A Long-term Study Evaluating Hepatotoxicity Associated With TURALIO™ (Pexidartinib) Treatment

Study Overview
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Brief Summary
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A study to evaluate the long-term risk of hepatic failure with TURALIO™ (pexidartinib) and the mechanism of liver injury based upon liver biopsy information among patients who received or are receiving TURALIO™ (pexidartinib) and experience hepatotoxicity.

Detailed Description
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This FDA post-marketing requirement study will evaluate the long-term risk of hepatic failure with TURALIO™ (pexidartinib) and the mechanism of liver injury based upon liver biopsy information among patients who received or are receiving TURALIO™ (pexidartinib) for symptomatic tenosynovial giant cell tumor (TGCT) associated with severe morbidity or functional limitations and not amenable to improvement with surgery, and who experience hepatotoxicity. A liver biopsy will be collected from enrolled patients for central laboratory analysis of macrophage and immune cell profiles to investigate possible mechanisms of the hepatotoxicity. Additionally, 4 blood samples will be collected to evaluate liver function, other relevant safety tests, peripheral immune cells, and for pharmacogenomic testing. Enrolled patients will be followed at least yearly for 10 years to assess long-term risk of hepatic failure.

Official Title
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A Long-term Study to Further Evaluate the Risk of Hepatotoxicity Associated With TURALIO™ (Pexidartinib) Treatment

Conditions
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Tenosynovial Giant Cell Tumor, Hepatotoxicity

Intervention / Treatment
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* Drug: TURALIO™


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult participants with symptomatic TGCT associated with severe morbidity or functional limitations and not amenable to improvement with surgery Age ≥18 years old Emergence of at least one of the following liver test abnormalities due to TURALIO™ (pexidartinib) exposure: Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >3 × upper limit of normal (ULN) with concurrent total bilirubin (TBIL) >2 × ULN Isolated TBIL >2 × ULN (excluding patients with Gilbert's syndrome) Isolated AST or ALT >10 × ULN Alkaline phosphatase (ALP) >2 x ULN with gamma-glutamyl transferase (GGT) >2 x ULN Consent to study procedures, long-term safety follow-up, and use of data from the TURALIO™ (pexidartinib) Risk Evaluation and Mitigation Strategy (REMS) program Exclusion Criteria: Not applicable

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Symptomatic TGCT Participants<br>Adult patients with symptomatic TGCT associated with severe morbidity or functional limitations and not amenable to improvement with surgery, and who experience moderate or severe hepatotoxicity due to use of TURALIO™ (pexidartinib). | Drug: TURALIO™<br>* This is a non-interventional, observational study to evaluate long-term risk of hepatic failure associated with TURALIO™ (pexidartinib) treatment. No study medication will be provided to the participants.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency of Hepatic Failure After Discontinuation of TURALIO™ (pexidartinib) | Hepatic failure is defined as severe liver injury with encephalopathy and impaired synthetic function (INR >= 1.5) as well as liver transplant and hepatic-related death. | Baseline up to 10 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Liver Test Abnormalities | Liver test abnormalities were defined as the following: Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >3 × upper limit of normal (ULN) with concurrent total bilirubin (TBIL) >2 × ULN; Isolated TBIL >2 × ULN (excluding patients with Gilbert's syndrome); Isolated AST or ALT >10 × ULN; Alkaline phosphatase (ALP) >2 x ULN with gamma-glutamyl transferase (GGT) >2 x ULN. | Baseline up to 10 years | 
| Number of Participants With A Liver Transplant |  | Baseline up to 10 years | 
| Number of Participants Experiencing Death |  | Baseline up to 10 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hepatotoxicity, Tenosynovial Giant Cell Tumor, Pexidartinib, TURALIO™