| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| treatment of anaemia in chronic renal failure patients not yet receiving dialysis |
|
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 8.0 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10054353 |
|
| 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 demonstrate efficacy of XM01 with respect to dose-dependent average increase of haemoglobin per week within the fixed dose phase. XM01 will be regarded as effective if there is a statistically significant difference in the increase of haemoglobin levels after treatment with 20 compared to 120 IU/kg XM01 three times weekly (tiw). |
|
| E.2.2 | Secondary objectives of the trial |
To demonstrate efficacy of XM01 with respect to the endpoints:
· No. of patients reaching haemoglobin (HB) response (i.e. HB >11.0 g/dL on two consecutive measurements in the adaptation phase w/o blood transfusions within preceding 3 mths)
· Time to achieve HB response
· Dose-response relationship of XM01 in the fixed dose phase
· Doses of XM01 or Epoetin beta at time of HB response
· Number of patients with blood transfusions and blood units per patient
· Measured HB, haematocrit and reticulocyte counts and their changes from baseline
To demonstrate safety and tolerability of XM01 with respect to:
· Adverse events (AEs), discontinuation due to AEs
· Tolerability (patient’s and investigator’s assessment)
· Vital signs (blood pressure, heart rate)
· Lab tests (clinical chemistry, haematology)
· Physical examination, body weight
· 12-lead ECG
· Changes in renal function characteristics
· Immunogenicity (antibody development to XM01 or Epoetin beta) |
|
| E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
| E.3 | Principal inclusion criteria |
Patients of any ethnic origin meeting all criteria listed below will be included in the study:
1. Above 21 years of age (inclusive).
2. Male or female sex.
3. Patients with chronic renal failure not yet receiving dialysis and having a glomerular filtration rate (GFR) < 60 mL/min/1.73 m3 within the last 3 months (estimated by Cockroft-Gault formula)
4. Patients who have not been treated with epoetin within the last 12 weeks or with epoetins with a longer half-life time (e.g. Darbepoetin alfa, continuous erythropoiesis receptor activator [CERA]) within the last 6 months.
5. Stable haemoglobin (at least three measurements within the last 8 weeks prior to randomisation, the difference between the highest and lowest value should be less than 2 g/dL).
6. Haemoglobin ≤ 10.0 g/dL (mean value of three measurements within the last 8 weeks, separated from each other by at least one week).
7. Serum ferritin >100 mg/L and transferrin saturation (TSAT) >20% (within the last 4 weeks prior to randomisation).
8. Patients who are able to understand and follow instructions and who are able to participate in the study for the entire period.
9. Written informed consent to participate in the study after receiving adequate previous information. |
|
| E.4 | Principal exclusion criteria |
Patients presenting with any of the following will not be included in the study:
1. Female patients of childbearing potential.
2. Patients requiring red blood cell transfusions.
3. Red blood cell transfusion within the last 8 weeks.
4. Uncontrolled severe hypertension defined as systolic blood pressure >180 mmHg and/or diastolic blood pressure >110 mmHg
5. History of myocardial infarction, cerebrovascular accident, percutaneous transluminal coronary angioplasty, or coronary artery bypass graft within 6 months prior to enrolment.
6. Congestive heart failure (New York Heart Association [NYHA] class 3 or 4).
7. Uncontrolled diabetes mellitus defined as HbA1c >8.0%.
8. Patients with known liver disease, or
elevated serum transaminase (aspartate aminotransferase [AST] or alanine aminotransferase [ALT]) greater than twice the upper limit of normal (ULN).
(Comment: Hepatitis B-virus surface antigen (HBsAg) carrier status or positive antibodies to hepatitis C virus (HCV) per se is not defined as an exclusion criterion if transaminases are within the normal range).
9. Severe metabolic acidosis (bicarbonate <18 mEq/L [<18 mmol/L]).
10. Tertiary or poorly controlled secondary hyperparathyroidism defined as intact parathyroid hormone (PTH) ≥ 10 times the ULN.
11. Severe endogenous depression or schizophrenia.
12. Current malignant disease.
13. Known bone marrow disease.
14. Current systemic infection or inflammatory disease.
15. Any cause for anaemia other than chronic renal failure.
16. Deficiency of vitamin B12 and/or folic acid (i.e. below lower limit of reference range)
17. Known to test positive for human immunodeficiency virus antibodies.
18. Concomitant therapy with immunosuppressive drugs or androgens or steroids (oral or intravenous).
19. Therapy with androgens within the last 3 months.
20. Patients with known hypersensitivity (drug intolerance or allergy) to Epoetin or excipients of the formulation.
21. Known presence of antibodies to Epoetin.
22. Known or suspected drug abuse or alcohol abuse.
23. Participation in a study with investigational drugs within 30 days prior to enrolment.
24. Planned travel activities outside the participating countries during the study.
Patients may be enrolled into this study more than once only in case the inclusion criteria Nos. 5, 6 or 7 are not fulfilled or the exclusion criterion No. 16 is fulfilled during the screening period. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
The primary endpoint is „dose-dependent average increase of haemoglobin per week within the fixed dose phase”. The average weekly increase will be calculated for each patient by the mean increment of haemoglobin per week within the fixed dose phase (Week 1 - Week 4).
All comparisons with Epoetin beta are of exploratory nature, only. |
|
| 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 | Information not present in EudraCT |
| 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 | 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 | Yes |
| E.8.1.7.1 | Other trial design description |
| Third party drug administration to achieve double blind conditions. |
|
| 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.8.3 |
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.8.5 | The trial involves multiple Member States | Yes |
| 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 | Information not present in EudraCT |
| 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 |
|
| 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
|
| last visit of last patient |
|
| 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 | 5 |
| E.8.9.1 | In the Member State concerned days | |
| 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 | 5 |
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