MIRACLE Study: A Study of Once-Monthly Intravenous Mircera in Hemodialysis Participants With Chronic Renal Anemia

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

This single-arm study will assess the long-term maintenance of hemoglobin levels, safety, and tolerability of once-monthly intravenous administration of Mircera in hemodialysis participants with chronic renal anemia. Those currently receiving darbepoetin alfa, epoetin alfa, or epoetin beta maintenance treatment will receive intravenous Mircera at a starting dose of 120, 200, or 360 micrograms (mcg) per month (based on the erythropoiesis stimulating agent [ESA] dose administered on Week -1). Subsequent doses will be adjusted to maintain hemoglobin levels within the country-specific target range (11 to 13 grams per deciliter [g/dL] for Switzerland and 10 to 12 g/dL for Austria).

Study Overview

• Status: Completed
• Conditions: Anemia
• Intervention / Treatment: Drug: Methoxy polyethylene glycol-epoetin beta

• Study Type: Interventional
• Enrollment (Actual): 120
• Phase: Phase 3

Contacts and Locations

Study Locations

• Austria
  • Bregenz, Austria, 6900
  • Feldkirch, Austria, 6807
  • Graz, Austria, 8020
  • Kufstein, Austria, 6330
  • Linz, Austria, 4020
  • Salzburg, Austria, 5020
  • St Pölten, Austria, 3100
  • Steyr, Austria, 4400
  • Wien, Austria, 1030
  • Wien, Austria, 1100
  • Wien, Austria, 1130
  • Wien, Austria, 1160
  • Wien, Austria, 1220
• Switzerland
  • Basel, Switzerland, 4031
  • Bellinzona, Switzerland, 6500
  • Burgdorf, Switzerland, 3400
  • Geneve, Switzerland, 1205
  • Lausanne, Switzerland, 1011
  • Liestal, Switzerland, 4410
  • Locarno, Switzerland, 6600
  • Lugano, Switzerland, 6903
  • Luzern, Switzerland, 6004
  • Mendrisio, Switzerland, 6850
  • Sion, Switzerland, 1951
  • St. Gallen, Switzerland, 9007
  • Zürich, Switzerland, 8037
  • Zürich, Switzerland, 8091

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:

• Adults greater than or equal to (≥) 18 years of age
• Chronic renal anemia
• Hemoglobin concentration in country-specific target range (Switzerland: 11 to 13 g/dL; Austria: 10 to 12 g/dL)
• Regular long-term hemodialysis therapy with the same mode of dialysis for ≥3 months
• Continuous intravenous or subcutaneous maintenance ESA treatment during previous 2 months

Exclusion Criteria:

• Transfusion of red blood cells during previous 2 months
• Significant acute or chronic bleeding, such as overt gastrointestinal bleeding
• Active malignant disease (except non-melanoma skin cancer)

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: Mircera in Renal Anemia; Participants will receive intravenous Mircera every 4 weeks for a total of 52 weeks in this single-arm study. The first dose of 120, 200, or 360 mcg will be determined by the dose of ESA received prior to administration of study treatment, while subsequent doses will be adjusted to maintain hemoglobin within a country-specific target range.	Drug: Methoxy polyethylene glycol-epoetin beta; Mircera will be administered intravenously every 4 weeks for a total of 52 weeks. The first dose of 120, 200, or 360 mcg will be determined by the dose of ESA received prior to administration of study treatment, while subsequent doses will be adjusted to maintain hemoglobin within a country-specific target range.; Other Names: Mircera

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Who Maintained Average Hb Within Plus/Minus (±) 1 g/dL of Reference Hb or Within Target Range During the Efficacy Evaluation Period (EEP)	Reference Hb was determined individually per participant as the average of all Hb values during a pre-treatment stability assessment (Weeks -4 to 0). During the EEP (Weeks 18 to 24), participants provided a total of four pre-dose blood samples for Hb monitoring while on treatment with Mircera/CERA. Sampling was also performed prior to each dialysis session. The average Hb during the EEP was calculated per participant and assessed against the reference value. The percentage of participants who had average Hb during the EEP in the country-specific target range (11.0 to 13.0 g/dL in Switzerland and 10.0 to 12.0 g/dL in Austria) and within ±1 g/dL of their individual reference Hb was determined as the primary endpoint. The 95 percent (%) confidence interval (CI) was calculated using the Pearson-Clopper method for exact confidence bounds.	At Weeks -4, -3, -2, -1, 0; pre-dose (0 hours) and immediately before dialysis (minimum 3 sessions per week) during Weeks 18, 20, 22, 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Change in Time-Adjusted Hb From Baseline to EEP	Reference Hb was determined individually per participant as the average of all Hb values during a pre-treatment stability assessment (Weeks -4 to 0). During the EEP (Weeks 18 to 24), participants provided a total of four pre-dose blood samples for Hb monitoring while on treatment with Mircera/CERA. Sampling was also performed prior to each dialysis session. The average Hb during the EEP was calculated per participant and assessed against the reference value. The mean change in Hb value between reference (i.e., "Baseline") Hb and the EEP average Hb was calculated and expressed in g/dL.	At Weeks -4, -3, -2, -1, 0; pre-dose (0 hours) and immediately before dialysis (minimum 3 sessions per week) during Weeks 18, 20, 22, 24
Mean Time Spent in the Target Range for Hb During the Long-Term Safety Period (LTSP)	During the LTSP (Weeks 18 to 52), participants provided a total of 16 pre-dose blood samples for Hb monitoring while on treatment with Mircera/CERA. Sampling was also performed prior to each dialysis session. Time spent in the country-specific target range (11.0 to 13.0 g/dL in Switzerland and 10.0 to 12.0 g/dL in Austria) was defined as time from first on-target Hb to time of last known on-target Hb, as collected during the EEP. Time spent in the target range was averaged among all participants and expressed in days.	Pre-dose (0 hours) and immediately before dialysis (minimum 3 sessions per week) during Weeks 18, 20, 22, 24, 26, 28, 30, 32, 34, 36, 38, 40, 42, 44, 46, 48
Percentage of Participants Who Maintained Average Hb Within Target Range Throughout the EEP	During the EEP (Weeks 18 to 24), participants provided a total of four pre-dose blood samples for Hb monitoring while on treatment with Mircera/CERA. Sampling was also performed prior to each dialysis session. The percentage of participants who had average Hb during the EEP in the country-specific target range (11.0 to 13.0 g/dL in Switzerland and 10.0 to 12.0 g/dL in Austria) was determined. The 95% CI was calculated using the Pearson-Clopper method for exact confidence bounds.	Pre-dose (0 hours) and immediately before dialysis (minimum 3 sessions per week) during Weeks 18, 20, 22, 24
Percentage of Hb Values Above or Below the Target Range During the LTSP	During the LTSP (Weeks 18 to 52), participants provided a total of 16 pre-dose blood samples for Hb monitoring while on treatment with Mircera/CERA. Sampling was also performed prior to each dialysis session. The percentage of all Hb values outside of the country-specific target range was determined and reported separately as Hb values above the upper bound (13.0 g/dL in Switzerland and 12.0 g/dL in Austria) and Hb values below the lower bound (11.0 g/dL in Switzerland and 10.0 g/dL in Austria).	Pre-dose (0 hours) and immediately before dialysis (minimum 3 sessions per week) during Weeks 18, 20, 22, 24, 26, 28, 30, 32, 34, 36, 38, 40, 42, 44, 46, 48
Mean Time Spent Above or Below the Target Range for Hb During the LTSP	During the LTSP (Weeks 18 to 52), participants provided a total of 16 pre-dose blood samples for Hb monitoring while on treatment with Mircera/CERA. Sampling was also performed prior to each dialysis session. Time spent outside the country-specific target range was defined as time from each off-target Hb to time of next on-target Hb, as collected during the LTSP. Time spent outside the target range was averaged among all participants and expressed in days, reported separately as time spent above the upper bound (13.0 g/dL in Switzerland and 12.0 g/dL in Austria) and time spent below the lower bound (11.0 g/dL in Switzerland and 10.0 g/dL in Austria).	Pre-dose (0 hours) and immediately before dialysis (minimum 3 sessions per week) during Weeks 18, 20, 22, 24, 26, 28, 30, 32, 34, 36, 38, 40, 42, 44, 46, 48
Mean Excursions Above or Below Target Range for Hb During the LTSP	During the LTSP (Weeks 18 to 52), participants provided a total of 16 pre-dose blood samples for Hb monitoring while on treatment with Mircera/CERA. Sampling was also performed prior to each dialysis session. Deviation from the country-specific target range was calculated as [Hb value minus country-specific upper bound] for deviations above the target range and [Hb value minus country-specific lower bound] for deviations below the target range. Deviations were averaged among all Hb values from all participants and expressed in g/dL, reported separately as mean deviation above the upper bound (13.0 g/dL in Switzerland and 12.0 g/dL in Austria) and mean deviation below the lower bound (11.0 g/dL in Switzerland and 10.0 g/dL in Austria).	Pre-dose (0 hours) and immediately before dialysis (minimum 3 sessions per week) during Weeks 18, 20, 22, 24, 26, 28, 30, 32, 34, 36, 38, 40, 42, 44, 46, 48
Mean Number of Months a Participant Required Dose Adjustment of Mircera/CERA During the DTP and LTSP	Study drug administration occurred monthly during the DTP (Weeks 0 to 16), which began with a pre-specified dose of Mircera/CERA according to the dose of ESA administered during Week -1. Subsequent doses could be adjusted throughout the study including during the LTSP (Weeks 18 to 52) on the basis of Hb levels or other modification criteria. The mean number of months required for dose adjustment for any reason was calculated and averaged among all participants during the DTP and LTSP.	Weeks 0, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48
Mean Dose of Mircera/CERA During the DTP and LTSP	Study drug administration occurred monthly during the DTP (Weeks 0 to 16), which began with a pre-specified dose of Mircera/CERA according to the dose of ESA administered during Week -1. Subsequent doses could be adjusted throughout the study including during the LTSP (Weeks 18 to 52) on the basis of Hb levels or other modification criteria. The dose received at each administration visit was averaged among all participants during the DTP and LTSP and expressed in mcg.	Weeks 0, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48
Percentage of Participants Who Received Blood Transfusions During the DTP and LTSP	The number of participants who received blood transfusion during the DTP (Weeks 0 and 16) and LTSP (Weeks 18 to 52) was reported.	From Week 0 (every week until Week 2, every 2 weeks until Week 48) through the final visit at Week 52

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): October 1, 2009
• Study Completion (Actual): October 1, 2009

Study Registration Dates

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

Study Record Updates

• Last Update Posted (Estimate): June 24, 2016
• Last Update Submitted That Met QC Criteria: May 19, 2016
• Last Verified: May 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Hematologic Diseases; Anemia; Hematinics; Epoetin Alfa
• Other Study ID Numbers: ML20826

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No