Effect of Bitopertin on the Liver and on Levels of Protoporphyrin IX in Bile, Blood, Liver, and Stool in Patients With Erythropoietic Protoporphyria/X-linked Protoporphyria and Increased Liver Stiffness and/or Liver Enzymes at Baseline
试验速览
- 阶段
- 1 期
- 状态
- 撤回
- 入组人数
- 10
- 主要终点
- Number of treatment emergent adverse events (TEAE)
研究概览
简要总结
The primary goal of this study is to assess safety and tolerability of bitopertin in subjects with Erythropoietic Protoporphyria (EPP) or X-linked Protoporphyria (XLP) and evidence of compensated liver disease.
详细描述
This in an open-label, investigator-initiated study of bitopertin (60 mg/day) in selected and carefully monitored participants with Erythropoietic Protoporphyria (EPP) or X-linked Protoporphyria (XLP) who have increased liver stiffness and/or elevated liver enzymes at baseline.This study is designed to evaluate whether bitopertin is effective in reducing hepatic and biliary levels of protoporphyrin IX (PP), which over time, with chronic and ongoing bitopertin treatment, will ameliorate and forestall progression of PP hepatopathy, providing an additional major benefit and reason for its chronic use in patients with EPP/XLP.
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
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of EEP or XLP that has been biochemically and genetically verified prior diagnosis of EPP or XLP
- •Age 18-75 years
- •Increased liver stiffness at baseline, defined as stiffness measurement [E value] by: Fibroscan >7 kPa; MRE that is >3.0 kPa; Velacur/Sonicincyte that is >6.0 kPa; and/or elevated liver enzymes: serum ALT > 2 X upper limit of normal (ULN), but not greater than 5 X ULN and/or serum AP > 2 X ULN, but not greater than 5 X ULN
- •INR < 1.4
- •Compensated liver disease at baseline, defined as lack of clinically evident ascites, encephalopathy, hepatocellular carcinoma, clinically evident icterus or jaundice, peripheral edema.
- •Willingness and ability to volunteer and provide informed consent for a long-term study that will include liver biopsies and collection of bile from the second portion of the duodenum, at baseline and at the end of study. In addition, follow-up visits will be planned every 26 weeks throughout the study, with plans for repeat routine/safety labs at each visit and for measures of liver stiffness and markers of hepatic status and fibrosis (Fib-4, APRI, ELF, Fibrotest) performed once every 6 months.
排除标准
- •Chronic hepatitis B, C, D, or E;
- •Human immunodeficiency (HIV) infection;
- •Alcohol use > 14 units/week for men or > 7 units/week for women;
- •Pregnancy or breast feeding among women;
- •Any known active malignancy other than small and localized squamous or basal cell carcinoma of the skin;
- •Advanced or decompensated heart, lung, kidney, liver, or neuro-psychiatric disease;
- •History of diagnosed depression or suicidality;
- •History of diagnosed substance abuse or poor impulse control;
- •Any other conditions that, in the opinion of the Investigator, renders the individual unfit to participate
研究组 & 干预措施
bitopertin
bitopertin 60 mg per day
干预措施: bitopertin (Drug)
结局指标
主要结局
Number of treatment emergent adverse events (TEAE)
时间窗: Week 104
Number of treatment emergent adverse events (TEAE). Adverse events that begin after the first administration of study drug, or existing adverse events that worsen after the first dose of study drug will be considered TEAEs.
次要结局
- Percent Change in Protoporphyrin IX (PP) Serum Levels(baseline to month 12, month 12 to month 24)
- Number of Participants with Change in Histopathology(baseline to month 24)
- Percent Change in Protoporphyrin IX (PP) Bile Levels(baseline to month 24)
- Percent Change in Protoporphyrin IX (PP) Liver Levels(baseline to month 12, baseline to month 24)
- Percent Change in Protoporphyrin IX (PP) Stool Levels(baseline to month 24)