A Study of Intravenous (iv) Mircera in Hemodialysis Patients With Chronic Renal Anemia

• ClinicalTrials.gov Identifier: NCT00048035
• Recruitment Status: Completed
• First Posted: October 25, 2002
• Results First Posted: December 20, 2016
• Last Update Posted: December 20, 2016
• Sponsor: Hoffmann-La Roche
• Information provided by (Responsible Party): Hoffmann-La Roche

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
Anemia	Drug: methoxy polyethylene glycol-epoetin beta [Mircera]	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 91 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open-label, Multicenter, Randomized Study to Determine Dose Conversion Factors at Different Frequencies of Administration After Switching From Maintenance Treatment With Intravenous Epoetin Alfa to Maintenance Treatment With Intravenous RO0503821 in Hemodialysis Patients With Chronic Renal Anemia.
• Study Start Date: March 2002
• Actual Primary Completion Date: June 2005
• Actual Study Completion Date: June 2005

Arms and Interventions

Arm	Intervention/treatment
Experimental: Cohort 1 (RO0503821 [0.25/150 1x/week]); Eligible participant will be administered RO0503821 (methoxy polyethylene glycol-epoetin beta [Mircera]) intravenously (IV) using a dose conversion factor of 0.25/150 microgram (mcg)/kilogram (kg) of the previous weekly erythropoiesis stimulating agents (ESA) dose, (equal to 62.50% 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 iv administration
Experimental: Cohort 2 (RO0503821 [0.25/150 1x/2week]); Eligible participant will be administered RO0503821 IV using a dose conversion factor of 0.25/150 mcg/kg of the previous weekly ESA dose, (equal to 62.50% assumed equi-effective dose) once in every two 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 iv administration
Experimental: Cohort 3 (RO0503821 [0.4/150 1x/week]); Eligible participant will be administered RO0503821 IV using a dose conversion factor of 0.40/150 mcg/kg of the previous weekly ESA dose, (equal to100% 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 iv administration
Experimental: Cohort 4 (RO0503821 [0.4/150 1x/2week]); Eligible participant will be administered RO0503821 IV using a dose conversion factor of 0.40/150 mcg/kg of the previous weekly ESA dose, (equal to 100% assumed equi-effective dose) once in every two 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 iv administration
Experimental: Cohort 5 (RO0503821 [0.6/150 1x/week]); Eligible participant will be administered RO0503821 IV using a dose conversion factor of 0.60/150 mcg/kg of the previous weekly ESA dose, (equal to150% 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 iv administration
Experimental: Cohort 6 (RO0503821 [0.6/150 1x/2week]); Eligible participant will be administered RO0503821 IV using a dose conversion factor of 0.60/150 mcg/kg of the previous weekly ESA dose, (equal to150% assumed equi-effective dose) once in every two 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 iv administration

Outcome Measures

Primary Outcome Measures :

1. Median Change From Baseline in Hemoglobin Levels to End of Initial Treatment Under Constant Dosing Regimen [ Time Frame: From Baseline (Day -28 to Day 1) to EOIT (Week 19) ]
   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 Week -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 value.

Secondary Outcome Measures :

1. Median Change From Baseline in Hematocrit Levels to End of Initial Treatment Under Constant Dosing Regimen [ Time Frame: From Baseline (Day -28 to Day 1) to EOIT (Week 19) ]
   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 value.
2. Number of Participants With Any Adverse Events, Any Serious Adverse Events, And Deaths [ Time Frame: Up to Week 126 ]
   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.
3. Number of Participants With Marked Laboratory Abnormalities [ Time Frame: Up to Week 126 ]
   Marked abnormality was defined as above and/or below a value which was considered to be potentially clinically relevant. The number of participants with marked lab abnormality across treatment groups were reported and presented. Marked laboratory abnormalities were analyzed according to the Roche specified limits for the following reference range: White blood cells (WBC) (3.0- 18.0 10^9/L), Platelets (100 - 550 10^9/L), Alanine aminotransferase (ALAT) [0 110 units per litre (U/L)], Alkaline Phosphatase (ALP) (0 - 220 U/L), Aspartate aminotransferase (ASAT) (0 - 80 U/L), Albumin >= 30 g/L, Phosphate [0.75 - 1.60 millimoles per liter (mmol/L)], Potassium (2.9 - 5.8 mmol/L), Glucose (2.80 - 11.10 mmol/L).
4. Mean Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure Before and After Dialysis [ Time Frame: From Baseline (Day -28 to Day 1) to Week 126 ]
   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) values were calculated as the mean of the screening assessment (SA) and run-in period (Week -2 and Week -1).
5. Mean Change in Pulse Rate [ Time Frame: Up to Week 126 ]
   Participants pulse rates in beats per minute (BpM) were analyzed at sitting position using descriptive statistical methods (ie, means, standard deviations and percentiles). The changes in pulse rate throughout the study were analysed at each study visit and mean change is reported.

Eligibility Criteria

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

Criteria

Inclusion Criteria:

• adult patients >=18 years of age;
• chronic renal anemia;
• on hemodialysis therapy for at least 3 months;
• receiving iv epoetin alfa during the 2 weeks 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 of the run-in phase, or during the run-in or study treatment period.

Contacts and Locations

Locations

United States, Alabama

Birmingham, Alabama, United States, 35211

United States, California

Los Angeles, California, United States, 90095

United States, Illinois

Maywood, Illinois, United States, 60153

United States, Kentucky

Louisville, Kentucky, United States, 40202-1718

United States, Michigan

Detroit, Michigan, United States, 48202-2689

Detroit, Michigan, United States, 48236

United States, Minnesota

Brooklyn Center, Minnesota, United States, 55430

United States, Nevada

Las Vegas, Nevada, United States, 89106

United States, New Jersey

Paterson, New Jersey, United States, 07503

United States, New York

Brooklyn, New York, United States, 11203

Mineola, New York, United States, 11501

New York, New York, United States, 10128

United States, Tennessee

Nashville, Tennessee, United States, 37232

United States, West Virginia

Morgantown, West Virginia, United States, 26506

Sponsors and Collaborators

Hoffmann-La Roche

Investigators

• Study Director: Clinical Trials; Hoffmann-La Roche

More Information

• Responsible Party: Hoffmann-La Roche
• ClinicalTrials.gov Identifier: NCT00048035
• Other Study ID Numbers: BA16285
• First Posted: October 25, 2002
• Results First Posted: December 20, 2016
• Last Update Posted: December 20, 2016
• Last Verified: October 2016

Additional relevant MeSH terms:

Anemia; Hematologic Diseases; Epoetin Alfa; Hematinics