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

• ClinicalTrials.gov Identifier: NCT00545571
• Recruitment Status: Completed
• First Posted: October 17, 2007
• Results First Posted: May 18, 2016
• Last Update Posted: June 24, 2016
• Sponsor: Hoffmann-La Roche
• Information provided by (Responsible Party): Hoffmann-La Roche

Study Description

Brief Summary:

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).

Condition or disease	Intervention/treatment	Phase
Anemia	Drug: Methoxy polyethylene glycol-epoetin beta	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 120 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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
• Study Start Date: October 2007
• Actual Primary Completion Date: October 2009
• Actual Study Completion Date: October 2009

Arms and Interventions

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 Name: Mircera

Outcome Measures

Primary Outcome Measures :

1. 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) [ Time Frame: 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 ]
   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.

Secondary Outcome Measures :

1. Mean Change in Time-Adjusted Hb From Baseline to EEP [ Time Frame: 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 ]
   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.
2. Mean Time Spent in the Target Range for Hb During the Long-Term Safety Period (LTSP) [ Time Frame: 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 ]
   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.
3. Percentage of Participants Who Maintained Average Hb Within Target Range Throughout the EEP [ Time Frame: Pre-dose (0 hours) and immediately before dialysis (minimum 3 sessions per week) during Weeks 18, 20, 22, 24 ]
   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.
4. Percentage of Hb Values Above or Below the Target Range During the LTSP [ Time Frame: 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 ]
   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).
5. Mean Time Spent Above or Below the Target Range for Hb During the LTSP [ Time Frame: 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 ]
   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).
6. Mean Excursions Above or Below Target Range for Hb During the LTSP [ Time Frame: 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 ]
   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).
7. Mean Number of Months a Participant Required Dose Adjustment of Mircera/CERA During the DTP and LTSP [ Time Frame: Weeks 0, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 ]
   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.
8. Mean Dose of Mircera/CERA During the DTP and LTSP [ Time Frame: Weeks 0, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 ]
   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.
9. Percentage of Participants Who Received Blood Transfusions During the DTP and LTSP [ Time Frame: From Week 0 (every week until Week 2, every 2 weeks until Week 48) through the final visit at Week 52 ]
   The number of participants who received blood transfusion during the DTP (Weeks 0 and 16) and LTSP (Weeks 18 to 52) was 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:

• 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)

Contacts and Locations

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

Sponsors and Collaborators

Hoffmann-La Roche

Investigators

• Study Director: Clinical Trials; Hoffmann-La Roche

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Hoffmann-La Roche
• ClinicalTrials.gov Identifier: NCT00545571
• Other Study ID Numbers: ML20826
• First Posted: October 17, 2007
• Results First Posted: May 18, 2016
• Last Update Posted: June 24, 2016
• Last Verified: May 2016

Additional relevant MeSH terms:

Anemia; Hematologic Diseases; Epoetin Alfa; Hematinics