Chronic kidney disease MedDRA version: 8.1 Level: LLT Classification code 10058124 Term: Nephrogenic anemia
Conditions
Sponsors
F. Hoffmann-La Roche Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Written informed consent 2. Adults patients (= 18 years old) with CKD stage 3 (creatinine clearance (CrCl)/ Glomerular filtration rate [GFR] 30-59 mL/min) or stage 4 (CrCl/GFR 15-29 mL/min) not requiring dialysis. CrCl/GFR will be estimated at the first screening visit with the Cockcroft-Gault equation or the abbreviated MDRD equation, derived from the full MDRD equation 3. Continuous sc maintenance darbepoetin alfa therapy with the same dosing interval (i.e., once a week, once every two weeks or once every month as per local label) for at least 8 weeks before screening and during the screening/baseline period (a maximum of one missed dose in the 12 weeks before randomization in case of weekly administration is allowed). 4. Stable sc maintenance darbepoetin alfa therapy during the screening/baseline period (no dose change is allowed) 5. Baseline Hb concentration between 10.5 and 13 g/dL (mean of three weekly Hb values determined in week -4, week -2 and visit # 1 before drug administration). Patients with a single Hb value =65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Need for dialysis therapy expected in the next 36 weeks or rapid progression of CKD (e.g., a CrCl/GFR decrease of more than 20% within 12 weeks) 2. Overt gastrointestinal bleeding within 8 weeks before screening or during the screening/baseline period 3. Renal allograft in place 4. Immunosuppressive therapy (other than corticosteroids for a chronic condition, cyclosporine, and monoclonal/polyclonal antibodies) in the 12 weeks before the first screening visit or occurring during the screening/baseline period 5. RBC transfusions within 8 weeks before screening or during the screening/baseline period 6. Hemoglobinopathies (e.g., homozygous sickle-cell disease, thalassemia of all types) 7. Hemolysis 8. Active malignant disease (except non-melanoma skin cancer). Patients with malignant disease who have been disease-free for at least the 5 previous years are eligible. 9. Chronic, uncontrolled or symptomatic inflammatory disease (e.g., rheumatoid arthritis, systemic lupus erythematosus) 10. Acute infection requiring antibiotics 11. Vitamin B12 deficiency 12. Folic acid deficiency 13. Uncontrolled or symptomatic secondary hyperparathyroidism 14. Poorly controlled hypertension necessitating interruption of epoetin or darbepoetin alfa treatment in the 6 months before screening 15. Epileptic seizure in the 6 months before screening or during the screening/baseline period 16. Pure red cell aplasia (PRCA) or history of PRCA 17. Chronic congestive heart failure (New York Heart Association Class IV) 18. High likelihood of early withdrawal or interruption of the study (e.g., myocardial infarction, severe or unstable coronary artery disease, stroke, severe liver disease within the 12 weeks before screening or during the screening/baseline period) 19. Planned elective surgery during the study period (patients who undergo vascular access surgery, cataract surgery or laser photocoagulation may continue to participate) 20. Life expectancy less than 12 months 21. Pregnancy or breast-feeding 22. Women of childbearing potential without effective contraception 23. Previous treatment with RO0503821 24. Administration of another investigational drug within 4 weeks before screening or planned during the study period 25. Known hypersensitivity to darbepoetin alfa, recombinant human erythropoietin, polyethylene glycol or to any constituent of the study or reference drug formulation 26. platelets > 500 x 10 9/L
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: - To demonstrate effectiveness of once-monthly subcutaneous (sc) administration of RO0503821 for anemia management in patients with chronic kidney disease (CKD) who are not on dialysis previously receiving sc darbepoetin alfa once a week, once every 2 weeks or once every month.;Secondary Objective: - To assess hemoglobin (Hb) concentration over time - To assess the safety and tolerability of sc administration of RO0503821 in this patient population ;Primary end point(s): The primary endpoint in this study will be the change in Hb concentration (g/dL) between the baseline and evaluation periods. The baseline period is defined as all assessments between the day of first study dose and the previous 30 days. The value on the day of the first dose is included in the baseline calculation as this assessment will be performed before the first dose is given. The average Hb value for each individual during the evaluation period will be calculated using the same method as for baseline. Subtracting the baseline value from the evaluation period value gives the change in Hb concentration (g/dL) between the baseline and evaluation period. Data missing at the end of the evaluation period (i.e., the last measured Hb value is before the end of the study) will be handled using the last observation carried forward method (LOCF). To correct for any increase in Hb caused by RBC transfusions, the Hb values measured within 3 weeks after a RBC transfusion will be replaced by the Hb value measured immediately before the transfusion. | — |
Countries
Czech Republic, France, Germany, Hungary, Italy, Spain, United Kingdom
Outcome results
None listed