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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT00545571
First received: October 16, 2007
Last updated: May 19, 2016
Last verified: May 2016
  Purpose
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 Intervention Phase
Anemia
Drug: Methoxy polyethylene glycol-epoetin beta
Phase 3

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
    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:
  • 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 ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: No ]
    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).

  • 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 ] [ Designated as safety issue: No ]
    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).

  • 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 ] [ Designated as safety issue: No ]
    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).

  • 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 ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: No ]
    The number of participants who received blood transfusion during the DTP (Weeks 0 and 16) and LTSP (Weeks 18 to 52) was reported.


Enrollment: 120
Study Start Date: October 2007
Study Completion Date: October 2009
Primary Completion Date: October 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00545571

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

Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT00545571     History of Changes
Other Study ID Numbers: ML20826 
Study First Received: October 16, 2007
Results First Received: April 12, 2016
Last Updated: May 19, 2016
Health Authority: Switzerland: Swissmedic

Additional relevant MeSH terms:
Anemia
Hematologic Diseases

ClinicalTrials.gov processed this record on December 09, 2016