NCT02174627已完成3 期
A Phase 3, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Safety and Efficacy of Roxadustat for the Treatment of Anemia in Chronic Kidney Disease Patients Not on Dialysis
适应症
干预措施
相关药物
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- AstraZeneca
- 入组人数
- 2,781
- 试验地点
- 1
- 主要终点
- Mean Change From Baseline in Hb Averaged Over Week 28 to Week 52
研究概览
简要总结
The purpose of the study is to evaluate the safety and efficacy of roxadustat for treatment of anemia in patients with chronic kidney disease not on dialysis
详细描述
This is a Phase 3, multicenter, randomized, double-blind, placebo-controlled study in anemic patients with Stage 3, 4 or 5 chronic kidney disease (CKD) who are not on dialysis.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 130 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Provision of informed consent prior to any study specific procedures.
- •Age ≥18 years at screening visit 1
- •eGFR <60 mL/min/1.73 m2, (calculated by central lab) corresponding to stage 3, 4 or 5CKD according to the Kidney Disease Outcomes Quality Initiative (KDOQI), not receiving dialysis
- •Mean of 2 most recent central laboratory Hb values during the screening period, obtained at least 7 days apart, must be <10.0 g/dL
- •Ferritin ≥50 ng/mL at randomization (obtained from screening visit)
- •TSAT ≥15 % at randomization (obtained from screening visit)
- •Serum folate level ≥ lower limit of normal (LLN) at randomization (obtained from screening visit)
- •Serum vitamin B12 level ≥LLN at randomization (obtained from screening visit)
- •Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤3 x upper limit of normal (ULN) and total bilirubin (Tbili) ≤1.5 x ULN at randomization (obtained from screening visit)
- •Body weight 45 to 160 kg
排除标准
- •Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site)
- •Previous randomization in the present study
- •Any erythropoietin analogue treatment within 6 weeks of randomization
- •New York Heart Association Class III or IV congestive heart failure at enrollment
- •Myocardial infarction (MI), acute coronary syndrome, stroke, seizure or a thrombotic/thromboembolic event (e.g., deep vein thrombosis or pulmonary embolism) within 12 weeks prior to randomization
- •History of chronic liver disease (e.g., chronic infectious hepatitis, chronic auto- immune liver disease, cirrhosis or fibrosis of the liver)
- •Known hereditary hematologic disease such as thalassemia, sickle cell anemia, a history of pure red cell aplasia or other known causes for anemia other than CKD
- •Known and untreated retinal vein occlusion or known and untreated proliferative diabetic retinopathy (risk for retinal vein thrombosis)
- •Diagnosis or suspicion (e.g. complex kidney cyst of Bosniak Category IIF, III or IV) of renal cell carcinoma on renal ultrasound (or other imaging procedure e.g. CT scan or MRI) conducted at screening or within 12 weeks prior to randomization
- •Systolic BP ≥160 mmHg or diastolic BP ≥95 mmHg (confirmed by repeated measurement), within 2 weeks prior to randomization. Patients may be rescreened once BP controlled
- •History of prostate cancer, breast cancer or any other malignancy, except the following: cancers determined to be cured or in remission for ≥5 years, curatively resected basal cell or squamous cell skin cancers, cervical cancer in situ, or resected colonic polyps
- •Positive for any of the following: human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg) or anti-hepatitis C virus antibody (anti-HCV Ab)
- •Chronic inflammatory diseases such as rheumatoid arthritis, systemic lupus erythematosus (SLE), ankylosing spondylitis, psoriatic arthritis or inflammatory bowel disease that is determined to be the principal cause of anemia
- •Known hemosiderosis, hemochromatosis or hypercoagulable condition
- •Any prior organ transplant or a scheduled organ transplantation date
- •Any red blood cell transfusion (RBC) during the screening period
- •Any current condition leading to active significant blood loss
- •Any treatment with roxadustat or a hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI)
- •Has received another new chemical entity (defined as a compound which has not been approved for marketing) or has participated in any other clinical study that included drug treatment within at least 1 month of the first administration of IP in this study. (Note: patients consented and screened, but not randomized in this study or a previous study are not excluded)
- •History of alcohol or drug abuse within 2 years prior to randomization
- •Females of childbearing potential, unless using contraception as detailed in the protocol or sexual abstinence
- •Pregnant or breastfeeding females
- •Known allergy to the investigational product or any of its ingredients
- •Any medical condition, including active, clinically significant infection, that in the opinion of the investigator or Sponsor may pose a safety risk to a patient in this study, which may confound efficacy or safety assessment or may interfere with study participation
研究组 & 干预措施
Roxadustat
Experimental
干预措施: Roxadustat (Drug)
Placebo
Placebo Comparator
干预措施: Placebo (Drug)
结局指标
主要结局
Mean Change From Baseline in Hb Averaged Over Week 28 to Week 52
时间窗: Baseline (Day 1, Week 0) and Week 28 to Week 52.
Baseline Hb was defined as the mean of the last 3 central laboratory Hb values from the screening and randomization visits. Mean change in Hb from baseline to mean value from Week 28 to Week 52 was analyzed using a missing at random (MAR) based multiple imputation analysis of covariance (ANCOVA) model with baseline Hb, baseline estimated glomerular filtration rate (eGFR), cardiovascular (CV) history, geographic region and treatment group as fixed effect covariates. The adjusted least squares (LS) mean estimates of change from baseline to mean during Week 28 to Week 52 are presented.
次要结局
- Proportion of Total Time of Interpolated Hb Values Greater Than or Equal To 10 g/dL From Week 28 to Week 52(Week 28 up to Week 52.)
- Annual Rate of eGFR Change From Baseline Prior to the Initiation of Dialysis or Kidney Transplant(Baseline (Day1, Week 0) up to EOS visit (4 weeks after the treatment period), with treatment duration up to 4 years.)
- Mean Change From Baseline in SF-36 Physical Functioning Sub-Score From Week 12 to Week 28(Baseline (Day 1, Week 0) and Week 12 to Week 28.)
- Percentage of Participants With Hb Response During the First 24 Weeks of Treatment(Baseline (Day 1, Week 0) up to Week 24.)
- Mean Change From Baseline in Short Form 36 (SF-36) Vitality Sub-Score From Week 12 to Week 28(Baseline (Day 1, Week 0) and Week 12 to Week 28.)
- Mean Change From Baseline in Hb Averaged Over Week 28 to Week 52 in Participants With Baseline High Sensitivity C-Reactive Protein (hsCRP) Greater Than the Upper Limit of Normal (ULN)(Baseline (Day 1, Week 0) and Week 28 to Week 52.)
- Mean Change in Low-Density Lipoprotein (LDL) Cholesterol From Baseline to Week 24(Baseline (Day 1, Week 0) and Week 24)
- Time-To-First Instance of Receiving a RBC Transfusion As Rescue Therapy(Baseline (Day1, Week 0) up to EOS visit (4 weeks after the treatment period) (or up to date of first RBC rescue therapy), with treatment duration up to 4 years.)
- Proportion of Total Time of Interpolated Hb Values Within the Interval of 10 to 12 g/dL From Week 28 to Week 52(Week 28 up to Week 52.)
- Time-To-First Instance of Receiving IV Iron, RBC Transfusion or Erythropoietin Analogue as Rescue Therapy(Baseline (Day1, Week 0) up to End of Study (EOS) visit (4 weeks after the treatment period) (or up to date of first rescue therapy), with treatment duration up to 4 years.)
研究者
研究点 (1)
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