Randomized, Double-blind, Multicenter, Parallel-group, Equivalence Study to Evaluate the Efficacy and Safety of HX575 Hexal AG vs ERYPO® for the Treatment of Anemia in Hemodialysis Patients
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- Sandoz
- 入组人数
- 478
- 试验地点
- 27
- 主要终点
- To Compare the Efficacy of HX575 Hexal AG and ERYPO® Janssen-Cilag.
研究概览
简要总结
This is a double-blind, randomized, multicenter, parallel-group, equivalence study involving about 462 clinically stable hemodialysis patients aged 18 years or above suffering from anemia and treated previously with a stable dose of ERYPO® intravenously.
详细描述
The primary objective of this Phase III study is the evaluation of therapeutic equivalence of HX575 Hexal AG and a comparator of epoetin alfa, ERYPO® in the maintenance intravenous treatment of renal anemia. Efficacy, dosage and safety of HX575 Hexal AG in the long-term treatment were assessed.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Receiving dialysis for at least 6 months (3 times weekly) before screening
- •Age: >=18
- •Clinically stable, i.e. hemoglobin within the established range (10.0 to 13.0 g/dl) for at least 12 weeks before screening
- •Stable intravenous dosage of ERYPO® three times weekly for at least 8 weeks before screening and during screening with a maximal weekly dosage of 300 IU/kg body weight (stable is defined as <25% change (up or down) in weekly dose and no change in frequency over 8 weeks prior screening and 10 weeks prior randomisation)
- •Baseline hemoglobin concentration of 10.0 to 13.0 g/dl (mean of two pre-randomization pre-dialysis samples of Hb at visit -2 and visit 1)
- •Serum ferritin >=100 µg/l and/or saturated transferrin levels >=20%
- •C-reactive protein <15 mg/l (< 5 mg/l: normal; >= 5 mg/l < 10 mg/l: +; >=10mg/l < 100 mg/l: ++; >=100 mg/l: +++)
- •Ability to follow study instructions and likely to complete all required visits
- •Written informed consent of the patient
排除标准
- •Anemia of non-renal causes
- •Primary hematologic disorder (e.g. myelodysplastic syndrome, sickle cell anemia, hematological malignancy, hemolytic anemia)
- •Evidence of severe hepatic dysfunction (ALT and/or AST above 2 x upper limit of normal range; or gamma-GT above 3 x upper limit of normal range)
- •Clinical evidence of current uncontrolled hyperparathyroidism (serum parathyroid hormone >1500 pg/mL).
- •Known history of bone marrow disease
- •Any red blood cell transfusion(s) during the last 12 weeks before screening or during the screening/baseline period
- •Insufficient concomitant iron treatment during the last 2 months before Visit -2
- •Uncontrolled hypertension, defined as a predialysis diastolic blood pressure measurement >=110 mmHg during the screening period
- •Congestive heart failure [New York Heart Association (NYHA) class III and IV]
- •Unstable angina pectoris, active cardiac disease, cardiac infarction during the last six months before screening
- •History of blood coagulation disease
- •Thrombocytopenia (platelet count <100.000/µl)
- •Leukopenia (white blood cell count < 2.000/µl)
- •Overt bleeding (acute or chronic bleeding within 2 months of inclusion) or hemolysis
- •Evidence of acute infectious disease or serious active inflammatory states within one months before screening (Visit -2) or during the screening/baseline period
- •Suspicion or known PRCA (pure red cell aplasia)
- •Previously diagnosed HIV or acute hepatitis infection
- •Treatment for epilepsy within the past 6 months
- •Planned surgery during the next 7 months (except vascular access surgery)
- •Any androgen therapy within 2 months before visit -2 and during the study
- •Therapy with immunosuppressants or any drug known to affect the hematocrit within 1 month before Visit -2 and during the study
- •Clinical evidence of malignant diseases
- •Pregnancy, breastfeeding women or women not using adequate birth control measures
- •Known history of severe drug related allergies
- •Known allergy to one of the ingredients of the test or reference products or hypersensitivity to mammalian-derived products
- •Simultaneous participation in another clinical study or participation in a study in the month preceding the start of this study or previously randomized in this study
- •Participation in an erythropoietin study in the 3 months preceding screening (visit -2)
- •Any other condition which at the investigator´s discretion may put the patient at risk or which may confound the study results
研究组 & 干预措施
HX575 epoetin alfa Hexal AG
Eligible patients were switched from the comparator ERYPO®, to epoetin alfa HX575 Hexal AG in ratio 2:1 to be intravenously treated with HX575 in pre-filled syringes for 24 weeks (solution for injection i.v.). The maximum weekly dose was 300 UI/kg body weight (given 1 to 3 times) to maintain hemoglobin levels between 10-13 g/dL.
干预措施: HX575 epoetin alfa Hexal AG (Drug)
ERYPO®, Janssen-Cilag
Eligible patients were randomized and continued to be treated with ERYPO® Janssen-Cilag in pre-filled syringes intravenously (solution for injection i.v.) for 24 weeks. The maximum weekly dose was 300 UI/kg body weight (given 1 to 3 times) to maintain hemoglobin levels between 10-13 g/dL.
干预措施: ERYPO®, Janssen-Cilag (Drug)
结局指标
主要结局
To Compare the Efficacy of HX575 Hexal AG and ERYPO® Janssen-Cilag.
时间窗: 28 weeks
Primary endpoint was the mean absolute change in Hb level between the screening/baseline and the evaluation period. A two-sided 95 % confidence interval for the difference in mean change (mean of evaluation period - mean of screening/baseline period) in Hb between epoetin alfa HX575 Hexal AG and ERYPO® Janssen-Cilag was computed. The difference was estimated from an analysis of a co-variance model including factors treatment, center, mean baseline Hb (\<11.5 and ≥11.5 g/dL) as factors and change of the mean weekly dose from screening/baseline to the evaluation period (of HX575 epoetin alfa Hexal AG or ERYPO® Janssen-Cilag) as a covariate. HX575 Hexal AG was considered at least as good as ERYPO® Janssen-Cilag if the 95 % confidence interval of the difference in mean changes in Hb levels between HX575 Hexal AG and ERYPO® Janssen-Cilag lied entirely within the interval \[-0.5 g/dL; 0.5 g/dL\]. Primary Endpoint was analyzed based on intent-to-treat (ITT) population.
次要结局
- Mean Absolute Change in Hemoglobin Level From the Screening/Baseline Period to the Evaluation Period - ITT Population(28 weeks)