A Study to Investigate the Effect of ASP1517 After Intermittent Oral Dosing in Dialysis Chronic Kidney Disease Patients With Anemia Compared With Darbepoetin as a Reference Drug

Study Overview
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Brief Summary
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This study is to evaluate safety and efficacy of intermittent oral dosing of ASP1517 in dialysis chronic kidney disease patients with anemia.

Detailed Description
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To evaluate the safety and the dose-response of ASP1517 on hemoglobin (Hb) correction when ASP1517 is applied intermittently in dialysis chronic kidney disease patients with anemia. To evaluate the treatment effect on Hb maintenance of ASP1517 administered intermittently in dialysis chronic kidney disease patients with anemia.

Official Title
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A Japanese, Phase 2, Multicenter, Randomized, 4-arm Parallel, Double-blind (Arms 1-3), Open-label (Arm 4), Active-comparator (Darbepoetin Alfa) Study of Intermittent Oral Dosing of ASP1517 in Hemodialysis-dependent Chronic Kidney Disease Patients With Anemia

Conditions
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Renal Anemia Associated With Chronic Renal Failure (CRF)

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients who diagnosed as a end-stage kidney disease (ESKD) and are receiving stable chronic maintenance dialysis 3 times per week for ≥ 12 weeks Patients who are receiving ESA for at least 8 weeks and the dose of ESA is within the dose range of ESA label Hb value at screening test is ≥10.0 g/dL Receiving hemodialysis via arteriovenous fistula (AVF) or arteriovenous graft (AVG) or via permanent catheter Most recent two Hb values before dialysis during washout period must be both <9.5 g/dL and one of two Hb values must be tested on first visit of the week Exclusion Criteria: Proliferative retinopathy, age-related macular degeneration, retinal vein occlusion and/or macular edema that is considered to require treatment Immunological disease with severe inflammation as assessed by the Investigator; even if the inflammation is in remission, the subject is excluded (e.g. lupus erythematosus, rheumatoid arthritis, Sjogren's syndrome, celiac disease, etc) Having a history of gastric/intestinal resection considered influential on the absorption of the drug in the gastrointestinal tract or active gastroparesis Uncontrollable hypertension (SBP ≥160 mmHg and DBP ≥110 mmHg, before dialysis, at screening test) Congestive heart failure (NYHA classification III or higher) Having a history of hospitalization for stroke, myocardial infarction or lung infarction within 24 weeks before 1st registration Positive for any of the following: human immunodeficiency virus (HIV); hepatitis B surface antigen (HBsAg); or anti-hepatitis C virus antibody (anti-HCV Ab) Anemia other than anemia due to low/absent renal production of EPO (e.g., iron deficiency anemia, hemolytic anemia, pancytopenia, etc) Pure red cell aplasia Using anabolic androgenic steroid, testosterone enanthate or mepitiostane within 6 weeks before 1st registration

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ASP1517 Low dose group<br>Participants received an oral dose of ASP1517 three times a week. | Drug: roxadustat<br>* oral<br>* Other names: ASP1517;|
| Experimental: ASP1517 Middle dose group<br>Participants received an oral dose of ASP1517 three times a week. | Drug: roxadustat<br>* oral<br>* Other names: ASP1517;|
| Experimental: ASP1517 High dose group<br>Participants received an oral dose of ASP1517 three times a week. | Drug: roxadustat<br>* oral<br>* Other names: ASP1517;|
| Active Comparator: Darbepoetin group<br>Participants received Darbepoetin alfa intravenously once a week. | Drug: darbepoetin alfa<br>* iv<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of rise in hemoglobin (g/dL/week) |  | Baseline and at Week-6 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cumulative number of responder patients | Responder is defined as a hemoglobin >10.0 g/dL and an increase in hemoglobin by >1.0 g/dL from baseline | up to Week-24 | 
| Percent of visits at which patients maintain hemoglobin between 10.0-12.0 g/dL after achieving hemoglobin ≥10.0 g/dL for each patients |  | for 28 weeks after dosing | 
| Percent of patients who maintain hemoglobin between 10.0-12.0 g/dL at each visit |  | for 28 weeks after dosing | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Chronic Renal Failure, ASP1517, Renal anemia