Anemia, Renal Insufficiency, Chronic
Conditions
Brief summary
The purpose of this study is to evaluate the efficacy and safety of molidustat in comparison to darbepoetin alfa in dialysis subjects with renal anemia who are treated with Erythropoiesis-Stimulating Agents (ESAs).
Interventions
Starting dose of molidustat will be titrated based on the subject's Hb (Hemoglobin) response. Administrated orally once daily (OD).
DRUGDarbepoetin alfa
Starting dose of darbepoetin alfa will be titrated based on the subject's Hb (Hemoglobin) response. Administrated weekly or once every two weeks by intravenous injection.
DRUGPlacebo of Molidustat (BAY85-3934)
Matching placebo of Molidustat.
DRUGPlacebo of Darbepoetin alfa
Matching placebo of Darbepoetin alfa.
Sponsors
Bayer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Subject with ESKD (end-stage kidney disease) on regular dialysis (including, hemodiafiltration, hemofiltration, hemodialysis, and other modalities except for peritoneal dialysis) weekly or more than weekly for at least 12 weeks prior to randomization * Body weight (after dialysis) \> 40 and ≤ 160 kg at screening * Male or female subject ≥ 20 years of age at screening * At least one kidney * Treated with weekly or bi-weekly dose of darbepoetin alfa, monthly or bi-weekly dose of epoetin beta pegol, OR weekly, biweekly, twice or three times per week dose of epoetin alfa/beta, and having had no more than one dose change within 8 weeks prior to randomization * Mean screening Hb level ≥ 9.5 and \< 12.0 g/dL (mean of all central laboratory Hb levels before dialysis \[at least 2 measurements must be taken ≥ 2 days apart\] during the screening period, AND all Hb level must be measured by the central laboratory, AND the difference between the lowest level and highest level is \< 1.2 g/dL), with the last screening Hb level measurement within 14 days prior to randomization * Ferritin ≥ 100 ng/mL or transferrin saturation ≥ 20% at screening * Serum folate level and serum vitamin B12 level above lower limit of normal (LLN) 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, poorly controlled arterial hypertension (defined as systolic BP (blood pressure) ≥ 180mmHg or diastolic BP ≥ 110mmHg) or hypotension (defined as systolic BP \< 90mmHg) at randomization * Proliferative choroidal or retinal disease, such as neovascular agerelated macular degeneration or proliferative diabetic retinopathy requiring invasive treatment (e.g., intraocular injections or laser photocoagulation) at screening
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The mean Hb level during the evaluation period | From week 33 to 36 |
| The change in mean Hb level during the evaluation period from baseline | Baseline and week 33 to 36 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Responder rate: proportion of responders among the subjects | From week 33 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 |
| Proportion of subjects who meet each component of the response | From week 33 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 |
| Hb level | Up to 52 weeks | — |
| Change in Hb level | Baseline and up to 52 weeks | — |
| Proportion of subjects whose mean hemoglobin level is in the target range | From week 33 to 36 | — |
| Proportion of subjects whose mean hemoglobin level is above the target range | From week 33 to 36 | — |
| EPO (Erythropoietin) serum concentration | At baseline, week 8, week 24 and week 52 | — |
| Proportion of subjects with hemoglobin levels in the target range | Up to 52 weeks | — |
| Proportion of subjects with hemoglobin levels above the target range | Up to 52 weeks | — |
| Proportion of subjects with hemoglobin levels below the target range | Up to 52 weeks | — |
| 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 8, week 24 and week 52 | — |
| Proportion of subjects whose mean hemoglobin level is below the target range | From week 33 to 36 | — |
| Area under the concentration-time curve (AUC) | At baseline, week 8, week 24 and week 52 | — |
Countries
Japan
Outcome results
None listed