E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Subjects with chronic kidney disease (CKD) previously enrolled in other efficacy and/or safety studies with HX575, after these subjects have participated in the earlier study. Pacientes con enfermedad renal crónica previamente incluídos en otros ensayos de eficacia y/o seguridad con HX575, tras su participación en el estudio anterior. |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10009120 |
E.1.2 | Term | Chronic renal failure anaemia |
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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 evaluate the long term safety of HX575 (recombinant human erythropoietin alfa)in subjects receiving stable doses of HX575 s.c. or i.v. The purpose of the current study is twofold: (1) To enlarge the long term safety database by providing safety data on the s.c. and on the i.v. administration of HX575 over an additional treatment period of up to three years (2) To bridge the time gap between the end of previous trials and commercial availability of HX575 in the patient specific country and indication |
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E.2.2 | Secondary objectives of the trial |
• To evaluate the local tolerability of HX575 at the injection site • To evaluate clinically relevant changes in laboratory parameters under therapy with HX575 • To evaluate clinically relevant changes in vital signs, in particular blood pressure under therapy with HX575
Exploratory objectives • To compare the incidence, frequency, extent, and/or severity of endpoints between subject groups receiving HX575 via the i.v. or the s.c. route • To assess the efficacy of HX575 |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Subjects must give written informed consent before any assessment is performed. Consent to participate in one of the three previous studies (see below) is not sufficient. 2. Male and female subjects having participated in one of the following studies: • Post-authorization safety study to prospectively monitor the incidence of relevant drug-related adverse events and EPO-related lack of efficacy among CKD subjects receiving HX575 recombinant human erythropoietin alfa i.v. (Protocol number: 2006-66-INJ-14, EUDRACT number: 2007-005728-34) • Randomized, controlled, double-blind multicenter safety study to evaluate the safety and immunogenicity of subcutaneous EPO HEXAL vs. ERYPO® in the treatment of anemia associated with chronic renal insufficiency in predialysis subjects (Protocol number: 2007-22-INJ-17 (HX02), EUDRACT number: 2007-001906-26) • An open label, single-arm, baseline-controlled, multicenter study to evaluate the efficacy, safety and immunogenicity of subcutaneous HX575 administered once a week (qw) and once every two weeks (q2w) in the treatment of anemia associated with chronic kidney disease in predialysis and dialysis subjects (Protocol number: HX575-304, EUDRACT number: 2008-002696-27) Treatment with any ESA other than the study drug is not permitted between the subject’s end of the previous study and enrollment into HX575-305. Thus the baseline visit of the HX575-305 study must be combined with the final visit of the previous study. 3. Subjects with controlled symptomatic anemia under s.c. or i.v. maintenance therapy with HX575 or a comparator in one of the above studies 4. HX575 is not commercially available for the subject’s specific indication or mode of application in the subject’s country 5. Continued ability to follow study instructions and high probability to appear to study visits 6. Compliant with s.c. self administration in previous study (if applicable) |
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E.4 | Principal exclusion criteria |
1. Subjects no longer requiring ESA therapy 2. History of malignancy of any organ system (other than localized basal cell carcinoma of the skin), treated or untreated, within the past 5 years, regardless of whether there is evidence of local recurrence or metastases. 3. Uncontrolled hypertension, defined as systolic blood pressure of > 160 mmHg and diastolic blood pressure measurement > 100 mmHg (average of two values with at least one day between measurements) 4. Known primary lack of efficacy (LOE), unexplained loss of effect to a recombinant erythropoietin product 5. History of PRCA or aplastic anemia 6. History of anti-erythropoietin antibodies 7. Cannot receive adequate antithrombotic prophylaxis for any reason 8. Pregnant women or nursing mothers 9. Women of childbearing potential who do not agree to maintain effective birth control during the study treatment period 10. Hypersensitivity to the active substance or to any of the excipients 11. Subjects with any form of psychiatric disorder which may invalidate communication 12. Previous participation in this study |
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E.5 End points |
E.5.1 | Primary end point(s) |
• Primary endpoints o Incidence and severity of all AEs and all drug related AEs (i.e. Adverse drug reactions ADRs) • Secondary endpoints o Local tolerability at the injection site o Clinically relevant changes in laboratory parameters |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Information not present in EudraCT |
E.6.2 | Prophylaxis | Information not present in EudraCT |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Information not present in EudraCT |
E.6.7 | Pharmacodynamic | Information not present in EudraCT |
E.6.8 | Bioequivalence | Information not present in EudraCT |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | Information not present in EudraCT |
E.6.12 | Pharmacoeconomic | Information not present in EudraCT |
E.6.13 | Others | Information not present in EudraCT |
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 | No |
E.8.1.1 | Randomised | No |
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 | 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 | 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.8.4.1 | Number of sites anticipated in Member State concerned | 10 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 200 |
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 |
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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
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•The study will end when the drug is commercially available for each subject’s specific indication in the subject’s country. However, study treatment will continue up to a maximum of three years after enrollment or until Competent Authorities have finally declined to grant a Marketing Authorization for HX575 in the specific indication. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 5 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 5 |