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

A Single Arm Open Label Study to Assess the Efficacy, Safety and Tolerability of Once-monthly Administration of Intravenous C.E.R.A. for the Maintenance of Haemoglobin Levels in Haemodialysis Patients With Chronic Renal Anaemia.

This single arm study will assess the efficacy, safety and tolerability of once-monthly administration of intravenous Mircera for the maintenance of hemoglobin levels in hemodialysis patients with chronic renal anemia. Patients will receive 4-weekly intravenous injections of Mircera, at a starting dose of 120, 200 or 360 micrograms. 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

• Study Type: Interventional
• Enrollment (Actual): 132
• Phase: Phase 3

Contacts and Locations

Study Locations

• Turkey
  • Adana, Turkey, 01330
    • Cukurova University Medical Faculty; Internal Medicine
  • Ankara, Turkey, 06100
    • Ankara Research and Training Hospital; The Clinic of Nephrology
  • Ankara, Turkey, 06100
    • Ankara University School of Medicine; Nephrology
  • Ankara, Turkey, 06100
    • Faith University School of Medicine; Nephrology
  • Ankara, Turkey, 06100
    • Hacettepe University Medical Faculty; Department of Internal Medicine
  • Ankara, Turkey, 06490
    • Baskent University Hospital; Transplantation
  • Ankara, Turkey, 06500
    • Gazi University School of Medicine; Nephrology
  • Aydin, Turkey, 09100
    • Adnan Menderes Uni School of Medicine; Physical Therapy & Rehabilitation
  • Diyarbakir, Turkey, 10000
    • Dicle Uni Medical Faculty; Internal Medicine
  • Edirne, Turkey, 22030
    • Trakya University Medical Faculty; Internal Medicine; Nephrology
  • Elazig, Turkey, 23110
    • Firat Uni School Of Medicine; Nephrology
  • Erzurum, Turkey, 25240
    • Ataturk University Medical Faculty; Department of Internal Medicine
  • Istanbul, Turkey, 34377
    • Sisli Etfal Research and Training Hospital; The Clinic of Nephrology
  • Istanbul, Turkey, 34390
    • Istanbul University Istanbul Medical Faculty; Department of Internal Medicine
  • Istanbul, Turkey, 34662
    • Marmara Uni School of Medicine; Nephrology
  • Izmir, Turkey, 35290
    • Izmir Ataturk Research and Training Hospital; The Clinic of Nephrology
  • Izmir, Turkey
    • Dokuz Eylul University School of Medicine; Nephrology
  • Kayseri, Turkey, 38039
    • Erciyes University School of Medicine; Nephrology
  • Malatya, Turkey, 44300
    • Inonu Uni School of Medicine
  • Mersin, Turkey, 33169
    • Mersin University Medical Faculty

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;
• continuous stable iv or sc maintenance epoetin therapy during previous 4 weeks;
• regular long-term hemodialysis therapy with the same mode of dialysis for previous 3 months.

Exclusion Criteria:

• transfusion of red blood cells during previous 2 months;
• poorly controlled hypertension requiring hospitalization or interruption of epoetin treatment in previous 6 months;
• significant acute or chronic bleeding.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: C.E.R.A. 120, 200, or 360 mcg; Eligible participants were administered Continuous Erythropoietin Receptor Activator (C.E.R.A.) at a dose of 120, 200, or 360 microgram (mcg), intravenously (IV), every 4 weeks i.e. Weeks 4, 8, 12, 16 and 20 but not on Weeks 24 and 28. The initial dose of C.E.R.A.was based on the last dose of the previous Erythropoiesis Stimulating Agent (ESA). The ESA therapy was administered from enrollment to the 4 weeks stability verification period (SVP), weekly, either as epoetin (<8000 IU, 8000-16000 IU, or >16000 IU) or darbepoetin alpha (<40 mcg, 40-80 mcg, or >80 mcg). A telephone follow-up visit took place 4 weeks after the end of C.E.R.A. treatment (Week 28).

Drug: methoxy polyethylene glycol-epoetin beta; 120, 200 or 360 micrograms iv every 4 weeks (starting dose)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Who Maintained Their Mean Hemoglobin Concentration Within +/- 1.0 Gram/Deciliter of Their Reference Hemoglobin Concentration and Between 10.0 and 12.0 Gram/Deciliter During the Efficacy Evaluation Period	The reference hemoglobin (Hb) value was taken as the time adjusted average of all Hb assessments during the SVP (Week -4 to Week 0). The time adjusted average Hb concentration of all the values recorded during the efficacy evaluation period (EEP) was calculated for each participant and their reference Hb concentration was subtracted from this value. The percentage of participants maintaining their average Hb concentration during the EEP within +/- 1 gram/deciliter (g/dL) of their reference Hb concentration and between the Hb range 10.0 -12.0 g/dL is presented. The EEP was defined as Week 16 to Week 24. Data missing at the end of the EEP was handled using the last value carried forward method, including any data missing due to withdrawal of participants following red blood cells (RBC) transfusion.	EEP (Week 16 to Week 24)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Change in Hemoglobin Concentration Between the Stability Verification Period and the Efficacy Evaluation Period	The mean change in the time-adjusted average Hb concentration between the two study periods The Stability Verification Period (SVP) and EEP is presented. The SVP was defined as Week -4 to Week 0. The EEP was defined as Week 16 to Week 24.	SVP (Week -4 to Week 0) and EEP (Week 16 to Week 24)
Percentage of Participants Maintaining Hemoglobin Concentration Within the Range of 10.0-12.0 Gram/Deciliter Throughout the Efficacy Evaluation Period	The time adjusted average Hb concentration of all the values recorded during the EEP was calculated for each participant. The percentage of participants maintaining their average Hb concentration during the EEP within the Hb concentration range of 10.0-12.0 g/dL is presented. The EEP was defined as Week 16 to Week 24.	EEP (Week 16 to Week 24)
Median Time Spent in the Hemoglobin Range 10.0-12.0 Gram/Deciliter During the Efficacy Evaluation Period	The Hb concentration was recorded for all the participants during the EEP. The median time spent (in days) by participants in the target range (10.0-12.0 g/dL) during the EEP is presented. The EEP was defined as Week 16 to Week 24.	EEP (Week 16 to Week 24)
Mean C.E.R.A. Dose Required to Maintain Hemoglobin Level Within the Range 10.0-12.0 Gram/Deciliter Throughout the Efficacy Evaluation Period	The mean dose of C.E.R.A. required to maintain Hb level between 10.0-12.0 g/dL during the EEP was calculated per participant and then summarized. The EEP was defined as Week 16 to Week 24. However, C.E.R.A. was not administered at the Week 24 visit. Therefore, the time period for calculation of mean C.E.R.A. dose during EEP is from Week 16 to Week 20.	EEP (Week 16 to Week 20)
Percentage of Participants Requiring Any Dose Adjustments in C.E.R.A. During the Dose Titration Period and Efficacy Evaluation Period	Dose adjustments were necessary when Hb increased or decreased by a clinically significant amount. The dose of C.E.R.A. was adjusted to maintain the individual participant's Hb within a range of +/- 1.0 g/dL of the reference Hb concentration and between 10.0 and 12.0 g/dL throughout the dose titration period (DTP) and the EEP (Week 1 to Week 24). The reference Hb value was taken as the time adjusted average of all Hb assessments during the SVP (Week -4 to Week 0).	DTP (Week 1 to Week 16), EEP (Week 16 to Week 24)
Mean Monthly Dose of C.E.R.A. During the Dose Titration Period and Efficacy Evaluation Period	The mean monthly dose of C.E.R.A. administered during the DTP and EEP was calculated per participant and then summarized.	DTP (Week 1 to Week 16), EEP (Week 16 to Week 24)
Mean Change From Baseline in Erythrocyte Mean Corpuscular Volume at Week 16 and Week 24	Mean change from Baseline in erythrocyte mean corpuscular volume (MCV) was calculated as the value at a specific week during the study minus the BL value. The Baseline was defined as Week -4 to Week 0.	BL (Week -4 to Week 0), Week 16, and Week 24
Mean Change From Baseline in Hematocrit at Week 16 and Week 24	The hematocrit, also called packed cell volume or erythrocyte volume fraction, is the volume percentage of red blood cells in the blood. Mean change from Baseline (BL) in hematocrit was calculated as the value at a specific week during the study minus the BL value. The BL was defined as Week -4 to Week 0.	BL (Week -4 to Week 0), Week 16, and Week 24
Mean Change From Baseline in Hemoglobin at Week 16 and Week 24	Mean change from BL in hemoglobin was calculated as the value at a specific week during the study minus the BL value. The BL was defined as Week -4 to Week 0.	BL (Week -4 to Week 0), Week 16, and Week 24
Mean Change From Baseline in Leucocytes and Platelet at Week 16 and Week 24	Mean change from BL in for each parameter (leucocytes and platelet) was calculated as the value at a specific week during the study minus the BL value. The BL was defined as Week -4 to Week 0.	BL (Week -4 to Week 0), Week 16, and Week 24
Mean Change From Baseline in Ferritin at Week 16 and Week 24	Mean change from BL in ferritin was calculated as the value at a specific week during the study minus the BL value. The BL was defined as Week -4 to Week 0.	BL (Week -4 to Week 0), Week 16, and Week 24
Mean Change From Baseline in Iron, Total Iron Binding Capacity, and Creatinine at Week 16 and Week 24	Mean change from BL in each parameter [iron, total iron binding capacity (TIBC), and creatinine] was calculated as the value at a specific week during the study minus the BL value. The BL was defined as Week -4 to Week 0.	BL (Week -4 to Week 0), Week 16, and Week 24
Mean Change From Baseline in Transferrin and Albumin at Week 16 and Week 24	Mean change from BL in each parameter (transferrin and albumin) was calculated as the value at a specific week during the study minus the BL value. The BL was defined as Week -4 to Week 0.	BL (Week -4 to Week 0), Week 16, and Week 24
Mean Change From Baseline in Transferrin Saturation at Week 16 and Week 24	Mean change from BL in transferrin saturation (TSAT) was calculated as the value at a specific week during the study minus the BL value. The BL was defined as Week -4 to Week 0.	BL (Week -4 to Week 0), Week 16, and Week 24
Mean Change From Baseline in C-Reactive Protein at Week 16 and Week 24	Mean change from BL in C-reactive protein was calculated as the value at a specific week during the study minus the BL value. The BL was defined as Week -4 to Week 0.	BL (Week -4 to Week 0), Week 16, and Week 24
Mean Change From Baseline in Phosphate and Potassium at Week 16 and Week 24	Mean change from BL in each parameter (phosphate and potassium) was calculated as the value at a specific week during the study minus the BL value. The BL was defined as Week -4 to Week 0.	BL (Week -4 to Week 0), Week 16, and Week 24
Mean Change From Baseline in Weight at Week 16 and Week 24	Mean change from BL in weight was calculated as the value at a specific week during the study minus the BL value. The BL was defined as Week -4 to Week 0.	BL (Week -4 to Week 0), Week 16, and Week 24
Mean Change in From Baseline in Blood Pressure at Week 16 and Week 24	Systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured before blood sampling and C.E.R.A. administration. Blood pressure was assessed both before and after the dialysis session for participants undergoing hemodialysis. Change from BL in blood pressure was calculated as the value at a specific week (W) during the study minus the BL value. The baseline was defined as Week -4 to Week 0.	Baseline (Week -4 to Week 0), Week 16, and Week 24
Number of Participants Taking Concomitant Medications	The number of participants taking different classes of concomitant medications at any time following enrollment into the study is presented.	Up to Week 28
Number of Participants With Any Adverse Events and Serious Adverse Events	An adverse event (AE) is any untoward medical occurrence in a participant who is administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be 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. 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.	Up to Week 28
Number of Participants With Reports of Anti-erythropoietin Antibodies	The number of participants with Anti-epoetin antibodies is presented.	Up to Week 24
Number of Participants Who Received Red Blood Cell Transfusions During the Dose Titration Period and Efficacy Evaluation Period	Red blood cell transfusions were permitted during the DTP and EEP (Week 1 to Week 24) in case of medical need. All participants requiring a blood transfusion were withdrawn from the study. The number of participants who were administered RBC transfusions during the DTP and EEP is presented.	Week 1 to Week 24

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche

Publications and helpful links

General Publications

• Locatelli F, Choukroun G, Truman M, Wiggenhauser A, Fliser D. Once-Monthly Continuous Erythropoietin Receptor Activator (C.E.R.A.) in Patients with Hemodialysis-Dependent Chronic Kidney Disease: Pooled Data from Phase III Trials. Adv Ther. 2016 Apr;33(4):610-25. doi: 10.1007/s12325-016-0309-6. Epub 2016 Mar 10.

Study record dates

Study Major Dates

• Study Start (Actual): May 14, 2008
• Primary Completion (Actual): June 22, 2010
• Study Completion (Actual): June 22, 2010

Study Registration Dates

• First Submitted: April 16, 2008
• First Submitted That Met QC Criteria: April 17, 2008
• First Posted (Estimate): April 18, 2008

Study Record Updates

• Last Update Posted (Actual): December 6, 2017
• Last Update Submitted That Met QC Criteria: November 2, 2017
• Last Verified: November 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Hematologic Diseases; Anemia; Hematinics; Epoetin Alfa
• Other Study ID Numbers: ML21096

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No