A Phase III, Randomized, Comparative, Open-label Study of Intravenous Iron Isomaltoside 1000 (Monofer®) administered by Infusions or Repeated Bolus Injections in Comparison with Oral Iron Sulphate in Subjects with Non-Dialysis Dependent Chronic Kidney Disease and with Renal-Related Anaemia.
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 350
- 试验地点
- 17
- 主要终点
- Intravenous iron isomaltoside 1000 (Monofer®) is non-inferior to oral iron sulphate in reducing renal related anemia in subjects with non-dialysis dependent chronic kidney disease (NDD-CKD), determined as ability to increase Hb.
研究概览
简要总结
Study Design:
Prospective, Open-label, Randomized, Comparative, Multi-centre Study with Two Treatment Groups:
A. Iron isomaltoside 1000 (Monofer®)
- Administered as intravenous infusions (A1)
· Maximum 1000 mg iron each week until full replacement dose is achieved (if the subject weight is between 35.1-45 kg maximum 750 mg iron/infusion or if the subject weight is between 30-35 kg maximum 500 mg iron/infusion).
· The infusion is diluted in 100 mL 0.9% sodium chloride and given over approximately 15 minutes.
- Administered as intravenous bolus injections (A2)
· The full iron replacement dose of iron isomaltoside 1000 (Monofer®) listed in the dosing table is administered as bolus injections of 500 mg administered undiluted over approximately 2 minutes, once per week until full replacement dose is achieved.
· In some cases the remaining dose on the last dosing day may be 250 mg e.g., on visit 4 if the full replacement dose is 1250mg,
· In these situations remaining 250 mg should be administered undiluted over approximately 2 minutes
-Iron sulphate administered orally (B)
· 100 mg elementary iron b.i.d. (200 mg daily) for 8 weeks.
Prohibited concomitant medication and therapy:
-
Blood transfusion.
-
Any iron supplementation other than investigational drugs.
-
Erythropoeisis-Stimulating Agents (ESA).
-
Medications which potentially yield a decrease in oral iron absorption, e.g. tetracycline, antacids, cholestyramine etc.
研究设计
- 研究类型
- Interventional
入排标准
- 年龄范围
- 18.00 Year(s) 至 65.00 Year(s)（—）
- 性别
- All
入选标准
- •Men and women, aged more than 18 years.
- •Subjects diagnosed with NDD-CKD with MDRD calculated eGFR between 15-59 mL/min.
- •Hb 11.0 g/dL (6.80 mmol/L)
- •Either or both of the following iron stores indicators below target {Serum ferritin < 200 ug/l and Transferrin saturation (TfS)<20%}.
- •Life expectancy beyond 12 months by Principal Investigator?s judgement.
- •Willingness to participate after informed consent and any authorization as required by local law ( e.g. Protected Health Information [PHI] for North America).
排除标准
- •Anaemia predominantly caused by factors other than renal impairment or iron deficiency (according to Principal Investigator s?
- •Iron overload or disturbances in utilisation of iron (e.g. haemochromatosis and haemosiderosis).
- •Drug hypersensitivity (i.e. previous hypersensitivity to Iron Dextran or iron mono- or disaccharide complexes or to iron sulphate or any excipients of the study drug.
- •Subjects with history of multiple allergies.
- •Decompensated liver cirrhosis and hepatitis (alanine aminotransferase (ALT) > 3 times upper normal limit)
- •Diagnosis of Hepatitis B and/or C confirmed by appropriate lab test.
- •Active acute or chronic infections ((assessed by clinical judgment), supplied with white blood cells (WBC) and C-reactive protein (CRP)).
- •Rheumatoid arthritis with symptoms or signs of active joint inflammation.
- •Pregnancy and nursing (To avoid pregnancy, women have to be postmenopausal (at least 12 months must have elapsed since last menstruation), surgically sterile, or women of child bearing potential must use one of the following contraceptives during the whole study period and after the study has ended for at least 5 times plasma biological half-life of the investigational medicinal product (5 days): Contraceptive pills, Intrauterine Devices (IUD), contraceptive depot injections (prolonged-release gestagen), subdermal implantation, vaginal ring, and transdermal patches).
- •Extensive active bleeding necessitating blood transfusion.
- •Planned elective surgery during the study.
- •Participation in any other clinical study within 3 months prior to screening.
- •Known intolerance to oral iron treatment.
- •Untreated B12 or folate deficiency.
- •I.V. or oral iron treatment or blood transfusion within 4 weeks prior to screening visit.
- •ESA treatment within 8 weeks prior to screening visit.
- •Serum ferritin > 500 μg/L.
- •Any other medical condition that, in the opinion of Principal Investigator, may cause the subject to be unsuitable for the completion of the study or place the subject at potential risk from being in the study or interfere with study drug evaluation.
- •Example, Uncontrolled Hypertension, Unstable Ischemic Heart Disease or Uncontrolled Diabetes Mellitus.
- •History of immunodeficiency, including positive HIV test result.
- •Body weight < 30 kilograms.
结局指标
主要结局
Intravenous iron isomaltoside 1000 (Monofer®) is non-inferior to oral iron sulphate in reducing renal related anemia in subjects with non-dialysis dependent chronic kidney disease (NDD-CKD), determined as ability to increase Hb.
时间窗: Wk 1, 2, 3, 4, and 8
次要结局
- 1. To assess other relevant haematology and biochemical parameters during the study.(2. Quality of Life assessment (QoL) by Linear Analog Scale Assessment (LASA).)