| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Anaemia of Chronic Kidney Disease |
| Anemia de Nefropatía crónica |
|
| 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 |
| Descenso en el número de glóbulos rojos, como resultado de Nefropatía crónica |
|
| 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 | 16.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10058132 |
| E.1.2 | Term | Renal anemia |
| E.1.2 | System Organ Class | 100000004851 |
|
| 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 of 16 weeks of titrated dose treatment with BAY 85 3934 versus darbepoetin alfa (hereafter called darbepoetin) as measured by haemoglobin (Hb) levels during the last 4 weeks of treatment (evaluation period). |
| Evaluar la eficacia de 16 semanas de tratamiento con dosis ajustadas de BAY 85-3934 frente a darbepoetina alfa (en adelante «darbepoetina») medida mediante las concentraciones de hemoglobina (Hb) durante las últimas 4 semanas de tratamiento (período de evaluación). |
|
| E.2.2 | Secondary objectives of the trial |
- Evaluate the safety and tolerability of 16 weeks of treatment with BAY 85-3934 when administered as a titrated dose versus darbepoetin.
- Evaluate the pharmacodynamics of BAY 85-3934 when administered as a titrated dose for 16 weeks.
- Evaluate the pharmacokinetics of BAY 85-3934 and optionally its metabolite, M-1, when administered as a titrated dose for 16 weeks.
The exploratory objective is to investigate selected parameters of kidney function and chronic kidney disease (CKD) progression, as well as parameters of iron metabolism and patient-reported outcomes (PROs). |
- Evaluar la seguridad y tolerabilidad de 16 semanas de tratamiento con BAY 85-3934 cuando se administra en dosis ajustadas frente a darbepoetina.
- Evaluar la farmacodinamia de BAY 85-3934 cuando se administra en dosis ajustadas durante 16 semanas.
- Evaluar la farmacocinética de BAY 85-3934 y, opcionalmente, de su metabolito M-1, cuando se administra en dosis ajustadas durante 16 semanas.
El objetivo exploratorio es investigar parámetros seleccionados de la función renal y de la progresión de la nefropatía crónica (NC), así como los parámetros del metabolismo del hierro y los resultados comunicados por el paciente (RCP). |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
- Male or female subjects >= 18 years of age with anemia of chronic kidney disease (CKD) at screening
- Estimated glomerular filtration rate (eGFR) of < 60 mL/min/1.73 m2 (Modification of Diet in Renal Disease 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)
- Treated with darbepoetin via intravenous (IV) or subcutaneous (SC) route with a weekly, bi-weekly, or monthly dose, having had no more than one dose change within 8 weeks prior to randomization
- At least one kidney
- Mean screening Hb concentration of 10.0 to 12.0 g/dL
- Men who agree to use adequate contraception when sexually active or women without childbearing potential |
- Sujetos de ambos sexos de 18 años o más con anemia por NC en el momento de la selección
- Filtración glomerular calculada menor de 60 ml/min/1,73 m2 (fórmula de Modification of Diet in Renal Disease [Modificación de la Dieta en la Nefropatía] o de Matsuo y cols.)
- No reciben diálisis y no se espera que comiencen la diálisis durante el período de tratamiento del estudio (al menos 16 semanas desde la aleatorización)
- Tratados con darbepoetina por vía i.v. o s.c. con una dosis semanal, quincenal o mensual, que no hayan experimentado más de un cambio de dosis en las 8 semanas anteriores a la aleatorización
- Al menos un riñón.
- Concentración media de Hb en el momento de la selección de 10,0 a 12,0 g/dl inclusive.
- Hombres que aceptan utilizar un método anticonceptivo adecuado si son sexualmente activos o mujeres que no pueden quedar embarazadas. |
|
| E.4 | Principal exclusion criteria |
- Subjects with significant acute or chronic bleeding, such as overt gastrointestinal bleeding
- Active hemolysis or diagnosis of hemolytic syndrome
- History of myelodysplastic syndrome, multiple myeloma, marrow fibrosis, or pure red-cell aplasia (PRCA)
- History of hemosiderosis or hemochromatosis
- Hereditary hemoglobinopathies (such as sickle cell disease and thalassemia major)
- Aplastic anemia
- Chronic lymphoproliferative diseases
- Proliferative choroidal or retinal disease, such as neovascular age-related macular degeneration or proliferative diabetic retinopathy that is likely to require invasive treatment (intraocular injections or laser photocoagulation) during the study
- Chronic inflammatory disease that could impact erythropoiesis (e.g., systemic lupus erythematosis, rheumatoid arthritis, celiac disease) even if it is currently in remission
- Known hypersensitivity to the study drugs (active substances or excipients of the preparations)
- Uncontrolled and symptomatic hyperparathyroidism
- Uncontrolled active infection
- 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
- Any allograft (including renal allograft) in place and on immunosuppressive therapy or a scheduled kidney transplant within the next 16 weeks (being on a waiting list does not exclude the subject) |
- Sujetos con hemorragia aguda o crónica significativa, por ejemplo, una hemorragia digestiva franca
- Hemólisis activa o diagnóstico de síndrome hemolítico
- Antecedentes de síndrome mielodisplásico, mieloma múltiple, fibrosis medular o APR
- Antecedentes de hemosiderosis o hemocromatosis
- Hemoglobinopatías hereditarias (como la anemia falciforme o la talasemia mayor)
- Anemia aplásica
- Enfermedades linfoproliferativas crónicas
- Enfermedad proliferativa coroidea o retiniana, como la degeneración macular neovascular relacionada con la edad o la retinopatía diabética proliferativa, que probablemente requiera tratamiento invasivo (inyecciones intraoculares o fotocoagulación con láser) durante el estudio
- Enfermedad inflamatoria crónica que pueda afectar a la eritropoyesis (como el lupus eritematoso sistémico, la artritis reumatoide o la enfermedad celíaca) aunque se encuentre en remisión en la actualidad.
- Hipersensibilidad conocida a los fármacos del estudio (principios activos o excipientes de los preparados)
- Hiperparatiroidismo no controlado y sintomático
- Infección activa no controlada
- Cáncer anterior o concurrente excepto carcinoma cervical in situ, carcinoma basocelular tratado, tumores vesicales superficiales (Ta, Tis y T1) o cualquier cáncer que haya recibido tratamiento curativo más de 3 años antes de la aleatorización
- Portadores de un aloinjerto de cualquier tipo (incluido el aloinjerto renal) y que reciben tratamiento inmunodepresor, o en los que se haya programado un trasplante de riñón en las 16 semanas siguientes (estar en la lista de espera no es motivo de exclusión) |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Change in local laboratory hemoglobin level from baseline to the average during the last 4 weeks treatment period. |
| Cambio en la concentración de Hb medida en el laboratorio local entre el inicio y las visitas postiniciales durante las últimas 4 semanas del período de tratamiento. |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| Baseline and week 12 to 16 |
| Basal y semanas 12 a 16. |
|
| E.5.2 | Secondary end point(s) |
1) Maintenance in hemoglobin target range (10.0 to 12.0 g/dL)
2) Change in hemoglobin level
3) Number of patients with hemoglobin levels outside the target range
4) Treatment exposure
5) Number of subjects requiring titration of dose
6) Number of participants with serious adverse events as a measure of safety and tolerability |
1) Media de las concentraciones de Hb en el intervalo objetivo (de 10,0 a 12,0 g/dl)
2)Cambio en la concentración de Hb
3) Número de pacientes con los niveles de HB fuera de intervalo objetivo.
4) Exposición al tratamiento
5) Número de sujetos que requieren un ajuste de la dosis
6) Número de sujetos con Acontecimientos adversos graves (AAG) como medida de seguridad y tolerabilidad. |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
1) Up to 16 weeks
2) Baseline up to 16 weeks
3) Week 12 to 16
4) Up to 16 weeks
5) Up to 16 weeks
6) Up to 16 weeks |
1) Hasta 16 semanas
2) Basal hasta 16 semanas
3) Semanas 12 a 16
4) Hasta 16 semanas
5) Hasta 16 semanas
6) Hasta 16 semanas |
|
| 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 | No |
| 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 | Yes |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | No |
| 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) | Yes |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 4 |
| 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 |
| Bulgaria |
| Italy |
| Japan |
| Romania |
| Australia |
| Germany |
| Hungary |
| Korea, Republic of |
| Spain |
| United Kingdom |
|
| 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
|
| LVLS |
| última visita del último paciente. |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 1 |
| E.8.9.1 | In the Member State concerned months | 0 |
| E.8.9.1 | In the Member State concerned days | 0 |
| 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 | 3 |
| E.8.9.2 | In all countries concerned by the trial days | 21 |
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