A Study of Monthly Intravenous C.E.R.A. (Mircera) in Hemodialysis Participants With Chronic Renal Anemia (CARISMA)

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 Hemodialysis Patients With Chronic Renal Anaemia

This single arm study will assess the efficacy, safety and tolerability of once-monthly administration of intravenous methoxy polyethylene glycolepoetin beta (Mircera) for the maintenance of hemoglobin levels in hemodialysis participants with chronic renal anemia. Participants currently receiving intravenous epoetin alfa or beta or darbepoetin alfa will receive intravenous Mircera at a starting dose of 120, 200 or 360 micrograms/month (based on the erythropoietin stimulating agent [ESA] dose administered on week -1). Subsequent doses will be adjusted to maintain hemoglobin levels within the target range of 10 to12 gram per deciliter (g/dL). The anticipated time on study treatment is 1-2 years, and the target sample size is 100-500 individuals.

Study Overview

• Status: Completed
• Conditions: Anemia
• Intervention / Treatment: Drug: Methoxy polyethylene glycol-epoetin beta (C.E.R.A.)

• Study Type: Interventional
• Enrollment (Actual): 351
• Phase: Phase 3

Contacts and Locations

Study Locations

• Italy
  • Acireale, Italy, 95024
  • Ancona, Italy, 60121
  • Anzio, Italy, 00042
  • Arenzano, Italy, 16011
  • Ascoli Piceno, Italy, 63100
  • Avellino, Italy, 83100
  • Benevento, Italy, 82100
  • Bollate, Italy, 20021
  • Borgomanero, Italy, 28021
  • Brescia, Italy, 25123
  • Brindisi, Italy, 72100
  • Cagliari, Italy, 09100
  • Castellammare, Italy, 80053
  • Catania, Italy, 95126
  • Catania, Italy, 95124
  • Cernusco Sul Naviglio, Italy, 20063
  • Chieri, Italy, 10023
  • Chieti, Italy, 66013
  • Civitavecchia, Italy, 00053
  • Cosenza, Italy, 87100
  • Ferrara, Italy, 44100
  • Firenze, Italy, 50100
  • Firenze, Italy, 50011
  • Foggia, Italy, 71100
  • Genova, Italy, 16132
  • La Spezia, Italy, 19124
  • Lecco, Italy, 23900
  • Legnano, Italy, 20025
  • Lodi, Italy, 26900
  • Lucera, Italy, 71036
  • Mantova, Italy, 46100
  • Matera, Italy, 75100
  • Milano, Italy, 20142
  • Milazzo, Italy, 98057
  • Montevarchi, Italy, 52025
  • Napoli, Italy, 80131
  • Napoli, Italy, 80137
  • Nocera Inferiore, Italy, 84014
  • Novara, Italy, 28100
  • Nuoro, Italy, 08100
  • Ostia Lido, Italy, 00121
  • Palermo, Italy, 90127
  • Pavia, Italy, 27100
  • Perugia, Italy, 06126
  • Piacenza, Italy, 29100
  • Pisa, Italy, 56100
  • Ravenna, Italy, 48100
  • Reggio Emilia, Italy, 42100
  • Roma, Italy, 00161
  • Roma, Italy, 00149
  • Roma, Italy, 00133
  • Roma, Italy, 00189
  • San Daniele Del Friuli, Italy, 33038
  • San Miniato, Italy, 56028
  • Sassari, Italy, 07100
  • Taranto, Italy, 74100
  • Torino, Italy, 10126
  • Udine, Italy, 33100
  • Verona, Italy, 37126
  • Vicenza, Italy, 36100

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:

• Chronic renal anemia;
• Continuous intravenous maintenance erythropoietin stimulating agent (ESA) treatment during previous month;
• Regular long term hemodialysis therapy with the same mode of dialysis for >=3 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: C.E.R.A.	Drug: Methoxy polyethylene glycol-epoetin beta (C.E.R.A.); Intravenous methoxy polyethylene glycol-epoetin beta (C.E.R.A.) at starting dose of 120, 200, or 360 micrograms every 4 weeks for 24 weeks.; Other Names: Mircera

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Maintaining Mean Hemoglobin Concentration Within Plus or Minus (+/-) 1 Gram Per Deciliter (g/dL) of Reference and Within the Target Range	Percentage of participants maintaining the mean hemoglobin concentration within +/- 1.0 g/dL of their reference hemoglobin value and within the target range of 10.0 to 12.0 g/dL during the efficacy evaluation period (EEP) was assessed. The reference hemoglobin value was defined on the basis of the 5 assessments recorded during the stability verification period (SVP) at Weeks -4, -3, -2, -1 and 0. The mean hemoglobin concentration for each individual participant during the EEP (Week 17 to Week 24) was estimated as a time adjusted average.	Week 17 up to Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Requiring Any Dose Adjustment	Percentage of participants requiring any adjustment in the dose of study drug during the dose titration period (DTP: Week 1 to Week 16) and EEP (Week 17 to Week 24) was reported.	Week 1 up to Week 16 and Week 17 up to Week 24
Change in Hemoglobin Concentration Between Reference SVP and EEP	The mean change of the time adjusted average of hemoglobin from reference value obtained during the SVP (Week -4 up to Week 0) and the value during EEP (Week 17 up to Week 24) was assessed.	Week -4 up to Week 0 and Week 17 up to Week 24
Percentage of Participants Maintaining Hemoglobin Concentration Within the Target Range	Percentage of participants maintaining hemoglobin concentration within the target range of 10.0 to 12.0 g/dL during EEP (Week 17 to Week 24) was assessed.	Week 17 up to Week 24
Median Time Spent by Participants With Hemoglobin Concentration in the Target Range During the EEP	Median time spent by participants with hemoglobin concentration within the target range of 10.0 to 12.0 g/dL during the EEP (Week 17 to Week 24) was assessed.	Week 17 up to Week 24
Number of Participants With Red Blood Cell Transfusion During the Study	Number of participant who underwent red blood cell transfusion during the study was reported.	Week -4 up to 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.
• Locatelli F, Mandolfo S, Menegato Adorati M, Villa G, Tarchini R, Pizzarelli F, Conte F, Guastoni C, Ricciardi B, Crotta A. Efficacy and safety of once-monthly continuous erythropoietin receptor activator in patients with chronic renal anemia. J Nephrol. 2013 Nov-Dec;26(6):1114-21. doi: 10.5301/jn.5000251. Epub 2013 Sep 13.

Study record dates

Study Major Dates

• Study Start: July 1, 2008
• Primary Completion (Actual): July 1, 2010
• Study Completion (Actual): July 1, 2010

Study Registration Dates

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

Study Record Updates

• Last Update Posted (Estimate): April 6, 2016
• Last Update Submitted That Met QC Criteria: March 8, 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: ML21438; 2007-005799-15 (EudraCT Number)