Clinical trial NCT03552393: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Anemia
Renal Insufficiency, Chronic
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2018-06-11
Enrollment: 40
Sex: ALL
Minimum age (years): 3
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Change in Hemoglobin (Hb) Concentration Between the Baseline and the Evaluation Period for Each Patient
timeFrame: Baseline up to Week 21
Secondary outcomes:
measure: 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
timeFrame: Week 17 up to Week 21
measure: Mean Hb Values and Change From Baseline
timeFrame: Baseline, Weeks 3, 5, 9, 13, 17, 19, 21, 25, 29, 33, 37, 41, 45
measure: Change in Mircera Dose Over Time
timeFrame: Week 1 to Week 17
measure: Ratio of Mircera Starting Dose (Week 1) to the Dose at Week 17
timeFrame: Week 1, Week 17
measure: Number of Participants With Adverse Events by Severity as Assessed by Highest World Health Organization (WHO) Toxicity Grade
timeFrame: Baseline up to Week 45
measure: Bioavailability (F) of Mircera in Pediatric Participants Based on Population PK Model
timeFrame: 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
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham; Pediatric Nephrology
state: Alabama
city: Loma Linda
country: United States
facility: Loma Linda University health
state: California
city: Atlanta
country: United States
facility: Emory University School of Med; Pediatrics
state: Georgia
city: Kansas City
country: United States
facility: Children'S Mercy Hospital; Pediatric Nephrology
state: Missouri
city: West Orange
country: United States
facility: RWJBarnabas Health
state: New Jersey
city: Greenville
country: United States
facility: East Carolina University; Brody School of Medicine
state: North Carolina
city: Dallas
country: United States
facility: UT Southwestern Medical Center; Pediatrics Dept.
state: Texas
city: Lille
country: France
facility: Hopital Jeanne De Flandre; Pediatrie
city: Paris
country: France
facility: Gh Necker Enfants Malades; Nephrologie
city: Strasbourg
country: France
facility: Höpital Hautepierre; Pediatrie 1
city: Budapest
country: Hungary
facility: Semmelweis University; 1st Department of Pediatrics, Pediatric Nephrology Center
city: Debrecen
country: Hungary
facility: Debreceni Egyetem Klinikai Központ; Gyermekklinika
city: Milano
country: Italy
facility: Clinica Pediatrica II De Marchi
state: Lombardia
city: Torino
country: Italy
facility: Ospedale Infantile Regina Margherita; U.O. Autonoma di Nefrologia, Dialisi e Trapianto
state: Piemonte
city: Vilnius
country: Lithuania
facility: Vilnius University Children's Hospital
city: Gdansk
country: Poland
facility: Uniwersyteckie Centrum Kliniczne; Klinika Chorob Nerek i Nadciśnienia Dzieci i Mlodziezy
city: Kraków
country: Poland
facility: Uniwersytecki Szpital Dziecięcy w Krakowie; Oddz.Nefrologii i Nadciśnienia Tętniczego/Stacja Dializ
city: Lodz
country: Poland
facility: Instytut "Centrum Zdrowia Matki Polki; Klinika Pediatrii i Immunologii i Nefrologii
city: Torun
country: Poland
facility: Szpital Specjalistyczny dla Dzieci i Doroslych; Oddzial Kliniczny Pediatrii i Nefrologii
city: Zabrze
country: Poland
facility: Szpital Kliniczny nr 1 im. prof. Szyszko; Oddz. Nefrologii Dzieciecej z Pododdziałem Dializoterapii
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron; Servicio de Nefrologia
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocio; Servicio de Nefrologia Pediatrica
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: