NCT03353454撤回3 期
Randomized Double-blind Placebo-controlled Phase 3 Study to Evaluate the Efficacy and Safety of Maralixibat (SHP625) in the Treatment of Pediatric Subjects With Progressive Familial Intrahepatic Cholestasis (PFIC)
适应症
干预措施
相关药物
试验速览
- 阶段
- 3 期
- 状态
- 撤回
- 主要终点
- Treatment Response as Measured by the Observer Itch Reported Outcome (ItchRO[Obs])
研究概览
简要总结
The purpose of this study is to determine if the investigational treatment (maralixibat) is safe and effective in pediatric participants with Progressive Familial Intrahepatic Cholestasis (PFIC).
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
- Double (Participant, Investigator)
入排标准
- 年龄范围
- — 至 18 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Informed consent and assent (as applicable for participants less than or equal to (<=) 18 years per Institutional Review Board/Ethics Committee (IRB)/Ethics Committee (EC) as appropriate.
- •Male or female participants between the ages of 12 months and 18 years inclusive (primary cohort) or birth to 18 years inclusive (exploratory cohort) at time of consent, with a body weight greater than or equal to (>=) 5 kilogram (kg).
- •Cholestasis as manifested by total sBA greater than (>) 3*upper limit of normal (ULN)
- •An average AM ItchRO(Obs) score >= 1.5 during the 4 weeks leading to the baseline visit
- •Diagnosis of PFIC based on:
- •a. Primary cohort: i. Participants with 2 documented mutant alleles in ABCB11 (PFIC2); participants without bile salt export pump (BSEP) function (biallelic truncating mutations in ABCB11) will not be enrolled into the primary cohort. b. Exploratory cohort: i. Participants with PFIC1/3/4 or PFIC2 with biallelic truncating mutationsiii.Infants from birth to <12 months of age with PFIC ii. Participants with PFIC after internal or external (eg, PEBD) biliary diversion surgery with unsatisfactory pruritus control or where biliary diversion was reversed.
排除标准
- •Chronic diarrhea requiring intravenous fluid or nutritional intervention for the diarrhea and/or its sequelae.
- •History of surgical disruption of the enterohepatic circulation (applies to primary cohort only).
- •Liver transplant
- •Decompensated cirrhosis (international normalized ratio [INR] >1.5, albumin <30 gram per liter [g/L], history or presence of clinically significant ascites, variceal hemorrhage, and/or encephalopathy).
- •ALT >15*ULN at screening.
- •History or presence of other liver disease.
- •History or presence of any other disease or condition known to interfere with the absorption, distribution, metabolism or excretion of drugs, including bile salt metabolism in the intestine (example [eg], inflammatory bowel disease), per investigator discretion.
- •Liver mass on imaging
- •Known diagnosis of human immunodeficiency virus (HIV) infection.
- •Any prior cancer diagnosis except for in situ carcinoma or cancers treated within 5 years of the screening visit (Visit 0) with no evidence of recurrence.
研究组 & 干预措施
Maralixibat (SHP625)
Experimental
Participants will be randomized to Maralixibat oral solution (up to 600 microgram per kilogram [mcg/kg]) orally twice daily for 26 weeks.
干预措施: Maralixibat (Drug)
Placebo
Placebo Comparator
Participants will receive placebo matched to maralixibat oral solution twice daily for 26 weeks.
干预措施: Placebo (Drug)
结局指标
主要结局
Treatment Response as Measured by the Observer Itch Reported Outcome (ItchRO[Obs])
时间窗: Baseline up to Week 26
Compare the percentage of participants on active treatment versus (vs.) placebo who meet response criteria which is defined as improvement in before midday (AM) Observer Itch Reported Outcome (ItchRO\[Obs\]) severity decrease from baseline demonstrated on at least 2 of the last 3 study visits.
次要结局
- Change From Baseline in Clinician Scratch Scale (CSS)(Baseline, Week 26)
- Change Over Time in Before Midday (AM) Itch Reported Outcome (ItchRO[Obs]) Score(Baseline up to Week 26)
- Change Over Time in After Midday (PM) Itch Reported Outcome (ItchRO[Obs]) Score(Baseline up to Week 26)
- Disappearance of Pruritus as Measured by Observer Itch Reported Outcome (ItchRO[Obs])(Baseline up to Week 26)
- Improvement in Height(Baseline up to Week 26)
- Improvement in Weight(Baseline up to Week 26)
- Change From Baseline in Nutritional Status as Measured by Mid-arm Circumference(Baseline, Week 26)
- Change From Baseline in Nutritional Status as Measured by Triceps Skin Fold(Baseline, Week 26)
- Change Over Time in Daily Average Itch Reported Outcome (ItchRO[Obs]) Score(Baseline up to Week 26)
- Treatment Response as Measured by the Observer Itch Reported Outcome (ItchRO[Obs]) and Serum Bile Acids (sBA)(Baseline up to Week 26)
- Normalization or Reduction From Baseline in Serum Bile Acids (sBA)(Baseline up to Week 26)
- Change From Baseline in Quality of Life as Measured by Pediatric Quality of Life Inventory (PedsQL)(Baseline, Week 26)
- Change From Baseline in Quality of Sleep as Measured by Children's Sleep Habits Questionnaire (CSHQ)(Baseline, Week 26)
- Normalization or Meaningful Reduction From Baseline of Alanine Aminotransferase (ALT)(Baseline up to Week 26)
- Normalization or Meaningful Decrease From Baseline of Total Bilirubin(Baseline up to Week 26)
- Change From Baseline in Biomarkers of Bile Acid Synthesis(Baseline, Week 26)
- Evaluate the safety of SHP625(Baseline up to Week 26)
- Plasma Levels of Maralixibat Over Time(Baseline, Week 6, 10, 14, 18, 22 and 26)
研究者
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