A Study of Subcutaneous (sc) Mircera in Dialysis Patients With Chronic Renal Anemia.

An Open-label, Multicenter, Randomized Study to Determine Dose Conversion Factors at Different Frequencies of Administration After Switching From Maintenance Treatment With Subcutaneous Epoetin Alfa or Beta to Maintenance Treatment With Subcutaneous RO0503821 in Dialysis Patients With Chronic Renal Anemia

This study will determine the appropriate dose and frequency of administration of sc Mircera maintenance therapy in dialysis patients with chronic renal anemia who were previously receiving sc epoetin alfa or beta. The anticipated time on study treatment is 3-12 months and the target sample size is 100-500 individuals.

Study Overview

• Status: Completed
• Conditions: Anemia
• Intervention / Treatment: Drug: methoxy polyethylene glycol-epoetin beta [Mircera]

• Study Type: Interventional
• Enrollment (Actual): 137
• Phase: Phase 2

Contacts and Locations

Study Locations

• Germany
  • Berlin, Germany, 10625
  • Mannheim, Germany, 68167
  • Villingen-schwenningen, Germany, 78054
  • Wiesloch, Germany, 69168
• Italy
  • Bari, Italy, 70124
  • Bergamo, Italy, 24128
  • Lecco, Italy, 23900
  • Lodi, Italy, 26900
  • Milano, Italy, 20122
  • Modena, Italy, 41100
  • Pavia, Italy, 27100
  • Vicenza, Italy, 36100
• Spain
  • Barcelona, Spain, 08036
  • Madrid, Spain, 28046
  • Madrid, Spain, 28007
  • Malaga, Spain, 29010
  • Santander, Spain, 39008
• United States
  • California
    • Los Angeles, California, United States, 90073
    • San Jose, California, United States, 95116-1906
  • Massachusetts
    • Boston, Massachusetts, United States, 02130
  • Ohio
    • Cleveland, Ohio, United States, 44106
  • Texas
    • Houston, Texas, United States, 77030
  • West Virginia
    • Morgantown, West Virginia, United States, 26506

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• adult patients >=18 years of age;
• chronic renal anemia;
• on dialysis (hemodialysis or peritoneal dialysis) therapy for at least 3 months;
• receiving sc epoetin alfa or beta for at least 3 months prior to the run-in period.

Exclusion Criteria:

• women who are pregnant, breastfeeding or using unreliable birth control methods;
• use of any investigational drug within 30 days preceding the run-in phase, or during the run-in or study treatment period.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

9

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort A (0.4/150, 1x/ Week); Eligible participant will be administered RO0503821 (methoxy polyethylene glycol-epoetin beta [Mircera]) SC using a dose conversion factor of 0.4/150 microgram (mcg)/ kilogram (kg) of the previous weekly erythropoiesis stimulating agents (ESA) dose, (equal to 50% assumed equi-effective dose) once weekly up to 19 weeks. After 19 weeks of core treatment period, participants will be followed-up for two optional treatment extension periods (54 weeks each).	Drug: methoxy polyethylene glycol-epoetin beta [Mircera]; Differing doses and frequencies of sc administration
Experimental: Cohort B (0.4/150, 1x/ 3 Weeks); Eligible participant will be administered RO0503821 SC using a dose conversion factor of 0.4/150 mcg/kg of the previous weekly ESA dose, (equal to 50% assumed equi-effective dose) once every three weeks up to 19 weeks. After 19 weeks of core treatment period, participants will be followed-up for two optional treatment extension periods (54 weeks each).	Drug: methoxy polyethylene glycol-epoetin beta [Mircera]; Differing doses and frequencies of sc administration
Experimental: Cohort C (0.4/150, 1x/ 4 Weeks); Eligible participant will be administered RO0503821 SC using a dose conversion factor of 0.4/150 mcg/kg of the previous weekly ESA dose, (equal to 50% assumed equi-effective dose) once every four weeks up to 21 weeks. After 21 weeks of core treatment period, participants will be followed-up for two optional treatment extension periods (54 weeks each).	Drug: methoxy polyethylene glycol-epoetin beta [Mircera]; Differing doses and frequencies of sc administration
Experimental: Cohort D (0.8/150, 1x/ Week); Eligible participant will be administered RO0503821 SC using a dose conversion factor of 0.8/150 mcg/kg of the previous weekly ESA dose, (equal to 100% assumed equi-effective dose) once weekly up to 19 weeks. After 19 weeks of core treatment period, participants will be followed-up for two optional treatment extension periods (54 weeks each).	Drug: methoxy polyethylene glycol-epoetin beta [Mircera]; Differing doses and frequencies of sc administration
Experimental: Cohort E (0.8/150, 1x/ 3 Weeks); Eligible participant will be administered RO0503821 SC using a dose conversion factor of 0.8/150 mcg/kg of the previous weekly ESA dose, (equal to 100% assumed equi-effective dose) once every three weeks up to 19 weeks. After 19 weeks of core treatment period, participants will be followed-up for two optional treatment extension periods (54 weeks each).	Drug: methoxy polyethylene glycol-epoetin beta [Mircera]; Differing doses and frequencies of sc administration
Experimental: Cohort F (0.8/150, 1x/ 4 Weeks); Eligible participant will be administered RO0503821 SC using a dose conversion factor of 0.8/150 mcg/kg of the previous weekly ESA dose, (equal to 100% assumed equi-effective dose) once every four weeks up to 21 weeks. After 21 weeks of core treatment period, participants will be followed-up for two optional treatment extension periods (54 weeks each).	Drug: methoxy polyethylene glycol-epoetin beta [Mircera]; Differing doses and frequencies of sc administration
Experimental: Cohort G (1.2/150, 1x/ Week); Eligible participant will be administered RO0503821 SC using a dose conversion factor of 1.2/150 mcg/kg of the previous weekly ESA dose, (equal to 150% assumed equi-effective dose) once weekly up to 19 weeks. After 19 weeks of core treatment period, participants will be followed-up for two optional treatment extension periods (54 weeks each).	Drug: methoxy polyethylene glycol-epoetin beta [Mircera]; Differing doses and frequencies of sc administration
Experimental: Cohort H (1.2/150, 1x/ 3 Weeks); Eligible participant will be administered RO0503821 SC using a dose conversion factor of 1.2/150 mcg/kg of the previous weekly ESA dose, (equal to 150% assumed equi-effective dose) once every three weeks up to 19 weeks. After 19 weeks of core treatment period, participants will be followed-up for two optional treatment extension periods (54 weeks each).	Drug: methoxy polyethylene glycol-epoetin beta [Mircera]; Differing doses and frequencies of sc administration
Experimental: Cohort I (1.2/150, 1x/ 4 Weeks); Eligible participant will be administered RO0503821 SC using a dose conversion factor of 1.2/150 mcg/kg of the previous weekly ESA dose, (equal to 150% assumed equi-effective dose) once every four weeks up to 21 weeks. After 21 weeks of core treatment period, participants will be followed-up for two optional treatment extension periods (54 weeks each).	Drug: methoxy polyethylene glycol-epoetin beta [Mircera]; Differing doses and frequencies of sc administration

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Median Change From Baseline in Hemoglobin Levels to End of Initial Treatment Under Constant Dosing Regimen	Median change from Baseline in hemoglobin (Hb) levels to end of initial treatment (EOIT) under constant dosing regimen was reported. For ease of interpretation, all individual slope values were multiplied by 42 to give an estimate of change in Hb values over six weeks. Baseline (Day -28 to Day 1) Hb values was calculated as the mean of the screening assessment (SA) and run-in period (Week -2 and -1). For all participants, an EOIT value was calculated as the last observed Hb value before a dose change or blood transfusion. For participants without any dose adjustments or blood transfusion, the EOIT value was identical to the Week 19 (or Week 21) value.	From Baseline (Day -28 to Day 1) to EOIT (Week 19 or Week 21)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Median Change From Baseline in Hematocrit Levels to End of Initial Treatment Under Constant Dosing Regimen	Median change from Baseline in hematocrit (Hct) levels to end of initial treatment under constant dosing regimen was reported. Baseline (Day -28 to Day 1) Hct values was calculated as the mean of the SA and run-in period (Weeks -2 and -1). For all participants, an EOIT value was calculated as the last observed Hct value before a dose change or blood transfusion. For participants without any dose adjustments or blood transfusion, the EOIT value was identical to the Week 19 (or Week 21) value.	From Baseline (Day -28 to Day 1) to EOIT (Week 19 or Week 21)
Mean Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure Before and After Dialysis	Mean Change from Baseline in systolic blood pressure (SBP) and diastolic blood pressure (DBP) is calculated as the end of treatment values minus the Baseline value. Baseline (Day -28 to Day 1) value is the measurements taken at screening assessment and run-in period (Weeks -2 and -1).	From Baseline (Day -28 to Day 1) to Week 126
Mean Change in Pulse Rate	Mean change in pulse rate was reported.	Up to Week 126
Number of Participants With Marked Laboratory Abnormalities	Participants with marked laboratory abnormalities were reported. Marked abnormality criteria: Serum glutamic oxaloacetic transaminase (SGOT); high >25 units per litre (U/L), albumin (low < 31 grams per litre [g/L]), total protein (< 60 g/L), phosphate (high >1.45 millimoles per litre [mmol/L]); Low <0.84 mmol/L), potassium (high >5 mmol/L; Low <3.5 mmol/L), platelets (low:<150×10^9/L), White blood cells ([WBCs]); high: 10.8×10^9/L and Low:4.3×10^9/L), basophils (high:>0.15×10^9/L), eosinophils (high:>0.70×10^9/L), lymphocytes (low:<1.50×10^9/L), and neutrophils (low:<1.83×10^9/L).	Up to Week 126
Number of Participants With Any Adverse Events, Any Serious Adverse Events, And Deaths	An Adverse Events (AEs) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Serious Adverse Events (SAEs) is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or is a significant medical event in the investigator's judgment or requires intervention to prevent one or other of these outcomes. The study design tested 3 different starting dose conversion factors at 3 different dosing schedules during the core study period. As study drug doses can be modified continually over time all results for the two long term safety periods were displayed by dose schedule group only.	Up to Week 126

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche

Publications and helpful links

General Publications

• Locatelli F, Villa G, de Francisco AL, Albertazzi A, Adrogue HJ, Dougherty FC, Beyer U; BA16286 Study Investigators. Effect of a continuous erythropoietin receptor activator (C.E.R.A.) on stable haemoglobin in patients with CKD on dialysis: once monthly administration. Curr Med Res Opin. 2007 May;23(5):969-79. doi: 10.1185/030079907x182103.

Study record dates

Study Major Dates

• Study Start: October 1, 2001
• Primary Completion (Actual): July 1, 2005
• Study Completion (Actual): July 1, 2005

Study Registration Dates

• First Submitted: August 15, 2006
• First Submitted That Met QC Criteria: August 15, 2006
• First Posted (Estimate): August 16, 2006

Study Record Updates

• Last Update Posted (Estimate): December 20, 2016
• Last Update Submitted That Met QC Criteria: October 26, 2016
• Last Verified: October 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Hematologic Diseases; Anemia; Hematinics; Epoetin Alfa
• Other Study ID Numbers: BA16286