LATINO Study: A Study of Mircera for the Maintenance Treatment of Dialysis Patients With Chronic Renal Anemia.

A Single-Arm Open-Label Study to Assess the Efficacy, Safety, and Tolerability of Once-Monthly Administration of Intravenous and/or Subcutaneous C.E.R.A for the Maintenance of Hemoglobin Levels in Dialysis Patients With Chronic Renal Anemia

This single arm study will assess the efficacy and safety of Mircera when administered once monthly, subcutaneously or intravenously, for the maintenance of hemoglobin levels in dialysis patients with chronic renal anemia. Patients currently receiving maintenance treatment with epoetin alfa will receive monthly injections of Mircera with a starting dose (120, 200 or 360 micrograms) derived from the dose of epoetin alfa they were receiving in the week preceding study start. 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): 163
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, 1155
  • Buenos Aires, Argentina, 1437
  • Buenos Aires, Argentina, 1663
  • Buenos Aires, Argentina, 1824
  • Córdoba, Argentina, 5000
  • Santa Fe, Argentina, 3000
• Brazil
  • Aracajú, Brazil, 49055-210
  • Curitiba, Brazil, 80050-350
  • Fortaleza, Brazil, 60430-370
  • Sao Paulo, Brazil, 05624-000
• Chile
  • Santiago, Chile, 056
• Colombia
  • Bogota, Colombia
  • Bogotá, Colombia
• Ecuador
  • Quito, Ecuador, 2569
• Mexico
  • Cuernavaca, Mexico, 62448
  • Mexico City, Mexico, 14000
  • Mexico City, Mexico, 14050
  • Mexico City, Mexico, 11520
  • Mexico City, Mexico, 03900
  • Monterrey, Mexico, 64710
• Peru
  • Callao, Peru, C 01
  • Callao, Peru, C01
  • Lima, Peru, L13
• Uruguay
  • Montevideo, Uruguay, 11600
  • Montevideo, Uruguay, 11800
• Venezuela
  • Caracas, Venezuela, 1060
  • Caracas, Venezuela, 1062
  • Maracaibo, Venezuela, 4002

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;
• hemodialysis or peritoneal dialysis, with same mode of dialysis for >=3 months before and throughout screening period;
• stable maintenance epoetin alfa therapy for past 2 months.

Exclusion Criteria:

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

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; Participants with chronic renal anaemia who were on dialysis and previously treated with intravenous (IV) or subcutaneous (SC) epoetin alfa, epoetin beta or darbepoetin alfa received monthly treatment with Continuous Erythropoietin Receptor Activator (C.E.R.A.) (methoxy polyethylene glycol-epoetin beta [Mircera]). The initial dose of C.E.R.A. was based on the last dose of the previous Erythropoiesis Stimulating Agent (ESA); 120, 200, or 360 micrograms (mcg) C.E.R.A., IV or SC, every 4 weeks for 48 weeks.

Drug: methoxy polyethylene glycol-epoetin beta [Mircera]; 120, 200 or 360 micrograms sc or iv monthly, starting dose

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Maintaining Their Mean Hb Concentration Within ±1.0 Gram/Deciliter of Their Reference Hb and Between 10.5 and 12.5 Gram/Deciliter	The haemoglobin (Hb) levels were recorded for each participant at enrollment and at different time points during the study up to Week 48. The reference Hb value was defined on the basis of individual participant's all assessments at Weeks -4, -3, -2, -1 and 0. The Hb value on the first day of first dose (Week 0) was included in the calculation, as this assessment was performed before the first dose was given. The percentage of participants maintaining their mean Hb concentration within +/-1.0 gram/deciliter (g/dL) of their reference Hb and between 10.5 and 12.5 g/dL are reported for efficacy evaluation period (EEP). Efficacy evaluation period was from Week 16 to Week 24 after completion of 16-week dose titration period (DTP).	EEP (Week 16 to 24)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Change in the Hb Concentration Between the Stability Verification Period and the EEP	The Hb levels were recorded for each participant at enrollment and at different time points during the study up to Week 48. The mean change in the Hb concentration between the Stability Verification Period (SVP) and the EEP is reported.	SVP (Week -4 to -1), EEP (Week 16 to 24)
Percentage of Participants Maintaining Hb Concentration Within The Target Range 10.5 and 12.5 g/dL Throughout the EEP	The Hb levels were recorded for each participant at enrollment and at different time points during the study up to Week 48. The percentage of participants maintaining their mean Hb concentration within the target range 10.5 and 12.5 g/dL throughout the EEP are reported.	EEP (Week 16 to 24)
Mean Time Spent by the Participants in the Hb Target Range 10.5-12.5 g/dL During EEP	The Hb levels were recorded for each participant at enrollment and at different time points during the study up to Week 48. The mean time (days) spent by the participants in the Hb target range 10.5 to 12.5 is reported.	EEP (Week 16 to 24)
Mean C.E.R.A Dose To Maintain Hb Level Within the Range 10.5-12.5 g/dL Throughout the EEP	The Hb levels were recorded for each participant at enrollment and at different time points during the study up to Week 48. The mean C.E.R.A dose required to maintain the Hb level within the range 10.5-12.5 g/dL throughout the EEP is presented.	EEP (Week 16 to 24)
Percentage of Participants Requiring Dose Adjustments of C.E.R.A During the DTP and EEP	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 10.5 and 12.5 g/dL throughout the DTP (Week 0 to Week 16) and the EEP (Weeks 16 to 24). The reference Hb value was taken as the mean of all Hb assessments during the stability verification period (Weeks -4, -3, -2, -1). The percentage of participants requiring C.E.R.A dose adjustments during the DTP and EEP are presented.	Baseline (Week 0) to Week 24
Mean Monthly Dose of C.E.R.A During the DTP and EEP	The initial dose of C.E.R.A. was 120, 200, or 360 mcg IV or SC every 4 weeks for 48 weeks, which was based on the last dose of the previous ESA. 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 10.5 and 12.5 g/dL throughout the DTP and the EEP. The reference Hb value was taken as the mean of all Hb assessments during the stability verification period. The mean monthly doses of C.E.R.A during the DTP and EEP are presented.	Baseline (Week 0) to Week 24
Incidence of Red Blood Cell Transfusions During the C.E.R.A. Treatment Phase	Red blood cell (RBC) transfusions were permitted during the treatment period in case of medical need. The pre-transfusion Hb level was measured before any transfusion was administered.	Baseline (Week 0) to Week 44
Number of Participants With Adverse Events and Serious Adverse Events	Adverse event (AE) and Serious adverse event (SAE) data was reported for the safety population which included all participants who entered into the study.	Up to Week 52
Mean Haemoglobin Levels Over Time	The Hb levels were recorded for each participant at enrollment and at different time points during the study up to Week 48. The standard reference range for Hb are as follows: Female: min-max for lower limit=11 to 13 g/dL and min-max for upper limit=14 to 18.1 g/dL; Male: min-max for lower limit=12 to 14.2 g/dL and min-max for upper limit=16 to 18.1 g/dL.	Baseline (Week 0), Week 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, and 48
Mean Hematocrit Levels Over Time	The haematocrit (HCT) levels in fraction were recorded for each participant at enrollment and at different time points during the study up to Week 48. The standard reference range for hematocrit are as follows: Female: min-max for lower limit=0.12 - 0.38 and min-max of upper limit=0.43 - 0.537; Male: min-max for lower limit=0.35 - 0.45 and min-max of upper limit=0.45 - 0.54.	Baseline (Week 0), Week 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, and 48
Mean White Blood Cells and Thrombocyte Levels Over Time	The white blood cells (WBC) and thrombocyte levels were recorded for each participant at enrollment and at different time points during the study up to Week 48. The standard reference ranges for WBC are as follows: Female/Male: min-max for lower limit= 3.5 - 5*10^9 cells/L and min-max of upper limit= 9 -13.5*10^9 cells/L. The standard reference ranges for thrombocyte are as follows: Female/Male: min-max for lower limit= 130 - 150*10^9 cells/L and min-max of upper limit= 300 - 450*10^9 cells/L.	Baseline (Week 0), Week 8, 16, 24, 32, 40, and 48
Mean Phosphate and Potassium Levels Over Time	The phosphate and potassium levels were recorded for each participant at enrollment and at different time points during the study up to Week 48. The standard reference ranges for phosphate are as follows: Female/Male: min-max for lower limit= 0.48435 - 0.9687 mmol/L and min-max for upper limit=1.45305 - 2.2603 mmol/L. The standard reference ranges for potassium are as follows: Female/Male: min-max for lower limit=3.1 - 3.7 mmol/L and min-max for upper limit=5 - 5.5 mmol/L.	Baseline (Week 0), Week 8, 16, 24, 32, 40, and 48
Mean Creatinine, Iron, and Total Iron Binding Capacity Levels Over Time	The creatinine, iron, and total iron binding capacity (TIBC) levels were recorded for each participant at enrollment and at different time points during the study up to Week 48. The standard reference ranges for creatinine are as follows: Female: min-max for lower limit=0 - 70.72 mmol/L and min-max for upper limit=79.56 - 123.76 mmol/L; Male: min-max for lower limit=0 - 70.72 mmol/L and min-max for upper limit=97.24 - 123.76 mmol/L. The standard reference ranges for iron are as follows: Female: min-max for lower limit=6.265 - 10.74 mmol/L and min-max for upper limit=25.06 - 32.22 mmol/L and Male: min-max for lower limit=6.265 - 11.635 mmol/L and min-max for upper limit=25.06 - 32.22 mmol/L. The standard reference ranges for TIBC are as follows: Female: min-max for lower limit=19.69 - 49.046 mmol/L and min-max for upper limit=62.65 - 88.963 mmol/L and Male: min-max for lower limit=19.69 - 52.089 mmol/L and min-max for upper limit=62.65 - 80.55 mmol/L.	Baseline (Week 0), Week 8, 16, 24, 32, 40, and 48
Mean Transferrin Saturation Levels Over Time	Transferrin saturation (TSAT) is the ratio of serum iron and total iron-binding capacity. Transferrin is a blood protein that picks up iron absorbed by the intestines and transports it from one location to another. When iron absorption is abnormally high, transferrin proteins become more saturated with iron. An elevated TS value therefore reflects an increase in iron absorption. The TSAT levels were recorded for each participant at enrollment and at different time points during the study up to Week 48. TSAT was calculated automatically in the electronic case report form (eCRF) according to the following formulae: TSAT= (Serum Iron*100)/(Transferrin*1.41) or TSAT=(Serum Iron*100)/TIBC. Calculated data was not provided by laboratory; therefore no reference range is available.	Baseline (Week 0), Week 8, 16, 24, 32, 40, and 48
Mean Albumin and Transferrin Levels Over Time	The albumin and transferrin levels were recorded for each participant at enrollment and at different time points during the study up to Week 48. The standard reference ranges for albumin are as follows: Female/Male: min-max for lower limit=30 - 35 g/L and min-max for upper limit=48 - 55 g/L. The standard reference ranges for transferrin are as follows: Female/Male: min-max for lower limit=1.5 - 2.3 g/L and min-max for upper limit=2.87 - 4.3 g/L.	Baseline (Week 0), Week 8, 16, 24, 32, 40, and 48
Mean C-Reactive Protein Levels Over Time	C-reactive protein (CRP) is produced by the liver. The level of CRP rises when there is inflammation throughout the body. The CRP test is a general test to check for inflammation in the body.The CRP levels were recorded for each participant at enrollment and at different time points during the study up to Week 48. The standard reference ranges for CRP are as follows: Female/Male: min-max for lower limit=0 - 10 mg/L and min-max for upper limit=0.5 - 30 mg/L.	Baseline (Week 0), 8, 16, 24, 32, 40, and 48
Mean Ferritin Levels Over Time	Ferritin is a protein found inside cells that stores iron so that the body can use it later. A ferritin test indirectly measures the amount of iron in your blood. The Ferritin levels were recorded for each participant at enrollment and at different time points during the study up to Week 48. The standard reference ranges for ferritin are as follows: Female: min-max for lower limit=6 - 50 mcg/L and min-max for upper limit=120 - 400 mcg/L; Male: min-max for lower limit=10 - 50 mcg/L and min-max for upper limit=200 - 400 mcg/L.	Baseline (Week 0), Week 8, 16, 24, 32, 40, and 48

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: October 1, 2007
• Primary Completion (Actual): May 1, 2010
• Study Completion (Actual): May 1, 2010

Study Registration Dates

• First Submitted: August 16, 2007
• First Submitted That Met QC Criteria: August 16, 2007
• First Posted (Estimate): August 17, 2007

Study Record Updates

• Last Update Posted (Estimate): April 29, 2016
• Last Update Submitted That Met QC Criteria: March 29, 2016
• Last Verified: March 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Hematologic Diseases; Anemia; Hematinics; Epoetin Alfa
• Other Study ID Numbers: ML20881