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.

Anemia Clinical Trial

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03552393
• Other study ID #: NH19708
• Secondary ID: 2016-004779-39
• Status: Completed
• Phase: Phase 2
• Start date: August 3, 2018
• Est. completion date: July 19, 2021

Study information

• Verified date: March 2022
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 40
• Est. completion date: July 19, 2021
• Est. primary completion date: July 19, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 3 Months to 17 Years

Eligibility

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

Related Conditions & MeSH terms

• Anemia
• Kidney Diseases
• Renal Insufficiency
• Renal Insufficiency, Chronic

Intervention

Drug:
• Mircera
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.

Locations

Country	Name	City	State
France	Hopital Jeanne De Flandre; Pediatrie	Lille
France	Gh Necker Enfants Malades; Nephrologie	Paris
France	Höpital Hautepierre; Pediatrie 1	Strasbourg
Hungary	Semmelweis University; 1st Department of Pediatrics, Pediatric Nephrology Center	Budapest
Hungary	Debreceni Egyetem Klinikai Központ; Gyermekklinika	Debrecen
Italy	Clinica Pediatrica II De Marchi	Milano	Lombardia
Italy	Ospedale Infantile Regina Margherita; U.O. Autonoma di Nefrologia, Dialisi e Trapianto	Torino	Piemonte
Lithuania	Vilnius University Children's Hospital	Vilnius
Poland	Uniwersyteckie Centrum Kliniczne; Klinika Chorob Nerek i Nadcisnienia Dzieci i Mlodziezy	Gdansk
Poland	Uniwersytecki Szpital Dzieciecy w Krakowie; Oddz.Nefrologii i Nadcisnienia Tetniczego/Stacja Dializ	Kraków
Poland	Instytut "Centrum Zdrowia Matki Polki; Klinika Pediatrii i Immunologii i Nefrologii	Lodz
Poland	Szpital Specjalistyczny dla Dzieci i Doroslych; Oddzial Kliniczny Pediatrii i Nefrologii	Torun
Poland	Szpital Kliniczny nr 1 im. prof. Szyszko; Oddz. Nefrologii Dzieciecej z Pododdzialem Dializoterapii	Zabrze
Spain	Hospital Universitari Vall d'Hebron; Servicio de Nefrologia	Barcelona
Spain	Hospital Universitario Virgen del Rocio; Servicio de Nefrologia Pediatrica	Sevilla
United States	Emory University School of Med; Pediatrics	Atlanta	Georgia
United States	University of Alabama at Birmingham; Pediatric Nephrology	Birmingham	Alabama
United States	UT Southwestern Medical Center; Pediatrics Dept.	Dallas	Texas
United States	East Carolina University; Brody School of Medicine	Greenville	North Carolina
United States	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

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

United States,  France,  Hungary,  Italy,  Lithuania,  Poland,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Baseline up to Week 21
Secondary	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.	Week 17 up to Week 21
Secondary	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.	Baseline, Weeks 3, 5, 9, 13, 17, 19, 21, 25, 29, 33, 37, 41, 45
Secondary	Change in Mircera Dose Over Time	A dose change was defined as a change in the administered dose strength compared to the preceding dose.	Week 1 to Week 17
Secondary	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.	Week 1, Week 17
Secondary	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.	Baseline up to Week 45
Secondary	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.	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