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Study to Determine Optimum Intravenous Starting Dose of MIRCERA for Treatment of Pediatric Participants With Anemia and Chronic Kidney Disease on Hemodialysis

Primary Purpose

Renal Anemia

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Methoxy Polyethylene Glycol-Epoetin Beta
Sponsored by
Hoffmann-La Roche
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Renal Anemia

Eligibility Criteria

5 Years - 17 Years (Child)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Children aged 5-17 years (in Russia only: 12-17 years) with clinically stable chronic renal anemia
  • Hemodialysis for greater than or equal to (>=) 8 weeks
  • Intravenous stable maintenance treatment with epoetin alfa, epoetin beta, or darbepoetin alfa for >= 8 weeks before screening and with no weekly dose change >= 25 percent (%) (increase or decrease) during the 2 weeks of screening

Exclusion Criteria:

  • Overt gastrointestinal bleeding within 8 weeks before screening or during the screening period
  • Red blood cell (RBC) transfusions within 8 weeks before screening or during the screening period
  • Active malignant disease
  • Pure red cell aplasia (PRCA) or history of PRCA
  • Pregnant or lactating females
  • Sexually active participants: not willing to use reliable contraception during treatment and for 90 days following the end of treatment

Sites / Locations

  • Royal Children'S Hospital; Department of Nephrology
  • Hôpital Enfants Reine Fabiola
  • UZ Leuven Gasthuisberg
  • Hopital Femme Mere Enfant; Ped Nephrologie Rhumatologie
  • Hopital Jeanne De Flandre; Cons Pediatrie
  • Hopital Timone Enfants; Nephrologie Hemodialyse
  • Hopital Arnaud De Villeneuve; Pediatrie I
  • Hôpital Robert Debré; Nephrologie pediatrique
  • Hopital Armand Trousseau; Pediatrie Nephrologie
  • Höpital Hautepierre; Pediatrie 1
  • KfH Nierenzentrum für Kinder und Jugendliche
  • KfH-Nierenzentrum fur Kinder und Jugendliche
  • Klinik der Uni zu Köln; Kinderklinik
  • Kinderklinik Memmingen; Kinderdialysezentrum
  • KfH-Nierenzentrum für Kinder und Jugendliche
  • Semmelweis University; 1st Department of Pediatrics, Pediatric Nephrology Center
  • Ospedale Pediatrico Bambino Gesu; U.O. Di Nefrologia E Dialisi
  • IRCCS G. Gaslini; U.O. Nefrologia, Dialisi e Trapianto
  • Ospedale Infantile Regina Margherita; U.O. Autonoma di Nefrologia, Dialisi e Trapianto
  • A.O. Di Padova; Dipartimento Di Pediatria U.O. Di Nefrologia Pediatrica, Dialisi e Trapianto
  • Uniwersyteckie Centrum Kliniczne; Klinika Chorob Nerek i Nadciśnienia Dzieci i Mlodziezy
  • Instytut "Centrum Zdrowia Matki Polki; Klinika Nefrologii i Dializoterapii
  • Dzieciecy Szpital Kliniczny; Klinika Nefrologii Dzieciecej
  • SPSZOZ Zdroje Oddzial Pediatrii; Nefrologii i Toksykologii ze Stacja Dializ
  • Wojewodzki Szpital Dzieciecy; Osrodek Chorob Nerek i Dializoterapii
  • Instytut Pomnik-Centrum Zdrowia Dziecka, Klinika Nefrologii, Transp. Nerek i Nadcisnienia Tetniczego
  • Akademia Medyczna im. Piastow Slaskich; Katedra i Klinika Nefrologii Pediatrycznej
  • Fundeni Clinical Institute
  • St. Maria Emergency Clinical Hospital for Children
  • DGCB St. Vladimir; Pediatric nephrologist
  • SBIH Children City Hospital #1; Dialysis department
  • Hospital Universitari Vall d'Hebron; Servicio de Nefrologia
  • Hospital Universitario La Paz: Nefrologia Pediatrica
  • Hospital Universitario Virgen del Rocio; Servicio de Nefrologia Pediatrica
  • Hospital Universitario la Fe; Servicio de Nefrologia Pediatrica
  • Chulalongkorn university Faculty of Medicine;Department of Pediatrics
  • Siriraj Hospital, Faculty of Medicine; Department of Pediatrics
  • Kiev city childrens nephrological center of hospital #1; Nephrology and RRT
  • Public Institution Zaporizhzhia City Multispecialty Children's Hospital #5; Allergologic

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

MIRCERA Group 1: Intermediate-Conversion-Factor Group

MIRCERA Group 2: High-Conversion-Factor Group

Arm Description

Participants will receive methoxy polyethylene glycol-epoetin beta (MIRCERA) IV injection at a starting dose based on an intermediate conversion factor from their previous Erythropoiesis-stimulating Agent (ESA) dose (4 * previous weekly epoetin dose [international units {IU}]/250 or 4 * previous weekly darbepoetin alfa dose [micrograms {mcg}]/1.1) once every 4 weeks for 20 weeks. Participants who will complete the 20 weeks of treatment with hemoglobin (Hb) level within ± 1 grams per deciliter (g/dL) of their baseline Hb level and within the target range of 10-12 g/dL will enter an optional 52-weeks safety extension period. During this period, the participants will continue to receive MIRCERA IV injection once every 4 weeks.

Participants will receive MIRCERA IV injection based on a high conversion factor from their previous ESA dose (4 * previous weekly epoetin dose [IU]/125 or 4 * previous weekly darbepoetin alfa dose [mcg]/0.55) once every 4 weeks for 20 weeks. Participants who will complete the 20 weeks of treatment with Hb within ± 1 g/dL of their baseline Hb and within the target range of 10-12 g/dL will enter an optional 52-weeks safety extension period. During this period, the participants will continue to receive MIRCERA IV injection once every 4 weeks.

Outcomes

Primary Outcome Measures

Change in Average Hb Concentration Between Baseline and Evaluation Period
A time adjusted average baseline Hb concentration for each individual was calculated using an area under the curve (AUC) approach from all available Hb measurements taken during the baseline period (Day -20 to Day 1). The average evaluation period Hb concentration for each individual was calculated using the same method, from all their available measurements taken during the evaluation period (Week 17 to Week 21). The change in Hb concentration between the baseline and evaluation periods was calculated by subtracting the baseline Hb concentration from the evaluation period Hb concentration.

Secondary Outcome Measures

Number of Participants With an Average Hb Concentration During the Evaluation Period Within ±1 g/dL of Their Baseline Hb
Baseline Hb value was defined as the average Hb concentration from all available Hb measurements taken during the baseline period (Day -20 to Day 1). The evaluation period Hb concentration was defined as the average Hb concentration from all available Hb measurements taken during the evaluation period (Week 17 to Week 21).
Number of Participants With an Average Hb Concentration During the Evaluation Period Above, Within or Below the Range of 10-12 g/dL
The evaluation period Hb concentration was defined as the average Hb concentration from all available Hb measurements taken during the evaluation period (Week 17 to Week 21).
Number of Participants With Blood Transfusions
Change in Average Reticulocyte Count Between the Baseline and Evaluation Period
A time adjusted average baseline reticulocyte count for each individual was calculated using an AUC approach from all available reticulocyte counts taken during the baseline period (Day -20 to Day 1). The average evaluation period reticulocyte count for each individual was calculated using the same method, from all their available measurements taken during the evaluation period (Weeks 17 to 21). The change in reticulocyte count between the baseline and evaluation periods was calculated by subtracting the baseline reticulocyte count from the evaluation period reticulocyte count. Relative reticulocytes were recorded conversion to absolute values was performed.
Maximum Observed Serum Concentration (Cmax) of MIRCERA
Cmax was defined as the highest serum concentration observed from all sample collection timepoints (as provided in timeframe) and was averaged out among participants and reported.
Area Under the Serum Concentration-Time Curve From 0 to 672 Hours (AUC0-672h) of MIRCERA
Area under the serum concentration versus time curve over 672 hours. AUC0-672h represents area under the serum concentration versus time curve from time zero to end of dosing interval (AUC0-tau).
Time to Reach Cmax (Tmax) of MIRCERA
Tmax was defined as the time (in hours) to achieve Cmax (Cmax was defined as the highest serum concentration observed over all sample collection timepoints [as provided in timeframe]). The median time, among all participants, was reported.
Apparent Terminal Phase Half-Life (t1/2) of MIRCERA
t1/2 was defined as the time (in hours) measured (from all sample collection timepoints [as provided in timeframe]) for the serum concentration to decrease by one half. The t1/2 was calculated as natural logarithm of 2 divided by λz; where λz = terminal elimination rate constant.

Full Information

First Posted
July 16, 2008
Last Updated
August 8, 2017
Sponsor
Hoffmann-La Roche
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1. Study Identification

Unique Protocol Identification Number
NCT00717366
Brief Title
Study to Determine Optimum Intravenous Starting Dose of MIRCERA for Treatment of Pediatric Participants With Anemia and Chronic Kidney Disease on Hemodialysis
Official Title
An Open-Label Multi-center, Multiple Dose Study to Determine the Optimum Starting Dose of Intravenous MIRCERA for Maintenance Treatment of Anemia in Pediatric Participants With Chronic Kidney Disease on Hemodialysis
Study Type
Interventional

2. Study Status

Record Verification Date
August 2017
Overall Recruitment Status
Completed
Study Start Date
July 2008 (undefined)
Primary Completion Date
March 2016 (Actual)
Study Completion Date
March 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hoffmann-La Roche

4. Oversight

5. Study Description

Brief Summary
This sequential study will assess the efficacy and safety of multiple doses of intravenous (IV) methoxy polyethylene glycol-epoetin beta (MIRCERA), and will determine the optimum starting dose for maintenance treatment of anemia in children with chronic kidney disease on hemodialysis. Pediatric participants will remain on epoetin alfa, epoetin beta or darbepoetin alfa during the screening period, after which they will receive IV MIRCERA monthly, at a starting dose related to the previous weekly epoetin or darbepoetin alfa dose. Depending on the response achieved, another group may be selected to receive a higher or a lower dose.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Renal Anemia

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
64 (Actual)

8. Arms, Groups, and Interventions

Arm Title
MIRCERA Group 1: Intermediate-Conversion-Factor Group
Arm Type
Experimental
Arm Description
Participants will receive methoxy polyethylene glycol-epoetin beta (MIRCERA) IV injection at a starting dose based on an intermediate conversion factor from their previous Erythropoiesis-stimulating Agent (ESA) dose (4 * previous weekly epoetin dose [international units {IU}]/250 or 4 * previous weekly darbepoetin alfa dose [micrograms {mcg}]/1.1) once every 4 weeks for 20 weeks. Participants who will complete the 20 weeks of treatment with hemoglobin (Hb) level within ± 1 grams per deciliter (g/dL) of their baseline Hb level and within the target range of 10-12 g/dL will enter an optional 52-weeks safety extension period. During this period, the participants will continue to receive MIRCERA IV injection once every 4 weeks.
Arm Title
MIRCERA Group 2: High-Conversion-Factor Group
Arm Type
Experimental
Arm Description
Participants will receive MIRCERA IV injection based on a high conversion factor from their previous ESA dose (4 * previous weekly epoetin dose [IU]/125 or 4 * previous weekly darbepoetin alfa dose [mcg]/0.55) once every 4 weeks for 20 weeks. Participants who will complete the 20 weeks of treatment with Hb within ± 1 g/dL of their baseline Hb and within the target range of 10-12 g/dL will enter an optional 52-weeks safety extension period. During this period, the participants will continue to receive MIRCERA IV injection once every 4 weeks.
Intervention Type
Drug
Intervention Name(s)
Methoxy Polyethylene Glycol-Epoetin Beta
Other Intervention Name(s)
MIRCERA, RO0503821
Intervention Description
Will be administered IV, every 4 weeks.
Primary Outcome Measure Information:
Title
Change in Average Hb Concentration Between Baseline and Evaluation Period
Description
A time adjusted average baseline Hb concentration for each individual was calculated using an area under the curve (AUC) approach from all available Hb measurements taken during the baseline period (Day -20 to Day 1). The average evaluation period Hb concentration for each individual was calculated using the same method, from all their available measurements taken during the evaluation period (Week 17 to Week 21). The change in Hb concentration between the baseline and evaluation periods was calculated by subtracting the baseline Hb concentration from the evaluation period Hb concentration.
Time Frame
Baseline (Day -20 to Day 1), Evaluation Period (Week 17 to Week 21)
Secondary Outcome Measure Information:
Title
Number of Participants With an Average Hb Concentration During the Evaluation Period Within ±1 g/dL of Their Baseline Hb
Description
Baseline Hb value was defined as the average Hb concentration from all available Hb measurements taken during the baseline period (Day -20 to Day 1). The evaluation period Hb concentration was defined as the average Hb concentration from all available Hb measurements taken during the evaluation period (Week 17 to Week 21).
Time Frame
Evaluation Period (Week 17 to Week 21)
Title
Number of Participants With an Average Hb Concentration During the Evaluation Period Above, Within or Below the Range of 10-12 g/dL
Description
The evaluation period Hb concentration was defined as the average Hb concentration from all available Hb measurements taken during the evaluation period (Week 17 to Week 21).
Time Frame
Evaluation Period (Week 17 to Week 21)
Title
Number of Participants With Blood Transfusions
Time Frame
Baseline to Week 20
Title
Change in Average Reticulocyte Count Between the Baseline and Evaluation Period
Description
A time adjusted average baseline reticulocyte count for each individual was calculated using an AUC approach from all available reticulocyte counts taken during the baseline period (Day -20 to Day 1). The average evaluation period reticulocyte count for each individual was calculated using the same method, from all their available measurements taken during the evaluation period (Weeks 17 to 21). The change in reticulocyte count between the baseline and evaluation periods was calculated by subtracting the baseline reticulocyte count from the evaluation period reticulocyte count. Relative reticulocytes were recorded conversion to absolute values was performed.
Time Frame
Baseline (Day -20 to Day 1), Evaluation Period (Week 17 to Week 21)
Title
Maximum Observed Serum Concentration (Cmax) of MIRCERA
Description
Cmax was defined as the highest serum concentration observed from all sample collection timepoints (as provided in timeframe) and was averaged out among participants and reported.
Time Frame
Pre-dose (with 1 hour before drug administration) and 2, 48 hours post dose on Week 9, at Weeks 10, 11, and 12, pre-dose (with 1 hour before drug administration) on Week 13
Title
Area Under the Serum Concentration-Time Curve From 0 to 672 Hours (AUC0-672h) of MIRCERA
Description
Area under the serum concentration versus time curve over 672 hours. AUC0-672h represents area under the serum concentration versus time curve from time zero to end of dosing interval (AUC0-tau).
Time Frame
Pre-dose (with 1 hour before drug administration) and 2, 48 hours post dose on Week 9, at Weeks 10, 11, and 12, pre-dose (with 1 hour before drug administration) on Week 13
Title
Time to Reach Cmax (Tmax) of MIRCERA
Description
Tmax was defined as the time (in hours) to achieve Cmax (Cmax was defined as the highest serum concentration observed over all sample collection timepoints [as provided in timeframe]). The median time, among all participants, was reported.
Time Frame
Pre-dose (with 1 hour before drug administration) and 2, 48 hours post dose on Week 9, at Weeks 10, 11, and 12, pre-dose (with 1 hour before drug administration) on Week 13
Title
Apparent Terminal Phase Half-Life (t1/2) of MIRCERA
Description
t1/2 was defined as the time (in hours) measured (from all sample collection timepoints [as provided in timeframe]) for the serum concentration to decrease by one half. The t1/2 was calculated as natural logarithm of 2 divided by λz; where λz = terminal elimination rate constant.
Time Frame
Pre-dose (with 1 hour before drug administration) and 2, 48 hours post dose on Week 9, at Weeks 10, 11, and 12, pre-dose (with 1 hour before drug administration) on Week 13

10. Eligibility

Sex
All
Minimum Age & Unit of Time
5 Years
Maximum Age & Unit of Time
17 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Children aged 5-17 years (in Russia only: 12-17 years) with clinically stable chronic renal anemia Hemodialysis for greater than or equal to (>=) 8 weeks Intravenous stable maintenance treatment with epoetin alfa, epoetin beta, or darbepoetin alfa for >= 8 weeks before screening and with no weekly dose change >= 25 percent (%) (increase or decrease) during the 2 weeks of screening Exclusion Criteria: Overt gastrointestinal bleeding within 8 weeks before screening or during the screening period Red blood cell (RBC) transfusions within 8 weeks before screening or during the screening period Active malignant disease Pure red cell aplasia (PRCA) or history of PRCA Pregnant or lactating females Sexually active participants: not willing to use reliable contraception during treatment and for 90 days following the end of treatment
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Trials
Organizational Affiliation
Hoffmann-La Roche
Official's Role
Study Director
Facility Information:
Facility Name
Royal Children'S Hospital; Department of Nephrology
City
Parkville
State/Province
Victoria
ZIP/Postal Code
3052
Country
Australia
Facility Name
Hôpital Enfants Reine Fabiola
City
Bruxelles
ZIP/Postal Code
1020
Country
Belgium
Facility Name
UZ Leuven Gasthuisberg
City
Leuven
ZIP/Postal Code
3000
Country
Belgium
Facility Name
Hopital Femme Mere Enfant; Ped Nephrologie Rhumatologie
City
Bron
ZIP/Postal Code
69677
Country
France
Facility Name
Hopital Jeanne De Flandre; Cons Pediatrie
City
Lille
ZIP/Postal Code
59037
Country
France
Facility Name
Hopital Timone Enfants; Nephrologie Hemodialyse
City
Marseille
ZIP/Postal Code
13385
Country
France
Facility Name
Hopital Arnaud De Villeneuve; Pediatrie I
City
Montpellier
ZIP/Postal Code
34295
Country
France
Facility Name
Hôpital Robert Debré; Nephrologie pediatrique
City
Paris
ZIP/Postal Code
75019
Country
France
Facility Name
Hopital Armand Trousseau; Pediatrie Nephrologie
City
Paris
ZIP/Postal Code
75571
Country
France
Facility Name
Höpital Hautepierre; Pediatrie 1
City
Strasbourg
ZIP/Postal Code
67098
Country
France
Facility Name
KfH Nierenzentrum für Kinder und Jugendliche
City
Hamburg
ZIP/Postal Code
20246
Country
Germany
Facility Name
KfH-Nierenzentrum fur Kinder und Jugendliche
City
Heidelberg
ZIP/Postal Code
69120
Country
Germany
Facility Name
Klinik der Uni zu Köln; Kinderklinik
City
Köln
ZIP/Postal Code
50937
Country
Germany
Facility Name
Kinderklinik Memmingen; Kinderdialysezentrum
City
Memmingen
ZIP/Postal Code
87700
Country
Germany
Facility Name
KfH-Nierenzentrum für Kinder und Jugendliche
City
Münster
ZIP/Postal Code
48149
Country
Germany
Facility Name
Semmelweis University; 1st Department of Pediatrics, Pediatric Nephrology Center
City
Budapest
ZIP/Postal Code
1083
Country
Hungary
Facility Name
Ospedale Pediatrico Bambino Gesu; U.O. Di Nefrologia E Dialisi
City
Roma
State/Province
Lazio
ZIP/Postal Code
00165
Country
Italy
Facility Name
IRCCS G. Gaslini; U.O. Nefrologia, Dialisi e Trapianto
City
Genova
State/Province
Liguria
ZIP/Postal Code
16148
Country
Italy
Facility Name
Ospedale Infantile Regina Margherita; U.O. Autonoma di Nefrologia, Dialisi e Trapianto
City
Torino
State/Province
Piemonte
ZIP/Postal Code
10126
Country
Italy
Facility Name
A.O. Di Padova; Dipartimento Di Pediatria U.O. Di Nefrologia Pediatrica, Dialisi e Trapianto
City
Padova
State/Province
Veneto
ZIP/Postal Code
35128
Country
Italy
Facility Name
Uniwersyteckie Centrum Kliniczne; Klinika Chorob Nerek i Nadciśnienia Dzieci i Mlodziezy
City
Gdansk
ZIP/Postal Code
80-294
Country
Poland
Facility Name
Instytut "Centrum Zdrowia Matki Polki; Klinika Nefrologii i Dializoterapii
City
Lodz
ZIP/Postal Code
93-338
Country
Poland
Facility Name
Dzieciecy Szpital Kliniczny; Klinika Nefrologii Dzieciecej
City
Lublin
ZIP/Postal Code
20-093
Country
Poland
Facility Name
SPSZOZ Zdroje Oddzial Pediatrii; Nefrologii i Toksykologii ze Stacja Dializ
City
Szczecin
ZIP/Postal Code
70-410
Country
Poland
Facility Name
Wojewodzki Szpital Dzieciecy; Osrodek Chorob Nerek i Dializoterapii
City
Torun
ZIP/Postal Code
87-100
Country
Poland
Facility Name
Instytut Pomnik-Centrum Zdrowia Dziecka, Klinika Nefrologii, Transp. Nerek i Nadcisnienia Tetniczego
City
Warszawa
ZIP/Postal Code
04-730
Country
Poland
Facility Name
Akademia Medyczna im. Piastow Slaskich; Katedra i Klinika Nefrologii Pediatrycznej
City
Wroclaw
ZIP/Postal Code
50-369
Country
Poland
Facility Name
Fundeni Clinical Institute
City
Bucharest
ZIP/Postal Code
022328
Country
Romania
Facility Name
St. Maria Emergency Clinical Hospital for Children
City
Iasi
ZIP/Postal Code
700309
Country
Romania
Facility Name
DGCB St. Vladimir; Pediatric nephrologist
City
Moscow
ZIP/Postal Code
107014
Country
Russian Federation
Facility Name
SBIH Children City Hospital #1; Dialysis department
City
Saint-Petersburg
ZIP/Postal Code
198205
Country
Russian Federation
Facility Name
Hospital Universitari Vall d'Hebron; Servicio de Nefrologia
City
Barcelona
ZIP/Postal Code
08035
Country
Spain
Facility Name
Hospital Universitario La Paz: Nefrologia Pediatrica
City
Madrid
ZIP/Postal Code
28046
Country
Spain
Facility Name
Hospital Universitario Virgen del Rocio; Servicio de Nefrologia Pediatrica
City
Sevilla
ZIP/Postal Code
41013
Country
Spain
Facility Name
Hospital Universitario la Fe; Servicio de Nefrologia Pediatrica
City
Valencia
ZIP/Postal Code
46009
Country
Spain
Facility Name
Chulalongkorn university Faculty of Medicine;Department of Pediatrics
City
Bangkok
ZIP/Postal Code
10310
Country
Thailand
Facility Name
Siriraj Hospital, Faculty of Medicine; Department of Pediatrics
City
Bangkok
ZIP/Postal Code
10700
Country
Thailand
Facility Name
Kiev city childrens nephrological center of hospital #1; Nephrology and RRT
City
Kiev
ZIP/Postal Code
04209
Country
Ukraine
Facility Name
Public Institution Zaporizhzhia City Multispecialty Children's Hospital #5; Allergologic
City
Zaporizhzhia
ZIP/Postal Code
69076
Country
Ukraine

12. IPD Sharing Statement

Learn more about this trial

Study to Determine Optimum Intravenous Starting Dose of MIRCERA for Treatment of Pediatric Participants With Anemia and Chronic Kidney Disease on Hemodialysis

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