Protoporphyria
Conditions
Keywords
Erythropoietic Protoporphyria, X-linked Protoporphyria, Bitopertin
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.
Interventions
DRUGbitopertin
bitopertin 60 mg will be taken once daily by mouth
Sponsors
Wake Forest University Health Sciences
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* 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.
Exclusion criteria
* 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
Contacts
PRINCIPAL_INVESTIGATORHerbert Bonkovsky, MD
Atrium Health Wake Forest Baptist
Outcome results
None listed