A Double-Blind, Randomized, Placebo-Controlled, Phase 3 Study to Demonstrate Efficacy and Safety of A4250 in Children With Progressive Familial Intrahepatic Cholestasis Types 1 and 2 (PEDFIC 1)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- Albireo
- 入组人数
- 62
- 试验地点
- 45
- 主要终点
- Percentage of Participants With at Least a 70% Reduction in Fasting Serum Bile Acid (s-BA) Concentration From Baseline to the End of Treatment or Reaching a Level <=70 Micromoles Per Liter (Mcmol/L) After 24 Weeks of Treatment
研究概览
简要总结
Double blind, randomized, placebo controlled, Phase 3 study to investigate the efficacy and safety of low doses and high doses of A4250 compared to placebo in children with progressive familial intrahepatic cholestasis (PFIC) types 1 and 2.
详细描述
Up to 50 sites in the following countries will take part in this study:
Australia, Belgium, Canada, France, Germany, Israel, Italy, Netherlands, Poland, Spain, Sweden, Turkey, United Kingdom, United States, and Saudi Arabia
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
- 6 Months 至 18 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •A male or female participant with a clinical diagnosis of PFIC Type 1 or 2 and with a body weight above 5 kg
- •Participant must have clinical genetic confirmation of PFIC-1 or PFIC-2
- •Participant must have elevated serum bile acid (s-BA) concentration
- •Participant must have history of significant pruritus and a caregiver reported observed scratching in the eDiary
- •Participant and/or legal guardian must sign informed consent (and assent) as appropriate.
- •Participants will be expected to have a consistent caregiver(s) for the duration of the study
- •Caregivers and age-appropriate participants (≥8 years of age) must be willing and able to use an eDiary device as required by the study
排除标准
- •Participant with pathologic variations of the ABCB11 gene that predict complete absence of the bile salt export pump (BSEP) protein
- •Participant with past medical history or ongoing presence of other types of liver disease including, but not limited to, the following:
- •Biliary atresia of any kind
- •Benign recurrent intrahepatic cholestasis, indicated by any history of normal s BAs
- •Suspected or proven liver cancer or metastasis to the liver on imaging studies
- •Histopathology on liver biopsy that is suggestive of alternate non-PFIC related etiology of cholestasis
- •Participant with past medical history or ongoing chronic diarrhea
- •Any participant with suspected or confirmed cancers except for basal cell carcinoma
- •Participant with a past medical history of chronic kidney disease with an impaired renal function and a glomerular filtration rate <70 mL/min/1.73 m^2
- •Participant with surgical history of disruption of the enterohepatic circulation (biliary diversion surgery) within 6 months prior to start of Screening Period
- •Participant has had a liver transplant or a liver transplant is planned within 6 months of randomization
- •Decompensated liver disease
- •Participant suffers from uncontrolled, recalcitrant pruritic condition other than PFIC
- •Participant who has been previously treated with an IBAT inhibitor whose pruritus has not responded to treatment
研究组 & 干预措施
A4250 low dose
Capsules for oral administration (40 ug/kg) once daily for 24 weeks
干预措施: A4250 (odevixibat) (Drug)
A4250 high dose
Capsules for oral administration (120 ug/kg) once daily for 24 weeks
干预措施: A4250 (odevixibat) (Drug)
Placebo
Capsules for oral administration (to match active) once daily for 24 weeks
干预措施: Placebo (Drug)
结局指标
主要结局
Percentage of Participants With at Least a 70% Reduction in Fasting Serum Bile Acid (s-BA) Concentration From Baseline to the End of Treatment or Reaching a Level <=70 Micromoles Per Liter (Mcmol/L) After 24 Weeks of Treatment
时间窗: From Baseline (Day 1) up to Week 24
Fasting s-BA baseline was calculated as the average of the last 2 values prior to the first dose. The end value was the average of the values at Weeks 22 and 24 after the start of double-blind treatment. Participants who had at least 70% reduction in fasting s-BA from baseline to the end of treatment or reached \<=70 mcmol/L after 24 weeks of treatment were considered as responder. Participants with missing average at the end of treatment were classified as non-responder. Percentages are rounded to hundredth decimal.
Percentage of Positive Pruritus Assessments at the Participant Level Based on the Albireo Observer-Reported Outcome (ObsRO) Instrument Over the 24-Week Treatment Period
时间窗: From Baseline (Day 1) up to Week 24
A positive pruritus assessment was defined as a scratching score of \<=1 or at least 1 point drop from baseline. The percentage of positive pruritus assessment was calculated as the number of positive pruritus assessments divided by the total number of reported assessments only when more than 50% of planned assessment recorded by each participant multiplied by 100.
次要结局
- Change From Baseline in Serum Alanine Aminotransferase (ALT) Concentration at Weeks 12 and 24(Baseline (Day 1) and Weeks 12 and 24)
- Change From Baseline in Fasting Serum Bile Acid at Weeks 12 and 24(Baseline (Day 1) and Weeks 12 and 24)
- Change From Baseline in Growth Parameters at Weeks 12 and 24(Baseline (Day 1) and Weeks 12 and 24)
- Percentage of Responders for Pruritus Assessments Based on Bi-Weekly and Monthly Scores Using the Albireo Observer-Reported Outcome Instrument at Weeks 12 and 24(Weeks 12 and 24)
- Change From Baseline in Sleep Parameters Based on the Albireo Observer-reported Outcome Instrument Over the 24-Week Treatment Period(Baseline (Day 1) and Weeks 1 to 4, Weeks 5 to 8, Weeks 9 to 12, Weeks 13 to 16, Weeks 17 to 20, and Weeks 21 to 24)
- Change From Baseline in Sleep Parameters Based on the Albireo Patient-Reported Outcome (PRO) Instrument Over the 24-Week Treatment Period(Baseline (Day 1) and Weeks 1 to 4, Weeks 5 to 8, Weeks 9 to 12, Weeks 13 to 16, Weeks 17 to 20, and Weeks 21 to 24)
- Percentage of Individual Assessments Meeting the Definition of a Positive Pruritus Assessment at the Participant Level Using the Albireo ObsRO Instrument Over the 24-Week Treatment Period(Baseline (Day 1) and Weeks 1 to 4, Weeks 5 to 8, Weeks 9 to 12, Weeks 13 to 16, Weeks 17 to 20, and Weeks 21 to 24)
- Percentage of Individual Assessments Meeting the Definition of a Positive Pruritus Assessment at the Participant Level Using the Albireo PRO Instrument Over the 24-Week Treatment Period(From Baseline (Day 1) up to Week 24)
- Number of Participants Underwent Biliary Diversion Surgery and Liver Transplantation(From Baseline (Day 1) up to Week 24)
- Number of Participants Achieved Positive Pruritus Assessment for >50% of the Time Based on the Albireo ObsRO and PRO Instruments Over the 24-Week Treatment Period(From Baseline (Day 1) up to Week 24)