An Efficacy and Safety Study of Epoetin Alfa for Initiation and Maintenance Treatment of Patients With Anemia Associated With Chronic Kidney Disease

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to demonstrate that once weekly and once every-2-weeks treatment with epoetin alfa, in patients with anemia associated with chronic kidney disease, is not less effective than the approved treatment with epoetin alfa that is given 3 times weekly with respect to changes in hemoglobin.

Detailed Description
-----------------
This is a open-label (all people know the identity of the intervention), randomized (the study medication is assigned by chance), multicenter study designed to show that 2 alternative dosing regimens, once weekly and once every-2-weeks (given at doses equivalent to 50 IU/kg 3 times a week) are not inferior to the 3-times-weekly dosing regimen. Approximately 375 patients with anemia will be enrolled in this study. Patients will be randomly assigned to receive epoetin alfa by subcutaneous (SC) injection according to one of the following 3 regimens: 3 times weekly (Group 1), once weekly (Group 2), or once every 2 weeks (Group 3) for 22 weeks. Thereafter, patients in Group 1 will be switched to the once-weekly dosing regimen for an additional 22 weeks, and patients in Groups 2 and 3 will continue their current treatment for an additional 22 weeks. The total duration of the open-label treatment phase is 44 weeks which will include initiation and maintenance treatment periods (with the goal of increasing, then maintaining, the hemoglobin level between 11.0 and 11.9 g/dL inclusive) and a safety period (to assess longer exposure to epoetin alfa treatment and any period of hemoglobin instability during the transition from 3-times-weekly to once-weekly dosing). Starting doses of epoetin alfa in the 3-times-weekly, once-weekly, and every-2-weeks groups will be 50 IU/kg, 10,000 IU, and 20,000 IU, respectively; thereafter adjusted according to weekly hemoglobin concentrations. Safety evaluations will include assessment of adverse events, laboratory tests, physical examinations, and vital signs.

Official Title
-----------------
A Randomized, Open Label, Multicenter Study of Epoetin Alfa Comparing Two Extended-Dosing Regimens, Once-Weekly and Every-Two-Weeks, With the Three-Times-Weekly Dosing Regimen for Initiation and Maintenance Treatment in Anemic Subjects With Chronic Kidney Disease

Conditions
-----------------
Anemia

Intervention / Treatment
-----------------
* Drug: Epoetin alfa 3 times weekly /once weekly
* Drug: Epoetin alfa once weekly
* Drug: Epoetin alfa once every two weeks


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Meet the diagnostic criteria for chronic kidney disease, defined as a glomerular filtration rate (GFR) more than or equal to 15 mL/min per 1.73 m2 and less than 60 mL/min per 1.73 m2 (Stages 3 and 4) as calculated by the central laboratory Require support of an erythropoietin receptor agonist Exclusion Criteria: Uncontrolled hypertension Serum ferritin level less than 50 ng/mL Serum iron overload Severe congestive heart failure Active infection

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TIW: Epoetin alfa 3 injections Weekly/Once Weekly<br>Participants will be administered with epoetin alfa 3 times weekly for 22 weeks (initial subcutaneous (SC) dose 50 IU/kg), then once weekly, for 22 weeks (initial SC dose 10,000 IU) | Drug: Epoetin alfa 3 times weekly /once weekly<br>* Epoetin alfa will be administered as a SC injections at initial dose of 50 IU/kg (3 times weekly for 22 weeks) and at initial dose of 10000 IU (once weekly for 22 weeks)<br>* Other names: PROCRIT;|
| Experimental: QW: Epoetin alfa once weekly<br>Participants will be administered with epoetin alfa once weekly for 44 weeks (initial subcutaneous dose 10,000 IU). | Drug: Epoetin alfa once weekly<br>* Epoetin alfa will be administered as a SC injection at initial dose of 10000 IU (once weekly for 44 weeks).<br>* Other names: PROCRIT;|
| Experimental: Q2W: Epoetin alfa once every two weeks<br>Participants will be administered with epoetin alfa once every 2 weeks for 44 weeks (initial subcutaneous dose 20,000 IU). | Drug: Epoetin alfa once every two weeks<br>* Epoetin alfa will be administered as a SC injection at initial dose of 20000 IU (once every 2 weeks for 44 weeks).<br>* Other names: PROCRIT;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Hb Concentration (g/dL) From Baseline to the Average of the Last 8 Weeks of Treatment Through Week 22 | The change is calculated as average hemoglobin (Hb) over the last 8 weeks subtracts the baseline Hb. Only Hb measurements up until a participant receives a transfusion or begins dialysis were included in calculating the average Hb during the last 8 weeks of treatment through Week 22. | From baseline through Week 22 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Participants With an Increase of ≥1 g/dL in Hb Concentration From Baseline by Week 9 | The change is calculated as average hemoglobin (Hb) over the last 8 weeks subtracts the baseline Hb. Only Hb measurements up until a participant receives a transfusion or begins dialysis were included. Hb increase is defined as the post-baseline Hb level minus the baseline Hb level. | From baseline to Week 9 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Anemia, Chronic Kidney disease, Kidney disease, Epoetin alfa, Procrit