Trial Outcomes & Findings for A Study of Monthly Intravenous C.E.R.A. (Mircera) in Hemodialysis Participants With Chronic Renal Anemia (NCT NCT00699348)

Last Updated: 2016-04-06

Results Overview

Percentage of participants maintaining the mean hemoglobin concentration within +/- 1.0 g/dL of their reference hemoglobin value and within the target range of 10.0 to 12.0 g/dL during the efficacy evaluation period (EEP) was assessed. The reference hemoglobin value was defined on the basis of the 5 assessments recorded during the stability verification period (SVP) at Weeks -4, -3, -2, -1 and 0. The mean hemoglobin concentration for each individual participant during the EEP (Week 17 to Week 24) was estimated as a time adjusted average.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

351 participants

Primary outcome timeframe

Week 17 up to Week 24

Results posted on

2016-04-06

Participant Flow

Participant milestones

Participant milestones
Measure	C.E.R.A. Adult participants with chronic renal disease and who had received intravenous epoetin (epoetin alfa, epoetin beta or darbepoetin alfa) maintenance treatment, received (after fulfilling all inclusion/exclusion criteria and 4 weeks stability verification period \[Week -4 to Week 0\]) intravenous methoxy polyethylene glycolepoetin beta (C.E.R.A.) at starting dose of 120, 200, or 360 microgram (mcg) every 4 weeks for 24 weeks.
Overall Study STARTED	351
Overall Study COMPLETED	261
Overall Study NOT COMPLETED	90

Reasons for withdrawal

Reasons for withdrawal
Measure	C.E.R.A. Adult participants with chronic renal disease and who had received intravenous epoetin (epoetin alfa, epoetin beta or darbepoetin alfa) maintenance treatment, received (after fulfilling all inclusion/exclusion criteria and 4 weeks stability verification period \[Week -4 to Week 0\]) intravenous methoxy polyethylene glycolepoetin beta (C.E.R.A.) at starting dose of 120, 200, or 360 microgram (mcg) every 4 weeks for 24 weeks.
Overall Study Death	6
Overall Study Adverse Event	15
Overall Study Withdrawal by Subject	11
Overall Study Protocol Violation	10
Overall Study Lack of Efficacy	8
Overall Study Failure to return	1
Overall Study Blood transfusion	24
Overall Study Renal transplantation	10
Overall Study Other	5

Baseline Characteristics

A Study of Monthly Intravenous C.E.R.A. (Mircera) in Hemodialysis Participants With Chronic Renal Anemia

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	C.E.R.A. n=351 Participants Adult participants with chronic renal disease and who had received intravenous epoetin (epoetin alfa, epoetin beta or darbepoetin alfa) maintenance treatment, received (after fulfilling all inclusion/exclusion criteria and 4 weeks stability verification period) intravenous C.E.R.A. at starting dose of 120, 200, or 360 mcg every 4 weeks for 24 weeks.
Age, Continuous	65.7 years STANDARD_DEVIATION 13.32 • n=93 Participants
Sex: Female, Male Female	149 Participants n=93 Participants
Sex: Female, Male Male	202 Participants n=93 Participants

PRIMARY outcome

Timeframe: Week 17 up to Week 24

Population: Per protocol (PP) population included all participants who received at least 1 dose of C.E.R.A. and for whom data for at least 1 follow-up variable was available with the exception of participants who did not fulfill the protocol specified inclusion criteria for this analysis set.

Outcome measures

Outcome measures
Measure	C.E.R.A. n=165 Participants Adult participants with chronic renal disease and who had received intravenous epoetin (epoetin alfa, epoetin beta or darbepoetin alfa) maintenance treatment, received (after fulfilling all inclusion/exclusion criteria and 4 weeks stability verification period) intravenous C.E.R.A. at starting dose of 120, 200, or 360 mcg every 4 weeks for 24 weeks.
Percentage of Participants Maintaining Mean Hemoglobin Concentration Within Plus or Minus (+/-) 1 Gram Per Deciliter (g/dL) of Reference and Within the Target Range	60.00 percentage of participants Interval 52.1 to 67.54

SECONDARY outcome

Timeframe: Week -4 up to Week 0 and Week 17 up to Week 24

Population: PP Population.

The mean change of the time adjusted average of hemoglobin from reference value obtained during the SVP (Week -4 up to Week 0) and the value during EEP (Week 17 up to Week 24) was assessed.

Outcome measures

Outcome measures
Measure	C.E.R.A. n=165 Participants Adult participants with chronic renal disease and who had received intravenous epoetin (epoetin alfa, epoetin beta or darbepoetin alfa) maintenance treatment, received (after fulfilling all inclusion/exclusion criteria and 4 weeks stability verification period) intravenous C.E.R.A. at starting dose of 120, 200, or 360 mcg every 4 weeks for 24 weeks.
Change in Hemoglobin Concentration Between Reference SVP and EEP	-0.10 g/dL Standard Deviation 0.98

SECONDARY outcome

Timeframe: Week 17 up to Week 24

Population: PP population.

Percentage of participants maintaining hemoglobin concentration within the target range of 10.0 to 12.0 g/dL during EEP (Week 17 to Week 24) was assessed.

Outcome measures

Outcome measures
Measure	C.E.R.A. n=165 Participants Adult participants with chronic renal disease and who had received intravenous epoetin (epoetin alfa, epoetin beta or darbepoetin alfa) maintenance treatment, received (after fulfilling all inclusion/exclusion criteria and 4 weeks stability verification period) intravenous C.E.R.A. at starting dose of 120, 200, or 360 mcg every 4 weeks for 24 weeks.
Percentage of Participants Maintaining Hemoglobin Concentration Within the Target Range	73.94 percentage of participants Interval 66.54 to 80.45

SECONDARY outcome

Timeframe: Week 17 up to Week 24

Population: PP population.

Median time spent by participants with hemoglobin concentration within the target range of 10.0 to 12.0 g/dL during the EEP (Week 17 to Week 24) was assessed.

Outcome measures

Outcome measures
Measure	C.E.R.A. n=165 Participants Adult participants with chronic renal disease and who had received intravenous epoetin (epoetin alfa, epoetin beta or darbepoetin alfa) maintenance treatment, received (after fulfilling all inclusion/exclusion criteria and 4 weeks stability verification period) intravenous C.E.R.A. at starting dose of 120, 200, or 360 mcg every 4 weeks for 24 weeks.
Median Time Spent by Participants With Hemoglobin Concentration in the Target Range During the EEP	44.0 days Interval 0.0 to 56.0

SECONDARY outcome

Timeframe: Week 1 up to Week 16 and Week 17 up to Week 24

Population: PP population.

Percentage of participants requiring any adjustment in the dose of study drug during the dose titration period (DTP: Week 1 to Week 16) and EEP (Week 17 to Week 24) was reported.

Outcome measures

Outcome measures
Measure	C.E.R.A. n=165 Participants Adult participants with chronic renal disease and who had received intravenous epoetin (epoetin alfa, epoetin beta or darbepoetin alfa) maintenance treatment, received (after fulfilling all inclusion/exclusion criteria and 4 weeks stability verification period) intravenous C.E.R.A. at starting dose of 120, 200, or 360 mcg every 4 weeks for 24 weeks.
Percentage of Participants Requiring Any Dose Adjustment DTP	70.3 percentage of participants
Percentage of Participants Requiring Any Dose Adjustment EEP	50.9 percentage of participants

SECONDARY outcome

Timeframe: Week -4 up to Week 52

Population: Safety population.

Number of participant who underwent red blood cell transfusion during the study was reported.

Outcome measures

Outcome measures
Measure	C.E.R.A. n=351 Participants Adult participants with chronic renal disease and who had received intravenous epoetin (epoetin alfa, epoetin beta or darbepoetin alfa) maintenance treatment, received (after fulfilling all inclusion/exclusion criteria and 4 weeks stability verification period) intravenous C.E.R.A. at starting dose of 120, 200, or 360 mcg every 4 weeks for 24 weeks.
Number of Participants With Red Blood Cell Transfusion During the Study	38 participants

Adverse Events

C.E.R.A.

Serious events: 98 serious events

Other events: 23 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	C.E.R.A. n=351 participants at risk Adult participants with chronic renal disease and who had received intravenous epoetin (epoetin alfa, epoetin beta or darbepoetin alfa) maintenance treatment, received (after fulfilling all inclusion/exclusion criteria and 4 weeks stability verification period) intravenous C.E.R.A. at starting dose of 120, 200, or 360 mcg every 4 weeks for 24 weeks.
Blood and lymphatic system disorders Anaemia	2.0% 7/351 • Up to 52 weeks Only adverse events with an onset date after the start of medication were included.
Cardiac disorders Acute coronary syndrome	0.28% 1/351 • Up to 52 weeks Only adverse events with an onset date after the start of medication were included.
Cardiac disorders Acute myocardial infarction	0.57% 2/351 • Up to 52 weeks Only adverse events with an onset date after the start of medication were included.
Cardiac disorders Angina pectoris	0.28% 1/351 • Up to 52 weeks Only adverse events with an onset date after the start of medication were included.
Cardiac disorders Angina unstable	0.28% 1/351 • Up to 52 weeks Only adverse events with an onset date after the start of medication were included.
Cardiac disorders Atrial fibrillation	0.57% 2/351 • Up to 52 weeks Only adverse events with an onset date after the start of medication were included.
Cardiac disorders Bradycardia	0.28% 1/351 • Up to 52 weeks Only adverse events with an onset date after the start of medication were included.
Cardiac disorders Cardiac disorder	0.28% 1/351 • Up to 52 weeks Only adverse events with an onset date after the start of medication were included.
Cardiac disorders Cardiac failure	0.57% 2/351 • Up to 52 weeks Only adverse events with an onset date after the start of medication were included.
Cardiac disorders Myocardial infarction	0.85% 3/351 • Up to 52 weeks Only adverse events with an onset date after the start of medication were included.
Cardiac disorders Myocardial ischaemia	0.57% 2/351 • Up to 52 weeks Only adverse events with an onset date after the start of medication were included.
Congenital, familial and genetic disorders Gastrointestinal angiodysplasia	0.28% 1/351 • Up to 52 weeks Only adverse events with an onset date after the start of medication were included.
Eye disorders Retinal detachment	0.57% 2/351 • Up to 52 weeks Only adverse events with an onset date after the start of medication were included.
Gastrointestinal disorders Abdominal pain	0.28% 1/351 • Up to 52 weeks Only adverse events with an onset date after the start of medication were included.
Gastrointestinal disorders Gastritis erosive	0.28% 1/351 • Up to 52 weeks Only adverse events with an onset date after the start of medication were included.
Gastrointestinal disorders Gastrointestinal haemorrhage	0.57% 2/351 • Up to 52 weeks Only adverse events with an onset date after the start of medication were included.
Gastrointestinal disorders Haemorrhoidal haemorrhage	0.28% 1/351 • Up to 52 weeks Only adverse events with an onset date after the start of medication were included.
Gastrointestinal disorders Intestinal ischaemia	0.28% 1/351 • Up to 52 weeks Only adverse events with an onset date after the start of medication were included.
Gastrointestinal disorders Large intestinal haemorrhage	0.28% 1/351 • Up to 52 weeks Only adverse events with an onset date after the start of medication were included.
Gastrointestinal disorders Melaena	0.28% 1/351 • Up to 52 weeks Only adverse events with an onset date after the start of medication were included.
Gastrointestinal disorders Rectal haemorrhage	0.57% 2/351 • Up to 52 weeks Only adverse events with an onset date after the start of medication were included.
General disorders Catheter site haemorrhage	0.28% 1/351 • Up to 52 weeks Only adverse events with an onset date after the start of medication were included.
General disorders Device malfunction	0.28% 1/351 • Up to 52 weeks Only adverse events with an onset date after the start of medication were included.
General disorders Pyrexia	0.85% 3/351 • Up to 52 weeks Only adverse events with an onset date after the start of medication were included.
General disorders Vessel puncture site haemorrhage	0.28% 1/351 • Up to 52 weeks Only adverse events with an onset date after the start of medication were included.
Hepatobiliary disorders Cholecystitis	0.28% 1/351 • Up to 52 weeks Only adverse events with an onset date after the start of medication were included.
Hepatobiliary disorders Cholelithiasis	0.57% 2/351 • Up to 52 weeks Only adverse events with an onset date after the start of medication were included.
Infections and infestations Bronchopneumonia	0.57% 2/351 • Up to 52 weeks Only adverse events with an onset date after the start of medication were included.
Infections and infestations Campylobacter intestinal infection	0.28% 1/351 • Up to 52 weeks Only adverse events with an onset date after the start of medication were included.
Infections and infestations Device related infection	0.57% 2/351 • Up to 52 weeks Only adverse events with an onset date after the start of medication were included.
Infections and infestations Influenza	0.57% 2/351 • Up to 52 weeks Only adverse events with an onset date after the start of medication were included.
Infections and infestations Lung infection	0.28% 1/351 • Up to 52 weeks Only adverse events with an onset date after the start of medication were included.
Infections and infestations Oropharyngitis fungal	0.28% 1/351 • Up to 52 weeks Only adverse events with an onset date after the start of medication were included.
Infections and infestations Osteomyelitis	0.28% 1/351 • Up to 52 weeks Only adverse events with an onset date after the start of medication were included.
Infections and infestations Pneumonia	0.85% 3/351 • Up to 52 weeks Only adverse events with an onset date after the start of medication were included.
Infections and infestations Sepsis	0.28% 1/351 • Up to 52 weeks Only adverse events with an onset date after the start of medication were included.
Infections and infestations Staphylococcal sepsis	0.28% 1/351 • Up to 52 weeks Only adverse events with an onset date after the start of medication were included.
Injury, poisoning and procedural complications Arteriovenous fistula aneurysm	0.28% 1/351 • Up to 52 weeks Only adverse events with an onset date after the start of medication were included.
Injury, poisoning and procedural complications Arteriovenous fistula thrombosis	2.6% 9/351 • Up to 52 weeks Only adverse events with an onset date after the start of medication were included.
Injury, poisoning and procedural complications Fall	0.28% 1/351 • Up to 52 weeks Only adverse events with an onset date after the start of medication were included.
Injury, poisoning and procedural complications Femur fracture	0.57% 2/351 • Up to 52 weeks Only adverse events with an onset date after the start of medication were included.
Injury, poisoning and procedural complications Head injury	0.28% 1/351 • Up to 52 weeks Only adverse events with an onset date after the start of medication were included.
Injury, poisoning and procedural complications Operative haemorrhage	0.28% 1/351 • Up to 52 weeks Only adverse events with an onset date after the start of medication were included.
Injury, poisoning and procedural complications Post procedural haematoma	0.28% 1/351 • Up to 52 weeks Only adverse events with an onset date after the start of medication were included.
Injury, poisoning and procedural complications Skin laceration	0.28% 1/351 • Up to 52 weeks Only adverse events with an onset date after the start of medication were included.
Injury, poisoning and procedural complications Traumatic haemorrhage	0.28% 1/351 • Up to 52 weeks Only adverse events with an onset date after the start of medication were included.
Injury, poisoning and procedural complications Vascular access complication	0.85% 3/351 • Up to 52 weeks Only adverse events with an onset date after the start of medication were included.
Investigations Haemoglobin decreased	0.85% 3/351 • Up to 52 weeks Only adverse events with an onset date after the start of medication were included.
Metabolism and nutrition disorders Cachexia	0.57% 2/351 • Up to 52 weeks Only adverse events with an onset date after the start of medication were included.
Metabolism and nutrition disorders Diabetic foot	0.28% 1/351 • Up to 52 weeks Only adverse events with an onset date after the start of medication were included.
Metabolism and nutrition disorders Hyperkalaemia	0.28% 1/351 • Up to 52 weeks Only adverse events with an onset date after the start of medication were included.
Musculoskeletal and connective tissue disorders Foot deformity	0.28% 1/351 • Up to 52 weeks Only adverse events with an onset date after the start of medication were included.
Musculoskeletal and connective tissue disorders Intervertebral disc protrusion	0.28% 1/351 • Up to 52 weeks Only adverse events with an onset date after the start of medication were included.
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	0.28% 1/351 • Up to 52 weeks Only adverse events with an onset date after the start of medication were included.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	0.28% 1/351 • Up to 52 weeks Only adverse events with an onset date after the start of medication were included.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Colon cancer	0.28% 1/351 • Up to 52 weeks Only adverse events with an onset date after the start of medication were included.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Gallbladder cancer	0.28% 1/351 • Up to 52 weeks Only adverse events with an onset date after the start of medication were included.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung carcinoma cell type unspecified recurrent	0.28% 1/351 • Up to 52 weeks Only adverse events with an onset date after the start of medication were included.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Prostate cancer	0.28% 1/351 • Up to 52 weeks Only adverse events with an onset date after the start of medication were included.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Squamous cell carcinoma	0.28% 1/351 • Up to 52 weeks Only adverse events with an onset date after the start of medication were included.
Nervous system disorders Cerebrovascular disorder	0.28% 1/351 • Up to 52 weeks Only adverse events with an onset date after the start of medication were included.
Nervous system disorders Nervous system disorder	0.28% 1/351 • Up to 52 weeks Only adverse events with an onset date after the start of medication were included.
Nervous system disorders Paraesthesia	0.28% 1/351 • Up to 52 weeks Only adverse events with an onset date after the start of medication were included.
Nervous system disorders Syncope	0.28% 1/351 • Up to 52 weeks Only adverse events with an onset date after the start of medication were included.
Nervous system disorders Transient ischaemic attack	1.1% 4/351 • Up to 52 weeks Only adverse events with an onset date after the start of medication were included.
Psychiatric disorders Depression	0.28% 1/351 • Up to 52 weeks Only adverse events with an onset date after the start of medication were included.
Renal and urinary disorders Haematuria	0.28% 1/351 • Up to 52 weeks Only adverse events with an onset date after the start of medication were included.
Respiratory, thoracic and mediastinal disorders Acute pulmonary oedema	1.1% 4/351 • Up to 52 weeks Only adverse events with an onset date after the start of medication were included.
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.57% 2/351 • Up to 52 weeks Only adverse events with an onset date after the start of medication were included.
Respiratory, thoracic and mediastinal disorders Epistaxis	0.28% 1/351 • Up to 52 weeks Only adverse events with an onset date after the start of medication were included.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.28% 1/351 • Up to 52 weeks Only adverse events with an onset date after the start of medication were included.
Respiratory, thoracic and mediastinal disorders Pulmonary oedema	0.57% 2/351 • Up to 52 weeks Only adverse events with an onset date after the start of medication were included.
Skin and subcutaneous tissue disorders Skin ulcer	0.28% 1/351 • Up to 52 weeks Only adverse events with an onset date after the start of medication were included.
Surgical and medical procedures Arteriovenous fistula operation	0.28% 1/351 • Up to 52 weeks Only adverse events with an onset date after the start of medication were included.
Surgical and medical procedures Implantable defibrillator insertion	0.28% 1/351 • Up to 52 weeks Only adverse events with an onset date after the start of medication were included.
Surgical and medical procedures Knee arthroplasty	0.28% 1/351 • Up to 52 weeks Only adverse events with an onset date after the start of medication were included.
Vascular disorders Angiopathy	0.85% 3/351 • Up to 52 weeks Only adverse events with an onset date after the start of medication were included.
Vascular disorders Deep vein thrombosis	0.28% 1/351 • Up to 52 weeks Only adverse events with an onset date after the start of medication were included.
Vascular disorders Haemorrhage	0.28% 1/351 • Up to 52 weeks Only adverse events with an onset date after the start of medication were included.
Vascular disorders Hypotension	0.28% 1/351 • Up to 52 weeks Only adverse events with an onset date after the start of medication were included.
Vascular disorders Necrosis ischaemic	0.28% 1/351 • Up to 52 weeks Only adverse events with an onset date after the start of medication were included.
Vascular disorders Peripheral arterial occlusive disease	0.57% 2/351 • Up to 52 weeks Only adverse events with an onset date after the start of medication were included.
Vascular disorders Peripheral ischaemia	1.1% 4/351 • Up to 52 weeks Only adverse events with an onset date after the start of medication were included.
Vascular disorders Thrombosis	0.28% 1/351 • Up to 52 weeks Only adverse events with an onset date after the start of medication were included.

Other adverse events

Other adverse events
Measure	C.E.R.A. n=351 participants at risk Adult participants with chronic renal disease and who had received intravenous epoetin (epoetin alfa, epoetin beta or darbepoetin alfa) maintenance treatment, received (after fulfilling all inclusion/exclusion criteria and 4 weeks stability verification period) intravenous C.E.R.A. at starting dose of 120, 200, or 360 mcg every 4 weeks for 24 weeks.
Vascular disorders Hypertension	6.6% 23/351 • Up to 52 weeks Only adverse events with an onset date after the start of medication were included.

Additional Information

Medical Communications

Hoffmann-LaRoche

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