A Randomized, Open-label, Active-controlled 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 Subjects
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 456
- 试验地点
- 3
- 主要终点
- Change From Baseline in Hemoglobin (Hb) to the Average Over the Primary Evaluation Period (PEP) (Weeks 20 to 26)
研究概览
简要总结
This study will be conducted to demonstrate the efficacy and safety of vadadustat administered three times weekly (TIW) compared to a long-acting erythropoiesis-stimulating agent (ESA) (Mircera®) for the maintenance treatment of anemia in hemodialysis participants.
详细描述
Following randomization, there will be 2 periods during the study:
- Conversion and Maintenance Period (Weeks 0 to 52): There will be a primary efficacy evaluation period (Weeks 20 to 26) and a secondary efficacy evaluation period (Weeks 46 to 52).
- Safety Follow-up Period (Early Termination [ET] and Follow-Up): post-treatment safety follow-up visit (ET/End of Treatment [EOT] +4 weeks) either in person or via telephone.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •≥18 years of age
- •Receiving chronic, outpatient in-center hemodialysis three times weekly (TIW) for end-stage kidney disease for at least 12 weeks prior to Screening Visit 1 (SV1)
- •Currently maintained on Mircera® (≤250 μg/month) with at least 2 doses received within 8 weeks prior to Screening Visit 2 (SV2)
- •Mean Screening hemoglobin (Hb) between 8.5 and 11.0 grams per deciliter (g/dL) (inclusive), as determined by the average of 2 Hb values measured by the central laboratory at least 4 days apart between SV1 and SV2
- •Serum ferritin ≥100 nanograms per milliliter (ng/mL) and transferrin saturation (TSAT) ≥20% during Screening
- •Folate and vitamin B12 measurements ≥ lower limit of normal during Screening
排除标准
- •Anemia due to a cause other than chronic kidney disease (CKD).
- •Clinically meaningful bleeding event within 8 weeks prior to Baseline
- •Red blood cell (RBC) transfusion within 8 weeks prior to Baseline
- •Having received any doses of darbepoetin alfa (Aranesp®) within 4 weeks prior to Baseline
- •Having received any doses of epoetin alfa (Epogen®) within 1 week prior to Baseline.
- •Current uncontrolled hypertension.
- •Acute coronary syndrome (hospitalization for unstable angina or myocardial infarction), surgical or percutaneous intervention for coronary, cerebrovascular or peripheral artery disease (aortic or lower extremity), surgical or percutaneous valvular replacement or repair, sustained ventricular tachycardia, hospitalization for heart failure (HF) or New York Heart Association Class IV HF, or stroke within 12 weeks prior to or during Screening.
- •Known hypersensitivity to vadadustat, Mircera®, or any of their excipients.
研究组 & 干预措施
Vadadustat high dose
Participants previously receiving Mircera® received vadadustat for up to 52 weeks with an initial dose of 900 mg.
干预措施: Vadadustat (Drug)
Vadadustat low dose
Participants previously receiving Mircera® received vadadustat for up to 52 weeks with an initial dose of 600 milligrams (mg).
干预措施: Vadadustat (Drug)
Mircera®
Participants will continue to receive Mircera® for up to 52 weeks.
干预措施: Mircera® (Drug)
结局指标
主要结局
Change From Baseline in Hemoglobin (Hb) to the Average Over the Primary Evaluation Period (PEP) (Weeks 20 to 26)
时间窗: Baseline; Weeks 20 to 26
The Baseline Hb was defined as the average of last 2 central laboratory Hb measurements of samples taken at or prior to the first dose. The average for the PEP was calculated as the average of all Hb measurements from the central laboratory within the three visit windows during Weeks 20 through 26. Analysis was conducted using an analysis of covariance (ANCOVA) model with multiple imputation for missing data with randomization stratification factors and Baseline Hb as covariates. Change from Baseline was calculated as PEP value minus the Baseline value.
次要结局
- Change From Baseline in Hb to the Average Over the Secondary Evaluation Period (SEP) (Weeks 46 to 52)(Baseline; Weeks 46 to 52)