A Study of Molidustat for Correction of Renal Anemia in Dialysis Subjects

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the efficacy and safety of Molidustat in dialysis subjects with renal anemia who are not treated with Erythropoiesis-Stimulating Agents (ESAs)

Official Title
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A Single Arm, Multicenter Study to Investigate the Efficacy and Safety of Oral Molidustat in Dialysis Subjects With Renal Anemia Who Are Not Treated With Erythropoiesis-Stimulating Agents (ESAs)

Conditions
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Anemia, Renal Insufficiency, Chronic

Intervention / Treatment
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* Drug: Molidustat (BAY85-3934)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject with end-stage kidney disease (ESKD) on dialysis (including, hemodiafiltration, hemodialysis, and other modalities except for peritoneal dialysis) weekly or more than weekly Body weight > 40 and ≤ 160 kg at screening Male or female subject ≥ 20 years of age at screening At least one kidney Not treated with ESAs and/or HIF-PH inhibitors within 8 weeks prior to randomization. However, in case of the patient washed out from ESAs, when the mean Hb (at least 2 central laboratory measurements must be taken ≥ 2 days apart before dialysis) has decrease to ≥ 0.5 dL from the Hb level (central laboratory measurement, before dialysis) after the last ESA administration, AND the interval from the last ESA administration to the study drug assignment was over 1 week for epoetin-alpha, 2 weeks for darbepoetin alpha or 4 weeks for epoetin beta pegol Mean of the last 2 Hb level (central laboratory measurement, before dialysis) during the screening period must be ≥ 8.0 and < 10.0 g/dL (2 measurements must be taken ≥ 2 days apart and the difference between the 2 measurements must be < 1.2 g/dL) with the last screening Hb measurement within 14 days prior to study drug assignment Ferritin ≥ 50 ng/mL at screening Exclusion Criteria: New York Heart Association (NYHA) Class III or IV congestive heart failure History of cardio- (cerebro-) vascular events (e.g., unstable angina, myocardial infarction, stroke, pulmonary thromboembolism, and acute limb ischemia) within 6 months prior to randomization Sustained and poorly controlled arterial hypertension (defined as systolic BP≥ 180mmHg or diastolic BP ≥ 110mmHg) or hypotension (defined as systolic BP < 90mmHg) at randomization Proliferative choroidal or retinal disease, such as neovascular age-related macular degeneration or proliferative diabetic retinopathy requiring invasive treatment (e.g., intraocular injections or laser photocoagulation)

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Molidustat (BAY85-3934)<br>Molidustat group | Drug: Molidustat (BAY85-3934)<br>* Starting dose of molidustat once daily (OD) will be titrated based on the subject's Hb (Hemoglobin) response<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of rise in Hb (Hemoglobin) level (g/dL/week) |  | Up to 8 weeks | 
| Responder rate: proportion of responders among the subjects | Responder is defined as meeting all of the following criteria: (i) Mean of the Hb levels in the target range (ii) ≥ 50% of the Hb levels in the target range (iii) No rescue treatment | Week 21 to 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of rise in Hb (Hemoglobin) level (g/dL/week) |  | Up to 4 weeks | 
| Proportion of subjects who meet each component of the response | Response: (i) Mean of the Hb levels in the target range (ii) ≥ 50% of the Hb levels in the target range (iii) No rescue treatment | Week 21 to 24 | 
| Cumulative proportion of subjects who achieve the lower limit of the target Hb range at least once at each visit |  | Up to 24 weeks | 
| Hb level |  | Baseline and up to 24 weeks | 
| Change in Hb level |  | Baseline and up to 24 weeks | 
| Proportion of subjects whose mean hemoglobin levels are above the target range during the evaluation period |  | Week 21 to 24 | 
| Proportion of subjects whose mean hemoglobin levels are below the target range during the evaluation period |  | Week 21 to 24 | 
| Proportion of subjects whose mean hemoglobin levels are in the target range during the evaluation period |  | Week 21 to 24 | 
| Proportion of subjects with hemoglobin levels above the target range |  | Up to 24 weeks | 
| Proportion of subjects with hemoglobin levels below the target range |  | Up to 24 weeks | 
| Proportion of subjects with hemoglobin levels in the target range |  | Up to 24 weeks | 
| Proportion of subjects whose maximum rise in Hb between each consecutive visits is above 0.5 g/dL/week | Defined as change in Hb level / duration between two visits (weeks) | Up to 24 weeks | 
| Number of participants with serious adverse events |  | Up to 24 weeks | 
| Maximum concentration (Cmax) of Molidustat |  | Baseline, Week 8, Week16 and Week 24 | 
| Area under the concentration-time curve (AUC) of Molidustat |  | Baseline, Week 8, Week16 and Week 24 | 
| EPO (Erythropoietin) serum concentration of Molidustat |  | Baseline, Week 8, Week16 and Week 24 |