL of their baseline Hb level and within the target range of 10-12 g/dL, entered an optional 52-weeks safety extension period. During this period, the participants continued to receive MIRCERA IV injection once every 4 weeks.
Apparent Terminal Phase Half-Life (t1/2) of MIRCERA	147 hours Geometric Coefficient of Variation 30.1	121 hours Geometric Coefficient of Variation 43.5

Adverse Events

MIRCERA Group 1: Intermediate-Conversion-Factor Group

Serious events: 4 serious events

Other events: 11 other events

Deaths: 0 deaths

MIRCERA Group 2: High-Conversion-Factor Group

Serious events: 17 serious events

Other events: 28 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Medical Communications

Hoffmann-La Roche

Phone: 800-821-8590

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
Publication restrictions are in place

Restriction type: OTHER

Measure	MIRCERA Group 1: Intermediate-Conversion-Factor Group n=16 participants at risk Participants received MIRCERA IV injection at a starting dose based on an intermediate conversion factor from their previous ESA dose (4 \* previous weekly epoetin dose \[IU\]/250 or 4 \* previous weekly darbepoetin alfa dose \[mcg\]/1.1) once every 4 weeks for 20 weeks. Participants who completed the 20 weeks of treatment and had Hb level within ± 1 g/dL of their baseline Hb level and within the target range of 10-12 g/dL, entered an optional 52-weeks safety extension period. During this period, the participants continued to receive MIRCERA IV injection once every 4 weeks.	MIRCERA Group 2: High-Conversion-Factor Group n=48 participants at risk Participants received MIRCERA IV injection based on a high conversion factor from their previous ESA dose (4 \* previous weekly epoetin dose \[IU\]/125 or 4 \* previous weekly darbepoetin alfa dose \[mcg\]/0.55) once every 4 weeks for 20 weeks. Participants who completed the 20 weeks of treatment and had Hb level within ± 1 g/dL of their baseline Hb level and within the target range of 10-12 g/dL, entered an optional 52-weeks safety extension period. During this period, the participants continued to receive MIRCERA IV injection once every 4 weeks.
Infections and infestations Device related infection	0.00% 0/16 • Baseline up to Week 73 Safety population included all participants who received at least one dose of study drug and had a safety follow-up visit.	6.2% 3/48 • Baseline up to Week 73 Safety population included all participants who received at least one dose of study drug and had a safety follow-up visit.
Infections and infestations Bronchitis	6.2% 1/16 • Baseline up to Week 73 Safety population included all participants who received at least one dose of study drug and had a safety follow-up visit.	2.1% 1/48 • Baseline up to Week 73 Safety population included all participants who received at least one dose of study drug and had a safety follow-up visit.
Infections and infestations Nasopharyngitis	0.00% 0/16 • Baseline up to Week 73 Safety population included all participants who received at least one dose of study drug and had a safety follow-up visit.	2.1% 1/48 • Baseline up to Week 73 Safety population included all participants who received at least one dose of study drug and had a safety follow-up visit.
Infections and infestations Orchitis	0.00% 0/16 • Baseline up to Week 73 Safety population included all participants who received at least one dose of study drug and had a safety follow-up visit.	2.1% 1/48 • Baseline up to Week 73 Safety population included all participants who received at least one dose of study drug and had a safety follow-up visit.
Infections and infestations Pharyngitis	0.00% 0/16 • Baseline up to Week 73 Safety population included all participants who received at least one dose of study drug and had a safety follow-up visit.	2.1% 1/48 • Baseline up to Week 73 Safety population included all participants who received at least one dose of study drug and had a safety follow-up visit.
Infections and infestations Pneumonia	0.00% 0/16 • Baseline up to Week 73 Safety population included all participants who received at least one dose of study drug and had a safety follow-up visit.	2.1% 1/48 • Baseline up to Week 73 Safety population included all participants who received at least one dose of study drug and had a safety follow-up visit.
Infections and infestations Staphylococcal scalded skin syndrome	6.2% 1/16 • Baseline up to Week 73 Safety population included all participants who received at least one dose of study drug and had a safety follow-up visit.	0.00% 0/48 • Baseline up to Week 73 Safety population included all participants who received at least one dose of study drug and had a safety follow-up visit.
Injury, poisoning and procedural complications Arteriovenous fistula thrombosis	6.2% 1/16 • Baseline up to Week 73 Safety population included all participants who received at least one dose of study drug and had a safety follow-up visit.	4.2% 2/48 • Baseline up to Week 73 Safety population included all participants who received at least one dose of study drug and had a safety follow-up visit.
Injury, poisoning and procedural complications Procedural haemorrhage	0.00% 0/16 • Baseline up to Week 73 Safety population included all participants who received at least one dose of study drug and had a safety follow-up visit.	4.2% 2/48 • Baseline up to Week 73 Safety population included all participants who received at least one dose of study drug and had a safety follow-up visit.
Injury, poisoning and procedural complications Arterial injury	0.00% 0/16 • Baseline up to Week 73 Safety population included all participants who received at least one dose of study drug and had a safety follow-up visit.	2.1% 1/48 • Baseline up to Week 73 Safety population included all participants who received at least one dose of study drug and had a safety follow-up visit.
Injury, poisoning and procedural complications Transplant failure	6.2% 1/16 • Baseline up to Week 73 Safety population included all participants who received at least one dose of study drug and had a safety follow-up visit.	0.00% 0/48 • Baseline up to Week 73 Safety population included all participants who received at least one dose of study drug and had a safety follow-up visit.
General disorders Thrombosis in device	0.00% 0/16 • Baseline up to Week 73 Safety population included all participants who received at least one dose of study drug and had a safety follow-up visit.	6.2% 3/48 • Baseline up to Week 73 Safety population included all participants who received at least one dose of study drug and had a safety follow-up visit.
General disorders Device dislocation	6.2% 1/16 • Baseline up to Week 73 Safety population included all participants who received at least one dose of study drug and had a safety follow-up visit.	0.00% 0/48 • Baseline up to Week 73 Safety population included all participants who received at least one dose of study drug and had a safety follow-up visit.
General disorders Non-cardiac chest pain	0.00% 0/16 • Baseline up to Week 73 Safety population included all participants who received at least one dose of study drug and had a safety follow-up visit.	2.1% 1/48 • Baseline up to Week 73 Safety population included all participants who received at least one dose of study drug and had a safety follow-up visit.
General disorders Pain	0.00% 0/16 • Baseline up to Week 73 Safety population included all participants who received at least one dose of study drug and had a safety follow-up visit.	2.1% 1/48 • Baseline up to Week 73 Safety population included all participants who received at least one dose of study drug and had a safety follow-up visit.
Vascular disorders Hypertension	0.00% 0/16 • Baseline up to Week 73 Safety population included all participants who received at least one dose of study drug and had a safety follow-up visit.	6.2% 3/48 • Baseline up to Week 73 Safety population included all participants who received at least one dose of study drug and had a safety follow-up visit.
Vascular disorders Hypotension	0.00% 0/16 • Baseline up to Week 73 Safety population included all participants who received at least one dose of study drug and had a safety follow-up visit.	2.1% 1/48 • Baseline up to Week 73 Safety population included all participants who received at least one dose of study drug and had a safety follow-up visit.
Gastrointestinal disorders Abdominal pain	0.00% 0/16 • Baseline up to Week 73 Safety population included all participants who received at least one dose of study drug and had a safety follow-up visit.	2.1% 1/48 • Baseline up to Week 73 Safety population included all participants who received at least one dose of study drug and had a safety follow-up visit.
Gastrointestinal disorders Diarrhoea	6.2% 1/16 • Baseline up to Week 73 Safety population included all participants who received at least one dose of study drug and had a safety follow-up visit.	0.00% 0/48 • Baseline up to Week 73 Safety population included all participants who received at least one dose of study drug and had a safety follow-up visit.
Metabolism and nutrition disorders Fluid overload	6.2% 1/16 • Baseline up to Week 73 Safety population included all participants who received at least one dose of study drug and had a safety follow-up visit.	2.1% 1/48 • Baseline up to Week 73 Safety population included all participants who received at least one dose of study drug and had a safety follow-up visit.
Cardiac disorders Pericarditis	0.00% 0/16 • Baseline up to Week 73 Safety population included all participants who received at least one dose of study drug and had a safety follow-up visit.	2.1% 1/48 • Baseline up to Week 73 Safety population included all participants who received at least one dose of study drug and had a safety follow-up visit.
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/16 • Baseline up to Week 73 Safety population included all participants who received at least one dose of study drug and had a safety follow-up visit.	2.1% 1/48 • Baseline up to Week 73 Safety population included all participants who received at least one dose of study drug and had a safety follow-up visit.
Nervous system disorders Intracranial haematoma	0.00% 0/16 • Baseline up to Week 73 Safety population included all participants who received at least one dose of study drug and had a safety follow-up visit.	2.1% 1/48 • Baseline up to Week 73 Safety population included all participants who received at least one dose of study drug and had a safety follow-up visit.
Renal and urinary disorders Lupus nephritis	0.00% 0/16 • Baseline up to Week 73 Safety population included all participants who received at least one dose of study drug and had a safety follow-up visit.	2.1% 1/48 • Baseline up to Week 73 Safety population included all participants who received at least one dose of study drug and had a safety follow-up visit.
Reproductive system and breast disorders Uterine haemorrhage	0.00% 0/16 • Baseline up to Week 73 Safety population included all participants who received at least one dose of study drug and had a safety follow-up visit.	2.1% 1/48 • Baseline up to Week 73 Safety population included all participants who received at least one dose of study drug and had a safety follow-up visit.

Measure	MIRCERA Group 1: Intermediate-Conversion-Factor Group n=16 participants at risk Participants received MIRCERA IV injection at a starting dose based on an intermediate conversion factor from their previous ESA dose (4 \* previous weekly epoetin dose \[IU\]/250 or 4 \* previous weekly darbepoetin alfa dose \[mcg\]/1.1) once every 4 weeks for 20 weeks. Participants who completed the 20 weeks of treatment and had Hb level within ± 1 g/dL of their baseline Hb level and within the target range of 10-12 g/dL, entered an optional 52-weeks safety extension period. During this period, the participants continued to receive MIRCERA IV injection once every 4 weeks.	MIRCERA Group 2: High-Conversion-Factor Group n=48 participants at risk Participants received MIRCERA IV injection based on a high conversion factor from their previous ESA dose (4 \* previous weekly epoetin dose \[IU\]/125 or 4 \* previous weekly darbepoetin alfa dose \[mcg\]/0.55) once every 4 weeks for 20 weeks. Participants who completed the 20 weeks of treatment and had Hb level within ± 1 g/dL of their baseline Hb level and within the target range of 10-12 g/dL, entered an optional 52-weeks safety extension period. During this period, the participants continued to receive MIRCERA IV injection once every 4 weeks.
Infections and infestations Nasopharyngitis	0.00% 0/16 • Baseline up to Week 73 Safety population included all participants who received at least one dose of study drug and had a safety follow-up visit.	29.2% 14/48 • Baseline up to Week 73 Safety population included all participants who received at least one dose of study drug and had a safety follow-up visit.
Infections and infestations Bronchitis	6.2% 1/16 • Baseline up to Week 73 Safety population included all participants who received at least one dose of study drug and had a safety follow-up visit.	6.2% 3/48 • Baseline up to Week 73 Safety population included all participants who received at least one dose of study drug and had a safety follow-up visit.
Infections and infestations Pharyngitis	0.00% 0/16 • Baseline up to Week 73 Safety population included all participants who received at least one dose of study drug and had a safety follow-up visit.	6.2% 3/48 • Baseline up to Week 73 Safety population included all participants who received at least one dose of study drug and had a safety follow-up visit.
Infections and infestations Urinary tract infection	6.2% 1/16 • Baseline up to Week 73 Safety population included all participants who received at least one dose of study drug and had a safety follow-up visit.	4.2% 2/48 • Baseline up to Week 73 Safety population included all participants who received at least one dose of study drug and had a safety follow-up visit.
Infections and infestations Viral infection	6.2% 1/16 • Baseline up to Week 73 Safety population included all participants who received at least one dose of study drug and had a safety follow-up visit.	4.2% 2/48 • Baseline up to Week 73 Safety population included all participants who received at least one dose of study drug and had a safety follow-up visit.
Infections and infestations Catheter site infection	6.2% 1/16 • Baseline up to Week 73 Safety population included all participants who received at least one dose of study drug and had a safety follow-up visit.	2.1% 1/48 • Baseline up to Week 73 Safety population included all participants who received at least one dose of study drug and had a safety follow-up visit.
Infections and infestations Gastroenteritis	6.2% 1/16 • Baseline up to Week 73 Safety population included all participants who received at least one dose of study drug and had a safety follow-up visit.	2.1% 1/48 • Baseline up to Week 73 Safety population included all participants who received at least one dose of study drug and had a safety follow-up visit.
Infections and infestations H1N1 influenza	12.5% 2/16 • Baseline up to Week 73 Safety population included all participants who received at least one dose of study drug and had a safety follow-up visit.	0.00% 0/48 • Baseline up to Week 73 Safety population included all participants who received at least one dose of study drug and had a safety follow-up visit.
Infections and infestations Conjunctivitis	6.2% 1/16 • Baseline up to Week 73 Safety population included all participants who received at least one dose of study drug and had a safety follow-up visit.	0.00% 0/48 • Baseline up to Week 73 Safety population included all participants who received at least one dose of study drug and had a safety follow-up visit.
Infections and infestations Oral herpes	6.2% 1/16 • Baseline up to Week 73 Safety population included all participants who received at least one dose of study drug and had a safety follow-up visit.	0.00% 0/48 • Baseline up to Week 73 Safety population included all participants who received at least one dose of study drug and had a safety follow-up visit.
Infections and infestations Upper respiratory tract infection	6.2% 1/16 • Baseline up to Week 73 Safety population included all participants who received at least one dose of study drug and had a safety follow-up visit.	0.00% 0/48 • Baseline up to Week 73 Safety population included all participants who received at least one dose of study drug and had a safety follow-up visit.
Nervous system disorders Headache	6.2% 1/16 • Baseline up to Week 73 Safety population included all participants who received at least one dose of study drug and had a safety follow-up visit.	27.1% 13/48 • Baseline up to Week 73 Safety population included all participants who received at least one dose of study drug and had a safety follow-up visit.
Nervous system disorders Paraesthesia	6.2% 1/16 • Baseline up to Week 73 Safety population included all participants who received at least one dose of study drug and had a safety follow-up visit.	0.00% 0/48 • Baseline up to Week 73 Safety population included all participants who received at least one dose of study drug and had a safety follow-up visit.
Gastrointestinal disorders Vomiting	12.5% 2/16 • Baseline up to Week 73 Safety population included all participants who received at least one dose of study drug and had a safety follow-up visit.	10.4% 5/48 • Baseline up to Week 73 Safety population included all participants who received at least one dose of study drug and had a safety follow-up visit.
Gastrointestinal disorders Abdominal pain	6.2% 1/16 • Baseline up to Week 73 Safety population included all participants who received at least one dose of study drug and had a safety follow-up visit.	6.2% 3/48 • Baseline up to Week 73 Safety population included all participants who received at least one dose of study drug and had a safety follow-up visit.
Gastrointestinal disorders Nausea	0.00% 0/16 • Baseline up to Week 73 Safety population included all participants who received at least one dose of study drug and had a safety follow-up visit.	6.2% 3/48 • Baseline up to Week 73 Safety population included all participants who received at least one dose of study drug and had a safety follow-up visit.
Gastrointestinal disorders Abdominal pain upper	6.2% 1/16 • Baseline up to Week 73 Safety population included all participants who received at least one dose of study drug and had a safety follow-up visit.	2.1% 1/48 • Baseline up to Week 73 Safety population included all participants who received at least one dose of study drug and had a safety follow-up visit.
Vascular disorders Hypertension	6.2% 1/16 • Baseline up to Week 73 Safety population included all participants who received at least one dose of study drug and had a safety follow-up visit.	18.8% 9/48 • Baseline up to Week 73 Safety population included all participants who received at least one dose of study drug and had a safety follow-up visit.
Metabolism and nutrition disorders Hyperkalaemia	6.2% 1/16 • Baseline up to Week 73 Safety population included all participants who received at least one dose of study drug and had a safety follow-up visit.	6.2% 3/48 • Baseline up to Week 73 Safety population included all participants who received at least one dose of study drug and had a safety follow-up visit.
Metabolism and nutrition disorders Hyperphosphataemia	0.00% 0/16 • Baseline up to Week 73 Safety population included all participants who received at least one dose of study drug and had a safety follow-up visit.	6.2% 3/48 • Baseline up to Week 73 Safety population included all participants who received at least one dose of study drug and had a safety follow-up visit.
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/16 • Baseline up to Week 73 Safety population included all participants who received at least one dose of study drug and had a safety follow-up visit.	8.3% 4/48 • Baseline up to Week 73 Safety population included all participants who received at least one dose of study drug and had a safety follow-up visit.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	6.2% 1/16 • Baseline up to Week 73 Safety population included all participants who received at least one dose of study drug and had a safety follow-up visit.	4.2% 2/48 • Baseline up to Week 73 Safety population included all participants who received at least one dose of study drug and had a safety follow-up visit.
General disorders Pyrexia	6.2% 1/16 • Baseline up to Week 73 Safety population included all participants who received at least one dose of study drug and had a safety follow-up visit.	6.2% 3/48 • Baseline up to Week 73 Safety population included all participants who received at least one dose of study drug and had a safety follow-up visit.
General disorders Malaise	6.2% 1/16 • Baseline up to Week 73 Safety population included all participants who received at least one dose of study drug and had a safety follow-up visit.	0.00% 0/48 • Baseline up to Week 73 Safety population included all participants who received at least one dose of study drug and had a safety follow-up visit.
Blood and lymphatic system disorders Thrombocytopenia	0.00% 0/16 • Baseline up to Week 73 Safety population included all participants who received at least one dose of study drug and had a safety follow-up visit.	8.3% 4/48 • Baseline up to Week 73 Safety population included all participants who received at least one dose of study drug and had a safety follow-up visit.
Ear and labyrinth disorders Ear pain	0.00% 0/16 • Baseline up to Week 73 Safety population included all participants who received at least one dose of study drug and had a safety follow-up visit.	6.2% 3/48 • Baseline up to Week 73 Safety population included all participants who received at least one dose of study drug and had a safety follow-up visit.
Ear and labyrinth disorders Vertigo	6.2% 1/16 • Baseline up to Week 73 Safety population included all participants who received at least one dose of study drug and had a safety follow-up visit.	0.00% 0/48 • Baseline up to Week 73 Safety population included all participants who received at least one dose of study drug and had a safety follow-up visit.
Endocrine disorders Hyperparathyroidism secondary	6.2% 1/16 • Baseline up to Week 73 Safety population included all participants who received at least one dose of study drug and had a safety follow-up visit.	2.1% 1/48 • Baseline up to Week 73 Safety population included all participants who received at least one dose of study drug and had a safety follow-up visit.
Injury, poisoning and procedural complications Contusion	6.2% 1/16 • Baseline up to Week 73 Safety population included all participants who received at least one dose of study drug and had a safety follow-up visit.	0.00% 0/48 • Baseline up to Week 73 Safety population included all participants who received at least one dose of study drug and had a safety follow-up visit.
Investigations Haemoglobin decreased	6.2% 1/16 • Baseline up to Week 73 Safety population included all participants who received at least one dose of study drug and had a safety follow-up visit.	0.00% 0/48 • Baseline up to Week 73 Safety population included all participants who received at least one dose of study drug and had a safety follow-up visit.