E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Anaemia in Patients with Chronic Renal Failure (CRF) not on Dialysis and not on Erythropoiesis Stimulating Agent (ESA) Treatment |
|
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10058116 |
E.1.2 | Term | Nephrogenic anaemia |
|
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 safety and efficacy of AF37702 Injection in the correction of anemia in patients with CRF not on dialysis and not on ESA treatment • To demonstrate the non-inferiority of AF37702 Injection to darbepoetin alfa in increasing Hgb in patients with CRF not on dialysis and not on ESA treatment
|
|
E.2.2 | Secondary objectives of the trial | |
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Patient has been informed of the investigational nature of this study and has given written informed consent in accordance with institutional, local, and national guidelines. 2. Males or females ≥ 18 years of age. 3. Females of child-bearing potential who are sexually active must be willing to practice a highly effective method of birth control for at least 4 weeks prior to randomization, and must be willing to continue contraception until at least 4 weeks after the last dose of study treatment. 4. Chronic Renal Failure with an estimated glomerular filtration rate < 60 mL/min/1.73m2 using the 4-variable Modification of Diet in Renal Disease (MDRD) formula within 4 weeks prior to randomization, and not expected to begin dialysis for at least 12 weeks. 5. Two consecutive Hgb values ≥ 8.0 g/dL and < 11.0 g/dL within 4 weeks prior to randomization, with ≤ 1.3 g/dL difference between the two values and no less than 5 days apart, with the last value within 10 days prior to randomization. 6. One transferrin saturation (TSAT) ≥ 20% or one ferritin level ≥ 100 ng/mL within 4 weeks prior to randomization. 7. One serum or red cell folate level ≥ lower limit of normal during the 4 weeks prior to randomization. 8. One vitamin B12 level ≥ lower limit of normal during the 4 weeks prior to randomization.
|
|
E.4 | Principal exclusion criteria |
1. Females who are pregnant or breast-feeding. 2. Treatment with an ESA in the 12 weeks prior to randomization. 3. Known intolerance to any ESA, parenteral iron supplementation, or PEGylated molecule. 4. Prior chronic hemodialysis or chronic peritoneal dialysis treatment. (Note: renal transplant patients who are at least 6 months post-transplant and have not had chronic dialysis post-transplant are eligible.) 5. Known bleeding or coagulation disorder. 6. Known hematologic disease or cause of anemia other than renal disease (e.g., pure red cell aplasia (PRCA), homozygous sickle-cell disease, thalassemia, multiple myeloma, hemolytic anemia, myelodysplastic syndrome etc.). 7. Poorly controlled hypertension within 4 weeks prior to randomization, per Investigator’s clinical judgment. 8. Any clinically significant medical disease or condition that, in the Investigator’s opinion, may interfere with protocol adherence or a patient’s ability to give informed consent. 9. Evidence of active malignancy within one year prior to randomization (Note for the purposes of this protocol, active malignancy does not include: non-melanoma skin cancer, carcinoma in situ that has been completely excised, other cancers for which treatment was completed at least one year ago with no continuing treatment and no evidence of metastatis, and other cancers that were diagnosed and treatment completed more than one year ago and within the past year are without evidence of metastasis and treated only with adjuvant hormonal therapy). 10. A scheduled kidney transplant (Note: patients currently on a transplant wait list are not excluded unless there is an identified donor). 11. Scheduled surgery that may be expected to lead to significant blood loss. 12. RBC or whole blood transfusion within 12 weeks prior to randomization. 13. Previous exposure to any investigational agent within 4 weeks prior to randomization, or planned receipt of an investigational agent, other than as specified by this protocol, during the study period. 14. Previous exposure to AF37702 Injection.
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
Primary Efficacy Endpoint Mean change in Hgb between baseline and the Evaluation Period. The baseline Hgb value is defined as the mean of three Hgb values: the two most recent Hgb values taken prior to the day of randomization and the value obtained on the day of randomization. The mean Hgb during the Evaluation Period for each patient will be calculated as the mean of the available Hgb values during Study Weeks 25 through 36.
|
|
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 | 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) | 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) | 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.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 50 |
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 | Yes |
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 patient, last visit is the end of the trial |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 5 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 5 |
E.8.9.2 | In all countries concerned by the trial days | 0 |