Trial Outcomes & Findings for A Study of Methoxy Polyethylene Glycol-epoetin Beta (Mircera) in Participants With Chronic Kidney Disease (PRIMAVERA) (NCT NCT01194154)

NCT ID: NCT01194154

Last Updated: 2017-05-10

Results Overview

The yearly reduction in eGFR was calculated using the MDRD-4 formula. This formula is based on age, sex, and serum creatinine and eGFR values are calculated as follows: GFR in milliliter per minute (mL/min) per 1.73 meter square (m\^2) = 175 x Serum Cr\^-1.154 x age\^-0.203 x 0.742 (if female). The yearly reduction rate (mL/min/1.73m\^2 / Year) is defined as -365.25 multiplied by Beta, where Beta is the slope parameter derived for each participants separately by simple linear regression of the change from baseline in participant's eGFR measurements (from Baseline to Visit 24) on the actual day of measurement.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

241 participants

Primary outcome timeframe

24 months

Results posted on

2017-05-10

Participant Flow

Total 241 participants were enrolled, 2 participants in the Mircera group and 4 participants in the placebo group did not receive medication.

Participant milestones

Participant milestones
Measure	Mircera Methoxy polyethylene glycol-epoetin beta 30 microgram (mcg) subcutaneous injection once monthly up to 24 months with sequential dose adjustments to 50 mcg or 75 mcg depending on change of hemoglobin values of more than 1.0 gram (g)/ deciliter (dL).	Placebo Placebo matching to Methoxy polyethylene glycol-epoetin beta subcutaneous injection once monthly up to 24 months.
Overall Study STARTED	117	124
Overall Study Full Analysis Set	115	120
Overall Study Safety Analysis Set	118	117
Overall Study COMPLETED	68	91
Overall Study NOT COMPLETED	49	33

Reasons for withdrawal

Reasons for withdrawal
Measure	Mircera Methoxy polyethylene glycol-epoetin beta 30 microgram (mcg) subcutaneous injection once monthly up to 24 months with sequential dose adjustments to 50 mcg or 75 mcg depending on change of hemoglobin values of more than 1.0 gram (g)/ deciliter (dL).	Placebo Placebo matching to Methoxy polyethylene glycol-epoetin beta subcutaneous injection once monthly up to 24 months.
Overall Study Adverse Event	12	7
Overall Study Lost to Follow-up	2	3
Overall Study Protocol Violation	0	1
Overall Study Withdrawal by Subject	5	6
Overall Study Blood pressure increase	5	3
Overall Study Hemoglobin decrease	0	1
Overall Study Hemoglobin increase	12	3
Overall Study Skipping of CERA treatment at two visits	3	0
Overall Study Treatment with prohibited medication	4	5
Overall Study Other	4	0
Overall Study Did not receive study medication	2	4

Baseline Characteristics

A Study of Methoxy Polyethylene Glycol-epoetin Beta (Mircera) in Participants With Chronic Kidney Disease (PRIMAVERA)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Mircera n=115 Participants Methoxy polyethylene glycol-epoetin beta 30 mcg subcutaneous injection once monthly up to 24 months with sequential dose adjustments to 50 mcg or 75 mcg depending on change of hemoglobin values of more than 1.0 g/dL.	Placebo n=120 Participants Placebo matching to Methoxy polyethylene glycol-epoetin beta subcutaneous injection once monthly up to 24 months.	Total n=235 Participants Total of all reporting groups
Age, Continuous	63.37 years STANDARD_DEVIATION 12.26 • n=5 Participants	62.97 years STANDARD_DEVIATION 14.30 • n=7 Participants	63.17 years STANDARD_DEVIATION 13.31 • n=5 Participants
Sex: Female, Male Female	44 Participants n=5 Participants	44 Participants n=7 Participants	88 Participants n=5 Participants
Sex: Female, Male Male	71 Participants n=5 Participants	76 Participants n=7 Participants	147 Participants n=5 Participants

PRIMARY outcome

Timeframe: 24 months

Population: FAS included all randomized participants who received at least one dose of the study medication and provided any successive eGFR measurement.

Outcome measures

Outcome measures
Measure	Mircera n=115 Participants Methoxy polyethylene glycol-epoetin beta 30 mcg subcutaneous injection once monthly up to 24 months with sequential dose adjustments to 50 mcg or 75 mcg depending on change of hemoglobin values of more than 1.0 g/dL.	Placebo n=120 Participants Placebo matching to Methoxy polyethylene glycol-epoetin beta subcutaneous injection once monthly up to 24 months.
Yearly Reduction Rate of Estimated Glomerular Filtration Rate (eGFR) Calculated by Modification of Diet in Renal Disease With 4 Variables (MDRD-4)	3.04 mL/min/1.73m^2/year Interval 1.2 to 4.87	0.82 mL/min/1.73m^2/year Interval -0.96 to 2.61

SECONDARY outcome

Timeframe: 24 months

Population: FAS included all randomized participants who received at least one dose of the study medication and provided any successive eGFR measurement.

The eGFR value calculated using the CKD-EPI equation. The formula used is based on age, sex, ethnicity, and serum creatinine and eGFR values are calculated as follows: GFR in mL/min per 1.73 m\^2 = 141 x min (SerumCr/k; 1)\^a x max(SerumCr/k; 1)\^(-1.209) x 0.993\^age x F x B, where k=0.7 for female (else=0.9); a=-0.329 for female (else=-0.411), F=1.018 for female (else=1), B=1.159 for black (else=1), min/max=minimum/maximum of listed values. The Yearly Reduction Rate (mL/min/1.73m\^2 / Year) is defined as -365.25 x Beta, where Beta is the slope parameter derived for each participant separately by simple linear regression of the change from baseline in participant's eGFR measurements (from Baseline to Visit 24) on the actual day of measurement.

Outcome measures

Outcome measures
Measure	Mircera n=115 Participants Methoxy polyethylene glycol-epoetin beta 30 mcg subcutaneous injection once monthly up to 24 months with sequential dose adjustments to 50 mcg or 75 mcg depending on change of hemoglobin values of more than 1.0 g/dL.	Placebo n=120 Participants Placebo matching to Methoxy polyethylene glycol-epoetin beta subcutaneous injection once monthly up to 24 months.
Yearly Reduction Rate of Estimated Glomerular Filtration Rate (eGFR) Calculated by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)	3.02 mL/min/1.73m^2/year Interval 1.03 to 5.0	0.78 mL/min/1.73m^2/year Interval -1.16 to 2.72

SECONDARY outcome

Timeframe: Baseline, Month 24

Population: FAS included all randomized participants who received at least one dose of the study medication and provided any successive eGFR measurement. Here, n=number of participants evaluable for each category.

Creatinine clearance was calculated according to the Cockcroft and Gault Formula. It measures rate creatinine (substance formed from metabolism of creatine) is cleared from blood by kidneys. Normal adult creatinine clearance is greater than or equal to (\>=) 90 mL/min. Change from baseline=CC at Week X minus CC at baseline where higher scores represented improved renal function.

Outcome measures

Outcome measures
Measure	Mircera n=115 Participants Methoxy polyethylene glycol-epoetin beta 30 mcg subcutaneous injection once monthly up to 24 months with sequential dose adjustments to 50 mcg or 75 mcg depending on change of hemoglobin values of more than 1.0 g/dL.	Placebo n=120 Participants Placebo matching to Methoxy polyethylene glycol-epoetin beta subcutaneous injection once monthly up to 24 months.
Change From Baseline in Calculated Creatinine Clearance (Cockcroft-Gault Equation) at Month 24 Baseline (n=115, 120)	53.18 mL/min Standard Deviation 15.95	52.48 mL/min Standard Deviation 16.04
Change From Baseline in Calculated Creatinine Clearance (Cockcroft-Gault Equation) at Month 24 Change at Month 24 (n=67, 91)	-2.97 mL/min Standard Deviation 10.52	-2.08 mL/min Standard Deviation 9.72

SECONDARY outcome

Timeframe: Baseline, Month 24

Serum creatinine is an indicator of kidney function. Creatinine is a substance formed from the metabolism of creatine, commonly found in blood, urine, and muscle tissue. It is removed from the blood by the kidneys and excreted in urine. Normal adult blood levels of creatinine=45 to 90 micromoles per liter (mcmol/L) for females, 60 to 110 mcmol/L for males, however normal values are age-dependent.

Outcome measures

Outcome measures
Measure	Mircera n=115 Participants Methoxy polyethylene glycol-epoetin beta 30 mcg subcutaneous injection once monthly up to 24 months with sequential dose adjustments to 50 mcg or 75 mcg depending on change of hemoglobin values of more than 1.0 g/dL.	Placebo n=120 Participants Placebo matching to Methoxy polyethylene glycol-epoetin beta subcutaneous injection once monthly up to 24 months.
Change From Baseline in Serum Creatinine Concentration at Month 24 Baseline (n=115, 120)	147.8 mcmol/L Standard Deviation 31.71	149.3 mcmol/L Standard Deviation 35.67
Change From Baseline in Serum Creatinine Concentration at Month 24 Change at Month 24 (n=68, 91)	7.04 mcmol/L Standard Deviation 27.23	4.04 mcmol/L Standard Deviation 30.99

SECONDARY outcome

Timeframe: Baseline, Month 24

Population: FAS included all randomized participants who received at least one dose of the study medication and provided any successive eGFR measurement. Number of Participants Analyzed (N) = number of participants evaluable and available with valid data for this outcome measure. Here, n=number of participants evaluable for each category.

UACR is defined as the ratio: milligram of albumin per gram of creatinine. The presence of albumin in the urine (macroalbuminuria) is a marker of kidney disease. Albumin and creatinine concentrations were obtained from spot urine samples.

Outcome measures

Outcome measures
Measure	Mircera n=110 Participants Methoxy polyethylene glycol-epoetin beta 30 mcg subcutaneous injection once monthly up to 24 months with sequential dose adjustments to 50 mcg or 75 mcg depending on change of hemoglobin values of more than 1.0 g/dL.	Placebo n=107 Participants Placebo matching to Methoxy polyethylene glycol-epoetin beta subcutaneous injection once monthly up to 24 months.
Change From Baseline in Urinary Albumin Creatinine Ratio (UACR) at Month 24 Change at Month 24 (n=43, 53)	173.8 mg/g Standard Deviation 573.3	70.59 mg/g Standard Deviation 546.8
Change From Baseline in Urinary Albumin Creatinine Ratio (UACR) at Month 24 Baseline (n=110, 107)	261.1 mg/g Standard Deviation 564.0	237.3 mg/g Standard Deviation 699.6

SECONDARY outcome

Timeframe: Baseline, Month 24

Cystatin C is a protein which is mainly used as a biomarker of kidney function. If kidney function and GFR decline, the blood levels of cystatin C rise.

Outcome measures

Outcome measures
Measure	Mircera n=115 Participants Methoxy polyethylene glycol-epoetin beta 30 mcg subcutaneous injection once monthly up to 24 months with sequential dose adjustments to 50 mcg or 75 mcg depending on change of hemoglobin values of more than 1.0 g/dL.	Placebo n=120 Participants Placebo matching to Methoxy polyethylene glycol-epoetin beta subcutaneous injection once monthly up to 24 months.
Change From Baseline in Serum Cystatin C Concentration at Month 24 Baseline (n=115, 120)	1.79 mg/L Standard Deviation 0.39	1.76 mg/L Standard Deviation 0.46
Change From Baseline in Serum Cystatin C Concentration at Month 24 Change at Month 24 (n=67, 91)	0.10 mg/L Standard Deviation 0.29	0.02 mg/L Standard Deviation 0.33

SECONDARY outcome

Timeframe: 24 months

Population: The Safety Analysis Set (SAF) included all participants who received at least one dose of study medication. Analysis for SAF was performed according to the study medication actually received (as treated population). Number of participants analyzed=participants evaluable for this measure.

An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability or incapacity; and congenital anomaly. Percentage of participants with AEs included participants affected with both SAEs and non-SAEs.

Outcome measures

Outcome measures
Measure	Mircera n=118 Participants Methoxy polyethylene glycol-epoetin beta 30 mcg subcutaneous injection once monthly up to 24 months with sequential dose adjustments to 50 mcg or 75 mcg depending on change of hemoglobin values of more than 1.0 g/dL.	Placebo n=117 Participants Placebo matching to Methoxy polyethylene glycol-epoetin beta subcutaneous injection once monthly up to 24 months.
Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) SAEs	35.6 percentage of participants	41.0 percentage of participants
Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) AEs	84.7 percentage of participants	86.3 percentage of participants

Adverse Events

Mircera

Serious events: 42 serious events

Other events: 95 other events

Deaths: 0 deaths

Placebo

Serious events: 48 serious events

Other events: 99 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Mircera n=118 participants at risk Methoxy polyethylene glycol-epoetin beta 30 mcg subcutaneous injection once monthly up to 24 months with sequential dose adjustments to 50 mcg or 75 mcg depending on change of hemoglobin values of more than 1.0 g/dL.	Placebo n=117 participants at risk Placebo matching to Methoxy polyethylene glycol-epoetin beta subcutaneous injection once monthly up to 24 months.
Infections and infestations Bronchitis	0.00% 0/118 • 24 months The Safety Analysis Set (SAF) included all participants who received at least one dose of the study medication. Analysis for SAF was performed according to the study medication actually received ('as treated' population).	7.7% 9/117 • 24 months The Safety Analysis Set (SAF) included all participants who received at least one dose of the study medication. Analysis for SAF was performed according to the study medication actually received ('as treated' population).
Infections and infestations Influenza	7.6% 9/118 • 24 months The Safety Analysis Set (SAF) included all participants who received at least one dose of the study medication. Analysis for SAF was performed according to the study medication actually received ('as treated' population).	7.7% 9/117 • 24 months The Safety Analysis Set (SAF) included all participants who received at least one dose of the study medication. Analysis for SAF was performed according to the study medication actually received ('as treated' population).
Infections and infestations Nasopharyngitis	24.6% 29/118 • 24 months The Safety Analysis Set (SAF) included all participants who received at least one dose of the study medication. Analysis for SAF was performed according to the study medication actually received ('as treated' population).	20.5% 24/117 • 24 months The Safety Analysis Set (SAF) included all participants who received at least one dose of the study medication. Analysis for SAF was performed according to the study medication actually received ('as treated' population).
Infections and infestations Urinary tract infection	10.2% 12/118 • 24 months The Safety Analysis Set (SAF) included all participants who received at least one dose of the study medication. Analysis for SAF was performed according to the study medication actually received ('as treated' population).	6.0% 7/117 • 24 months The Safety Analysis Set (SAF) included all participants who received at least one dose of the study medication. Analysis for SAF was performed according to the study medication actually received ('as treated' population).
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/118 • 24 months The Safety Analysis Set (SAF) included all participants who received at least one dose of the study medication. Analysis for SAF was performed according to the study medication actually received ('as treated' population).	6.8% 8/117 • 24 months The Safety Analysis Set (SAF) included all participants who received at least one dose of the study medication. Analysis for SAF was performed according to the study medication actually received ('as treated' population).
Musculoskeletal and connective tissue disorders Osteoarthritis	5.1% 6/118 • 24 months The Safety Analysis Set (SAF) included all participants who received at least one dose of the study medication. Analysis for SAF was performed according to the study medication actually received ('as treated' population).	0.00% 0/117 • 24 months The Safety Analysis Set (SAF) included all participants who received at least one dose of the study medication. Analysis for SAF was performed according to the study medication actually received ('as treated' population).
Musculoskeletal and connective tissue disorders Pain in extremity	0.00% 0/118 • 24 months The Safety Analysis Set (SAF) included all participants who received at least one dose of the study medication. Analysis for SAF was performed according to the study medication actually received ('as treated' population).	5.1% 6/117 • 24 months The Safety Analysis Set (SAF) included all participants who received at least one dose of the study medication. Analysis for SAF was performed according to the study medication actually received ('as treated' population).
Gastrointestinal disorders Diarrhoea	9.3% 11/118 • 24 months The Safety Analysis Set (SAF) included all participants who received at least one dose of the study medication. Analysis for SAF was performed according to the study medication actually received ('as treated' population).	11.1% 13/117 • 24 months The Safety Analysis Set (SAF) included all participants who received at least one dose of the study medication. Analysis for SAF was performed according to the study medication actually received ('as treated' population).
Gastrointestinal disorders Nausea	0.00% 0/118 • 24 months The Safety Analysis Set (SAF) included all participants who received at least one dose of the study medication. Analysis for SAF was performed according to the study medication actually received ('as treated' population).	6.8% 8/117 • 24 months The Safety Analysis Set (SAF) included all participants who received at least one dose of the study medication. Analysis for SAF was performed according to the study medication actually received ('as treated' population).
General disorders Oedema peripheral	9.3% 11/118 • 24 months The Safety Analysis Set (SAF) included all participants who received at least one dose of the study medication. Analysis for SAF was performed according to the study medication actually received ('as treated' population).	8.5% 10/117 • 24 months The Safety Analysis Set (SAF) included all participants who received at least one dose of the study medication. Analysis for SAF was performed according to the study medication actually received ('as treated' population).
Respiratory, thoracic and mediastinal disorders Cough	11.0% 13/118 • 24 months The Safety Analysis Set (SAF) included all participants who received at least one dose of the study medication. Analysis for SAF was performed according to the study medication actually received ('as treated' population).	8.5% 10/117 • 24 months The Safety Analysis Set (SAF) included all participants who received at least one dose of the study medication. Analysis for SAF was performed according to the study medication actually received ('as treated' population).
Vascular disorders Hypertension	9.3% 11/118 • 24 months The Safety Analysis Set (SAF) included all participants who received at least one dose of the study medication. Analysis for SAF was performed according to the study medication actually received ('as treated' population).	12.0% 14/117 • 24 months The Safety Analysis Set (SAF) included all participants who received at least one dose of the study medication. Analysis for SAF was performed according to the study medication actually received ('as treated' population).

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