A Phase 3, Randomized, Double-Blind, Placebo Controlled Study of the Efficacy and Safety of Roxadustat (FG-4592) for the Treatment of Anemia in Chronic Kidney Disease Patients Not on Dialysis
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- FibroGen
- 入组人数
- 922
- 试验地点
- 3
- 主要终点
- United States (US FDA) Submission: Mean Change From Baseline in Hb (g/dL) Over Weeks 28 to 52 Regardless of Rescue Therapy
研究概览
简要总结
The purpose of this study is to determine whether roxadustat is safe and effective in the treatment of anemia in participants with chronic kidney disease and not on dialysis.
详细描述
There is a screening period of up to 6 weeks, a variable treatment period for individual participants. In order to complete the treatment period simultaneously for all study participants, the minimum treatment duration may be less than 52 weeks, with a maximum treatment duration of up to 3 years after the last participant is randomized, and a post-treatment follow-up period of 4 weeks. Participants who prematurely discontinued from treatment will be expected to complete the Early Termination (ET) and End of Study (EOS) visits. Such participants will be considered non-completers, but they will be expected to participate in long-term follow-up (LTFU) for cardiovascular events (CV) of interest, vital status, and hospitalizations until overall study closure unless the participant withdrew consent for this LTFU data collection. Participants were randomized in a 2:1 ratio to receive either roxadustat or placebo in a double-blind manner.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Chronic kidney disease Stages 3, 4, or 5 and not receiving dialysis
- •Anemia qualified by measurements of hemoglobin values during screening
- •Additional blood work must be in a safe range for study entry
- •Body weight 45 to 160 kilograms (kg)
- •Willingness to use contraception if of child-bearing potential
排除标准
- •Treatment with an erythropoiesis-stimulating agent (ESA) within 12 weeks prior to study participation
- •More than 1 dose of intravenous iron within 12 weeks prior to study participation
- •Blood transfusion within 8 weeks prior to study participation
- •Active infection
- •Chronic liver disease
- •Severe congestive heart failure, recent heart attack, stroke, seizure, or blood clot
- •Uncontrolled blood pressure within 2 weeks prior to study participation
- •Renal cell carcinoma
- •History of malignancy, including multiple myeloma or other myelodysplastic syndrome
- •Chronic inflammatory disease that could impact red blood cell production
- •Any prior organ transplant or a scheduled organ transplantation
- •Anticipated elective surgery that is expected to lead to significant blood loss or anticipated elective heart procedure
- •Gastrointestinal bleeding
- •Any prior treatment with roxadustat or a hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI)
- •Recent use of an investigational drug or treatment, or participation in an investigational study
研究组 & 干预措施
Roxadustat
Participants will receive roxadustat tablets orally 3 times a week (TIW). The initial dose will be according to the tiered weight-based approach, with starting roxadustat doses of 70 milligrams (mg) TIW to participants weighing <70 kilograms (kg) and roxadustat doses of 100 mg TIW to participants weighing ≥70 kg. Dose-titration (up to a maximum dose of 300 mg) will be performed based upon regular measurement of Hb levels until the participant achieves central Hb value of ≥11.0 grams/deciliter (g/dL) and Hb increase from baseline (BL) of ≥1.0 g/dL at 2 consecutive study visits, separated by at least 5 days. Once target Hb level is reached, the participant will enter the maintenance period during which roxadustat dosage will be adjusted every 4 weeks to maintain participant's Hb level within the target range of 10.0 g/dL and 12.0 g/dL. The maximum treatment duration will be up to 234.9 weeks.
干预措施: Roxadustat (Drug)
Placebo
Participants will receive roxadustat-matching placebo tablets orally TIW. The initial dose will be according to the tiered weight-based approach, with starting roxadustat-matching placebo doses of 70 mg TIW to participants weighing <70 kg and roxadustat-matching placebo doses of 100 mg TIW to participants weighing ≥70 kg. Dose-titration (up to a maximum dose of 300 mg) will be performed based upon regular measurement of Hb levels until the participant achieves central Hb value of ≥11.0 g/dL and Hb increase from BL of ≥1.0 g/dL at 2 consecutive study visits, separated by at least 5 days. Once target Hb level is reached, the participant will enter the maintenance period during which roxadustat dosage will be adjusted every 4 weeks to maintain participant's Hb level within the target range of 10.0 g/dL and 12.0 g/dL. The maximum treatment duration will be up to 208.1 weeks.
干预措施: Placebo (Drug)
结局指标
主要结局
United States (US FDA) Submission: Mean Change From Baseline in Hb (g/dL) Over Weeks 28 to 52 Regardless of Rescue Therapy
时间窗: Baseline (Day 1, Week 0), Weeks 28 to 52
The change in Hb from baseline to the average level during the evaluation period (defined as Week 28 until Week 52) is reported. Hb values under the influence of a rescue therapy were not censored. The intermittent missing hemoglobin data were imputed for each treatment relying on non-missing data from all participants within each treatment group using the Monte Carlo Markov Chain (MCMC) imputation model, Monotone missing data were imputed by regression from its own treatment group. Baseline Hb was defined as the mean of up to 4 last central laboratory values prior to the first dose of study drug.
Ex-US Submission: Number (%) of Participants Who Achieved a Hb Response During the First 24-Weeks of Treatment Censoring for Rescue Therapy
时间窗: Baseline up to Week 24
The number of participants who achieved a Hb response at 2 consecutive visits at least 5 days apart during the first 24 weeks of treatment, without rescue therapy (that is, red blood cell \[RBC\] transfusion, erythropoiesis-stimulating agent \[ESA\], or intravenous \[IV\] iron) are reported. A Hb response is defined, using central laboratory values, as the following: * Hb ≥11 g/dL and Hb increase from baseline by ≥1 g/dL in participants with baseline Hb \>8 g/dL, or * An increase in Hb by ≥2 g/dL in participants with baseline Hb ≤8.0 g/dL
次要结局
- Mean Change From Baseline in Hb Averaged Over Weeks 28 to 52 Regardless of Rescue Therapy in Participants With Baseline C-Reactive Protein (CRP) >Upper Limit of Normal (ULN)(Baseline (Day 1, Week 0), Weeks 28 to 52)
- Number (%) of Participants With Hb ≥10 g/dL Averaged Over Weeks 28 to 36 With Censoring for Rescue Therapy(Weeks 28 to 36)
- Mean Change From Baseline in Hb Averaged Over Weeks 28 to 36 With Censoring for Rescue Therapy(Baseline (Day 1, Week 0), Weeks 28 to 36)
- Mean Change From Baseline in Low-Density Lipoprotein (LDL) Cholesterol Averaged Over Weeks 12 to 28(Baseline (Day 1, Week 0), Weeks 12 to 28)
- Number (%) of Participants Who Received Rescue Therapy in the First 24 Weeks and in the First 52 Weeks of Treatment(Baseline (Day 1, Week 0) up to Week 24 and up to Week 52)
- Rate of Change in eGFR From Baseline up to 12 Months (Linear Random Coefficient Model With Observed Data)(Baseline, Month 12)
- Number of Participants Who Received Blood/RBC Transfusion in the First 52 Weeks of Treatment(Baseline up to Week 52)
- Change From Baseline in Short Form 36 (SF-36) Version 2 Physical Functioning Subscore and Vitality Subscore at Weeks 12 to 28(Baseline (Day 1, Week 0), Weeks 12 to 28)
- Number (%) of Participants Who Experienced Exacerbation of Hypertension(Baseline up to Week 52)
- Mean Change From Baseline in Mean Arterial Pressure (MAP) Averaged Over Weeks 20 to 28(Baseline, Weeks 20 to 28)