A Phase 2, Randomized, Open-Label, Dose Titration, Safety and Efficacy Study of FG-4592 for the Correction of Anemia in Newly Initiated Dialysis Patients Not on Erythropoiesis-Stimulating Agent Treatment
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- FibroGen
- 入组人数
- 60
- 主要终点
- Maximum Change From Baseline in Hb During Weeks 3-13
研究概览
简要总结
The purpose of this study is to evaluate efficacy and safety of roxadustat in the correction of anemia in participants with end-stage renal disease who recently started dialysis.
详细描述
Participants on hemodialysis (HD) will be randomized to 3 treatment arms (A, B, and C) of in a 1:1:1 ratio to receive no iron supplementation, oral iron supplementation, and IV iron supplementation, respectively, in addition to roxadustat. At the same time, participants on peritoneal dialysis (PD) will be enrolled into Arm D. Arm E will enroll either HD or PD participants, and is an optional, confirmatory/supplemental treatment arm with flexible dosing and flexible iron supplementation based on the evaluation of data from the previous 4 treatment arms.
Initial roxadustat dose will be based on a tiered, weight-based dosing scheme (low weight [40 to 60 kilograms {kg}], medium weight [>60 to 90 kg], and heavy weight [>90 to 140 kg] participants will receive 60, 100, and 140 milligrams [mg] roxadustat, respectively). Dose adjustments will be implemented (up to a maximum roxadustat dose of 140, 200, and 300 mg for low, medium, and high weight participants, respectively) during Weeks 5 and 9, depending on the hemoglobin (Hb) level and rate of Hb rise in the previous 4 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
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Receiving HD or PD for native kidney end-stage renal disease (ESRD) for 2 weeks to 4 months, prior to randomization
- •Mean of the 2 most recent Hb values during the screening period, obtained at least 7 days apart, must be <10.0 grams (g)/deciliter (dL), with a difference of ≤1.0 g/dL between the 2 values
- •Body weight 40 to 140 kilograms (kg)
排除标准
- •Previously received erythropoiesis-stimulating agents
- •Received IV iron within 4 weeks of randomization
- •Received red blood cell transfusion within 8 weeks prior to randomization or anticipated need for transfusion during the treatment period
- •Positive for any of the following: human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), or anti-hepatitis C virus antibody (anti-HCV Ab)
- •History of chronic liver disease
- •Clinically significant infection
- •New York Heart Association Class III or IV congestive heart failure
- •History of 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
- •Chronic inflammatory disease that could impact erythropoiesis (for example, systemic lupus erythematosis, rheumatoid arthritis, celiac disease) even if it is currently in remission
- •History of other blood disorders
- •Active hemolysis or diagnosis of hemolytic syndrome
- •Known bone marrow fibrosis
- •Uncontrolled or symptomatic secondary hyperparathyroidism
- •History of alcohol or drug abuse within a year prior to randomization, or anticipated inability to avoid consumption of more than 3 alcoholic beverages per day
- •History of allergy or sensitivity to oral or IV iron therapy
- •Seizure disorder or receiving anti-epilepsy medication for seizure disorder within 12 weeks prior to randomization
- •Pregnant or breast-feeding females
研究组 & 干预措施
Arm A + E (Participants on HD): Roxadustat Only, No Iron
Participants on HD will receive roxadustat capsules at the applicable dose (up to a maximum roxadustat dose of 140, 200, and 300 mg) based on weight and Hb level, administered orally 3 times weekly (TIW) for 12 weeks.
干预措施: Roxadustat (Drug)
Arm B (Participants on HD): PO Iron (Ferrous Fumarate or Ferrous Gluconate) Between 50 and 195 mg
Participants on HD will receive roxadustat capsules at the applicable dose (up to a maximum roxadustat dose of 140, 200, and 300 mg) based on weight and Hb level, administered orally TIW with iron (ferrous fumarate or ferrous gluconate) PO at doses containing elemental iron between 50 and 195 mg daily (depending on the type of iron formulation available in their countries) for 12 weeks.
干预措施: Roxadustat (Drug)
Arm B (Participants on HD): PO Iron (Ferrous Fumarate or Ferrous Gluconate) Between 50 and 195 mg
Participants on HD will receive roxadustat capsules at the applicable dose (up to a maximum roxadustat dose of 140, 200, and 300 mg) based on weight and Hb level, administered orally TIW with iron (ferrous fumarate or ferrous gluconate) PO at doses containing elemental iron between 50 and 195 mg daily (depending on the type of iron formulation available in their countries) for 12 weeks.
干预措施: Oral Iron (Drug)
Arm C (Participants on HD): IV Iron (Ferric Gluconate Complex in Sucrose or Equivalent) 60 mg
Participants on HD will receive roxadustat capsules at the applicable dose (up to a maximum roxadustat dose of 140, 200, and 300 mg) based on weight and Hb level, administered orally TIW with approximately 60 mg IV iron (ferric gluconate complex in sucrose injection [for example, Ferrlecit®] or equivalent) once a week for 12 weeks.
干预措施: Roxadustat (Drug)
Arm C (Participants on HD): IV Iron (Ferric Gluconate Complex in Sucrose or Equivalent) 60 mg
Participants on HD will receive roxadustat capsules at the applicable dose (up to a maximum roxadustat dose of 140, 200, and 300 mg) based on weight and Hb level, administered orally TIW with approximately 60 mg IV iron (ferric gluconate complex in sucrose injection [for example, Ferrlecit®] or equivalent) once a week for 12 weeks.
干预措施: IV Iron (Drug)
Arm D (Participants on PD): PO Iron (Ferrous Fumarate or Ferrous Gluconate) Between 50 and 195 mg
Participants on PD will receive roxadustat capsules at the applicable dose (up to a maximum roxadustat dose of 140, 200, and 300 mg) based on weight and Hb level, administered orally TIW with iron (ferrous fumarate or ferrous gluconate) PO at doses containing elemental iron between 50 and 195 mg daily (depending on the type of iron formulation available in their countries) for 12 weeks.
干预措施: Roxadustat (Drug)
Arm D (Participants on PD): PO Iron (Ferrous Fumarate or Ferrous Gluconate) Between 50 and 195 mg
Participants on PD will receive roxadustat capsules at the applicable dose (up to a maximum roxadustat dose of 140, 200, and 300 mg) based on weight and Hb level, administered orally TIW with iron (ferrous fumarate or ferrous gluconate) PO at doses containing elemental iron between 50 and 195 mg daily (depending on the type of iron formulation available in their countries) for 12 weeks.
干预措施: Oral Iron (Drug)
结局指标
主要结局
Maximum Change From Baseline in Hb During Weeks 3-13
时间窗: Baseline, Weeks 3-13
Baseline Hb was defined as the mean of the last 3 central laboratory Hb values prior to the first dose administration. This outcome measure is derived from the maximum change from baseline during Weeks 3-13, without last observation carried forward (LOCF) imputation.
次要结局
- Mean Change From Baseline in Hb During Weeks 2-5, 6-9, and 10-13(Baseline, Weeks 2-5, 6-9, and 10-13)
- Number of Participants With Mean Hb Values in Excess of 13.0 and 14.0 g/dL at Weeks 6-9 and 10-13(Weeks 6-9 and 10-13)
- Number of Participants With Mean Hb Values <10.0 g/dL at Weeks 6-9 and 10-13(Weeks 6-9 and 10-13)
- Number of Participants Whose Maximum Hb Achieved During Treatment Was at Least 1.0 g/dL Increase From Baseline and Was ≥11.0 g/dL(Week 3 to 13)
- Number of Participants Whose Maximum Hb Achieved During Treatment Was at Least 1.0 g/dL Increase From Baseline and Was ≥10.0 g/dL(Week 3 to 13)
- Number of Participants With a Hb Response, Defined as an Increase in Hb by ≥1.0 g/dL From Baseline, by Weeks 5, 9, and 13(Weeks 5, 9, and 13)
- Number of Participants Who Achieved Maximum Hb During Weeks 3-13(Weeks 3-13)
- Number of Participants With a Maximum Change From Baseline in Hb During Weeks 3-13(Baseline, Weeks 3-13)
- Median Time to Hb Response (Increase in Hb by ≥1.0 g/dL From Baseline)(Baseline up to Week 13)
- Weekly Dose at First Hb Response (Increase in Hb by ≥1.0 g/dL From Baseline)(Baseline up to Week 13)
- Number of Participants Requiring Dose Increase at Weeks 5 and 9(Weeks 5 and 9)
- Number of Participants Requiring Dose Reduction or Dose Discontinuation Due to Excessive Erythropoiesis(Weeks 5 and 9)
- Change From Baseline in Ferritin at Week 13(Baseline, Week 13)
- Change From Baseline in Transferrin Saturation (TSAT) at Week 13(Baseline, Week 13)
- Change From Baseline in Reticulocyte Hemoglobin Content at Week 13(Baseline, Week 13)
- Number of Participants With Mean Hb Values 11.0-13.0 g/dL at Weeks 6-9 and 10-13(Weeks 6-9 and 10-13)
- Number of Participants With Mean Hb Values Within 11.0-13.0 g/dL During Weeks 10-13 Among Those With Maximum Hb ≥11.0 g/dL and Change of Hb ≥1 g/dL(Weeks 10-13)
- Number of Participants With Mean Hb Values Within 10.0-13.0 g/dL During Weeks 10-13 Among Those With Maximum Hb ≥10.0 g/dL and Change of Hb ≥1 g/dL(Weeks 10-13)
- Number of Participants Requiring Rescue Treatment With an Erythropoiesis-Stimulating Agent (ESA), Red Blood Cells (RBC) Transfusion, or IV Iron (Excluding Arm C)(Baseline up to Week 13)
- Number of Participants Requiring Therapeutic Phlebotomy(Baseline up to Week 13)
- Number of Participants Withdrawn From the Study Due to Inadequate Efficacy(Baseline up to Week 16)
- Change From Baseline in Short Form 36 (SF-36) Version 2 Physical Functioning Subscore and Vitality Subscore at Weeks 9 and 13(Baseline, Weeks 9 and 13)
- Change From Baseline in Functional Assessment of Cancer Therapy-Anemia (FACT-An) Total Score at Weeks 9 and 13(Baseline, Weeks 9 and 13)
- Number of Participants With Potentially Clinically Significant Laboratory Tests(Baseline up to Week 16)
- Number of Participants With TEAEs(Baseline up to Week 16)