| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| diabetic and transplanted CKD stage III patients |
|
| E.1.1.1 | Medical condition in easily understood language |
| progressive renal disease in diabetic patients or in patients with a kidney transplant |
| fortschreitenden Nierenfunktionsstörung bei Diabetes-Patienten oder bei Patienten nach Nierentransplantation |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Nutritional and Metabolic Diseases [C18] |
| 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 | 10064848 |
| E.1.2 | Term | Chronic kidney disease |
| E.1.2 | System Organ Class | 100000004857 |
|
| 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 |
| The objective of this study is to investigate if treatment with methoxy polyethylene glycol-epoetin beta has a protective effect on the kidney of CKD stage III patients. This renoprotective influence will be defined as a slowing of disease progression, reflected by the yearly decline of GFR. The GFR will be estimated based on serum creatinine using the 4-variable-MDRD formula. All laboratory parameters, including serum creatinine, will be analyzed by a central laboratory to ensure homogenous results. |
|
| E.2.2 | Secondary objectives of the trial |
| Secondary objective includes the assessment of whether an effect on urinary protein creatinine ratio, serum creatinine and cystatine C can be disclosed and if there are differences between patients pre-dialysis and post-kidney-Tx (who fulfill the CKD-criteria). Furthermore, safety parameters concerning adverse events – especially drop out due to increase of Hb, drop out due to increase of blood pressure, anti-erythropoietin antibodies and acute rejection - will be captured. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Willingness to give written informed consent, written consent for data collection ("Datenschutzrechtliche Einwilligung") and willingness to participate and to comply with the study protocol
2. Adult patients (≥18 years)
3. For diabetic patients: Type 2 diabetes mellitus with HbA1c > 7% or anti-diabetic treatment (Two values from medical routine < 1 year prior Screening or measured by central laboratory at Screening Visit)
4. For renal allograft recipients: Status at least 6 months post Tx
5. CKD Stage III (eGFR between 30-59 ml/min/1.73 m2 (MDRD equation, 4 variables)) (Value from medical routine < 1 month prior Screening or measured by central laboratory at Screening Visit)
6. UACR < 3000 mg/g creatinine or total protein < 3000 mg/24h urine sample where applicable (Values from medical routine < 3 months prior Screening or measured by the central laboratory at Screening Visit)
|
|
| E.4 | Principal exclusion criteria |
1. Hb-level < 11 or > 14 g/dL (value from local measurement at screening)
2. Average SBP > 140 mm Hg or average DBP > 90 mm Hg (Value from medical routine < 1 month prior Screening. Average of two measurements with a 1 to 5 min. interval, taken with the patient sitting (or standing: for elderly subjects, diabetic patients, or when postural hypotension may be frequent))
3. Initiation of ACEI or ARB or aliskiren treatment less than 3 months before screening.
4. Present and known iron deficiency measured with the parameters serum ferritin and TSAT (despite adequate treatment)
5. HbA1c >9%
6. Documented and suspected gastrointestinal bleeding within 8 weeks before inclusion
7. Reasons for subnormal Hb-levels between 11-14 g/dL other than impaired kidney function
8. Myocardial infarction or stroke in the 6 months prior to inclusion
9. Severe and instable coronary artery disease (CAD)
10. Manifest chronic congestive heart failure (New York Heart Association Class III to IV)
11. Epileptic seizures in the 6 months prior to inclusion
12. RBC transfusions within 2 months before inclusion
13. Hemoglobinopathies (e.g. homozygous sickle-cell disease, thalassemia of all types)
14. Hemolysis
15. Active malignant disease i.e. disease free survival for less than 5 years, except non-melanoma skin cancer. Basal cell carcinoma of the skin under curative treatment is not considered as active malignant disease.
16. Chronic, uncontrolled or symptomatic inflammatory disease (e.g. rheumatoid arthritis, systemic lupus erythematodes)
17. Acute infection or sepsis
18. CRP > 15 mg/L
19. Apparent vitamin B12 deficiency despite adequate treatment
20. Apparent folic acid deficiency despite adequate treatment
21. Pure red cell aplasia or a history of PRCA
22. Platelets > 500 x 109/L or < 100 x 109/L
23. Antidiabetic treatment with glitazones
24. Planned elective surgery (except laser photocoagulation, cataract and vascular access surgery)
25. Apparent life expectancy less than 24 months
26. Treatment with an ESA within the last 6 months prior to inclusion
27. Patients who received an additional organ transplant, other than kidney
28. Transplanted patients with previous (last 6 months) or active mTOR (Sirolimus, Everolimus) based immunosuppressive regimen
29. Present and known Hepatitis B - infection
30. Patients suffering from recurrence of original renal disease (e.g. IgA-nephropathy, FSGS)
31. Patients with relevant stenosis of the renal artery
32. Administration of any investigational drug within 30 days (or five times the half life of this investigational drug, independent of verum or placebo treatment) preceding the study start. Investigational drug is defined as any material (placebo or drug) dispensed under the provision of a study protocol
33. Patients who have received any investigational drug under the provision of this protocol
34. Patients currently in treatment or interventional follow up of another clinical trial
35. Women lactating, pregnant or of childbearing potential not using a highly effective contraceptive method (allowed methods of birth control, i.e. with a failure rate of less than 1 % per year, are implants, injectables, combined oral contraceptives, IUDs (only hormone spirals), sexual abstinence or vasectomized partner)
36. Positive pregnancy test (serum, β-HCG) at screening/visit 0
37. Known hypersensitivity to epoetin beta or any constituents of the Mircera® formulation
38. Patients who are underage or patients who are incapable of understanding the aim, importance and consequences of the study and to give legal informed consent (according to § 40 Abs. 4 and § 41 Abs. 2 und Abs. 3 AMG)
39. Patients with a history of a psychological illness or condition such as to interfere with the patient’s ability to understand the requirements of the study
40. Patients who may be dependent on the sponsor or investigator
41. Patients who suffer from myelofibrosis
42. Diagnosed hematological disease other than CKD stage III |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Change in eGFR over time (MDRD equation, 4 variables) |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
| E.5.2 | Secondary end point(s) |
Change of UACR
Change in serum creatinine
Change in serum cystatin C
Adverse events
Drop out due to increase in Hb
Drop out due to increase in blood pressure
Appearance of anti erythropoietin antibodies
Acute rejection
|
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
| 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 | No |
| 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) | 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 | Yes |
| E.8.1.4 | Double blind | No |
| 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 | 2 |
| 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 | 30 |
| 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 | No |
| 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
|
The end of the study is defined as the date of the last visit of the last patient.
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 4 |
| E.8.9.1 | In the Member State concerned months | 8 |
| E.8.9.1 | In the Member State concerned days | 0 |
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