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
- Registration Number
- NCT07123363
- Lead Sponsor
- Wake Forest University Health Sciences
- Brief Summary
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.
- Detailed Description
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.
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- All
- Target Recruitment
- 10
- 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.
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description bitopertin bitopertin bitopertin 60 mg per day
- Primary Outcome Measures
Name Time Method Number of treatment emergent adverse events (TEAE) 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.
- Secondary Outcome Measures
Name Time Method Percent Change in Protoporphyrin IX (PP) Serum Levels baseline to month 12, month 12 to month 24 To assess effects of bitopertin on levels of protoporphyrin IX (PP) and other porphyrins in the whole blood, plasma, and red blood cells
Number of Participants with Change in Histopathology baseline to month 24 To assess effects of bitopertin on hepatic histopathology the number of participants with change in histopathologic evidence will be tracked. Histopathology consists of histopathologic evidence of hepatic fibrosis, necroinflammation, fat, cholestasis, bile plugs, birefringent brown deposits in the liver, or other histopathology, as estimated by an experienced hepato-pathologist.
Percent Change in Protoporphyrin IX (PP) Bile Levels baseline to month 24 the percent change of Protoporphyrin IX (PP) in bile will be used to assess effects of bitopertin on PP levels
Percent Change in Protoporphyrin IX (PP) Liver Levels baseline to month 12, baseline to month 24 the percent change in Protoporphyrin IX (PP) in the liver will be measured by change in liver stiffness measured by vibration controlled elastography with use of dedicated instruments designed for this purpose (Fibroscan, Velocur)
Percent Change in Protoporphyrin IX (PP) Stool Levels baseline to month 24 the percent change in Protoporphyrin IX (PP) in stool will be used to assess effects of bitopertin on PP levels