| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Treatment of anemia in subjects with chronic kidney disease (CKD). |
| Trattamento dell'anemia in soggetti affetti da insufficienza renale cronica. |
|
| 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 | 14.1 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10058116 |
| E.1.2 | Term | Nephrogenic anaemia |
| E.1.2 | System Organ Class | 10005329 - Blood and lymphatic system disorders |
|
| 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 assess the effect of anemia therapy with darbepoetin alfa on the composite event comprising all-cause mortality and cardiovascular (CV) events (including myocardial ischemia, congestive heart failure [CHF], myocardial infarction [MI], and cerebrovascular accident [CVA]) in subjects with both CKD and type 2 diabetes mellitus (DM). |
| Valutare l'effetto del trattamento dell'anemia con darbepoetina alfa sull'evento composto, comprendente tutte le cause di morte e gli eventi cardiovascolari (compresi l'Ischemia Miocardica, l'Insufficienza Cardiaca Congestizia, l'Infarto Miocardico e l'Evento Cerebrovascolare) in soggetti affetti da Insufficienza Renale Cronica e Diabete Mellito di Tipo II. |
|
| E.2.2 | Secondary objectives of the trial |
| To assess the effect of darbepoetin alfa on the time to end-stage renal disease (ESRD). To assess the effect of anemia therapy with darbepoetin alfa on CV mortality and the individual components of the composite event: all-cause mortality and CV events. To assess the effect of darbepoetin alfa on the change in the rate of decline in glomerular filtration rate (eGFR) and patient-reported fatigue. |
| Valutare l'effetto del trattamento dell'anemia con darbepoetina alfa sulla mortalita' causata da eventi cardiovascolari e sui singoli componenti dell'evento composto: tutte le cause di morte e gli eventi cardiovascolari.Valutare l'effetto della darbepoetina alfa sull'incidenza dell'Insufficienza Renale da Ultimo Stadio (ESRD),sulla riduzione della velocita' di filtrazione glomerulare stimata (eGFR) e sul senso di affaticamento riferito dal paziente. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
| - Before any study-specific procedure, the appropriate informed consent must be obtained (see Section 12.1). - at least 18 years old. - Clinical history of type 2 DM defined as:32 a. hyperglycemia not requiring insulin therapy or, b. hyperglycemia requiring insulin when either i. The period between diagnosis and the initiation of insulin therapy is > 1 year and/or, ii. C-peptide levels are elevated above normal. - Clinical history of CKD (at any point prior to registration) defined as: a. creatinine clearance or eGFR > 20 mL/min and < 60 mL/min or, b. serum creatinine > 1.2 mg/dL for all females, > 1.5 mg/dL for black males, and > 1.3 mg/dL for non-black males. - An eGFR during the screening period > 20 mL/min and < 60 mL/min measured by the following MDRD equation: eGFR = 186 x [Serum creatinine]-1.154 x [Age]-0.203 x [0.742 if subject is female] x [1.210 if subject is black] - Mean Hb < 11.0 g/dL (mean of 2 values taken at least 6 days apart during the screening period, using the hemoglobin point of care device). - Mean Tsat > 15% (mean of 2 values taken at least 6 days apart during the screening period). |
| - Before any study-specific procedure, the appropriate informed consent must be obtained (see Section 12.1). - at least 18 years old. - Clinical history of type 2 DM defined as:32 a. hyperglycemia not requiring insulin therapy or, b. hyperglycemia requiring insulin when either i. The period between diagnosis and the initiation of insulin therapy is > 1 year and/or, ii. C-peptide levels are elevated above normal. - Clinical history of CKD (at any point prior to registration) defined as: a. creatinine clearance or eGFR > 20 mL/min and < 60 mL/min or, b. serum creatinine > 1.2 mg/dL for all females, > 1.5 mg/dL for black males, and > 1.3 mg/dL for non-black males. - An eGFR during the screening period > 20 mL/min and < 60 mL/min measured by the following MDRD equation: eGFR = 186 x [Serum creatinine]-1.154 x [Age]-0.203 x [0.742 if subject is female] x [1.210 if subject is black] - Mean Hb < 11.0 g/dL (mean of 2 values taken at least 6 days apart during the screening period, using the hemoglobin point of care device). - Mean Tsat > 15% (mean of 2 values taken at least 6 days apart during the screening period). |
|
| E.4 | Principal exclusion criteria |
| - Anticipating or scheduled for a living related-donor kidney transplant, or a prior recipient of a kidney transplant. - Uncontrolled hypertension defined as diastolic BP >110 mm Hg or systolic BP > 180 mmHg on 2 separate occasions during screening. - Use of any erythropoietic protein (eg, rHuEPO; Procrit, Eprex, Neorecormon, Epogen, Aranesp) within 12 weeks of randomization. - Prior history (within 12 weeks of randomization) of CV events including: a. Myocardial ischemia b. Hospitalization for CHF c. MI d. CVA - Grand mal seizure within the 12 weeks prior to randomization. - Major surgery within 12 weeks prior to subject randomization (excluding vascular access surgery). - Currently receiving intravenous antibiotic therapy for systemic infection. - Known HIV positive. - Clinical evidence of current malignancy with the exception of basal cell or squamous cell carcinoma of the skin and cervical intraepithelial neoplasia. - Currently receiving systemic chemotherapy and/or radiotherapy. - Active bleeding. - Hematologic disease (eg, sickle cell disease, myelodysplastic syndromes, hematologic malignancy); myeloma; hemolytic anemia, thalassemia. - Subject is currently enrolled in or has not yet completed at least 30 days since ending other investigational product trial(s), or subject is receiving other investigational agent(s). - Subject is pregnant (eg, positive HCG test) or is breast-feeding. Females must have a negative serum pregnancy test (or definitive evidence to demonstrate lack of pregnancy) within 21 days prior to randomization if they are of childbearing potential, unless there is a documented history of amenorrhea. - Subject is not using adequate contraceptive precautions, as determined by the investigator. - Subject has known sensitivity to any of the products to be administered during dosing. - Subject has previously entered this trial (this does not include subjects who rescreen). - Subject will not be available for follow-up assessments. - Subject has any disorder (excluding illiteracy or visual impairment) that compromises the ability of the subject to give written informed consent and/or to comply with study procedures. Subjects are ineligible for participation in the functional capacity sub-study if (in addition to the above) they: 1. Have intrinsic walking limitations (eg, amputation, stroke) 2. Do not consent to participate in the sub-study |
| - Anticipating or scheduled for a living related-donor kidney transplant, or a prior recipient of a kidney transplant. - Uncontrolled hypertension defined as diastolic BP >110 mm Hg or systolic BP > 180 mmHg on 2 separate occasions during screening. - Use of any erythropoietic protein (eg, rHuEPO; Procrit, Eprex, Neorecormon, Epogen, Aranesp) within 12 weeks of randomization. - Prior history (within 12 weeks of randomization) of CV events including: a. Myocardial ischemia b. Hospitalization for CHF c. MI d. CVA - Grand mal seizure within the 12 weeks prior to randomization. - Major surgery within 12 weeks prior to subject randomization (excluding vascular access surgery). - Currently receiving intravenous antibiotic therapy for systemic infection. - Known HIV positive. - Clinical evidence of current malignancy with the exception of basal cell or squamous cell carcinoma of the skin and cervical intraepithelial neoplasia. - Currently receiving systemic chemotherapy and/or radiotherapy. - Active bleeding. - Hematologic disease (eg, sickle cell disease, myelodysplastic syndromes, hematologic malignancy); myeloma; hemolytic anemia, thalassemia. - Subject is currently enrolled in or has not yet completed at least 30 days since ending other investigational product trial(s), or subject is receiving other investigational agent(s). - Subject is pregnant (eg, positive HCG test) or is breast-feeding. Females must have a negative serum pregnancy test (or definitive evidence to demonstrate lack of pregnancy) within 21 days prior to randomization if they are of childbearing potential, unless there is a documented history of amenorrhea. - Subject is not using adequate contraceptive precautions, as determined by the investigator. - Subject has known sensitivity to any of the products to be administered during dosing. - Subject has previously entered this trial (this does not include subjects who rescreen). - Subject will not be available for follow-up assessments. - Subject has any disorder (excluding illiteracy or visual impairment) that compromises the ability of the subject to give written informed consent and/or to comply with study procedures. Subjects are ineligible for participation in the functional capacity sub-study if (in addition to the above) they: 1. Have intrinsic walking limitations (eg, amputation, stroke) 2. Do not consent to participate in the sub-study |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Primary Endpoint: Time to the composite event comprising all-cause mortality and CV events including: • Myocardial ischemia • CHF • MI • CVA |
| Endpoint Primario: tempo di insorgenza di un evento composto che puo' portare a decesso o al verificarsi di eventi cardiovascolari tra cui: Ischemia Miocardica, Insufficienza Cardiaca Congestizia, Infarto Miocardico, Evento Cerebrovascolare. Endpoint Secondari: Tempo di insorgenza di tutte le cause di morte, Tempo di insorgenza di decessi causati da Eventi Cardiovascolari, Tempo di insorgenza di Ischemia Miocardica, Tempo di insorgenza di Infarto Miocardico, Tempo di insorgenza di un Evento Cerebrovascolare, Tempo di insorgenza di Insufficienza Cardiaca Congestizia, Tempo di insorgenza di Insufficienza Renale da Ultimo Stadio (ESRD), Velocita' di riduzione della eGFR rispetto al baseline, Variazioni del senso di affaticamento riportato alla 25a settimana. Altri Endpoint di Interesse: Tempo richiesto per la rivascolarizzazione cardiaca, Variazioni nel rapporto proteine/creatinina urinaria rispetto al baseline, Utilizzazione delle risorse sanitarie (HRU) nel periodo in cui il paziente sara' seguito. Variazioni dei risultati riferiti dal paziente (PRO) alla 25a settimana rispetto al baseline. Endpoint di Sicurezza: Natura, frequenza, gravita', reazione al trattamento e risultati di tutti gli eventi avversi. Variazioni cliniche significative nei parametri di laboratorio e nella pressione sanguigna. Attivita' sierica della proteina anti-eritropoietica |
|
| 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 | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| 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) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| 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 | 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) | No |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 1 |
| 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 | 42 |
| E.8.5 | The trial involves multiple Member States | No |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | No |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
| 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
| |
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | |
| E.8.9.1 | In the Member State concerned months | |
| E.8.9.1 | In the Member State concerned days | |
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