NCT03029208已完成3 期
A 52-week Open-label (Sponsor-blind), Randomized, Active-controlled, Parallel-group, Multi-center Study to Evaluate the Efficacy and Safety of Daprodustat Compared to Recombinant Human Erythropoietin in Subjects With Anemia Associated With Chronic Kidney Disease Who Are Initiating 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
- 入组人数
- 312
- 试验地点
- 1
- 主要终点
- Mean Change From Baseline in Hemoglobin (Hgb) During Evaluation Period (Week 28 to Week 52)
研究概览
简要总结
The purpose of this multi-center study is to evaluate the efficacy and safety of daprodustat in subjects with anemia associated with CKD.
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
- None
入排标准
- 年龄范围
- 18 Years 至 99 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •18 to 99 years of age inclusive.
- •Planning to start chronic dialysis within the next 6 weeks (from the date of the screening visit) OR have started and received dialysis (as specified below) for end-stage renal disease for a maximum of <=90 days immediately prior to randomization and is not expected to stop dialysis during the duration of the trial: HD >=2 times per week or PD >=4 times per week including incremental schedule; subjects on continuous ambulatory peritoneal dialysis (CAPD) and automated peritoneal dialysis (APD) are eligible.
- •Hemoglobin concentration as measured by HemoCue (range inclusive): 8 to 10.5 g/dL (5-6.5 millimoles per liter [mmol/L]) at screening and 8-11.0 g/dL (5 to 6.8 mmol/L) at randomization.
- •Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the consent form and in this protocol.
排除标准
- •Planned living-related or living-unrelated kidney transplant during the study.
- •Ferritin: <=100 nanograms per milliliter (ng/mL) (<=100 micrograms per liter [mcg/L]) at screening or after IV iron supplementation.
- •Transferrin saturation (TSAT): <=20% at screening or after IV iron supplementation.
- •Vitamin B12 (cobalamin): Below the lower limit of the reference range at screening or after vitamin B12 supplementation.
- •Folate: <2.0 ng/mL (<4.5 nanomoles per liter [nmol/L]) at screening.
- •Aplasias: History of bone marrow aplasia or pure red cell aplasia (PRCA).
- •Other causes of anemia: Untreated pernicious anemia, thalassemia major, sickle cell disease, or myelodysplastic syndrome.
- •Gastrointestinal (GI) bleeding: Evidence of actively bleeding gastric, duodenal, or esophageal ulcer disease or clinically significant GI bleeding <=10 weeks prior to screening through to randomization (Day 1).
- •Use of any Erythropoiesis-stimulating agent (ESA) treatment within 8 weeks prior to screening except for limited use as part of dialysis initiation. Note : Limited use is defined as no more than 6 weeks of short acting ESA (rhEPO or biosimilars; maximum of 20000 unit total) or long acting ESA (darbepoetin alfa [maximum of 100 mcg total] or methoxy polyethylene glycol-epoetin beta [maximum of 125 mcg total]) received before or after starting dialysis.
- •Myocardial infarction or acute coronary syndrome: <=10 weeks prior to screening through to randomization (Day 1).
- •Stroke or transient ischemic attack: <=10 weeks prior to screening through to randomization (Day 1).
- •Chronic Class IV heart failure, as defined by the New York Heart Association (NYHA) functional classification system.
- •Current uncontrolled hypertension as determined by the Investigator that would contraindicate the use of rhEPO.
- •QT correction using Bazett's (QTcB) (Day 1): QTcB >500 milliseconds (msec), or QTcB >530 msec in subjects with bundle branch block. There is no QTc exclusion for subjects with a predominantly ventricular paced rhythm.
- •Liver disease (any one of the following):
- •Alanine transaminase (ALT) >2 times upper limit of normal (ULN) (screening only).
- •Bilirubin >1.5 times ULN (screening only) (NOTE: Isolated bilirubin >1.5 times ULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).
- •Current unstable liver or biliary disease per investigator assessment, generally defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, persistent jaundice, or cirrhosis. NOTE: Stable chronic liver disease (including asymptomatic gallstones, chronic hepatitis B or C, or Gilbert's syndrome) are acceptable if subject otherwise meets entry criteria.
- •History of malignancy within the 2 years prior to screening through to randomization (Day 1), or currently receiving treatment for cancer, or complex kidney cyst (i.e. Bosniak Category II F, III or IV) >3 centimeter (cm). The only exception is localized squamous cell or basal cell carcinoma of the skin that has been definitively treated >=10 weeks prior to screening.
- •History of severe allergic or anaphylactic reactions or hypersensitivity to excipients in the investigational product or to darbepoetin alfa.
- •Use of strong Cytochrome P4502C8 (CYP2C8) inhibitors (example gemfibrozil) or strong CYP2C8 inducers (example rifampin/rifampicin).
- •Use of other investigational agent or device prior to screening through to randomization (Day 1). At screening, this exclusion applies to use of the investigational agent within 30 days or within five half-lives (whichever is longer).
- •Any prior treatment with daprodustat for treatment duration of >30 days.
- •Females only: Subject is pregnant [as confirmed by a positive serum human chorionic gonadotropin (hCG) test for females of reproductive potential (FRP) only], subject is breastfeeding, or subject is of reproductive potential and does not agree to follow one of the contraceptive options in the List of Highly Effective Methods for Avoiding Pregnancy.
- •Any other condition, clinical or laboratory abnormality, or examination finding that the investigator considers would put the subject at unacceptable risk, which may affect study compliance (example intolerance to rhEPO) or prevent understanding of the aims or investigational procedures or possible consequences of the study.
研究组 & 干预措施
Daprodustat treated anemic subjects
Experimental
Subjects will receive oral daprodustat once daily.
干预措施: Daprodustat (Drug)
Daprodustat treated anemic subjects
Experimental
Subjects will receive oral daprodustat once daily.
干预措施: Iron therapy (Drug)
Darbepoetin alfa treated anemic subjects
Active Comparator
Subjects will receive darbepoetin alfa subcutaneously or intravenously.
干预措施: Darbepoetin alfa (Drug)
Darbepoetin alfa treated anemic subjects
Active Comparator
Subjects will receive darbepoetin alfa subcutaneously or intravenously.
干预措施: Iron therapy (Drug)
结局指标
主要结局
Mean Change From Baseline in Hemoglobin (Hgb) During Evaluation Period (Week 28 to Week 52)
时间窗: Baseline (Pre-dose on Day 1) and evaluation period (Week 28 to Week 52)
Blood samples were collected from participants for Hgb measurement. Hgb during the evaluation period was defined as the mean of all available post-randomization Hgb values (on and off-treatment) during the evaluation period (Week 28 to Week 52). For the primary analysis missing post-Baseline Hgb values were imputed using pre-specified multiple imputations. Change from Baseline was defined as the average of post-randomization values during the evaluation period minus Baseline value. Baseline was defined as the latest non-missing pre-dose assessment on or before the randomization date. An analysis of covariance (ANCOVA) model including randomization stratification factors Baseline Hgb and treatment was performed to obtain a point estimate and two-sided 95 percent (%) confidence interval (CI) for the treatment difference (daprodustat-darbepoetin alfa).
次要结局
- Average Monthly Intravenous Iron Dose (Milligrams) From Baseline to Week 52(Baseline (Day 1) to Week 52)
- Change From Baseline in Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP), Mean Arterial Blood Pressure (MAP) at Week 52(Baseline (Day 1) and Week 52)
- Number of Hgb Responders (Hgb in the Analysis Range of 10 to 11.5 Grams/Deciliter) During Evaluation Period (Week 28 to Week 52)(Weeks 28 to 52)
- Number of Participants Permanently Stopping Randomized Treatment Due to Meeting Rescue Criteria(Up to Week 52)
- Percentage of Time for Which Hgb Was Within the Analysis Range (10 to 11.5 g/dL) During Evaluation Period (Week 28 to Week 52): Superiority Analysis(Weeks 28 to 52)
- Change From Baseline in Mental Component Score (MCS) Using SF-36 HRQoL Questionnaire at Weeks 8, 12, 28, 52(Baseline (Day 1), Weeks 8, 12, 28 and 52)
- Change From Baseline in Chronic Kidney Disease- Anemia Symptoms Questionnaire (CKD-AQ) at Week 52(Baseline (Day 1) and Week 52)
- Change From Baseline in SBP, DBP, MAP at End of Treatment(Baseline (Day 1) and end of treatment (last on-treatment value until Week 52))
- Blood Pressure (BP) Exacerbation Events Rate Per 100 Participant Years(Up to Week 52)
- Number of Participants With at Least One Blood Pressure Exacerbation Event During Study(Up to Week 52)
- Change From Baseline in Post-randomization Hgb at Week 52(Baseline (Day 1) and Week 52)
- Percentage of Time for Which Hgb Was Within the Analysis Range (10 to 11.5 g/dL) During Evaluation Period (Week 28 to Week 52): Non-inferiority Analysis(Weeks 28 to 52)
- Change From Baseline in SF-36 HRQoL Scores for Bodily Pain, General Health, Mental Health, Role-Emotional, Role-Physical, Social Functioning at Weeks 8, 12, 28, 52(Baseline (Day 1), Weeks 8, 12, 28 and 52)
- Change From Baseline in Physical Component Score (PCS) Using Short Form (SF)-36 Health-related Quality of Life (HRQoL) Questionnaire at Weeks 8, 12, 28, 52(Baseline (Day 1), Weeks 8, 12, 28 and 52)
- Change From Baseline in Health Utility EuroQol 5 Dimensions 5 Level (EQ-5D-5L) Questionnaire Score at Week 52(Baseline (Day 1) and Week 52)
- Change From Baseline in Vitality Scores Using SF-36 HRQoL Questionnaire at Weeks 28, 52(Baseline (Day 1), Weeks 28 and 52)
- Change From Baseline in Patient Global Impression of Severity (PGI-S)(Baseline (Day 1), Weeks 8, 12, 28 and 52)
- Maximum Observed Concentration (Cmax) of Daprodustat (GSK1278863) and Its Metabolites GSK2391220 (M2), GSK2506104 (M3), and GSK2531401 (M13)(Pre-Dose, 0.5, 1, 2 and 3 hours post-dose; each pharmacokinetic sample was taken at Week 4 or 8 or 12)
- Change From Baseline in Physical Functioning Domain Scores Using SF-36 HRQoL Questionnaire at Weeks 28, 52(Baseline (Day 1), Weeks 28 and 52)
- Change From Baseline in EQ Visual Analogue Scale (EQ-VAS) at Week 52(Baseline (Day 1) and Week 52)
- Observed Concentration at Dosing Interval (Ctau) of Daprodustat (GSK1278863) and Its Metabolites GSK2391220 (M2), GSK2506104 (M3), and GSK2531401 (M13)(Pre-Dose, 0.5, 1, 2 and 3 hours post-dose; each pharmacokinetic sample was taken at Week 4 or 8 or 12)
- Plasma Concentration of Daprodustat (GSK1278863) and Its Metabolites GSK2391220 (M2), GSK2506104 (M3), and GSK2531401 (M13)(Pre-dose, 0.5, 1, 2 and 3 hours post-dose; each pharmacokinetic sample was taken at Week 4 or 8 or 12)
研究者
研究点 (1)
Loading locations...
相似试验
撤回
3 期
Study to Evaluate the Safety and Efficacy of Oral Vadadustat in Pediatric Participants With Anemia of Chronic Kidney DiseaseAnemia of Chronic Kidney DiseaseNCT05082571Akebia Therapeutics71
撤回
3 期
Study to Evaluate the Safety and Efficacy of Oral Vadadustat in Pediatric Participants With Anemia of Chronic Kidney Disease Naive to Erythropoiesis-Stimulating AgentsAnemia of Chronic Kidney DiseaseNCT05082584Akebia Therapeutics71
招募中
1 期
First-line Treatment With Dacomitinib Plus Anlotinib for Patients With Advanced NSCLC With EGFR 21L858R MutationsNon-Small Cell Lung Cancer (NSCLC)NCT05271916Shanghai Chest Hospital140
进行中（未招募）
3 期
Durvalumab Plus Tremelimumab as First-line Treatment in Chinese Patients With uHCCHepatocellular CarcinomaNCT05557838AstraZeneca214
已完成
3 期
Study Evaluating the Efficacy and Safety of Dose Conversion From a Long-acting Erythropoiesis-stimulating Agent (Mircera®) to Three Times Weekly Oral Vadadustat for the Maintenance Treatment of Anemia in Hemodialysis SubjectsAnemia Associated With Chronic Kidney Disease (CKD)NCT04707768Akebia Therapeutics456