Anemia, Renal Insufficiency, Chronic
Conditions
Brief summary
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)
Interventions
Starting dose of molidustat once daily (OD) will be titrated based on the subject's Hb (Hemoglobin) response
Sponsors
Bayer
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Rate of rise in Hb (Hemoglobin) level (g/dL/week) | Up to 8 weeks | — |
| Responder rate: proportion of responders among the subjects | Week 21 to 24 | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | — |
| Rate of rise in Hb (Hemoglobin) level (g/dL/week) | Up to 4 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 | Up to 24 weeks | Defined as change in Hb level / duration between two visits (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 | — |
| Proportion of subjects with hemoglobin levels below the target range | Up to 24 weeks | — |
| Proportion of subjects who meet each component of the response | Week 21 to 24 | 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 |
Countries
Japan
Outcome results
None listed