E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Anaemia of Chronic Kidney Disease |
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E.1.1.1 | Medical condition in easily understood language |
A decrease in the number of red blood cells as a result of chronic kidney disease |
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E.1.1.2 | Therapeutic area | Diseases [C] - Blood and lymphatic diseases [C15] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 16.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10058123 |
E.1.2 | Term | Renal anaemia |
E.1.2 | System Organ Class | 100000004851 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the efficacy for up to 16 weeks of fixed dose treatment with BAY 85-3934 versus placebo as measured by haemoglobin (Hb) levels. |
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E.2.2 | Secondary objectives of the trial |
To evaluate the safety and tolerability of BAY 85-3934 when administered as a fixed dose for up to 16 weeks versus placebo.
To evaluate the pharmacodynamics (PD) of BAY 85-3934 when administered as a fixed dose for up to 16 weeks.
To evaluate the pharmacokinetics (PK) of BAY 85-3934 and optionally, its metabolite M-1, when administered as a fixed dose for up to 16 weeks.
To investigate selected parameters of kidney function and chronic kidney disease (CKD) progression as well as parameters of iron metabolism and patient reported outcomes (PRO).
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Men who agree to use adequate contraception when sexually active or women without childbearing potential
• Male or female subjects ≥ 18 years of age with anemia of CKD at screening
• Estimated glomerular filtration rate of < 60 mL/min/1.73 m2 (Modification of Diet in Renal Disease [MDRD] or the formula according to Matsuo, et al)
• Not on dialysis and not expected to begin dialysis during the treatment period of the study (at least 16 weeks from randomization)
• Not treated with any ESA within 8 weeks before randomization
• Mean screening Hb concentration < 10.0 g/dL
• Body weight of 45 kg to 125 kg, inclusive, at screening |
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E.4 | Principal exclusion criteria |
• Subjects with significant acute or chronic bleeding, such as overt gastrointestinal bleeding
• Chronic inflammatory disease that could impact erythropoiesis (e.g., systemic lupus erythematosis, rheumatoid arthritis, celiac disease) even if it is currently in remission
• Previous or concurrent cancer except cervical carcinoma in situ, treated basal cell carcinoma, superficial bladder tumors (Ta, Tis, and T1) or any cancer curatively treated > 3 years prior to randomization
• Subjects treated with any ESA within the 8 weeks before randomization
• Red blood cell (RBC) containing transfusion within the 8 weeks before randomization
• History of cardio- (cerebro-) vascular events (e.g., unstable angina, myocardial infarction, stroke, transient ischemic attack, deep vein thrombosis, pulmonary embolism) within the last 6 months from initial screening visit
• Severe rhythm or conduction disorders (e.g., HR < 50 or > 110 bpm, atrial fibrillation or flutter, prolonged QT > 500 msec, second or third degree atrioventricular [AV] block)
• New York Heart Association Class III or IV congestive heart failure
• Severe hepatic insufficiency (defined as alanine aminotransferase [ALT], aspartate aminotransferase [AST], or gamma glutamyl transferase [GGT] > 3 x the upper limit of normal [ULN], total bilirubin > 2 mg/dL, or Child-Pugh B and C) or active hepatitis, in the investigator’s opinion |
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E.5 End points |
E.5.1 | Primary end point(s) |
1) Change in local laboratory haemoglobin level from baseline to the average during the last 4 weeks treatment period |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
1) Baseline and week 12 to 16 |
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E.5.2 | Secondary end point(s) |
1) Change in local laboratory haemoglobin level from baseline
2) Speed of change in haemoglobin level per unit time
3) Treatment exposure (Duration)
4) Number of participants with serious adverse events as a measure of safety and tolerability
5) Pharmacodynamics characterized by erythropoietin concentration
6) Pharmacodynamics characterized by reticulocyte count |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1) Baseline up to 12 weeks
2) Up to 16 weeks
3) Up to 16 weeks
4) Up to 16 weeks
5) Several time points up to 16 weeks
6) Several time points up to 16 weeks |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 6 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 24 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Australia |
Bulgaria |
Germany |
Hungary |
Italy |
Japan |
Korea, Republic of |
Romania |
United Kingdom |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 0 |
E.8.9.1 | In the Member State concerned months | 9 |
E.8.9.1 | In the Member State concerned days | 12 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 2 |