| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| anaemic chronic renal failure patients not yet receiving dialysis |
|
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 9 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10009119 |
|
| 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 the non-inferiority of XM01 compared to Epoetin beta in terms of efficacy, based on the change of haemoglobin from baseline (mean of Visits 1, 2 and 3) to end of treatment (mean of Weeks 15-26, efficacy evaluation period). |
|
| E.2.2 | Secondary objectives of the trial |
• To compare the efficacy of XM01 versus Epoetin beta during the efficacy evaluation period (Weeks 15-26) based on the secondary efficacy endpoints (for detailed parameters see protocol page 23)
• To compare safety and tolerability of XM01 and Epoetin beta in chronic renal failure patients on maintenance treatment with Epoetin beta.
• To compare the immunogenicity of XM01 and Epoetin beta at the randomisation, at the beginning of efficacy evaluation period and at the end of the study. |
|
| 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. Patients being treated for known renal anaemia, on maintenance treatment with Epoetin beta.
2. Aged ≥18 years.
3. Male or female.
4. Patients with chronic renal failure not yet receiving dialysis and having a glomerular filtration rate (GFR) < 60 mL/min/1.73 m2 within the last three months (estimated by Cockroft-Gault formula).
5. Patients should be on maintenance treatment with once, two or three times weekly s.c. administration of Epoetin beta for at least 3 months prior to enrolment.
6. Patients should be on stable therapy with Epoetin which refers to a stable haemoglobin level defined as: at least four measurements within the last eight weeks with the difference between the highest and lowest value of less than 2 g/dL. There should be at least 1 week between each of the four haemoglobin measurements.
7. Haemoglobin concentration ≥ 9.5 g/dL and <12.0 g/dL within the last eight weeks (mean value of four measurements, separated from each other by at least a week).
8. Serum ferritin >100 µg/L or TSAT >20% (within the last four weeks prior to enrolment).
9. Able to understand and follow instructions and able to participate in the study for the entire period.
10. Signed and dated written informed consent. |
|
| E.4 | Principal exclusion criteria |
Patients presenting at Visit 1 with any of the following will not be included in the study:
1. Female patients of childbearing potential.
2. Patients with active bleeding.
3. Red blood cell transfusion within the last three months.
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 the six months prior to enrolment.
6. Congestive heart failure (New York Heart Association [NYHA]13 class III or IV).
7. 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).
8. Severe metabolic acidosis (bicarbonate <18 mEq/L [18 mmol/L]).
9. Tertiary or poorly controlled secondary hyperparathyroidism defined as intact parathyroid hormone (PTH) ≥ 10 times the ULN.
10. Severe endogenous depression or schizophrenia.
11. Current malignant disease.
12. Current systemic infection or inflammatory disease.
13. Known positive test for human immunodeficiency virus (HIV) antibodies.
14. Concomitant therapy with immunosuppressive drugs, steroids (oral or intravenous) or androgens.
15. Therapy with androgens within the last 3 months prior to enrolment.
16. Patients with resistance to Epoetin (more than 300 IU/kg/week).
17. Patients who have been treated with Epoetins with a longer half life time (e.g. novel erythropoiesis stimulating protein [NESP], continuous erythropoietin receptor activator [CERA]) within the last 6 months.
18. Known hypersensitivity (drug intolerance or allergy) to Epoetin or excipients of the formulation.
19. Known presence of antibodies to Epoetin.
20. Known or suspected drug abuse or alcohol abuse.
21. Participation in a study with investigational drugs within 30 days prior to enrolment.
22. Planned travel activities outside the participating countries during the study.
Under no circumstances may patients be enrolled into this study more than once. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
The primary endpoint is the change of haemoglobin level from baseline (mean of Visits 1, 2, and 3) to end of treatment (mean of Weeks 15-26, efficacy evaluation period).
Haemoglobin will be measured weekly throughout the study. The baseline haemoglobin value will be the mean value of Visit 1, 2, and 3 measurements. The end of treatment value will be the mean of 12 weeks (Weeks 15-26) haemoglobin measurements.
On days when the administration of study medication coincides with scheduled haematological analysis, blood samples must be taken before the administration of study medication.
All blood samples taken for haematological analysis will be assayed for haemoglobin as part of the efficacy assessments. Other haematological variables such as platelet count, white blood cell (WBC) count, etc. will also be assessed but are considered as part of the safety laboratory assessments. |
|
| 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 | Information not present in EudraCT |
| E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
| E.7.1.3 | Other | Information not present in EudraCT |
| 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 | 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
|
| The whole study will be completed when the 30 day observation period for adverse events has been finished for the last patient in the last country. |
|
| 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 | 4 |
| 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 | 4 |
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