An Integrated Pharmacokinetic and Safety Open-label Basket Trial of Daprodustat for the Treatment of Anemia Associated With Chronic Kidney Disease in Male and Female Children and Adolescents Aged 3 Months to Under 18 Years Requiring or Not Requiring Dialysis
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 4
- 试验地点
- 1
- 主要终点
- Number of Participants With Any Adverse Events (AEs) and Serious Adverse Events (SAEs)
研究概览
简要总结
This is an international, multicenter trial, evaluating pharmacokinetics (PK) (4 weeks), safety (52 weeks), and hemoglobin (Hgb) response (52 weeks) to daprodustat in children and adolescent participants with anemia associated with chronic kidney disease (CKD) incorporating 2 independent sub-trials (Non dialysis [ND] and Dialysis [D]). This study will enroll participants with anemia associated with CKD, in 2 distinct sub-populations differing only by their CKD stage and dialysis requirement (ND: CKD stage 3 to 5 not yet receiving dialysis and D: CKD stage 5d undergoing peritoneal dialysis [PD] or hemodialysis [HD]).
The maximum duration of the study will be approximately 60 weeks, including Screening period (up to 4 weeks), treatment period (52 weeks), and follow-up period (4 weeks).
Outcome measures are identical for the ND and D sub-trials, but will be separately assessed in each sub- trials, overall and within each age subgroups (12 to less than [<] 18 years, 6 to <12 years, 2 to <6 years, and 3 months to <2 years). Except for PK and dose change, which is within each age group only.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 3 Months 至 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participant must be 3 months to less than (<)18 years of age.
- •Anemia associated with CKD stage 3, 4, 5 (not on dialysis) or who have dialysis-dependent CKD, defined as Hgb 7.0 to 11.0 g/dL (if not using erythropoiesis stimulating agents [ESAs]) or Hgb 9.5 to 12.0 g/dL if using ESAs.
- •Written informed consent or assent as appropriate.
排除标准
- •Kidney transplant recipient with a functioning allograft.
- •Scheduled for elective kidney transplantation within 3 months.
- •Transferrin saturation (TSAT) < 20 percent (%), or Ferritin <25 nanogram (ng)/milliliter (mL).
- •History of bone marrow aplasia or pure red cell aplasia.
- •Active hemolysis.
- •Other causes of anemia.
- •Active gastrointestinal bleeding within the last 4 weeks.
- •Active or previous malignancy within the last 2 years.
- •Acute or chronic infection requiring antimicrobial therapy.
- •History of significant thrombotic or thromboembolic events within the last 8 weeks.
- •Heart failure (HF) New York Heart Association (NYHA) Class IV
- •Uncontrolled hypertension.
- •Alanine aminotransferase (ALT) >2× upper limit of normal (ULN), bilirubin >1.5× ULN (unless bilirubin is fractionated and direct bilirubin <35%), and cirrhosis or current unstable liver or biliary disease.
研究组 & 干预措施
Daprodustat
All participants will receive daprodustat for up to 52 weeks.
干预措施: Daprodustat (Drug)
结局指标
主要结局
Number of Participants With Any Adverse Events (AEs) and Serious Adverse Events (SAEs)
时间窗: Up to 56 weeks
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. SAEs are defined as any untoward medical occurrence that, at any dose: results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; or other situations as per medical and scientific judgement of the Investigator.
Number of Participants With Adverse Event of Special Interests (AESIs)
时间窗: Up to 56 weeks
AESIs are AEs of scientific interest specific to the drug class as per investigator assessment. AESI included: Death, Myocardial Infarction (MI), stroke, Heart Failure (HF), thromboembolic events, thrombosis of vascular access, Thrombosis and/or tissue ischemia secondary to excessive erythropoiesis, New diagnosis of hypertension or worsening of existing hypertension, Cancer related mortality and tumor progression and recurrence, Esophageal and gastric erosions. Number of participants with any AESIs have been presented.
Number of Participants With AEs Leading to Study Intervention Discontinuation
时间窗: Up to 52 weeks
All AEs leading to study intervention discontinuation were collected. Number of participants with any AEs leading to study intervention discontinuation have been presented
次要结局
- Change From Baseline in Clinical Chemistry Parameter: Creatinine(Baseline (Day 1), at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52)
- Change From Baseline in Clinical Chemistry Parameters: Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP) and Aspartate Aminotransferase (AST)(Baseline (Day 1), at Weeks 4, 8, 12, 24, 32, 36, 40, 48, and 52)
- Change From Baseline in Hematology Parameter: Hematocrit(Baseline (Day 1), at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52)
- Change From Baseline in Hematology Parameter: Reticulocytes/Erythrocytes(Baseline (Day 1), at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52)
- Change From Baseline in Hematology Parameter: Erythrocytes(Baseline (Day 1), at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52)
- Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Leukocytes and Platelet Count(Baseline (Day 1), at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52)
- Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Volume(Baseline (Day 1), at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52)
- Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Hemoglobin(Baseline (Day 1), at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52)
- Change From Baseline in Clinical Chemistry Parameters: Calcium, Potassium, Sodium, Blood Urea Nitrogen (BUN)(Baseline (Day 1), at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52)
- Change From Baseline in Clinical Chemistry Parameters: Bilirubin and Direct Bilirubin(Baseline (Day 1), at Weeks 4, 8, 12, 24, 32, 36, 40, 48, and 52)
- Change From Baseline in Clinical Chemistry Parameter: Protein(Baseline (Day 1), at Weeks 4, 8, 12, 24, 32, 36, 40, 48, and 52)
- Change From Baseline in Clinical Chemistry Parameter: Ferritin(Baseline (Day 1), at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52)
- Change From Baseline in Clinical Chemistry Parameter: Transferrin Saturation(Baseline (Day 1), at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52)
- Change From Baseline in Clinical Chemistry Parameter: Estimated Glomerular Filtration Rate(Baseline (Day 1), at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52)
- Change From Baseline in Hematology Parameter: Prothrombin International Normalized Ratio(Baseline (Day 1), at Weeks 4, 8, 12, 24, 32, 36, 40, 48, and 52)
- Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)(Baseline (Day 1), at Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52)
- Change From Baseline in Heart Rate (HR)(Baseline (Day 1), at Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52)
- Change From Baseline in Weight(Baseline (Day 1), at Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52)
- Change From Baseline in Height(Baseline (Day 1), at Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52)
- Absolute Values of Hemoglobin (Hgb)(Baseline (Day 1), at Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52)
- Change From Baseline in Hemoglobin (Hgb)(Baseline (Day 1), at Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52)
- Number of Participants With Hgb Values Above, Below and Within the Target Range (10 to 12 g/dL)(Baseline (Day 1), at Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52)
- Change in Daprodustat Dose From Starting Dose at Each Study Time Point(Day 1 (Baseline), at Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, and 48)
- Number of Participants With 0 to 10, or Greater Than (>) 10 Dose Adjustments(Up to Week 52)
- Daprodustat Dose at Each Study Time Point(Baseline (Day 1), at Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, and 48)
- Maximum Plasma Concentration (Cmax) of Daprodustat(Day 1: 1, 2 and 6 hours Post-dose; Week 2: Pre-dose and 1, 2 and 6 hours Post-dose)
- Area Under the Curve (AUC) at Steady State of Daprodustat(Day 1: 1, 2 and 6 hours Post-dose; Week 2: Pre-dose and 1, 2 and 6 hours Post-dose)
- Plasma Concentrations of Daprodustat and Metabolites at Pre-dose (Ctrough)(Pre-dose on Week 2)