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.
- Conditions
- AnemiaRenal Insufficiency, Chronic
- Interventions
- Drug: Mircera
- Registration Number
- NCT03552393
- Lead Sponsor
- Hoffmann-La Roche
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 40
- 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.
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Mircera Mircera Mircera will be administered subcutaneously once every 4 weeks
- Primary Outcome Measures
Name Time Method Change in Hemoglobin (Hb) Concentration Between the Baseline and the Evaluation Period for Each Patient Baseline up to Week 21 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
Name Time Method 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 Week 17 up to Week 21 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 Baseline, Weeks 3, 5, 9, 13, 17, 19, 21, 25, 29, 33, 37, 41, 45 The mean Hb concentration over time and the mean change in Hb from baseline over time are presented.
Change in Mircera Dose Over Time Week 1 to Week 17 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 Week 1, 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 Baseline up to Week 45 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 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 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.
Trial Locations
- Locations (22)
Emory University School of Med; Pediatrics
🇺🇸Atlanta, Georgia, United States
University of Alabama at Birmingham; Pediatric Nephrology
🇺🇸Birmingham, Alabama, United States
East Carolina University; Brody School of Medicine
🇺🇸Greenville, North Carolina, United States
Uniwersyteckie Centrum Kliniczne; Klinika Chorob Nerek i Nadciśnienia Dzieci i Mlodziezy
🇵🇱Gdansk, Poland
Hospital Universitario Virgen del Rocio; Servicio de Nefrologia Pediatrica
🇪🇸Sevilla, Spain
Ospedale Infantile Regina Margherita; U.O. Autonoma di Nefrologia, Dialisi e Trapianto
🇮🇹Torino, Piemonte, Italy
Children'S Mercy Hospital; Pediatric Nephrology
🇺🇸Kansas City, Missouri, United States
Loma Linda University health
🇺🇸Loma Linda, California, United States
RWJBarnabas Health
🇺🇸West Orange, New Jersey, United States
Hopital Jeanne De Flandre; Pediatrie
🇫🇷Lille, France
Gh Necker Enfants Malades; Nephrologie
🇫🇷Paris, France
UT Southwestern Medical Center; Pediatrics Dept.
🇺🇸Dallas, Texas, United States
Höpital Hautepierre; Pediatrie 1
🇫🇷Strasbourg, France
Clinica Pediatrica II De Marchi
🇮🇹Milano, Lombardia, Italy
Debreceni Egyetem Klinikai Központ; Gyermekklinika
🇭🇺Debrecen, Hungary
Vilnius University Children's Hospital
🇱🇹Vilnius, Lithuania
Instytut "Centrum Zdrowia Matki Polki; Klinika Pediatrii i Immunologii i Nefrologii
🇵🇱Lodz, Poland
Uniwersytecki Szpital Dziecięcy w Krakowie; Oddz.Nefrologii i Nadciśnienia Tętniczego/Stacja Dializ
🇵🇱Kraków, Poland
Szpital Kliniczny nr 1 im. prof. Szyszko; Oddz. Nefrologii Dzieciecej z Pododdziałem Dializoterapii
🇵🇱Zabrze, Poland
Hospital Universitari Vall d'Hebron; Servicio de Nefrologia
🇪🇸Barcelona, Spain
Semmelweis University; 1st Department of Pediatrics, Pediatric Nephrology Center
🇭🇺Budapest, Hungary
Szpital Specjalistyczny dla Dzieci i Doroslych; Oddzial Kliniczny Pediatrii i Nefrologii
🇵🇱Torun, Poland