A Phase 3 Multi-center, Randomized, Open-label, Active-comparator (Darbepoetin Alfa) Conversion Study of Intermittent Oral Dosing of ASP1517 in Non-dialysis Chronic Kidney Disease Patients With Anemia
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 334
- 试验地点
- 66
- 主要终点
- Change from baseline in the average Hemoglobin (Hb)
研究概览
简要总结
The objective of this study is to evaluate the efficacy and safety of ASP1517 when converted from recombinant human erythropoietin (rHuEPO) or darbepoetin alfa (DA), compared to DA in the treatment of anemia in non-dialysis chronic kidney disease patients. Another uncontrolled cohort will be included to evaluate the efficacy and safety of ASP1517 in patients converted from epoetin beta pegol (CERA). This study will also assess the safety/efficacy of long term treatment of ASP1517 (52 weeks).
详细描述
This study consists of the following three cohorts. Cohort 1; subjects converted from rHuEPO or DA to ASP1517, Cohort 2; subjects converted from rHuEPO or DA to DA, Cohort 3; subjects converted from epoetin beta pegol (CERA) to ASP1517. In Cohort 1 and 3, ASP1517 will be administered orally for 52 weeks. In Cohort 2, DA will be administered subcutaneously for 24 weeks.
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
- 20 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subjects who were diagnosed with non-dialysis Chronic Kidney Disease and who are considered not to require renal replacement therapy during the study period
- •Subjects with renal anemia who have been receiving erythropoiesis stimulating agent (ESA) by subcutaneous injection and whose Hb values are considered stable.
- •Mean of the subject's two most recent Hb values before randomization during the Screening Period must be ≥10.0 g/dL and ≤12.0 g/dL
- •Either transferrin saturation ≥ 20% or serum ferritin ≥ 100 ng/mL
- •Female subject must either:
- •Be of non-childbearing potential:
- •post-menopausal, or
- •documented surgically sterile Or, if of childbearing potential,
- •Agree not to try to become pregnant during the study and for 28 days after the final study drug administration
- •And have a negative urine pregnancy test at pre-screening
- •And, if heterosexually active, agree to consistently use two forms of highly effective birth control* (at least one of which must be a barrier method) starting at pre-screening and throughout the study period and continued for 28 days after the final study drug administration.
- •Female subject must agree not to breastfeed starting at pre-screening and throughout the study period, and continued for 28 days after the final study drug administration.
- •Female subject must not donate ova starting at pre-screening and throughout the study period, and continued for 28 days after the final study drug administration.
- •Male subject and their female spouse/partners who are of childbearing potential must be using two forms of highly effective birth control (at least one of which must be a barrier method) starting at pre-screening and continue throughout the study period, and for 12 weeks after the final study drug administration
- •Male subject must not donate sperm starting at pre-screening and throughout the study period and, for 12 weeks after the final study drug administration
排除标准
- •Concurrent retinal neovascular lesion untreated or macular edema untreated, and patients with any condition that significantly compromises the ability to visualize the retina
- •Concurrent autoimmune disease with inflammation that could impact erythropoiesis
- •History of gastric/intestinal resection considered influential on the absorption of drugs in the gastrointestinal tract (excluding resection of gastric or colon polyps) or concurrent gastro-paresis
- •Uncontrolled hypertension
- •Concurrent congestive heart failure (NYHA Class III or higher)
- •History of hospitalization for treatment of stroke, myocardial infarction, or pulmonary embolism within 12 weeks before the pre-screening assessment
- •Positive for hepatitis B surface antigen (HBsAg) or anti-hepatitis C virus (HCV) antibody at the pre-screening assessment, or positive for human immunodeficiency virus (HIV) in a past test
- •Concurrent other form of anemia than renal anemia
- •History of pure red cell aplasia
- •Having received treatment with protein anabolic hormone, testosterone enanthate, or mepitiostane within 6 weeks before the pre-screening assessment
- •Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT), or total bilirubin that is greater than the criteria, or previous or concurrent another serious liver disease at pre-screening assessment
- •Previous or current malignant tumor (no recurrence for at least 5 years is eligible.)
- •Having undergone red blood transfusion and/or a surgical procedure consider to promote anemia and/or ophthalmological surgery within 4 weeks before the pre-screening assessment
- •Having undergone a kidney transplantation
- •History of serious drug allergy including anaphylactic shock
- •Having a previous history of treatment with ASP1517 or participation in this study
- •Participation in another clinical study or post-marketing clinical study (including that of a medical device) within 12 weeks before informed consent acquisition
研究组 & 干预措施
rHuEPO or DA to ASP1517
Participants will receive roxadustat according to the prior randomization treatment, with starting doses of 70mg thrice weekly (TIW) to participants on <4500 IU/week of rHuEPO or <20 microgram (μg)/week of darbepoetin alfa (DA) and 100mg TIW to participants on ≥4500 IU/week rHuEPO or ≥ 20 μg/week DA. Participants roxadustat dosage will be adjusted every 4 weeks to maintain Hb level within the target range 10.0 to 12.0 g/dL. Dose adjustment steps will be as follows: 20, 40, 50, 70, 100, 150, 200, 250, 300 mg.
干预措施: roxadustat (Drug)
rHuEPO or DA to DA
Participants will receive DA according to the prior randomization treatment, with starting doses of 15 μg/2weeks to participants on ≤ 1500 IU/week of rHuEPO or <11.25 microgram (μg)/week of DA, 30μg/2weeks to participants on >1500 to <6000 IU/week of rHuEPO or ≥ 11.25 to < 22.5 μg/week of DA, 60μg/2weeks to participants on ≥ 6000 IU/week of rHuEPO or ≥ 22.5 to < 37.5 μg/week of DA, 90μg/2weeks to participants on ≥ 37.5 to < 52.5 μg/week of DA, 120μg/2weeks to participants on ≥ 52.5 to < 75 μg/week of DA, 180μg/2weeks to participants on ≥ 75 μg/week of DA. Participant's roxadustat dosage will be adjusted every 4 weeks to maintain Hb level within the target range 10.0 to 12.0 g/dL. Dose adjustment steps will be as follows: 15, 30, 60, 90, 120, and 180 μg.
干预措施: DA (Drug)
Epoetin beta pegol to ASP1517
Participants will receive roxadustat according to the prior registration treatment, with starting doses of 70mg thrice weekly (TIW) to participants on ≤100 μg/week of Epoetin beta pegol and 100mg TIW to participants on >100 μg/week of Epoetin beta pegol. Participant's roxadustat dosage will be adjusted every 4 weeks to maintain Hb level within the target range 10.0 to 12.0 g/dL. Dose adjustment steps will be as follows: 20, 40, 50, 70, 100, 150, 200, 250, 300 mg.
干预措施: roxadustat (Drug)
结局指标
主要结局
Change from baseline in the average Hemoglobin (Hb)
时间窗: Baseline and Weeks 18 to 24
次要结局
- Average Hb from Week 18 to Week 24(Up to Week 24)
- Number of Participants Who Achieved the Average Hb level of 10.0 to 12.0 g/dL For Weeks 18 to 24(Weeks 18 to 24)
- Number of participants who achieve the target Hb level at each week(Up to Week 52)
- Quality of life assessed by EQ-5D-5L(Up to Week 52)
- Change from baseline in Hb to each post-dosing time point(Baseline and Up to Week 52)
- Proportion of time points that achieve the target Hb level from Weeks 18 to 24(Up to Week 24)
- Rate of rise in Hb levels (g/dL/week) from week 0 to at the earliest date of week 4, time of discontinuation, or time of dose adjustment(Up to Week 4)
- Quality of life assessed by WPAI:ANS(Up to Week 52)
- Quality of life assessed by FACT-An(Up to Week 52)
- Average Reticulocyte Level(Up to Week 52)
- Average Soluble Transferrin Receptor Level(Up to Week 52)
- Average Soluble Transferrin Level(Up to Week 52)
- Number of participants with abnormal Vital signs and/or adverse events related to treatment(Up to Week 52)
- Safety assessed by incidence of adverse events(Up to Week 52)
- Safety assessed by standard 12-lead electrocardiogram(Up to Week 52)
- Average Hb from weeks 44 to 52(Up to Week 52)
- Number of Participants Who Achieved the Average Hb level of 10.0 to 12.0 g/dL For Weeks 44 to 52(Weeks 44 to 52)
- Proportion of time points that achieve the target Hb level from Weeks 44 to 52(Up to Week 52)
- Average Ferrum Level(Up to Week 52)
- Safety assessed by ophthalmological examination: optical coherence tomography(Up to Week 24)
- Safety assessed by ophthalmological examination: visual acuity(Up to Week 24)
- Number of participants with abnormal Laboratory values and/or adverse events related to treatment(Up to Week 52)
- Average Hematocrit Level(Up to Week 52)
- Safety assessed by body weight(Up to Week 52)
- Safety assessed by ophthalmological examination: Fundoscopy(Up to Week 24)
- Plasma concentration of unchanged ASP1517(Up to Week 24)
- Average Reticulocyte Hemoglobin Content Level(Up to Week 52)
- Number of Occurence of Hospitalizations(Up to Week 52)
- Duration of Hospitalization(Up to week 52)
- Average Ferritin Level(Up to Week 52)
- Average Transferrin Level(Up to Week 52)
- Average Total Iron Binding Capacity Level(Up to Week 52)
- Quality of life assessed by SF-36(Up to Week 52)
- Change from baseline in the average Hb from weeks 44 to 52(Baseline and Up to Week 52)