Evaluation of Monthly Darbepoetin Alfa Dosing for Correction of Anemia in Non-dialysis Chronic Kidney Disease

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to determine whether once monthly (QM) dosing of darbepoetin alfa is non-inferior to that of once every 2 week (Q2W) dosing of darbepoetin alfa for the correction of anemia in patients with Chronic Kidney Disease who are not receiving dialysis.

Official Title
-----------------
A Multicenter, Randomised, Double-Blind Study Comparing De Novo Once Monthly and Once Every 2 Week Darbepoetin Alfa Dosing for the Correction of Anemia in Subjects With Chronic Kidney Disease Not Receiving Dialysis

Conditions
-----------------
Anemia, Chronic Kidney Disease

Intervention / Treatment
-----------------
* Drug: darbepoetin alfa


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: ≥ 18 years of age Diagnosis of chronic kidney disease with eGFR of 15-59 mL/min/1.73 m2 (MDRD equation) Two consecutive screening Hb values taken at least 7 days apart must each be <10.0 g/dL TSAT ≥ 15% Exclusion Criteria: Upper or lower GI bleeding within 6 months before enrolment ESA use within 12 weeks before enrolment Uncontrolled hypertension Systemic haematologic disorders Prior history within 12 weeks before enrollment of events including: Acute myocardial ischemia, unstable angina, myocardial infarction, hospitalization for congestive heart failure, stroke or transient ischaemic attack, limb ischaemia, deep vein thrombosis, thromboembolism. Grand mal seizure within 6 months prior to enrolment Evidence of, or received chemotherapy or radiation therapy for, a malignancy within 5 years prior to enrolment. Red blood cell transfusion within 12 weeks prior to enrolment Androgen therapy within 8 weeks prior to enrolment Pregnancy or breast feeding, or inadequate contraception Currently receiving immunosuppressive therapy

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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Q2W<br>Q2W administration of darbepoetin alfa. | Drug: darbepoetin alfa<br>* Drug administered either Q2W or QM using a prefilled syringe. Allowable doses of: 10, 20, 30, 40, 50, 60, 80, 100, 130, 150, 200, 300, 400 or 600 mcg.<br>* Other names: Placebo;|
| Active Comparator: QM<br>QM administration of darbepoetin alfa | Drug: darbepoetin alfa<br>* Drug administered either Q2W or QM using a prefilled syringe. Allowable doses of: 10, 20, 30, 40, 50, 60, 80, 100, 130, 150, 200, 300, 400 or 600 mcg.<br>* Other names: Placebo;|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hb Change Between Baseline and the Evaluation Period (Average of Weeks 29-33) | The Adjusted Analysis is the primary analysis and includes treatment group and baseline Hb value as covariates. Non-inferiority is concluded if the lower limit of the 95% confidence interval for the mean difference is above -0.5g/dL. | Baseline Week 33 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Achievement of Both a Hb >= 10.0 g/dL and a >= 1.0 g/dL Increase From Baseline at Any Time Point Following de Novo Darbepoetin Alfa Administration. |  | Baseline to Week 33 | 
| Hb at Baseline |  | Baseline | 
| Hb at Week 3 |  | Week 3 | 
| Hb at Week 5 |  | Week 5 | 
| Hb at Week 7 |  | Week 7 | 
| Hb at Week 9 |  | Week 9 | 
| Hb at Week 11 |  | Week 11 | 
| Hb at Week 13 |  | Week 13 | 
| Hb at Week 15 |  | Week 15 | 
| Hb at Week 17 |  | Week 17 | 
| Hb at Week 19 |  | Week 19 | 
| Hb at Week 21 |  | Week 21 | 
| Hb at Week 23 |  | Week 23 | 
| Hb at Week 25 |  | Week 25 | 
| Hb at Week 27 |  | Week 27 | 
| Hb at Week 29 |  | Week 29 | 
| Hb at Week 31 |  | Week 31 | 
| Hb at Week 33 |  | Week 33 | 
| Darbepoetin Alfa Dose at Week 1 | Although the endpoint is related to dose, the sample is from the Primary Analysis Set which requires a Hb value in the evaluation period | Week 1 | 
| Darbepoetin Alfa Dose at Week 3 | Although the endpoint is related to dose, the sample is from the Primary Analysis Set which requires a Hb value in the evaluation period | Week 3 | 
| Darbepoetin Alfa Dose at Week 5 | Although the endpoint is related to dose, the sample is from the Primary Analysis Set which requires a Hb value in the evaluation period | Week 5 | 
| Darbepoetin Alfa Dose at Week 7 | Although the endpoint is related to dose, the sample is from the Primary Analysis Set which requires a Hb value in the evaluation period | Week 7 | 
| Darbepoetin Alfa Dose at Week 9 | Although the endpoint is related to dose, the sample is from the Primary Analysis Set which requires a Hb value in the evaluation period | Week 9 | 
| Darbepoetin Alfa Dose at Week 11 | Although the endpoint is related to dose, the sample is from the Primary Analysis Set which requires a Hb value in the evaluation period | Week 11 | 
| Darbepoetin Alfa Dose at Week 13 | Although the endpoint is related to dose, the sample is from the Primary Analysis Set which requires a Hb value in the evaluation period | Week 13 | 
| Darbepoetin Alfa Dose at Week 15 | Although the endpoint is related to dose, the sample is from the Primary Analysis Set which requires a Hb value in the evaluation period | Week 15 | 
| Darbepoetin Alfa Dose at Week 17 | Although the endpoint is related to dose, the sample is from the Primary Analysis Set which requires a Hb value in the evaluation period | Week 17 | 
| Darbepoetin Alfa Dose at Week 19 | Although the endpoint is related to dose, the sample is from the Primary Analysis Set which requires a Hb value in the evaluation period | Week 19 | 
| Darbepoetin Alfa Dose at Week 21 | Although the endpoint is related to dose, the sample is from the Primary Analysis Set which requires a Hb value in the evaluation period | Week 21 | 
| Darbepoetin Alfa Dose at Week 23 | Although the endpoint is related to dose, the sample is from the Primary Analysis Set which requires a Hb value in the evaluation period | Week 23 | 
| Darbepoetin Alfa Dose at Week 25 | Although the endpoint is related to dose, the sample is from the Primary Analysis Set which requires a Hb value in the evaluation period | Week 25 | 
| Darbepoetin Alfa Dose at Week 27 | Although the endpoint is related to dose, the sample is from the Primary Analysis Set which requires a Hb value in the evaluation period | Week 27 | 
| Darbepoetin Alfa Dose at Week 29 | Although the endpoint is related to dose, the sample is from the Primary Analysis Set which requires a Hb value in the evaluation period | Week 29 | 
| Darbepoetin Alfa Dose at Week 31 | Although the endpoint is related to dose, the sample is from the Primary Analysis Set which requires a Hb value in the evaluation period | Week 31 | 
| Darbepoetin Alfa Dose During the Evaluation Period (Average of Weeks 29-33) | Although the endpoint is related to dose, the sample is from the Primary Analysis Set which requires a Hb value in the evaluation period | Weeks 29-33 | 
| Ratio of Darbepoetin Alfa Dose to Baseline at Week 3 | Although the endpoint is related to dose, the sample is from the Primary Analysis Set which requires a Hb value in the evaluation period | Week 3 | 
| Ratio of Darbepoetin Alfa Dose to Baseline at Week 5 | Although the endpoint is related to dose, the sample is from the Primary Analysis Set which requires a Hb value in the evaluation period | Week 5 | 
| Ratio of Darbepoetin Alfa Dose to Baseline at Week 7 | Although the endpoint is related to dose, the sample is from the Primary Analysis Set which requires a Hb value in the evaluation period | Week 7 | 
| Ratio of Darbepoetin Alfa Dose to Baseline at Week 9 | Although the endpoint is related to dose, the sample is from the Primary Analysis Set which requires a Hb value in the evaluation period | Week 9 | 
| Ratio of Darbepoetin Alfa Dose to Baseline at Week 11 | Although the endpoint is related to dose, the sample is from the Primary Analysis Set which requires a Hb value in the evaluation period | Week 11 | 
| Ratio of Darbepoetin Alfa Dose to Baseline at Week 13 | Although the endpoint is related to dose, the sample is from the Primary Analysis Set which requires a Hb value in the evaluation period | Week 13 | 
| Ratio of Darbepoetin Alfa Dose to Baseline at Week 15 | Although the endpoint is related to dose, the sample is from the Primary Analysis Set which requires a Hb value in the evaluation period | Week 15 | 
| Ratio of Darbepoetin Alfa Dose to Baseline at Week 17 | Although the endpoint is related to dose, the sample is from the Primary Analysis Set which requires a Hb value in the evaluation period | Week 17 | 
| Ratio of Darbepoetin Alfa Dose to Baseline at Week 19 | Although the endpoint is related to dose, the sample is from the Primary Analysis Set which requires a Hb value in the evaluation period | Week 19 | 
| Ratio of Darbepoetin Alfa Dose to Baseline at Week 21 | Although the endpoint is related to dose, the sample is from the Primary Analysis Set which requires a Hb value in the evaluation period | Week 21 | 
| Ratio of Darbepoetin Alfa Dose to Baseline at Week 23 | Although the endpoint is related to dose, the sample is from the Primary Analysis Set which requires a Hb value in the evaluation period | Week 23 | 
| Ratio of Darbepoetin Alfa Dose to Baseline at Week 25 | Although the endpoint is related to dose, the sample is from the Primary Analysis Set which requires a Hb value in the evaluation period | Week 25 | 
| Ratio of Darbepoetin Alfa Dose to Baseline at Week 27 | Although the endpoint is related to dose, the sample is from the Primary Analysis Set which requires a Hb value in the evaluation period | Week 27 | 
| Ratio of Darbepoetin Alfa Dose to Baseline at Week 29 | Although the endpoint is related to dose, the sample is from the Primary Analysis Set which requires a Hb value in the evaluation period | Week 29 | 
| Ratio of Darbepoetin Alfa Dose to Baseline at Week 31 | Although the endpoint is related to dose, the sample is from the Primary Analysis Set which requires a Hb value in the evaluation period | Week 31 | 
| Dose of Darbepoetin Alfa at the First Achievement of a Hb ≥10.0 g/dL and a ≥1.0 g/dL Increase From Baseline (Weeks 1-33) | Although the endpoint is related to dose, the sample is from the Primary Analysis Set which requires a Hb value in the evaluation period | Weeks 1-33 | 
| Time to First Achievement of a Hb ≥10.0 g/dL and a ≥1.0 g/dL Increase From Baseline (Weeks 1-33) |  | Weeks 1-33 | 
| Ratio of Darbepoetin Alfa Dose to Baseline at the Evalaution Period (Average of Weeks 29-33) | Although the endpoint is related to dose, the sample is from the Primary Analysis Set which requires a Hb value in the evaluation period | Evaluation Period | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
CKD, Anemia, correction, darbepoetin alfa