A randomized, controlled, open-label, multi-center, parallel-group study to compare the efficacy and safety of RO0503821 with that of darbepoetin alfa administered intravenously at extended dosing intervals for the maintenance treatment of anemia in patients with chronic kidney disease who are on hemodialysis

Conditions: Chronic renal anemia
MedDRA version: 8.1Level: PTClassification code 10058116Term: Nephrogenic anaemia

Registration Number: EUCTR2005-004510-33-FI

Lead Sponsor: F. Hoffmann-La Roche Ltd

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 488

Inclusion Criteria

1. Written informed consent
2. Adult patients (= 18 years old) with chronic renal anemia
3. Regular long-term hemodialysis three times weekly for at least 12 weeks before screening and during the screening/baseline period
4. Kt/V = 1.2 or URR = 65%
5. Baseline hemoglobin concentration between 11.0 and 13.0 g/dL (mean of the weekly hemoglobin values determined in weeks -4 to -1)
6. Stable baseline hemoglobin concentration (defined as an absolute difference less than or equal to 1 g/dL between the mean hemoglobin values determined in weeks -4 and -3 and the mean hemoglobin values determined in weeks -2 and -1)
7. Continuous intravenous once-weekly maintenance darbepoetin therapy for at least 8 weeks before screening and during the screening/baseline period
8. Stable intravenous once-weekly maintenance darbepoetin therapy during the screening/baseline period (a maximum of one dose change according to approved labeling)
9. Adequate iron status defined as serum ferritin = 100 ng/mL or TSAT = 20% (or percentage of hypochromic RBCs < 10%) (mean of two values determined in weeks -4 and -3)

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1. History of treatment with any ESA at a dosing interval longer than once-weekly since the start of dialysis treatment
2. Overt gastrointestinal bleeding within 8 weeks before screening or during the screening/baseline period
3. RBC transfusions within 8 weeks before screening or during the screening/baseline period
4. Hemoglobinopathies (e.g., homozygous sickle-cell disease, thalassemia of all types)
5. Hemolysis
6. Active malignancy (except non-melanoma skin cancer). Patients with malignant disease who have been disease-free for at least the 5 previous years are eligible
7. Chronic, uncontrolled or symptomatic inflammatory disease (e.g., rheumatoid arthritis, systemic lupus erythematosus)
8. Acute infection
9. CRP > 30 mg/L
10. Temporary (untunneled) dialysis access catheter
11. Vitamin B12 deficiency
12. Folic acid deficiency
13. Uncontrolled or symptomatic secondary hyperparathyroidism
14. Poorly controlled hypertension necessitating interruption of treatment with erythropoiesis stimulating agents in the 3 months before screening or during the screening/baseline period
15. Epileptic seizure in the 6 months before screening or during the screening/baseline period
16. Platelets > 500 x 10 exp9/L
17. Pure red cell aplasia
18. Chronic congestive heart failure (New York Heart Association Class IV)
19. High likelihood of early withdrawal or interruption of the study (e.g. myocardial infarction, severe or unstable coronary artery disease, stroke or severe liver disease within the 12 weeks before screening or during the screening/baseline period)
20. Planned elective surgery during the study period (patients who undergo vascular access surgery, cataract surgery or laser photocoagulation may continue to participate)
21. Life expectancy less than 12 months
22. Pregnancy or breast-feeding
23. Women of childbearing potential without effective contraception
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 formulations
26. Previous treatment with RO0503821

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: Primary:<br>- To compare the efficacy of RO0503821 administered intravenously at extended dosing intervals with that of darbepoetin alfa in the maintenance of hemoglobin concentrations in hemodialysis patients on intravenous darbepoetin alfa maintenance treatment of chronic renal anemia<br>;Secondary Objective: Secondary:<br>- To assess the safety and tolerability of intravenous administration of RO0503821 in hemodialysis patients on intravenous darbepoetin alfa maintenance treatment of chronic renal anemia<br>;Primary end point(s): - The proportion of all randomized patients with an average Hb decrease from baseline not exceeding 1.0 g/dL and an average Hb = 10.5 g/dL in weeks 50-53<br>

Secondary Outcome Measures