A Study of Monthly Subcutaneous (SC) Mircera for Maintenance Treatment of Participants With Chronic Kidney Disease on Peritoneal Dialysis (MISTRAL)

A Single Arm, Open-Label, Multicentre Study to Assess the Maintenance of Haemoglobin Levels With Once Monthly Subcutaneous Administration of C.E.R.A (Continuous Erythropoietin Receptor Activator) in Patients With Chronic Kidney Disease on Peritoneal Dialysis

This single-arm study will assess the efficacy and safety of monthly administration of SC Mircera for the maintenance of hemoglobin levels in participants with chronic kidney disease on peritoneal dialysis. Participants currently receiving maintenance treatment with SC erythropoietin stimulating agents (ESAs) will receive monthly SC injections of Mircera, with the starting dose derived from the last weekly ESA they had been receiving.

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 96
• Phase: Phase 3

Contacts and Locations

Study Locations

• France
  • Ajaccio, France, 20303
    • Ch Notre Dame Misericorde; Hemodialyse
  • Annonay, France, 07103
    • Centre Hospitalier; Hemodialyse
  • Arras, France, 62022
    • Ch D Arras; Nephrologie
  • Auxerre, France, 89011
    • Ch D Auxerre; Nephrologie Hemodialyse
  • Besancon, France, 25030
    • CHU Saint Jacques; Centre De Dialyse
  • Beuvry, France, 62660
    • Ch Germon Et Gauthier; Hemodialyse
  • Bordeaux, France, 33077
    • Polyclin Bordeaux Nord Aquitaine; Nephrologie - Hemodialyse
  • Cabestany, France, 66330
    • Centre D Hemodialyse Saint Roch
  • Caen, France, 14033
    • Hopital Clemenceau; Nephrologie Hemodialyse
  • Cannes, France, 06401
    • Hôpital Des Brousailles; Service de Néphrologie
  • Chalon Sur Saone, France, 71100
    • CH William Morey; Nephrologie
  • Chambery, France, 73011
    • Ch De Chambery; Nephrologie
  • Charleville Mezieres, France, 08011
    • Hopital Manchester; Nephrologie Hemodialyse
  • Chartres, France, 28018
    • Ch Hotel Dieu; Nephrologie
  • Cherbourg Octeville, France, 50102
    • Ch Du Cotentin Site De Cherbourg; Nephrologie
  • Colmar, France, 68024
    • Hopital Louis Pasteur; Nephrologie - Hemodialyse
  • Creil, France, 60109
    • Ch Laennec; Nephrologie Hemodialyse
  • Dijon, France, 21079
    • Hopital Du Bocage; Nephrologie
  • Dunkerque, France, 59385
    • Ch De Dunkerque; Nephrologie
  • Evreux, France, 27023
    • Chi Eure Seine D Evreux; Nephrologie
  • La Tronche, France, 38701
    • Agduc Muller
  • Le Petit Quevilly, France, 76143
    • Anider; Pharmacie
  • Lille, France, 59037
    • Hopital Calmette; Medecine General & Nephrologie Serv.
  • Lisieux, France, 14107
    • Ch Robert Bisson; Nephrologie
  • Lyon, France, 69008
    • Aural
  • Melun, France, 77011
    • Hopital Marc Jacquet; Nephrologie Hemodialyse
  • Metz, France, 57003
    • Hopital Saint Andre; Nephrologie
  • Nantes, France, 44202
    • Echo Nantes Confluent; Uad Montfort
  • Niort, France, 79021
    • Ch Georges Renon; Nephrologie Hemodialyse
  • Orleans, France, 45100
    • Hopital de La Source; Service de Nephrologie & Hemodialyse
  • Paris, France, 75877
    • Hopital Bichat Claude Bernard; Nephrologie
  • Paris, France, 75651
    • Ch Pitie Salpetriere; Nephrologie Hemodialyse
  • Paris, France, 75970
    • Hopital Tenon; Nephrologie Dialyse
  • Paris, France, 75014
    • Unite Autodialyse Paris 14; Dialyse A Domicile
  • Poitiers, France, 86021
    • Chu La Miletrie;Nephrologie Transplantation
  • Pontoise, France, 95300
    • Ch Rene Dubos; Dialyse Peritoneale
  • Quimper, France, 29107
    • Chi De Cornouaille; Nephrologie
  • Reims, France, 51092
    • Hopital De La Maison Blanche; Nephrologie Hemodialyse
  • Rodez, France, 12027
    • Ch De Bourran; Nephrologie Hemodialyse
  • Saint Lo, France, 50009
    • Memorial France Etats Unis; Nephrologie
  • Saint-Denis, France, 97400
    • Aurar; Aurar St Denis
  • Saint-Pierre, France, 97410
    • Aurar
  • Saintes, France, 17108
    • CH de Saintonge; Unite 1 Med Interne Nephrologie
  • Soissons, France, 02209
    • Ch De Soissons; Medecine 5
  • St Maurice, France, 94415
    • Hopital National; Nephrologie Hemodialyse
  • St Priest En Jarez, France, 42277
    • HOPITAL NORD; NEPH Transplantation Reanimation
  • Strasbourg, France, 67091
    • Hopital Civil; Nephrologie Clinique Medicale B
  • Tours, France, 37044
    • Arauco; Arauco Tours Bretonneau
  • Valence, France, 26953
    • Ch De Valence; Departement Medecine
  • Vandoeuvre-les-nancy, France, 54511
    • ALTIR
  • Vannes, France, 56017
    • CH Bretagne Atlantique de Vannes; Hemodialyse
  • Vittel, France, 88804
    • Ch De Vittel; Nephrologie Hemodialyse

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 kidney disease-related anemia on peritoneal dialysis for ≥3 months
• Continuous SC maintenance stable ESA therapy for 4 weeks prior to study start

Exclusion Criteria:

• Transfusion of red blood cells during previous 8 weeks
• Poorly controlled hypertension requiring interruption of ESA treatment in previous 6 months
• Significant acute or chronic bleeding during previous 8 weeks

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 SC methoxy polyethylene glycol-epoetin beta (Mircera) every 4 weeks for a total of 48 weeks in this single-arm study. The first dose of 120 or 200 micrograms (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 the target range.

Drug: Methoxy polyethylene glycol-epoetin beta; Mircera will be administered SC every 4 weeks for a total of 48 weeks. The first dose of 120 or 200 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 the target range.; Other Names: Mircera; CERA

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Who Maintained Average Hb Value Within Target Range During the EEP	Participants provided pre-dose blood samples for Hb monitoring while on treatment with Mircera/CERA. The average Hb during the EEP (Weeks 16 to 24) was calculated per participant and assessed against the target range. The percentage of participants who had average Hb during the EEP in the target range (10 to 12 g/dL) was determined as the primary endpoint. The 95 percent (%) confidence interval (CI) was calculated using the Pearson-Clopper method for exact confidence bounds.	Weeks 16 to 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Hb Values Within Target Range During the EEP	During the EEP (Weeks 16 to 24), participants provided a total of three pre-dose blood samples for Hb monitoring while on treatment with Mircera/CERA. The percentage of participants who had at least one, two, or all three Hb values during the EEP in the target range (10 to 12 g/dL) was determined.	Weeks 16 to 24
Change in Hb Value From Baseline to the EEP	Reference Hb was determined individually per participant as the average of all Hb values during a pre-treatment screening period (Weeks -4 to 0). Participants provided pre-dose blood samples for Hb monitoring while on treatment with Mircera/CERA. The average Hb during the EEP (Weeks 16 to 24) 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.	Baseline and Weeks 16 to 24
Time Spent in the Target Range for Hb During the EEP and the Overall Treatment Period	Participants provided pre-dose blood samples for Hb monitoring while on treatment with Mircera/CERA. Time spent in the target range (10 to 12 g/dL) was defined as time from first on-target Hb measurement to time of last known on-target Hb measurement, as collected during the EEP (Weeks 16 to 24) and the overall treatment period (Weeks 0 to 48). Time spent in the target range was averaged among all participants and expressed in weeks.	Weeks 16 to 24 and Weeks 0 to 48
Percentage of Participants With Hb Value Within Plus/Minus (±) 1 g/dL of Reference Hb and Within the Target Range by Study Visit	Reference Hb was determined individually per participant as the average of all Hb values during a pre-treatment screening period (Weeks -4 to 0). Participants provided pre-dose blood samples for Hb monitoring while on treatment with Mircera/CERA. The percentage of participants who had average Hb during the EEP (Weeks 16 to 24) and follow-up (Weeks 28 to 48) in the target range (10 to 12 g/dL) and within ±1 g/dL of their individual reference Hb was determined by study visit.	Baseline and Weeks 16, 20, 24, 28, 32, 36, 40, 44, 48
Percentage of Participants With Cycles or Excursions	Participants provided pre-dose blood samples for Hb monitoring while on treatment with Mircera/CERA. Cycles were defined as a change in Hb greater than (>) 1.5 g/dL lasting longer than 8 weeks. Excursions were defined as half of one full cycle, or an increase ("up" excursions) or decrease ("down" excursions) >1.5 g/dL lasting longer than 4 weeks according to Hb measurements collected during the study. The percentage of participants with at least one cycle or excursion during Weeks 4 to 44 was calculated.	Weeks 4 to 44
Percentage of Participants With Up Excursions	Participants provided pre-dose blood samples for Hb monitoring while on treatment with Mircera/CERA during the DAP, EEP, and follow-up. Excursions were defined as half of one full cycle, or an increase ("up" excursions) or decrease ("down" excursions) in Hb >1.5 g/dL lasting longer than 4 weeks. The percentage of participants with at least one up excursion was calculated for Weeks 4 to 16, Weeks 16 to 24, and Weeks 24 to 44.	Weeks 4 to 16, Weeks 16 to 24, Weeks 24 to 44
Percentage of Participants With Down Excursions	Participants provided pre-dose blood samples for Hb monitoring while on treatment with Mircera/CERA during the DAP, EEP, and follow-up. Excursions were defined as half of one full cycle, or an increase ("up" excursions) or decrease ("down" excursions) in Hb >1.5 g/dL lasting longer than 4 weeks. The percentage of participants with at least one down excursion was calculated for Weeks 4 to 16, Weeks 16 to 24, and Weeks 24 to 44.	Weeks 4 to 16, Weeks 16 to 24, Weeks 24 to 44
Percentage of Participants Who Required Any Dose Adjustment of Mircera/CERA	Study drug administration occurred monthly during treatment (Weeks 0 to 48), which began with a pre-specified dose of Mircera/CERA according to the dose of ESA administered during the initial 4-week screening period. Subsequent doses could be adjusted on the basis of Hb levels or other modification criteria. The percentage of participants who required any dose adjustment (including decreased dose, increased dose, and dose not performed) was calculated for Weeks 4 to 20, Weeks 24 to 48, and Weeks 4 to 48.	Weeks 4 to 20, Weeks 24 to 48, Weeks 4 to 48
Number of Dose Adjustments of Mircera/CERA	Study drug administration occurred monthly during treatment (Weeks 0 to 48), which began with a pre-specified dose of Mircera/CERA according to the dose of ESA administered during the initial 4-week screening period. Subsequent doses could be adjusted on the basis of Hb levels or other modification criteria. The number of dose adjustments performed for each participant was averaged among all participants for Weeks 4 to 20, Weeks 24 to 48, and Weeks 4 to 48.	Weeks 4 to 20, Weeks 24 to 48, Weeks 4 to 48
Absolute Change in Dose of Mircera/CERA by Study Week	Study drug administration occurred monthly during treatment (Weeks 0 to 48), which began with a pre-specified dose of Mircera/CERA according to the dose of ESA administered during the initial 4-week screening period. Subsequent doses could be adjusted on the basis of Hb levels or other modification criteria. The absolute difference in dose from the previous week was calculated at each visit and averaged among all participants.	Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48
Percent Change in Dose of Mircera/CERA by Study Week	Study drug administration occurred monthly during treatment (Weeks 0 to 48), which began with a pre-specified dose of Mircera/CERA according to the dose of ESA administered during the initial 4-week screening period. Subsequent doses could be adjusted on the basis of Hb levels or other modification criteria. The percent difference in dose from the previous week was calculated at each visit as [(current dose minus previous week dose) divided by previous week dose] multiplied by 100, and averaged among all participants.	Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48
Percentage of Participants Requiring Blood Transfusions	The percentage of participants who received at least one red blood cell transfusion during the overall treatment period (Weeks 0 to 48) was calculated.	Weeks 0 to 48

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche

Study record dates

Study Major Dates

• Study Start (Actual): September 30, 2008
• Primary Completion (Actual): July 31, 2011
• Study Completion (Actual): July 31, 2011

Study Registration Dates

• First Submitted: August 18, 2008
• First Submitted That Met QC Criteria: August 18, 2008
• First Posted (Estimate): August 19, 2008

Study Record Updates

• Last Update Posted (Actual): June 23, 2017
• Last Update Submitted That Met QC Criteria: May 30, 2017
• Last Verified: May 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urologic Diseases; Renal Insufficiency; Kidney Diseases; Renal Insufficiency, Chronic; Hematinics; Epoetin Alfa
• Other Study ID Numbers: ML21421; 2008-001747-18 (EudraCT Number)