Back to resultsAscertain the Optimal Starting Dose of Mircera Given Subcutaneously for Maintenance Treatment of Anemia in Pediatric Patients With Chronic Kidney Disease on Dialysis or Not Yet on Dialysis.
Primary Purpose
Anemia, Renal Insufficiency, Chronic
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Mircera
Sponsored by
About this trial
This is an interventional treatment trial for Anemia
Eligibility Criteria
Inclusion Criteria:
- Pediatric participants 3 months to 17 years of age with clinically stable chronic renal anemia
- CKD with estimated glomerular filtration rate (eGFR) of < 45 mL/min/1.73 m2 (determined by the Bedside Schwartz formula) or dialysis treatment for at least 8 weeks before the first dose of Mircera
- For participants on peritoneal dialysis (PD): a weekly Kt/V≥ 1.8
- For participants on hemodialysis (HD): adequate HD, urea reduction ratio (URR) > 65% or Kt/V > 1.2 for participants on HD three times per week.
Participants with fewer than or more than three HD sessions per week should have a weekly Kt/V≥ 3.6.
- Baseline Hb concentration 10.0-12.0 g/dL determined from the mean of two Hb values measured at Visit 1 (Week -3) and Visit 2 (Week -1)
- Stable SC maintenance treatment with epoetin alfa, epoetin beta, or darbepoetin alfa with the same dosing interval for at least 6 weeks before the first dose of Mircera
- Stable dose of epoetin alfa, epoetin beta, or darbepoetin alfa treatment with no weekly dose change > 25% (increase or decrease) for at least 4 weeks before the first dose of Mircera
- Adequate iron status defined as ferritin≥100 ng/mL or transferrin saturation (TSAT)≥ 20% (or percentage of hypochromic red cells < 10%); mean of two values measured during screening.
Exclusion Criteria:
- Overt gastrointestinal bleeding within 8 weeks before screening or during the screening period
- RBC transfusions within 8 weeks before screening or during the screening period
- Hemoglobinopathies (e.g., homozygous sickle-cell disease, thalassemia of all types) Hemolytic anemia, Active malignant disease
- PD subjects with an episode of peritonitis within the past 30 days prior to screening and/or during the screening period
- Uncontrolled or symptomatic inflammatory disease (e.g., systemic lupus erythematosus)
- Uncontrolled hypertension as assessed by the investigator
- Epileptic seizures within 3 months prior to screening and during the screening period
- Administration of any investigational drug within 4 weeks prior to screening or planned during the study
- Severe hyperparathyroidism (intact parathyroid hormone [PTH]≥ 1000 pg/mL or whole PTH≥ 500 pg/mL) or biopsy-proven bone marrow fibrosis
- Kidney transplant with use of immunosuppressive therapies known to exacerbate anemia
- Known hypersensitivity to recombinant human erythropoietin (EPO), polyethylene glycol, or any constituent of the study drug formulation
- Anti-EPO antibody (AEAB)-mediated pure red cell aplasia (PRCA) or history of AEAB mediated PRCA or positive AEAB test result in the absence of PRCA
- High likelihood of early withdrawal or interruption of the study (e.g., planned living donor kidney transplant within 5 months of study start)
- Planned elective surgery during the entire study period
Sites / Locations
- University of Alabama at Birmingham; Pediatric Nephrology
- Loma Linda University health
- Emory University School of Med; Pediatrics
- Children'S Mercy Hospital; Pediatric Nephrology
- RWJBarnabas Health
- East Carolina University; Brody School of Medicine
- UT Southwestern Medical Center; Pediatrics Dept.
- Hopital Jeanne De Flandre; Pediatrie
- Gh Necker Enfants Malades; Nephrologie
- Höpital Hautepierre; Pediatrie 1
- Semmelweis University; 1st Department of Pediatrics, Pediatric Nephrology Center
- Debreceni Egyetem Klinikai Központ; Gyermekklinika
- Clinica Pediatrica II De Marchi
- Ospedale Infantile Regina Margherita; U.O. Autonoma di Nefrologia, Dialisi e Trapianto
- Vilnius University Children's Hospital
- Uniwersyteckie Centrum Kliniczne; Klinika Chorob Nerek i Nadciśnienia Dzieci i Mlodziezy
- Uniwersytecki Szpital Dziecięcy w Krakowie; Oddz.Nefrologii i Nadciśnienia Tętniczego/Stacja Dializ
- Instytut "Centrum Zdrowia Matki Polki; Klinika Pediatrii i Immunologii i Nefrologii
- Szpital Specjalistyczny dla Dzieci i Doroslych; Oddzial Kliniczny Pediatrii i Nefrologii
- Szpital Kliniczny nr 1 im. prof. Szyszko; Oddz. Nefrologii Dzieciecej z Pododdziałem Dializoterapii
- Hospital Universitari Vall d'Hebron; Servicio de Nefrologia
- Hospital Universitario Virgen del Rocio; Servicio de Nefrologia Pediatrica
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Mircera
Arm Description
Mircera will be administered subcutaneously once every 4 weeks
Outcomes
Primary Outcome Measures
Change in Hemoglobin (Hb) Concentration Between the Baseline and the Evaluation Period for Each Patient
The Hb change from baseline was calculated on a per-participant basis using an individual's average for both the baseline and evaluation periods and taking the difference. The baseline period was defined as the time between the day of first study dose and the previous 35 days. The evaluation period was defined as the period between Week 17 and Week 21, inclusive.
Secondary Outcome Measures
Number of Participants With an Average Hb Concentration During the Evaluation Period Within ± 1 g/dL of Their Baseline Hb and Above, Within or Below the Range of 10-12 g/dL
Number of participants with an average Hb concentration during the evaluation period within ± 1 g/dL of their baseline Hb is reported as well as the number of participants with an average Hb concentration above, within or below the range of 10-12 g/dL. The evaluation period was defined as the period between Week 17 and Week 21 inclusive.
Mean Hb Values and Change From Baseline
The mean Hb concentration over time and the mean change in Hb from baseline over time are presented.
Change in Mircera Dose Over Time
A dose change was defined as a change in the administered dose strength compared to the preceding dose.
Ratio of Mircera Starting Dose (Week 1) to the Dose at Week 17
The ratio of Mircera dose was calculated as the median (min-max) ratio of starting dose (Week 1) to the dose at Week 17. Participants who withdrew before Week 17 or who were not administered a Mircera dose at Week 17 visit due to the applicable dose adjustment rules were excluded from the ratio computation.
Number of Participants With Adverse Events by Severity as Assessed by Highest World Health Organization (WHO) Toxicity Grade
An adverse event is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product, any new disease, or exacerbation of existing disease (a worsening in the character, frequency, or severity of a known condition), recurrence of an intermittent medical condition or any deterioration in a laboratory value or other clinical test.
Bioavailability (F) of Mircera in Pediatric Participants Based on Population PK Model
Bioavailability (F) is defined as the percentage of the administered drug, that reaches the systemic circulation. A population PK model was developed for Mircera that adequately describes pediatric data: a 1-compartment model with first order absorption and elimination processes. The bioavailability (F) was estimated using all the data points listed under time frame using the population PK model.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03552393
Brief Title
Ascertain the Optimal Starting Dose of Mircera Given Subcutaneously for Maintenance Treatment of Anemia in Pediatric Patients With Chronic Kidney Disease on Dialysis or Not Yet on Dialysis.
Official Title
An Open-Label, Single-Arm, Multicenter Study to Ascertain the Optimal Starting Dose of MIRCERA® Given Subcutaneously for the Maintenance Treatment of Anemia in Pediatric Patients With Chronic Kidney Disease on Dialysis or Not Yet on Dialysis.
Study Type
Interventional
2. Study Status
Record Verification Date
March 2022
Overall Recruitment Status
Completed
Study Start Date
August 3, 2018 (Actual)
Primary Completion Date
July 19, 2021 (Actual)
Study Completion Date
July 19, 2021 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hoffmann-La Roche
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
Ascertain the starting dose of Mircera given subcutaneously for the maintenance treatment of anemia in pediatric participants with chronic kidney disease (CKD) on dialysis or not yet on dialysis when switching from stable subcutaneous (SC) maintenance treatment with epoetin alfa, epoetin beta, or darbepoetin alfa.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Anemia, Renal Insufficiency, Chronic
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
40 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Mircera
Arm Type
Experimental
Arm Description
Mircera will be administered subcutaneously once every 4 weeks
Intervention Type
Drug
Intervention Name(s)
Mircera
Other Intervention Name(s)
Methoxy polyethylene glycol-epoetin beta
Intervention Description
The initial dose of Mircera will be one of nine starting doses corresponding to the prefilled syringe strengths based on the total weekly erythropoiesis-stimulating agent (ESA) dose during the screening period.
Primary Outcome Measure Information:
Title
Change in Hemoglobin (Hb) Concentration Between the Baseline and the Evaluation Period for Each Patient
Description
The Hb change from baseline was calculated on a per-participant basis using an individual's average for both the baseline and evaluation periods and taking the difference. The baseline period was defined as the time between the day of first study dose and the previous 35 days. The evaluation period was defined as the period between Week 17 and Week 21, inclusive.
Time Frame
Baseline up 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 and Above, Within or Below the Range of 10-12 g/dL
Description
Number of participants with an average Hb concentration during the evaluation period within ± 1 g/dL of their baseline Hb is reported as well as the number of participants with an average Hb concentration above, within or below the range of 10-12 g/dL. The evaluation period was defined as the period between Week 17 and Week 21 inclusive.
Time Frame
Week 17 up to Week 21
Title
Mean Hb Values and Change From Baseline
Description
The mean Hb concentration over time and the mean change in Hb from baseline over time are presented.
Time Frame
Baseline, Weeks 3, 5, 9, 13, 17, 19, 21, 25, 29, 33, 37, 41, 45
Title
Change in Mircera Dose Over Time
Description
A dose change was defined as a change in the administered dose strength compared to the preceding dose.
Time Frame
Week 1 to Week 17
Title
Ratio of Mircera Starting Dose (Week 1) to the Dose at Week 17
Description
The ratio of Mircera dose was calculated as the median (min-max) ratio of starting dose (Week 1) to the dose at Week 17. Participants who withdrew before Week 17 or who were not administered a Mircera dose at Week 17 visit due to the applicable dose adjustment rules were excluded from the ratio computation.
Time Frame
Week 1, Week 17
Title
Number of Participants With Adverse Events by Severity as Assessed by Highest World Health Organization (WHO) Toxicity Grade
Description
An adverse event is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product, any new disease, or exacerbation of existing disease (a worsening in the character, frequency, or severity of a known condition), recurrence of an intermittent medical condition or any deterioration in a laboratory value or other clinical test.
Time Frame
Baseline up to Week 45
Title
Bioavailability (F) of Mircera in Pediatric Participants Based on Population PK Model
Description
Bioavailability (F) is defined as the percentage of the administered drug, that reaches the systemic circulation. A population PK model was developed for Mircera that adequately describes pediatric data: a 1-compartment model with first order absorption and elimination processes. The bioavailability (F) was estimated using all the data points listed under time frame using the population PK model.
Time Frame
Pre-dose at Week 1, 9, 17; Post-dose at Week 3, Week 19 and additional sample taken between 24 hours and 5 days at participant's convenience
10. Eligibility
Sex
All
Minimum Age & Unit of Time
3 Months
Maximum Age & Unit of Time
17 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Pediatric participants 3 months to 17 years of age with clinically stable chronic renal anemia
CKD with estimated glomerular filtration rate (eGFR) of < 45 mL/min/1.73 m2 (determined by the Bedside Schwartz formula) or dialysis treatment for at least 8 weeks before the first dose of Mircera
For participants on peritoneal dialysis (PD): a weekly Kt/V≥ 1.8
For participants on hemodialysis (HD): adequate HD, urea reduction ratio (URR) > 65% or Kt/V > 1.2 for participants on HD three times per week.
Participants with fewer than or more than three HD sessions per week should have a weekly Kt/V≥ 3.6.
Baseline Hb concentration 10.0-12.0 g/dL determined from the mean of two Hb values measured at Visit 1 (Week -3) and Visit 2 (Week -1)
Stable SC maintenance treatment with epoetin alfa, epoetin beta, or darbepoetin alfa with the same dosing interval for at least 6 weeks before the first dose of Mircera
Stable dose of epoetin alfa, epoetin beta, or darbepoetin alfa treatment with no weekly dose change > 25% (increase or decrease) for at least 4 weeks before the first dose of Mircera
Adequate iron status defined as ferritin≥100 ng/mL or transferrin saturation (TSAT)≥ 20% (or percentage of hypochromic red cells < 10%); mean of two values measured during screening.
Exclusion Criteria:
Overt gastrointestinal bleeding within 8 weeks before screening or during the screening period
RBC transfusions within 8 weeks before screening or during the screening period
Hemoglobinopathies (e.g., homozygous sickle-cell disease, thalassemia of all types) Hemolytic anemia, Active malignant disease
PD subjects with an episode of peritonitis within the past 30 days prior to screening and/or during the screening period
Uncontrolled or symptomatic inflammatory disease (e.g., systemic lupus erythematosus)
Uncontrolled hypertension as assessed by the investigator
Epileptic seizures within 3 months prior to screening and during the screening period
Administration of any investigational drug within 4 weeks prior to screening or planned during the study
Severe hyperparathyroidism (intact parathyroid hormone [PTH]≥ 1000 pg/mL or whole PTH≥ 500 pg/mL) or biopsy-proven bone marrow fibrosis
Kidney transplant with use of immunosuppressive therapies known to exacerbate anemia
Known hypersensitivity to recombinant human erythropoietin (EPO), polyethylene glycol, or any constituent of the study drug formulation
Anti-EPO antibody (AEAB)-mediated pure red cell aplasia (PRCA) or history of AEAB mediated PRCA or positive AEAB test result in the absence of PRCA
High likelihood of early withdrawal or interruption of the study (e.g., planned living donor kidney transplant within 5 months of study start)
Planned elective surgery during the entire study period
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
University of Alabama at Birmingham; Pediatric Nephrology
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35233
Country
United States
Facility Name
Loma Linda University health
City
Loma Linda
State/Province
California
ZIP/Postal Code
92354
Country
United States
Facility Name
Emory University School of Med; Pediatrics
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
Facility Name
Children'S Mercy Hospital; Pediatric Nephrology
City
Kansas City
State/Province
Missouri
ZIP/Postal Code
64108
Country
United States
Facility Name
RWJBarnabas Health
City
West Orange
State/Province
New Jersey
ZIP/Postal Code
07052
Country
United States
Facility Name
East Carolina University; Brody School of Medicine
City
Greenville
State/Province
North Carolina
ZIP/Postal Code
27834
Country
United States
Facility Name
UT Southwestern Medical Center; Pediatrics Dept.
City
Dallas
State/Province
Texas
ZIP/Postal Code
75390
Country
United States
Facility Name
Hopital Jeanne De Flandre; Pediatrie
City
Lille
ZIP/Postal Code
59037
Country
France
Facility Name
Gh Necker Enfants Malades; Nephrologie
City
Paris
ZIP/Postal Code
75743
Country
France
Facility Name
Höpital Hautepierre; Pediatrie 1
City
Strasbourg
ZIP/Postal Code
67098
Country
France
Facility Name
Semmelweis University; 1st Department of Pediatrics, Pediatric Nephrology Center
City
Budapest
ZIP/Postal Code
1083
Country
Hungary
Facility Name
Debreceni Egyetem Klinikai Központ; Gyermekklinika
City
Debrecen
ZIP/Postal Code
4032
Country
Hungary
Facility Name
Clinica Pediatrica II De Marchi
City
Milano
State/Province
Lombardia
ZIP/Postal Code
20122
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
Vilnius University Children's Hospital
City
Vilnius
ZIP/Postal Code
LT-08406
Country
Lithuania
Facility Name
Uniwersyteckie Centrum Kliniczne; Klinika Chorob Nerek i Nadciśnienia Dzieci i Mlodziezy
City
Gdansk
ZIP/Postal Code
80-952
Country
Poland
Facility Name
Uniwersytecki Szpital Dziecięcy w Krakowie; Oddz.Nefrologii i Nadciśnienia Tętniczego/Stacja Dializ
City
Kraków
ZIP/Postal Code
30-663
Country
Poland
Facility Name
Instytut "Centrum Zdrowia Matki Polki; Klinika Pediatrii i Immunologii i Nefrologii
City
Lodz
ZIP/Postal Code
93-338
Country
Poland
Facility Name
Szpital Specjalistyczny dla Dzieci i Doroslych; Oddzial Kliniczny Pediatrii i Nefrologii
City
Torun
ZIP/Postal Code
87-100
Country
Poland
Facility Name
Szpital Kliniczny nr 1 im. prof. Szyszko; Oddz. Nefrologii Dzieciecej z Pododdziałem Dializoterapii
City
Zabrze
ZIP/Postal Code
41-800
Country
Poland
Facility Name
Hospital Universitari Vall d'Hebron; Servicio de Nefrologia
City
Barcelona
ZIP/Postal Code
08035
Country
Spain
Facility Name
Hospital Universitario Virgen del Rocio; Servicio de Nefrologia Pediatrica
City
Sevilla
ZIP/Postal Code
41013
Country
Spain
12. IPD Sharing Statement
Learn more about this trial
Ascertain the Optimal Starting Dose of Mircera Given Subcutaneously for Maintenance Treatment of Anemia in Pediatric Patients With Chronic Kidney Disease on Dialysis or Not Yet on Dialysis.
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