Trial Outcomes & Findings for A Study for Monthly Methoxy Polyethylene Glycol-Epoetin Beta Treatment in Patients With Chronic Renal Anaemia (NCT NCT01066000)

Last Updated: 2017-11-13

Results Overview

The proportion of participants with their mean haemoglobin (Hb) concentration (g/dL) within the target range during the efficacy evaluation period was assessed. The target range is the reference Hb not \>12 g/dL and not \< 10 g/dL.

Recruitment status

TERMINATED

Study phase

PHASE4

Target enrollment

33 participants

Primary outcome timeframe

Up to Week 24

Results posted on

2017-11-13

Participant Flow

The study was conducted at 10 sites in the Indonesia and the study period was from 05 October 2009 to 12 September 2011.

Of the 85 screened participants 52 were screening failure due to abnormal haemoglobin concentration and 33 were enrolled in the study.

Participant milestones

Participant milestones
Measure	Mircera Eligible participants received methoxy polyethylene glycol-epoetin beta (Mircera) intravenously (IV), once every four weeks for 24 weeks. Participants received a starting dose of Mircera 100, 150 or 200 microgram (mcg) which was based on the Epoetin dose of\<8000, 8000-16000, or \>16000 International units \[IU\]/Week, administered during the week preceding the switch to the study drug.
Overall Study STARTED	33
Overall Study COMPLETED	24
Overall Study NOT COMPLETED	9

Reasons for withdrawal

Reasons for withdrawal
Measure	Mircera Eligible participants received methoxy polyethylene glycol-epoetin beta (Mircera) intravenously (IV), once every four weeks for 24 weeks. Participants received a starting dose of Mircera 100, 150 or 200 microgram (mcg) which was based on the Epoetin dose of\<8000, 8000-16000, or \>16000 International units \[IU\]/Week, administered during the week preceding the switch to the study drug.
Overall Study Protocol Violation	4
Overall Study Death	3
Overall Study Withdrawal by Subject	1
Overall Study Adverse Event	1

Baseline Characteristics

A Study for Monthly Methoxy Polyethylene Glycol-Epoetin Beta Treatment in Patients With Chronic Renal Anaemia

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Mircera n=33 Participants Eligible participants received Mircera IV, once every four weeks for 24 weeks. Participants received a starting dose of Mircera 100, 150 or 200 mcg which was based on the Epoetin dose of \<8000, 8000-16000, or \>16000 IU/Week, administered during the week preceding the switch to the study drug.
Age, Continuous	58.7 years STANDARD_DEVIATION 13.4 • n=5 Participants
Sex: Female, Male Female	13 Participants n=5 Participants
Sex: Female, Male Male	20 Participants n=5 Participants

PRIMARY outcome

Timeframe: Up to Week 24

Population: Intent to treat (ITT) population was defined as all participants who entered study and took at least one dose of study drug. The ITT and safety population were identical. At Week 24, data of 24 participants were included whereas 9 participants were excluded from the analysis as they discontinued the study before analysis of this outcome measure.

Outcome measures

Outcome measures
Measure	Mircera n=24 Participants Eligible participants received Mircera IV, once every four weeks for 24 weeks. Participants received a starting dose of Mircera 100, 150 or 200 mcg which was based on the Epoetin dose of \<8000, 8000-16000, or \>16000 IU/Week, administered during the week preceding the switch to the study drug.
Proportion of Participants Maintaining Average Haemoglobin During the Efficacy Evaluation Period Within the Target Range (10-12 g/dl)	45.8 Percentage of participants

SECONDARY outcome

Timeframe: Up to Week 28

Population: Safety population included all participants who entered into the study and took at least one dose of study drug.The ITT and safety population were identical. Data of maximum number of participants (33 participants) available at the time of analysis were analysed and reported.

An adverse event (AE) was defined as any untoward medical occurrence that occurred during the course of the trial after study treatment had started. An adverse event was therefore any unfavourable and unintended sign, symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug. A Serious adverse event (SAE) is any untoward medical occurrence that at any dose results in death, are life threatening, requires hospitalization or prolongation of hospitalization or results in disability/incapacity, and congenital anomaly/birth defect. The AEs were assessed from baseline to every visit throughout the treatment, post study drug discontinuation, and follow up period.

Outcome measures

Outcome measures
Measure	Mircera n=33 Participants Eligible participants received Mircera IV, once every four weeks for 24 weeks. Participants received a starting dose of Mircera 100, 150 or 200 mcg which was based on the Epoetin dose of \<8000, 8000-16000, or \>16000 IU/Week, administered during the week preceding the switch to the study drug.
Number of Participants With Adverse Events and Serious Adverse Events Number of participants serious AE	4 Participants
Number of Participants With Adverse Events and Serious Adverse Events Total number of participants with at least one AE	15 Participants

SECONDARY outcome

Timeframe: Up to Week 24

Population: ITT population was defined as all participants who entered study and took at least one dose of study drug. The ITT and safety population were identical. At Week 24, data of 24 participants were included whereas 9 participants were excluded from the analysis as they discontinued the study before analysis of this outcome measure.

The mean haemoglobin (Hb) concentration (g/dL) change from the baseline (Week 0) till efficacy evaluation period (EEP) was assessed and reported.

Outcome measures

Outcome measures
Measure	Mircera n=24 Participants Eligible participants received Mircera IV, once every four weeks for 24 weeks. Participants received a starting dose of Mircera 100, 150 or 200 mcg which was based on the Epoetin dose of \<8000, 8000-16000, or \>16000 IU/Week, administered during the week preceding the switch to the study drug.
Mean Change in Haemoglobin Concentration From Screening Period and Efficacy Evaluation Period At baseline	10.89 g/dL Standard Deviation 0.48
Mean Change in Haemoglobin Concentration From Screening Period and Efficacy Evaluation Period Mean change at EEP	0.04 g/dL Standard Deviation 1.23

SECONDARY outcome

Timeframe: Up to Week 24

The proportion of participants maintaining haemoglobin concentration within the haemoglobin range 10-12g/dL throughout the efficacy evaluation period (EEP) was assessed and reported.

Outcome measures

Outcome measures
Measure	Mircera n=24 Participants Eligible participants received Mircera IV, once every four weeks for 24 weeks. Participants received a starting dose of Mircera 100, 150 or 200 mcg which was based on the Epoetin dose of \<8000, 8000-16000, or \>16000 IU/Week, administered during the week preceding the switch to the study drug.
Proportion of Participants Maintaining Haemoglobin Concentration Within the Haemoglobin Range 10-12g/dL Throughout the Efficacy Evaluation Period Participants maintaining Hb >10 g/dl	62.5 Percentage of participants
Proportion of Participants Maintaining Haemoglobin Concentration Within the Haemoglobin Range 10-12g/dL Throughout the Efficacy Evaluation Period Participants maintaining Hb within 10-12 g/dl	16.7 Percentage of participants

SECONDARY outcome

Timeframe: Up to Week 24

Mean time spent in the haemoglobin range 10 - 12 g/dL during the efficacy evaluation period (EEP) was assessed and reported.

Outcome measures

Outcome measures
Measure	Mircera n=24 Participants Eligible participants received Mircera IV, once every four weeks for 24 weeks. Participants received a starting dose of Mircera 100, 150 or 200 mcg which was based on the Epoetin dose of \<8000, 8000-16000, or \>16000 IU/Week, administered during the week preceding the switch to the study drug.
Mean Time Spent by Participants in the Haemoglobin Range of 10 - 12 g/dL During the Efficacy Evaluation Period	3.92 Weeks Standard Deviation 2.39

SECONDARY outcome

Timeframe: Up to Week 24

Mean number of months per participant requiring dose adjustment during the dose titration and evaluation periods was assessed and reported.

Outcome measures

Outcome measures
Measure	Mircera n=24 Participants Eligible participants received Mircera IV, once every four weeks for 24 weeks. Participants received a starting dose of Mircera 100, 150 or 200 mcg which was based on the Epoetin dose of \<8000, 8000-16000, or \>16000 IU/Week, administered during the week preceding the switch to the study drug.
Mean Number of Months Per Participant Requiring Dose Adjustment During the Dose Titration and Evaluation Periods	1 Months Standard Deviation 3.5

SECONDARY outcome

Timeframe: Baseline, Week 4, Week 8, Week 12, Week 16, and Week 20

Population: ITT population was defined as all participants who entered into study and took at least one dose of study drug. The ITT and safety population were identical. Data of maximum number of participants (24 participants) available at the time of analysis were analysed and 9 participants discontinued the study before this analysis.

Mean monthly dose of methoxy polyethylene glycol-epoetin beta during the dose titration and evaluation periods was assessed and reported.

Outcome measures

Outcome measures
Measure	Mircera n=24 Participants Eligible participants received Mircera IV, once every four weeks for 24 weeks. Participants received a starting dose of Mircera 100, 150 or 200 mcg which was based on the Epoetin dose of \<8000, 8000-16000, or \>16000 IU/Week, administered during the week preceding the switch to the study drug.
Mean Monthly Dose of Methoxy Polyethylene Glycol-epoetin Beta During the Dose Titration and Evaluation Periods At Baseline	97.9 μg/month Standard Deviation 14.6
Mean Monthly Dose of Methoxy Polyethylene Glycol-epoetin Beta During the Dose Titration and Evaluation Periods At Week 4	103.1 μg/month Standard Deviation 19.9
Mean Monthly Dose of Methoxy Polyethylene Glycol-epoetin Beta During the Dose Titration and Evaluation Periods At Week 8	107.3 μg/month Standard Deviation 37.9
Mean Monthly Dose of Methoxy Polyethylene Glycol-epoetin Beta During the Dose Titration and Evaluation Periods At Week 12	119 μg/month Standard Deviation 43.8
Mean Monthly Dose of Methoxy Polyethylene Glycol-epoetin Beta During the Dose Titration and Evaluation Periods At Week 16	114.6 μg/month Standard Deviation 53.6
Mean Monthly Dose of Methoxy Polyethylene Glycol-epoetin Beta During the Dose Titration and Evaluation Periods At Week 20	120.8 μg/month Standard Deviation 73.2

SECONDARY outcome

Timeframe: Up to Week 28

A marked laboratory abnormality is defined as above and/or below the normal range of a laboratory parameter which was considered to be potentially clinically relevant. The number of participants with marked laboratory abnormality are presented. Marked laboratory abnormalities were analyzed according to the Roche specified limits for the following reference range: Haemoglobin (Hb) (11.7-17.3 g/dL), Haematocrit (Hct) (35-47%), White blood cells (WBC) (3.6-11.0 10\^3/µL), Red blood cells (RBC) (3.8- 5.9 10\^6/µL), MCV (80-100 fL) Platelets (150-440 10\^3/µL), Iron (37-158 µg/dL), Ferritin (10-365 ng/mL), Transferrin (170-340 mg/dL), TIBC (250-450 µg/dL), TSAT (15-50%), Albumin (3.4-4.8 g/dL), hs-CRP (\<= 10.000 mg/dL), Potassium (3.5-5.1 mmol/L), and Phosphorus (2.7-4.5 mg/dL).

Outcome measures

Outcome measures
Measure	Mircera n=33 Participants Eligible participants received Mircera IV, once every four weeks for 24 weeks. Participants received a starting dose of Mircera 100, 150 or 200 mcg which was based on the Epoetin dose of \<8000, 8000-16000, or \>16000 IU/Week, administered during the week preceding the switch to the study drug.
Number of Participants With Marked Laboratory Abnormalities At Week 24, Potassium-High	3 Participants
Number of Participants With Marked Laboratory Abnormalities At Baseline, Hb-Low	30 Participants
Number of Participants With Marked Laboratory Abnormalities At Baseline, Hct-Low	28 Participants
Number of Participants With Marked Laboratory Abnormalities At Baseline, WBC-Low	1 Participants
Number of Participants With Marked Laboratory Abnormalities At Baseline, WBC-High	2 Participants
Number of Participants With Marked Laboratory Abnormalities At Baseline, MCV-Low	3 Participants
Number of Participants With Marked Laboratory Abnormalities At Baseline, MCV- High	4 Participants
Number of Participants With Marked Laboratory Abnormalities At Baseline, RBC-Low	1 Participants
Number of Participants With Marked Laboratory Abnormalities At Baseline, RBC -High	2 Participants
Number of Participants With Marked Laboratory Abnormalities At Baseline, Platelets-Low	7 Participants
Number of Participants With Marked Laboratory Abnormalities At Baseline, Iron-Low	10 Participants
Number of Participants With Marked Laboratory Abnormalities At Baseline, Iron-High	1 Participants
Number of Participants With Marked Laboratory Abnormalities At Baseline, Feritin-High	25 Participants
Number of Participants With Marked Laboratory Abnormalities At Baseline, Transferin-Low	9 Participants
Number of Participants With Marked Laboratory Abnormalities At Baseline, TIBC-Low	24 Participants
Number of Participants With Marked Laboratory Abnormalities At Baseline, TSAT-Low	8 Participants
Number of Participants With Marked Laboratory Abnormalities At Baseline, TSAT-High	8 Participants
Number of Participants With Marked Laboratory Abnormalities At Baseline, Albumin-Low	3 Participants
Number of Participants With Marked Laboratory Abnormalities At Baseline, hs-CRP-High	2 Participants
Number of Participants With Marked Laboratory Abnormalities At Baseline, Potassium-High	9 Participants
Number of Participants With Marked Laboratory Abnormalities At Baseline, Phosphorus-High	19 Participants
Number of Participants With Marked Laboratory Abnormalities At Week 8, Hb-Low	22 Participants
Number of Participants With Marked Laboratory Abnormalities At Week 8, Hct-Low	22 Participants
Number of Participants With Marked Laboratory Abnormalities At Week 8, WBC-High	3 Participants
Number of Participants With Marked Laboratory Abnormalities At Week 8, MCV-Low	5 Participants
Number of Participants With Marked Laboratory Abnormalities At Week 8, RBC -High	25 Participants
Number of Participants With Marked Laboratory Abnormalities At Week 8, Platelets-Low	1 Participants
Number of Participants With Marked Laboratory Abnormalities At Week 8, Platelets-High	21 Participants
Number of Participants With Marked Laboratory Abnormalities At Week 8, Iron-Low	1 Participants
Number of Participants With Marked Laboratory Abnormalities At Week 8, Iron-High	22 Participants
Number of Participants With Marked Laboratory Abnormalities At Week 8, Feritin-High	6 Participants
Number of Participants With Marked Laboratory Abnormalities At Week 8, Transferin-Low	6 Participants
Number of Participants With Marked Laboratory Abnormalities At Week 8, TIBC-Low	24 Participants
Number of Participants With Marked Laboratory Abnormalities At Week 24, Hb-Low	18 Participants
Number of Participants With Marked Laboratory Abnormalities At Week 24, Hct-Low	14 Participants
Number of Participants With Marked Laboratory Abnormalities At Week 24, WBC-High	2 Participants
Number of Participants With Marked Laboratory Abnormalities At Week 24, RBC -High	4 Participants
Number of Participants With Marked Laboratory Abnormalities At Week 24, Platelets-Low	4 Participants
Number of Participants With Marked Laboratory Abnormalities At Week 24, Platelets-High	1 Participants
Number of Participants With Marked Laboratory Abnormalities At Week 24, Iron-Low	4 Participants
Number of Participants With Marked Laboratory Abnormalities At Week 24, Iron-High	1 Participants
Number of Participants With Marked Laboratory Abnormalities At Week 24, Feritin-High	8 Participants
Number of Participants With Marked Laboratory Abnormalities At Week 24, Transferin-Low	6 Participants
Number of Participants With Marked Laboratory Abnormalities At Week 24, Transferin-High	1 Participants
Number of Participants With Marked Laboratory Abnormalities At Week 24, TIBC-Low	12 Participants
Number of Participants With Marked Laboratory Abnormalities At Week 24, TSAT-Low	1 Participants
Number of Participants With Marked Laboratory Abnormalities At Week 24, TSAT-High	3 Participants
Number of Participants With Marked Laboratory Abnormalities At Week 24, Albumin-High	1 Participants
Number of Participants With Marked Laboratory Abnormalities At Week 24, hs-CRP-High	2 Participants
Number of Participants With Marked Laboratory Abnormalities At Week 24,Potassium-Low	2 Participants
Number of Participants With Marked Laboratory Abnormalities At Week 24, Phosphorus-High	11 Participants

Adverse Events

Mircera

Serious events: 4 serious events

Other events: 15 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Mircera n=33 participants at risk Eligible participants received Mircera IV, once every four weeks for 24 weeks. Participants received a starting dose of Mircera 100, 150 or 200 mcg which was based on the Epoetin dose of \<8000, 8000-16000, or \>16000 IU/Week, administered during the week preceding the switch to the study drug.
Nervous system disorders Decrease of state awareness	3.0% 1/33 • Up to 28 weeks Serious adverse events and non-serious adverse events are reported in Safety Analysis Set, which consists of all participants who received at least one dose of study medication and had a safety assessment performed post baseline.
Renal and urinary disorders Colic renal	3.0% 1/33 • Up to 28 weeks Serious adverse events and non-serious adverse events are reported in Safety Analysis Set, which consists of all participants who received at least one dose of study medication and had a safety assessment performed post baseline.
Cardiac disorders Cardiovascular event	3.0% 1/33 • Up to 28 weeks Serious adverse events and non-serious adverse events are reported in Safety Analysis Set, which consists of all participants who received at least one dose of study medication and had a safety assessment performed post baseline.
Cardiac disorders Acute myocardial infarction	3.0% 1/33 • Up to 28 weeks Serious adverse events and non-serious adverse events are reported in Safety Analysis Set, which consists of all participants who received at least one dose of study medication and had a safety assessment performed post baseline.

Other adverse events

Other adverse events
Measure	Mircera n=33 participants at risk Eligible participants received Mircera IV, once every four weeks for 24 weeks. Participants received a starting dose of Mircera 100, 150 or 200 mcg which was based on the Epoetin dose of \<8000, 8000-16000, or \>16000 IU/Week, administered during the week preceding the switch to the study drug.
Infections and infestations Hepatitis	3.0% 1/33 • Up to 28 weeks Serious adverse events and non-serious adverse events are reported in Safety Analysis Set, which consists of all participants who received at least one dose of study medication and had a safety assessment performed post baseline.
General disorders Fever	3.0% 1/33 • Up to 28 weeks Serious adverse events and non-serious adverse events are reported in Safety Analysis Set, which consists of all participants who received at least one dose of study medication and had a safety assessment performed post baseline.
Nervous system disorders Headache	9.1% 3/33 • Up to 28 weeks Serious adverse events and non-serious adverse events are reported in Safety Analysis Set, which consists of all participants who received at least one dose of study medication and had a safety assessment performed post baseline.
Nervous system disorders Dizziness	3.0% 1/33 • Up to 28 weeks Serious adverse events and non-serious adverse events are reported in Safety Analysis Set, which consists of all participants who received at least one dose of study medication and had a safety assessment performed post baseline.
Nervous system disorders Decrease of state of awareness	3.0% 1/33 • Up to 28 weeks Serious adverse events and non-serious adverse events are reported in Safety Analysis Set, which consists of all participants who received at least one dose of study medication and had a safety assessment performed post baseline.
Blood and lymphatic system disorders Anemia	3.0% 1/33 • Up to 28 weeks Serious adverse events and non-serious adverse events are reported in Safety Analysis Set, which consists of all participants who received at least one dose of study medication and had a safety assessment performed post baseline.
Vascular disorders Haemorrhoid	3.0% 1/33 • Up to 28 weeks Serious adverse events and non-serious adverse events are reported in Safety Analysis Set, which consists of all participants who received at least one dose of study medication and had a safety assessment performed post baseline.
Vascular disorders Hypertension	3.0% 1/33 • Up to 28 weeks Serious adverse events and non-serious adverse events are reported in Safety Analysis Set, which consists of all participants who received at least one dose of study medication and had a safety assessment performed post baseline.
Skin and subcutaneous tissue disorders Itching	3.0% 1/33 • Up to 28 weeks Serious adverse events and non-serious adverse events are reported in Safety Analysis Set, which consists of all participants who received at least one dose of study medication and had a safety assessment performed post baseline.
Musculoskeletal and connective tissue disorders Back pain	3.0% 1/33 • Up to 28 weeks Serious adverse events and non-serious adverse events are reported in Safety Analysis Set, which consists of all participants who received at least one dose of study medication and had a safety assessment performed post baseline.
Musculoskeletal and connective tissue disorders Osteoarthritis	3.0% 1/33 • Up to 28 weeks Serious adverse events and non-serious adverse events are reported in Safety Analysis Set, which consists of all participants who received at least one dose of study medication and had a safety assessment performed post baseline.
Immune system disorders Allergy	3.0% 1/33 • Up to 28 weeks Serious adverse events and non-serious adverse events are reported in Safety Analysis Set, which consists of all participants who received at least one dose of study medication and had a safety assessment performed post baseline.
Immune system disorders Food allergy	3.0% 1/33 • Up to 28 weeks Serious adverse events and non-serious adverse events are reported in Safety Analysis Set, which consists of all participants who received at least one dose of study medication and had a safety assessment performed post baseline.
Cardiac disorders Acute myocardial infarction	3.0% 1/33 • Up to 28 weeks Serious adverse events and non-serious adverse events are reported in Safety Analysis Set, which consists of all participants who received at least one dose of study medication and had a safety assessment performed post baseline.
Cardiac disorders Cardiovascular event	3.0% 1/33 • Up to 28 weeks Serious adverse events and non-serious adverse events are reported in Safety Analysis Set, which consists of all participants who received at least one dose of study medication and had a safety assessment performed post baseline.
Reproductive system and breast disorders Menstruate	3.0% 1/33 • Up to 28 weeks Serious adverse events and non-serious adverse events are reported in Safety Analysis Set, which consists of all participants who received at least one dose of study medication and had a safety assessment performed post baseline.
Gastrointestinal disorders Diarrhea	3.0% 1/33 • Up to 28 weeks Serious adverse events and non-serious adverse events are reported in Safety Analysis Set, which consists of all participants who received at least one dose of study medication and had a safety assessment performed post baseline.
Renal and urinary disorders Hematuria	6.1% 2/33 • Up to 28 weeks Serious adverse events and non-serious adverse events are reported in Safety Analysis Set, which consists of all participants who received at least one dose of study medication and had a safety assessment performed post baseline.
Renal and urinary disorders Colic renal	3.0% 1/33 • Up to 28 weeks Serious adverse events and non-serious adverse events are reported in Safety Analysis Set, which consists of all participants who received at least one dose of study medication and had a safety assessment performed post baseline.

Additional Information

Roche Trial Information Hotline

F. Hoffmann-La Roche AG

Phone: +41 616878333

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