E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Treatment of Anemia in Hemodialysis Patients Previously Treated With Epoetin |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 8.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10002272 |
E.1.2 | Term | Anemia |
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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 determine the dose ranges of AF37702 Injection, administered intravenously (IV) or subcutaneously (SC) using every-4-week (Q4W) or every-2-week (Q2W) dosing schedules that maintain hemoglobin (Hgb) within 1.0 g/dL below baseline to 1.5 g/dL above baseline, inclusive, in hemodialysis patients whose Hgb values were stable on Epoetin |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives of the study are to: • Evaluate and compare the safety of AF37702 Injection administered by IV or SC injection using every-4-week (Q4W) or every-2-week (Q2W) dosing schedules; • Evaluate and compare the pharmacodynamics (PD) of AF37702 Injection administered by IV or SC injection using a Q4W or Q2W dosing schedule; • Evaluate and compare the pharmacokinetic (PK) profile of AF37702 Injection administered by IV or SC injection using a Q4W or Q2W dosing schedule in a subset of hemodialysis patients (i.e. evaluate PK parameters such as: Cmax, AUC0-t, AUC0-∞, t½ß, Vd, Vss, and CL). |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
a. Patient is informed of the investigational nature of this study and has given written, witnessed informed consent in accordance with institutional, local, and national guidelines b. Males or females ≥ 18 years of age. Pre-menopausal females (with the exception of those who are surgically sterile) must have a negative pregnancy test at screening; those who are sexually active must practice a highly effective method of birth control for at least 4 weeks prior to study start, and must be willing to continue contraception until at least 4 weeks after the last dose of study drug c. Clinically stable on hemodialysis for ≥ 3 months prior to study start d. Epoetin (alfa or beta) maintenance therapy, ≥ 50 and ≤ 200 U/kg/wk, at the same dosing frequency, continuously prescribed for 8 weeks prior to study start e. Three mid- or end-of-week Hgb values of ≥ 10.0 and ≤ 12.5 g/dL in the 4 weeks prior to study start, with ≤ 1.2 g/dL difference between any of the three values f. One TSAT > 20% within 4 weeks prior to study start g. One ferritin level ≥ 100 ng/mL within 4 weeks prior to study start h. One serum or red cell folate level ≥ lower limit of normal during the 4 weeks prior to study start i. One vitamin B12 level ≥ lower limit of normal during the 4 weeks prior to study start j. One C-reactive protein (CRP) level ≤ 30 mg/L within 4 weeks prior to study start k. Urea clearance/volume (Kt/V) ≥ 1.2 within 4 weeks prior to study start l. One white blood cell count (WBC) ≥ 3.0 x 109/L within 4 weeks prior to study start m. One platelet count ≥ 100 x 109/L and ≤ 500 x 109/L within 4 weeks prior to study start |
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E.4 | Principal exclusion criteria |
a. Pregnant or breast-feeding patients b. Known intolerance to any erythropoiesis stimulating agent, parenteral iron supplementation or PEGylated molecules c. History of antibodies to any erythropoiesis stimulating agent or history of pure red cell aplasia (PRCA) d. Known bleeding or coagulation disorder e. Known hematologic disease (e.g., homozygous sickle-cell disease, thalassemia of all types, multiple myeloma, hemolytic anemia) f. Uncontrolled or symptomatic inflammatory disease (e.g., rheumatoid arthritis, systemic lupus erythematosus, etc.) g. Known history of seizure disorder or received anti-epileptic medication within the previous 6 months h. Uncontrolled or symptomatic secondary hyperparathyroidism, per Investigator’s clinical judgment i. Poorly controlled hypertension within 4 weeks prior to study start, per Investigator’s clinical judgment j. Chronic congestive heart failure of New York Heart Association class III or IV k. High likelihood of early withdrawal or interruption of the study (e.g., myocardial infarction, severe or unstable coronary artery disease, stroke, respiratory, autoimmune, neuropsychiatric, or neurological abnormalities, liver disease including active hepatitis B or C, active HIV disease, or any other clinically significant medical diseases or conditions in the prior 6 months that may, in the Investigator’s opinion, interfere with safety, assessment, or follow-up of the patient) l. Evidence of malignancy within the past 5 years (except non-melanoma skin cancer which is not an exclusion criterion) m. Life expectancy < 12 months n. Temporary (untunneled) dialysis access catheter o. Anticipated elective surgery during the study period, that may be expected to lead to significant blood loss, including vascular access surgery such as an arteriovenous fistula or graft, or a scheduled kidney transplant p. RBC or whole blood transfusion within 12 weeks prior to study start q. Received antibiotics for systemic infection within 2 weeks prior to study start r. Previous exposure to any investigational agent within 6 weeks prior to study start, or planned receipt of an investigational agent, other than as specified by this protocol, during the study period |
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E.5 End points |
E.5.1 | Primary end point(s) |
• Hgb change from baseline to the average during weeks 21-28; • Average weekly Hgb (absolute value and change from baseline) throughout the trial; • Proportion of patients with Hgb within 1.0 g/dL below baseline to 1.5 g/dL above baseline, inclusive, during weeks 21-28 ; • Proportion of patients who maintain Hgb within the baseline range of 10.0 to 12.5 g/dL during Weeks 21-28; • Proportion of patients who maintain Hgb within 0.5 g/dL of the baseline Hgb range (i.e. 9.5 to 13.0 g/dL) during Weeks 21-28; • Frequency of red blood cell (RBC) or whole blood transfusions throughout the trial; • Number (%) of patients requiring dose adjustments throughout the trial; • Average dose of study drug (per 4-week period); • Adverse events (AEs) and serious adverse events (SAEs); • Additional pharmacologic parameters including RBCs, hematocrit, reticulocyte count (absolute and AUC), and measures of iron status [e.g., ferritin and transferrin saturation (TSAT)]; • Pharmacokinetic parameters including Cmax, AUC0-t, AUC0-∞, t½ß, Vd, Vss, and CL (in a subset of study patients).
Results of the PK and pharmacodynamic analyses will be used to confirm the starting conversion level that best predicts the monthly dose of AF37702 Injection (administered Q4W or Q2W) to maintain Hgb stable based on the weekly dose of Epoetin. |
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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 | Yes |
E.6.7 | Pharmacodynamic | Yes |
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) | 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 | 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 | Yes |
E.8.1.7.1 | Other trial design description |
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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 | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 5 |
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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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 | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
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 | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |