Anemia, Renal Insufficiency, Chronic
Conditions
Brief summary
The purpose of this study is to evaluate the efficacy and safety of molidustat in non-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
DRUGDarbepoetin alfa
Starting dose of darbepoetin alfa once every 2 weeks will be titrated based on the subject's Hb (Hemoglobin) response
Sponsors
Bayer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Subjects with estimated glomerular filtration rate (eGFR)\< 60 mL/min/1.73m\^2 (Chronic kidney disease \[CKD\] stages 3 to 5) * Body weight \> 40 and ≤ 160 kg at screening * Male or female subject ≥ 20 years of age at screening * Not on dialysis and not expected to start dialysis during the study period * Not treated with ESAs and/or HIF-PH inhibitors within 8 weeks prior to randomization * Mean of the last 2 central laboratory Hb levels during the screening period must be ≥ 8.0 and \< 11.0 g/dL (2 measurements must be taken ≥ 2 days apart and the difference between the 2 measurements must be \< 1.2 g/dL) and the last measurements must be taken within 14 days prior to randomization * 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 |
|---|---|
| Mean Hb (Hemoglobin) level | From week 30 to 36 |
| Change in hemoglobin level from baseline to the average during the evaluation period | Baseline and week 30 to 36 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of subjects whose mean hemoglobin level is above the target range | From week 30 to 36 | — |
| Proportion of subjects whose mean hemoglobin level is below the target range | From week 30 to 36 | — |
| Proportion of subjects with hemoglobin levels in the target range | Up to 52 weeks | — |
| Responder rate: proportion of responders among the subjects | From week 30 to 36 | 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 |
| Rate of rise in Hb (Hemoglobin) level (g/dL/week) | Up to 8 weeks | — |
| Proportion of subjects who meet each component of the response | From week 30 to 36 | 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 |
| Cumulative proportion of subjects who achieve the lower limit of the target Hb range at least once | Up to 52 weeks | — |
| Proportion of subjects with hemoglobin levels above the target range | Up to 52 weeks | — |
| Hb level | Baseline and up to 52 weeks | — |
| Proportion of subjects whose mean hemoglobin level is in the target range | From week 30 to 36 | — |
| Proportion of subjects whose maximum rise in Hb between each consecutive visits is above 0.5 g/dL/week | Up to 52 weeks | Defined as change in Hb level / duration between two visits (weeks) |
| Number of participants with serious adverse events | Up to 52 weeks | — |
| Maximum concentration (Cmax) | At baseline, week 12, week 24 and week 52 | — |
| Area under the concentration-time curve (AUC) | At baseline, week 12, week 24 and week 52 | — |
| EPO (Erythropoietin) serum concentration | At baseline, week 12, week 24 and week 52 | — |
| Change in Hb level | Baseline and up to 52 weeks | — |
| Proportion of subjects with hemoglobin levels below the target range | Up to 52 weeks | — |
Countries
Japan
Outcome results
None listed