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department leadership decided not to proceed with study
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| bitopertin | Experimental | bitopertin 60 mg per day |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| bitopertin | Drug | bitopertin 60 mg will be taken once daily by mouth |
|
| Measure | Description | Time Frame |
|---|---|---|
| Number of treatment emergent adverse events (TEAE) | 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. | Week 104 |
| Measure | Description | Time Frame |
|---|---|---|
| Percent Change in Protoporphyrin IX (PP) Serum Levels | To assess effects of bitopertin on levels of protoporphyrin IX (PP) and other porphyrins in the whole blood, plasma, and red blood cells | baseline to month 12, month 12 to month 24 |
| Number of Participants with Change in Histopathology |
| Measure | Description | Time Frame |
|---|---|---|
| Patient Global Impression of Severity | Three items with total score range 3-15. Higher score indicates higher level of erythropoietic protoporphyria severity | baseline, week 26, week 52, week 78, week 104 |
| Patient Global Impression of Change |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Herbert Bonkovsky, MD | Atrium Health Wake Forest Baptist | Principal Investigator |
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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. |
| baseline to month 24 |
| Percent Change in Protoporphyrin IX (PP) Bile Levels | the percent change of Protoporphyrin IX (PP) in bile will be used to assess effects of bitopertin on PP levels | baseline to month 24 |
| Percent Change in Protoporphyrin IX (PP) Liver Levels | 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) | baseline to month 12, baseline to month 24 |
| Percent Change in Protoporphyrin IX (PP) Stool Levels | the percent change in Protoporphyrin IX (PP) in stool will be used to assess effects of bitopertin on PP levels | baseline to month 24 |
Five items with total score range 5-25. Higher score indicates erythropoietic protoporphyria have gotten worse since start of the study.
| baseline, week 26, week 52, week 78, week 104 |
| Patient-Reported Outcomes Measurement Information System - Social Isolation | Seven items with total score range 3-15. Higher score indicates poor quality of life. | baseline, week 26, week 52, week 78, week 104 |
| Serum of Level of Bitopertin | Trough concentrations of bitopertin will measured by using HPLC-mass spectroscopic procedures | baseline, week 26, week 52, week 78, week 104 |
| ID | Term |
|---|---|
| D046351 | Protoporphyria, Erythropoietic |
| C567464 | Protoporphyria, Erythropoietic, X-Linked Dominant |
| ID | Term |
|---|---|
| D017094 | Porphyrias, Hepatic |
| D008107 | Liver Diseases |
| D004066 | Digestive System Diseases |
| D012873 | Skin Diseases, Genetic |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D011164 | Porphyrias |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
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| ID | Term |
|---|---|
| C550631 | (4-(3-fluoro-5-trifluoromethylpyridin-2-yl)piperazin-1-yl)(5-methanesulfonyl-2-(2,2,2-trifluoro-1-methylethoxy)phenyl)methanone |
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