Clinical Study of R744 to Hemodialysis Patients

Study Overview
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Brief Summary
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This study used as the comparative drug (epoetin beta) will assess the efficacy and safety of intravenous injections of R744 in renal anemia patients on Hemodialysis patients.

Official Title
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Switch and Maintenance Study of Intravenous Injections of R744 to Hemodialysis Patients ( Phase III, Double Blind Study in Comparison With Epoetin Beta).

Conditions
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Hemodialysis Patients

Intervention / Treatment
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* Drug: R744
* Drug: R744
* Drug: rHuEPO
* Drug: rHuEPO
* Drug: R744 placebo
* Drug: rHuEPO placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients who have been receiving hemodialysis 3 times a week for at least 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 week for at least 8 weeks before registration Within 4 weeks before registration, patients who have been receiving a rHuEPO preparation 750IU (3 times a week), 1,500IU (twice a week (1st and 2nd hemodialysis day of the week, or1st and 3rd hemodialysis day of the week)), 1,500IU (3 times a week), or 3,000IU (twice a week (1st and 2nd hemodialysis day of the week, or1st and 3rd hemodialysis day of the week)), and patients who have not change dosage and administration. Patients whose pre-dialysis Hb concentrations has been between ≥ 9.0 g/dL and ≤12.0 g/dL and mean value of pre-dialysis Hb concentrations has been between ≥ 9.5 g/dL and ≤11.5 g/dL determined at the beginning of each week within 8 weeks before registration Patients whose transferrin saturation has been ≥ 20 % or ferritin has been ≥ 100ng/mL at any 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 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, testosterone propionate, methyltestosterone 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 subinvestigator

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: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br> | Drug: R744<br>* 100μg/4week for 8 weeks, then 50 250μg/4week for 16 weeks<br>* Other names: methoxy polyethylene glycol-epoetin beta;Drug: rHuEPO placebo<br>* 0 IU 2 or 3 times/week for 8 weeks, then 1 3 times/week for 16 weeks<br>|
| Experimental: 2<br> | Drug: R744<br>* 150μg/4week for 8 weeks, then 50 250μg/4week for 16 weeks<br>* Other names: methoxy polyethylene glycol-epoetin beta;Drug: rHuEPO placebo<br>* 0 IU 2 or 3 times/week for 8 weeks, then 1 3 times/week for 16 weeks<br>|
| Active Comparator: 3<br> | Drug: rHuEPO<br>* 2250IU or 3000IU(i.v.) 2 or 3 times/week for 8 weeks, then 750 9000IU(i.v.)/1 3week for 16 weeks<br>Drug: R744 placebo<br>* 0 μg/4week for 24 weeks<br>|
| Active Comparator: 4<br> | Drug: rHuEPO<br>* 4500IU or 6000IU(i.v.) 2 or 3times/week for 8 weeks, then 750 9000IU(i.v.)/1 3week for 16 weeks<br>Drug: R744 placebo<br>* 0 μg/4week for 24 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Variation of Hb concentration from baseline Hb concentration in evaluation period |  | week 17 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of patients who maintain Hb concentration in the range of baseline ± 1.0g/dL and maintain Hb concentration in the range of ≥ 9.0g/dL and ≤ 12.0g/dL in evaluation period |  | week 17 24 | 
| Rate of patients who maintain Hb concentration within ±1.0g/dL of reference Hb |  | week 17 24 | 
| Adverse events |  | throughout study | 
| Laboratory measurements |  | throughout study | 
| Vital signs, standard 12-lead ECG |  | throughout study | 
| Anti-R744 antibody titer |  | throughout study | 
| Anti-Epoetin beta antibody titer |  | throughout study |