| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated | | Anaemia in Chronic Kidney Disease (CKD) | |
| MedDRA Classification |
| 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 | Demonstrate non-inferiority of efficacy between twice weekly (BIW) and once weekly QW dose schedules of Dynepo in previously EPO-naïve patients (pts), as measured by Hb at Week 24.
Demonstrate non-inferiority of efficacy between QW and once every two weeks Q2W dose schedules of Dynepo in patients previously stable on EPO, as measured by Hb over Weeks (Wks) 16 to 24.
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| E.2.2 | Secondary objectives of the trial | Demonstrate non-inferiority of efficacy between QW & Q2W dose schedules in pts previously stable on EPO, measured by average doser ever Wks 16-24. Compare efficacy between BIW and QW in EPO-naïve pts, and between QW & Q2W in pts stable on EPO measured by: a)no.(%) of pts who achieve Hb of >=11g/dL at Wks 16, 24 & over Wks 16-24, b) Hct at Wks 16, 24 & over Wks 16-24, c)no.(%) of pts who achieve the Hct target range of 33%-36% at Wks 16 & 24 & over Wks 16-24, d) the no. (%) of pts who achieve both Hb of >=11g/dL & the Hct target range of 33%-36% at Wks 16 & 24 and over Wks 16-24. Compare average dose, over Wks 9-16, 16-24 & 9-24 between dose schedules.Compare efficacy between BIW & QW in EPO-naïve pts, & QW & Q2W measured by Hb at Wk 16 & over Wks 16-24, Hb at Wks 16 & 24 respectively.Investigate the safety of BIW & QW in EPO-naïve pts & safety of QW & Q2W in pts stable on EPO.
Investigate efficacy and safety switching administration frequencies & efficacy and safety in pts with DM. | |
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria | To be eligible for inclusion, each patient must meet all of the following criteria at Screening, and must continue to fulfil these criteria at Baseline:
Aged at least 18 years.
Male, or non-pregnant, non-lactating female patients who agree to comply with the contraceptive requirements of the protocol.
Patients with CKD (KDOQI stages III–V).
Stable on any dose less than or equal to 10,000IU/week of sc EPO or requiring initiation of EPO treatment.
Those currently receiving EPO treatment must have been receiving a stable dose, that was effective in managing Hb levels, for at least 30 days immediately prior to randomisation in the study.
Those requiring initiation of EPO treatment must have Hb levels of greater than or equal to 8g/dL and <11g/dL.
Transferrin saturation greater than or equal to 20% and ferritin greater than or equal to 100ng/mL.
The patient must understand and be able and willing and likely to fully comply with study procedures and restrictions. The patient must be deemed likely to be available for all scheduled study visits.
Written, signed and dated informed consent to participate in the study must be given by the patient or a legally acceptable representative, in accordance with the ICH GCP Guideline E6 and applicable regulations, before completing any study-related procedures.
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| E.4 | Principal exclusion criteria | Patients are excluded from the study if any of the following criteria are met at Screening or at Baseline:
Uncontrolled hypertension (defined as a diastolic pressure value >95mmHg, or a systolic value >160mmHg, which remains at that level despite being at dry weight and on more than two medications at maximal dose).
Thrombocytopenia (platelet count <75,000/mm3).
Active bleeding disorder (diathesis) (for example, Gastro-intestinal or Genito-urinary tract bleeding).
Known Human Immunodeficiency Virus (HIV) infection.
Impaired hepatic function (Aspartate Transaminase [AST], Alanine Transaminase [ALT] >3x Upper Limit of Normal [ULN]).
Current or recurrent disease that could affect the action, absorption or disposition of the investigational product, or clinical or laboratory assessments.
Clinically relevant haematologic, oncologic, cardiovascular, hepatic, neurologic, endocrine, infectious, inflammatory or other major systemic disease making implementation of the protocol or interpretation of the results difficult.
Mental condition rendering the patient unable to understand the nature, scope or possible consequences of the study.
Patient unlikely to comply with the protocol.
Current or relevant previous history of serious, severe or unstable (acute or progressive) physical or psychiatric illness, any medical disorder that may require treatment or make the patient unlikely to fully complete the study, or any condition that presents undue risk from the investigational product or procedures.
Requiring doses of EPO >10,000IU/week.
Two or more doses of prescribed EPO treatment missed or withheld by physician order in the 14 days immediately prior to randomisation in the study.
Treatment with immunosuppressive drugs (other than corticosteroids for a chronic condition) in the 30 days immediately prior to randomisation in the study.
Androgen therapy in the 30 days immediately prior to randomisation in the study.
Known or suspected intolerance or hypersensitivity to EPO therapy or any of the stated ingredients of Dynepo.
Known to have Ab against EPO.
Patients with a history of alcohol or other substance abuse within the last year.
Treatment with any investigational drug in the 30 days immediately prior to randomisation in the study.
Patients that have previously been randomised into this study. | |
| E.5 End points |
| E.5.1 | Primary end point(s) | Mean Hb concentration calculated at Week 24 and over Weeks 16 to 24.
Secondary Endpoints
Patients' average weekly dose/kg over weeks 9 to 16, 16 to 24 and 9 to 24.
Number (%) of patients who achieve Hb of equal to or more than 11g/dL at Weeks 16 and 24 and over Weeks 16 to 24.
Mean Hct concentration calculated at Weeks 16 and 24 and over Weeks 16 to 24.
Number (%) of patients who achieve the Hct target range of 33%-36% at Weeks 16 and 24 and over Weeks 16 to 24.
Patients’ average weekly dose/kg over Weeks 9 to 16, 16 to 24 and 9 to 24.
Mean Hb concentration calculated at Week 16.
Number (%) of patients who achieve both Hb of equal to or more than 11g/dL and the Hct target range of 33%-36% at Weeks 16 and 24 and over Weeks 16 to 24.
Number (%) of patients with a positive Ab response to Dynepo.
Number (%) of patients shown to have neutralising Ab.
Blood pressure changes from Baseline.
Changes in Left Ventricular Ejection Fraction (LVEF) from the Screening visit.
Renal function using estimated Glomerular Filtration Rate (eGFR).
Retinopathy in diabetic patients.
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| 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 | Yes |
| 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) | 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 | Yes |
| E.8.1.3 | Single blind | No |
| 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 | No |
| E.8.2.3 | Other | Yes |
| E.8.2.3.1 | Comparator description | |
| 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 | 9 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 68 |
| 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 | 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 | |
| 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 |
