Clinical Study of R744 to Predialysis Patients

Study Overview
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Brief Summary
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This study will assess the efficacy and safety of subcutaneous or intravenous R744 in renal anemia patients on Predialysis.

Official Title
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Switch and Maintenance Study of Subcutaneous or Intravenous Injections of R744 to Predialysis Patients ( Phase Ⅲ Study ).

Conditions
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Anemia in Pre-Dialysis Patients

Intervention / Treatment
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* Drug: R744
* Drug: R744


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients whose serum creatinine level has been ≥ 2.0 mg/dL or creatinine clearance has been ≥ 30 mL /min at any one time point within 12 weeks before registration Patients aged ≥ 20 years at the time of obtaining consent Patients who have been receiving a rHuEPO preparation at least once a month for at least 8 weeks before registration Patients whose mean value of Hb concentrations determined within 8 weeks before registration has been between ≥ 10.0 g/dL and <13.0 g/dL Patients whose transferrin saturation has been ≥ 20 % or ferritin has been ≥ 100ng/mL at any one time point within 8 weeks before registration Exclusion Criteria: Patients with hardly controllable hypertension (patients whose diastolic blood pressure has been ≥ 100 mmHg on more than 1/3 of the determining occasions within 12 weeks before registration) Patients with congestive cardiac failure (≥ Class III in NYHA cardiac function classification) Female patients who are pregnant, lactating, possibly pregnant or not willing to take a contraceptive measure in the period from the day of starting the treatment with the study drug to 90 days after the day of the last dose of the study drug Patients with complication of myocardial infarction, pulmonary infarction or cerebral infarction (excluding asymptomatic cerebral infarction) Patients who are applicable to the following criteria ⅰ), ⅱ), ⅲ), and whose mean value of Hb concentrations determined within 8 weeks before registration has been > 12.0 g/dL ⅰ)Patients with an anamnesis of myocardial infarction, pulmonary infarction or cerebral infarction (excluding asymptomatic cerebral infarction) ⅱ)Patients with complication of unstable angina pectoris or controlled angina pectoris (hardly controlled regardless of drug treatment or interventional treatment ) ⅲ)Patients with congestive cardiac failure (≥ Class II in Fontaine arteriosclerosis obliterans classification) Patients confirmed to have serious allergy or serious drug allergy (shock, anaphylactoid symptom) Patients hypersensitive to a rHuEPO preparation Patients with malignant tumor (including hemic malignant tumor), severe infection, systemic hemic disease (osteomyelodysplasia syndrome, hemoglobinopathy, etc.), hemolytic anemia or apparent hemorrhagic lesion such as digestive tract hemorrhage Patients who have received an anabolic hormone preparation, testosterone enanthate or mepitiostane within 12 weeks before registration Patients who have received another investigational drug within 12 weeks before registration Patients who have received R744 before registration Patients whose AST(GOT) value ≥ 100 IU/L or ALT(GPT) value ≥ 100 IU/L before registration Patients who have received erythrocyte transfusion within 16 weeks before registration Patients for whom a surgical operation accompanied by marked bleeding is planned during the study period In addition, patients who are judged as ineligible to participate in this study by the investigator or sub-investigator

Ages Eligible for Study
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Minimum Age: 20 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: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br> | Drug: R744<br>* 100μg(s.c./i.v.)/4 week for 8 weeks, then 25 400μg(s.c./i.v.)/4 week for 40 weeks<br>* Other names: methoxy polyethylene glycol-epoetin beta;|
| Experimental: 2<br> | Drug: R744<br>* 150μg(s.c./i.v.)/4 week for 8 weeks, then 25 400μg(s.c./i.v.)/4 week for 40 weeks<br>* Other names: methoxy polyethylene glycol-epoetin beta;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ratio of Maintenance of target Hb concentration |  | 24th and 48th week | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Slope of regression line of Hb concentration (g/dL/week) |  | 24th week | 
| Rate of patients who maintain Hb concentration in the range of baseline ± 1.0g/dL |  | 24th week | 
| Ratio of Maintenance of Hb concentration |  | 24th and 48th week | 
| Adverse events |  | 24th and 48th week | 
| Laboratory measurements |  | 24th and 48th week | 
| Vital signs, standard 12-lead ECG |  | 24th and 48th week | 
| Anti-R744 antibody titer |  | 24th and 48th week |