Trial Outcomes & Findings for A Study of Mircera for the Maintenance Treatment of Participants With Chronic Renal Anemia (NCT NCT00550680)
NCT ID: NCT00550680
Last Updated: 2016-03-30
Results Overview
Reference Hb was determined individually per participant as the average of all Hb values during a pre-treatment stability assessment (Weeks -4 to 0). During the EEP (Weeks 17 to 24), participants provided a total of four blood samples for Hb monitoring while on treatment with Mircera/CERA. The average Hb during the EEP was calculated per participant and assessed against the reference value. The percentage of participants who had average Hb during the EEP in the target range of 10.5 to 12.5 g/dL and within ±1 g/dL of their individual reference Hb was determined as the primary endpoint. The 95 percent (%) confidence interval (CI) was calculated using the Pearson-Clopper method for exact confidence bounds.
COMPLETED
PHASE3
208 participants
Weeks -4, -3, -2, -1,and 0; pre-dose (0 hours) during Weeks 18, 20, 22, and 24
2016-03-30
Participant Flow
Participant milestones
| Measure |
Mircera in Renal Anemia
Participants with chronic renal anemia who were previously treated with erythropoiesis-stimulating agent (ESA) therapy received intravenous methoxy polyethylene glycol-epoetin beta (Mircera), also known as continuous erythropoietin receptor activator (CERA), every 4 weeks for a total of 24 weeks in this single-arm study. The first dose of 120, 200, or 360 micrograms (mcg) was based upon the dose of ESA received prior to administration of study treatment, while subsequent doses were adjusted to maintain hemoglobin (Hb) concentrations within target of 10.5 and 12.5 grams per deciliter (g/dL).
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|---|---|
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Overall Study
STARTED
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208
|
|
Overall Study
COMPLETED
|
152
|
|
Overall Study
NOT COMPLETED
|
56
|
Reasons for withdrawal
| Measure |
Mircera in Renal Anemia
Participants with chronic renal anemia who were previously treated with erythropoiesis-stimulating agent (ESA) therapy received intravenous methoxy polyethylene glycol-epoetin beta (Mircera), also known as continuous erythropoietin receptor activator (CERA), every 4 weeks for a total of 24 weeks in this single-arm study. The first dose of 120, 200, or 360 micrograms (mcg) was based upon the dose of ESA received prior to administration of study treatment, while subsequent doses were adjusted to maintain hemoglobin (Hb) concentrations within target of 10.5 and 12.5 grams per deciliter (g/dL).
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|---|---|
|
Overall Study
Administrative Reasons
|
1
|
|
Overall Study
Adverse Event
|
5
|
|
Overall Study
Death
|
3
|
|
Overall Study
Early Improvement
|
1
|
|
Overall Study
Lost to Follow-up
|
3
|
|
Overall Study
Lack of Efficacy
|
1
|
|
Overall Study
Other
|
10
|
|
Overall Study
Protocol Violation
|
7
|
|
Overall Study
Refused Treatment
|
19
|
|
Overall Study
Screen Failure
|
6
|
Baseline Characteristics
A Study of Mircera for the Maintenance Treatment of Participants With Chronic Renal Anemia
Baseline characteristics by cohort
| Measure |
Mircera in Renal Anemia
n=188 Participants
Participants with chronic renal anemia who were previously treated with ESA therapy received intravenous Mircera/CERA, every 4 weeks for a total of 24 weeks in this single-arm study. The first dose of 120, 200, or 360 mcg was based upon the dose of ESA received prior to administration of study treatment, while subsequent doses were adjusted to maintain Hb concentrations within target of 10.5 and 12.5 g/dL.
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|---|---|
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Age, Continuous
|
62.6 years
STANDARD_DEVIATION 14.49 • n=93 Participants
|
|
Sex: Female, Male
Female
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73 Participants
n=93 Participants
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Sex: Female, Male
Male
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115 Participants
n=93 Participants
|
PRIMARY outcome
Timeframe: Weeks -4, -3, -2, -1,and 0; pre-dose (0 hours) during Weeks 18, 20, 22, and 24Population: Per Protocol (PP) Population: All participants who received at least one dose of Mircera/CERA and provided data for at least one follow-up assessment, and who fulfilled inclusion/exclusion criteria per study protocol.
Reference Hb was determined individually per participant as the average of all Hb values during a pre-treatment stability assessment (Weeks -4 to 0). During the EEP (Weeks 17 to 24), participants provided a total of four blood samples for Hb monitoring while on treatment with Mircera/CERA. The average Hb during the EEP was calculated per participant and assessed against the reference value. The percentage of participants who had average Hb during the EEP in the target range of 10.5 to 12.5 g/dL and within ±1 g/dL of their individual reference Hb was determined as the primary endpoint. The 95 percent (%) confidence interval (CI) was calculated using the Pearson-Clopper method for exact confidence bounds.
Outcome measures
| Measure |
Mircera in Renal Anemia
n=149 Participants
Participants with chronic renal anemia who were previously treated with ESA therapy received intravenous Mircera/CERA, every 4 weeks for a total of 24 weeks in this single-arm study. The first dose of 120, 200, or 360 mcg was based upon the dose of ESA received prior to administration of study treatment, while subsequent doses were adjusted to maintain Hb concentrations within target of 10.5 and 12.5 g/dL.
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|---|---|
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Percentage of Participants Who Maintained Average Hb Within Plus/Minus (±) 1 g/dL of Reference Hb and Within Target Range During the Efficacy Evaluation Period (EEP)
|
53.7 percentage of participants
Interval 45.4 to 61.9
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SECONDARY outcome
Timeframe: At Weeks -4, -3, -2, -1, and 0; pre-dose (0 hours) during Weeks 18, 20, 22, and 24Population: Intent-to-Treat (ITT) Population: All participants who received at least one dose of Mircera/CERA and provided data for at least one follow-up assessment.
Reference Hb was determined individually per participant as the average of all Hb values during a pre-treatment stability assessment (Weeks -4 to 0). During the EEP (Weeks 17 to 24), participants provided a total of four blood samples for Hb monitoring while on treatment with Mircera/CERA. The average Hb during the EEP was calculated per participant and assessed against the reference value. The mean change in Hb value between reference (i.e., "Baseline") Hb and the EEP average Hb was calculated and expressed in g/dL.
Outcome measures
| Measure |
Mircera in Renal Anemia
n=187 Participants
Participants with chronic renal anemia who were previously treated with ESA therapy received intravenous Mircera/CERA, every 4 weeks for a total of 24 weeks in this single-arm study. The first dose of 120, 200, or 360 mcg was based upon the dose of ESA received prior to administration of study treatment, while subsequent doses were adjusted to maintain Hb concentrations within target of 10.5 and 12.5 g/dL.
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|---|---|
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Mean Change in Time-Adjusted Hb From Baseline to EEP
|
0.0 g/dL
Standard Deviation 1.17
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SECONDARY outcome
Timeframe: Pre-dose (0 hours) during Weeks 18, 20, 22, and 24Population: ITT Population
During the EEP (Weeks 17 to 24), participants provided a total of four blood samples for Hb monitoring while on treatment with CERA/Mircera. The percentage of participants who maintained each single Hb measurement in the target range of 10.5 to 12.5 g/dL was determined. The 95% CI was calculated using the Pearson-Clopper method for exact confidence bounds.
Outcome measures
| Measure |
Mircera in Renal Anemia
n=187 Participants
Participants with chronic renal anemia who were previously treated with ESA therapy received intravenous Mircera/CERA, every 4 weeks for a total of 24 weeks in this single-arm study. The first dose of 120, 200, or 360 mcg was based upon the dose of ESA received prior to administration of study treatment, while subsequent doses were adjusted to maintain Hb concentrations within target of 10.5 and 12.5 g/dL.
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|---|---|
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Percentage of Participants Whose Hb Remained Within Target Range Throughout the EEP
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53.7 percentage of participants
Interval 46.3 to 61.0
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SECONDARY outcome
Timeframe: Pre-dose (0 hours) during Weeks 18, 20, 22, and 24Population: ITT Population
During the EEP (Weeks 17 to 24), participants provided a total of four blood samples for Hb monitoring while on treatment with Mircera/CERA. Time spent in the target range of 10.5 to 12.5 g/dL was defined as time from first on-target Hb to time of last known on-target Hb, as collected during the EEP. Time spent in the target range was averaged among all participants and expressed in days.
Outcome measures
| Measure |
Mircera in Renal Anemia
n=187 Participants
Participants with chronic renal anemia who were previously treated with ESA therapy received intravenous Mircera/CERA, every 4 weeks for a total of 24 weeks in this single-arm study. The first dose of 120, 200, or 360 mcg was based upon the dose of ESA received prior to administration of study treatment, while subsequent doses were adjusted to maintain Hb concentrations within target of 10.5 and 12.5 g/dL.
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|---|---|
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Mean Time Spent in the Target Range for Hb During the EEP
|
34 days
Standard Deviation 18.1
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SECONDARY outcome
Timeframe: Weeks 0, 4, 8, 12, 16, 20, and 24Population: ITT Population; number (n) of participants who entered each treatment period was reported.
Study drug administration occurred monthly during the DTP (Weeks 0 to 16), which began with a pre-specified dose of Mircera/CERA according to the dose of ESA administered during Week -1. Subsequent doses could be adjusted throughout the study including during the EEP (Weeks 17 to 24) on the basis of Hb levels or other modification criteria. The percentage of participants who required a dose adjustment for any reason was calculated during the DTP and EEP.
Outcome measures
| Measure |
Mircera in Renal Anemia
n=187 Participants
Participants with chronic renal anemia who were previously treated with ESA therapy received intravenous Mircera/CERA, every 4 weeks for a total of 24 weeks in this single-arm study. The first dose of 120, 200, or 360 mcg was based upon the dose of ESA received prior to administration of study treatment, while subsequent doses were adjusted to maintain Hb concentrations within target of 10.5 and 12.5 g/dL.
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|---|---|
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Percentage of Participants Who Required Any Dose Adjustment of Mircera/CERA During the Dose Titration Period (DTP) and EEP
DTP (n=187)
|
68 percentage of participants
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Percentage of Participants Who Required Any Dose Adjustment of Mircera/CERA During the Dose Titration Period (DTP) and EEP
EEP (n=160)
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38 percentage of participants
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SECONDARY outcome
Timeframe: Continuously and at every visit from Week 0 (every week until Week 2, thereafter every 2 weeks) through Week 24Population: All Enrolled Population: Includes all participants enrolled into the study regardless of treatment received.
The number of participants who were prematurely withdrawn from the study to receive a blood transfusion during treatment, including the DTP (Weeks 0 and 16) and/or EEP (Weeks 17 to 24), was reported.
Outcome measures
| Measure |
Mircera in Renal Anemia
n=208 Participants
Participants with chronic renal anemia who were previously treated with ESA therapy received intravenous Mircera/CERA, every 4 weeks for a total of 24 weeks in this single-arm study. The first dose of 120, 200, or 360 mcg was based upon the dose of ESA received prior to administration of study treatment, while subsequent doses were adjusted to maintain Hb concentrations within target of 10.5 and 12.5 g/dL.
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|---|---|
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Number of Participants Prematurely Withdrawn From the Study to Receive Blood Transfusion
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3 participants
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Adverse Events
Mircera in Renal Anemia
Serious adverse events
| Measure |
Mircera in Renal Anemia
n=188 participants at risk
Participants with chronic renal anemia who were previously treated with ESA therapy received intravenous Mircera/CERA, every 4 weeks for a total of 24 weeks in this single-arm study. The first dose of 120, 200, or 360 mcg was based upon the dose of ESA received prior to administration of study treatment, while subsequent doses were adjusted to maintain Hb concentrations within target of 10.5 and 12.5 g/dL.
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|---|---|
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Cardiac disorders
Acute myocardial infarction
|
0.53%
1/188 • Continuously and at every visit from Week -4 (every week until Week 2, every 2 weeks until Week 24) through Week 28
Safety Population
|
|
Cardiac disorders
Angina pectoris
|
0.53%
1/188 • Continuously and at every visit from Week -4 (every week until Week 2, every 2 weeks until Week 24) through Week 28
Safety Population
|
|
Cardiac disorders
Atrial fibrillation
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0.53%
1/188 • Continuously and at every visit from Week -4 (every week until Week 2, every 2 weeks until Week 24) through Week 28
Safety Population
|
|
Cardiac disorders
Cardiac arrest
|
1.1%
2/188 • Continuously and at every visit from Week -4 (every week until Week 2, every 2 weeks until Week 24) through Week 28
Safety Population
|
|
Cardiac disorders
Cardiac valve disease
|
0.53%
1/188 • Continuously and at every visit from Week -4 (every week until Week 2, every 2 weeks until Week 24) through Week 28
Safety Population
|
|
Cardiac disorders
Myocardial ischaemia
|
0.53%
1/188 • Continuously and at every visit from Week -4 (every week until Week 2, every 2 weeks until Week 24) through Week 28
Safety Population
|
|
Gastrointestinal disorders
Gastroduodenal haemorrhage
|
0.53%
1/188 • Continuously and at every visit from Week -4 (every week until Week 2, every 2 weeks until Week 24) through Week 28
Safety Population
|
|
Gastrointestinal disorders
Gastrointestinal haemorrhage
|
1.1%
2/188 • Continuously and at every visit from Week -4 (every week until Week 2, every 2 weeks until Week 24) through Week 28
Safety Population
|
|
General disorders
Pyrexia
|
1.6%
3/188 • Continuously and at every visit from Week -4 (every week until Week 2, every 2 weeks until Week 24) through Week 28
Safety Population
|
|
Hepatobiliary disorders
Cholecystitis
|
0.53%
1/188 • Continuously and at every visit from Week -4 (every week until Week 2, every 2 weeks until Week 24) through Week 28
Safety Population
|
|
Hepatobiliary disorders
Cholecystitis acute
|
0.53%
1/188 • Continuously and at every visit from Week -4 (every week until Week 2, every 2 weeks until Week 24) through Week 28
Safety Population
|
|
Hepatobiliary disorders
Cholelithiasis
|
0.53%
1/188 • Continuously and at every visit from Week -4 (every week until Week 2, every 2 weeks until Week 24) through Week 28
Safety Population
|
|
Infections and infestations
Arteriovenous graft site infection
|
0.53%
1/188 • Continuously and at every visit from Week -4 (every week until Week 2, every 2 weeks until Week 24) through Week 28
Safety Population
|
|
Infections and infestations
Cellulitis
|
0.53%
1/188 • Continuously and at every visit from Week -4 (every week until Week 2, every 2 weeks until Week 24) through Week 28
Safety Population
|
|
Infections and infestations
Diabetic gangrene
|
0.53%
1/188 • Continuously and at every visit from Week -4 (every week until Week 2, every 2 weeks until Week 24) through Week 28
Safety Population
|
|
Infections and infestations
Diverticulitis
|
0.53%
1/188 • Continuously and at every visit from Week -4 (every week until Week 2, every 2 weeks until Week 24) through Week 28
Safety Population
|
|
Infections and infestations
Gangrene
|
0.53%
1/188 • Continuously and at every visit from Week -4 (every week until Week 2, every 2 weeks until Week 24) through Week 28
Safety Population
|
|
Infections and infestations
Gastroenteritis
|
0.53%
1/188 • Continuously and at every visit from Week -4 (every week until Week 2, every 2 weeks until Week 24) through Week 28
Safety Population
|
|
Infections and infestations
Respiratory tract infection
|
1.1%
2/188 • Continuously and at every visit from Week -4 (every week until Week 2, every 2 weeks until Week 24) through Week 28
Safety Population
|
|
Infections and infestations
Septic shock
|
0.53%
1/188 • Continuously and at every visit from Week -4 (every week until Week 2, every 2 weeks until Week 24) through Week 28
Safety Population
|
|
Infections and infestations
Urinary tract infection
|
0.53%
1/188 • Continuously and at every visit from Week -4 (every week until Week 2, every 2 weeks until Week 24) through Week 28
Safety Population
|
|
Injury, poisoning and procedural complications
Arteriovenous fistula site complication
|
0.53%
1/188 • Continuously and at every visit from Week -4 (every week until Week 2, every 2 weeks until Week 24) through Week 28
Safety Population
|
|
Injury, poisoning and procedural complications
Arteriovenous fistula site haematoma
|
0.53%
1/188 • Continuously and at every visit from Week -4 (every week until Week 2, every 2 weeks until Week 24) through Week 28
Safety Population
|
|
Injury, poisoning and procedural complications
Arteriovenous graft thrombosis
|
1.6%
3/188 • Continuously and at every visit from Week -4 (every week until Week 2, every 2 weeks until Week 24) through Week 28
Safety Population
|
|
Injury, poisoning and procedural complications
Contusion
|
0.53%
1/188 • Continuously and at every visit from Week -4 (every week until Week 2, every 2 weeks until Week 24) through Week 28
Safety Population
|
|
Musculoskeletal and connective tissue disorders
Dactylitis
|
0.53%
1/188 • Continuously and at every visit from Week -4 (every week until Week 2, every 2 weeks until Week 24) through Week 28
Safety Population
|
|
Nervous system disorders
Hydrocephalus
|
0.53%
1/188 • Continuously and at every visit from Week -4 (every week until Week 2, every 2 weeks until Week 24) through Week 28
Safety Population
|
|
Nervous system disorders
Syncope
|
0.53%
1/188 • Continuously and at every visit from Week -4 (every week until Week 2, every 2 weeks until Week 24) through Week 28
Safety Population
|
|
Nervous system disorders
Tremor
|
0.53%
1/188 • Continuously and at every visit from Week -4 (every week until Week 2, every 2 weeks until Week 24) through Week 28
Safety Population
|
|
Renal and urinary disorders
Haematuria
|
1.1%
2/188 • Continuously and at every visit from Week -4 (every week until Week 2, every 2 weeks until Week 24) through Week 28
Safety Population
|
|
Renal and urinary disorders
Nephrolithiasis
|
0.53%
1/188 • Continuously and at every visit from Week -4 (every week until Week 2, every 2 weeks until Week 24) through Week 28
Safety Population
|
|
Renal and urinary disorders
Obstructive uropathy
|
0.53%
1/188 • Continuously and at every visit from Week -4 (every week until Week 2, every 2 weeks until Week 24) through Week 28
Safety Population
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
0.53%
1/188 • Continuously and at every visit from Week -4 (every week until Week 2, every 2 weeks until Week 24) through Week 28
Safety Population
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonia aspiration
|
0.53%
1/188 • Continuously and at every visit from Week -4 (every week until Week 2, every 2 weeks until Week 24) through Week 28
Safety Population
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary hypertension
|
0.53%
1/188 • Continuously and at every visit from Week -4 (every week until Week 2, every 2 weeks until Week 24) through Week 28
Safety Population
|
|
Surgical and medical procedures
Amputation
|
0.53%
1/188 • Continuously and at every visit from Week -4 (every week until Week 2, every 2 weeks until Week 24) through Week 28
Safety Population
|
|
Surgical and medical procedures
Nephrectomy
|
0.53%
1/188 • Continuously and at every visit from Week -4 (every week until Week 2, every 2 weeks until Week 24) through Week 28
Safety Population
|
|
Vascular disorders
Thrombophlebitis superficial
|
0.53%
1/188 • Continuously and at every visit from Week -4 (every week until Week 2, every 2 weeks until Week 24) through Week 28
Safety Population
|
|
Vascular disorders
Thrombosis
|
1.1%
2/188 • Continuously and at every visit from Week -4 (every week until Week 2, every 2 weeks until Week 24) through Week 28
Safety Population
|
Other adverse events
| Measure |
Mircera in Renal Anemia
n=188 participants at risk
Participants with chronic renal anemia who were previously treated with ESA therapy received intravenous Mircera/CERA, every 4 weeks for a total of 24 weeks in this single-arm study. The first dose of 120, 200, or 360 mcg was based upon the dose of ESA received prior to administration of study treatment, while subsequent doses were adjusted to maintain Hb concentrations within target of 10.5 and 12.5 g/dL.
|
|---|---|
|
Vascular disorders
Hypertension
|
5.3%
10/188 • Continuously and at every visit from Week -4 (every week until Week 2, every 2 weeks until Week 24) through Week 28
Safety Population
|
Additional Information
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