Table 1. Phase 3 clinical study... | American Society of Hematology

Table 1.

Phase 3 clinical study liver-related exclusion criteria and SmPC/PI-listed liver-related contraindications for valoctocogene roxaparvovec gene therapy for HA

Phase 3 study liver-related exclusion criteria¹⁴	European SmPC-listed liver-related contraindications and precautions²³	US PI-listed liver-related contraindications and precautions²⁴
Any of the following laboratory results: ALT >1.25× ULN AST >1.25× ULN GGT >1.25× ULN Total bilirubin >1.25× ULN ALP >1.25× ULN INR ≥1.4 Prior liver biopsy showing fibrosis of stage 3 or 4 on the Batts-Ludwig or METAVIR scoring systems, or an equivalent grade fibrosis on an alternative scale Cirrhosis of any etiology as assessed by liver ultrasound Chronic or active HBV infection as evidenced by positive serology testing (HBsAg, HBsAb, and HBcAb) and confirmatory HBV DNA testing Active HCV infection as evidenced by detectable HCV RNA or currently on antiviral therapy History of hepatic malignancy	Contraindicated in patients with: Significant fibrosis (stage 3 or 4 on the Batts-Ludwig scale or equivalent) Cirrhosis Acute or uncontrolled chronic hepatic infections Not recommended in patients with: Other liver disorders ALT >1.25 × ULN∗ AST >1.25 × ULN∗ GGT >1.25 × ULN∗ ALP >1.25 × ULN∗ Total bilirubin >1.25 × ULN∗ INR ≥1.4 History of hepatic malignancy Taking efavirenz	Contraindicated in patients with: Significant fibrosis (stage 3 or 4 on the Batts-Ludwig scale or equivalent) Cirrhosis Active hepatic infections, either acute or uncontrolled chronic infections Not recommended in patients with: Other liver disorders ALT >1.25 × ULN∗ AST >1.25 × ULN∗ GGT >1.25 × ULN∗ ALP >1.25 × ULN∗ Total bilirubin >1.25 × ULN∗ INR ≥1.4 Taking efavirenz

Phase 3 study liver-related exclusion criteria¹⁴	European SmPC-listed liver-related contraindications and precautions²³	US PI-listed liver-related contraindications and precautions²⁴
Any of the following laboratory results: ALT >1.25× ULN AST >1.25× ULN GGT >1.25× ULN Total bilirubin >1.25× ULN ALP >1.25× ULN INR ≥1.4 Prior liver biopsy showing fibrosis of stage 3 or 4 on the Batts-Ludwig or METAVIR scoring systems, or an equivalent grade fibrosis on an alternative scale Cirrhosis of any etiology as assessed by liver ultrasound Chronic or active HBV infection as evidenced by positive serology testing (HBsAg, HBsAb, and HBcAb) and confirmatory HBV DNA testing Active HCV infection as evidenced by detectable HCV RNA or currently on antiviral therapy History of hepatic malignancy	Contraindicated in patients with: Significant fibrosis (stage 3 or 4 on the Batts-Ludwig scale or equivalent) Cirrhosis Acute or uncontrolled chronic hepatic infections Not recommended in patients with: Other liver disorders ALT >1.25 × ULN∗ AST >1.25 × ULN∗ GGT >1.25 × ULN∗ ALP >1.25 × ULN∗ Total bilirubin >1.25 × ULN∗ INR ≥1.4 History of hepatic malignancy Taking efavirenz	Contraindicated in patients with: Significant fibrosis (stage 3 or 4 on the Batts-Ludwig scale or equivalent) Cirrhosis Active hepatic infections, either acute or uncontrolled chronic infections Not recommended in patients with: Other liver disorders ALT >1.25 × ULN∗ AST >1.25 × ULN∗ GGT >1.25 × ULN∗ ALP >1.25 × ULN∗ Total bilirubin >1.25 × ULN∗ INR ≥1.4 Taking efavirenz

ALP, alkaline phosphatase; GGT, gamma-glutamyl transferase; HBsAb, hepatitis B surface antibody; HBsAg, hepatitis B surface antigen; INR, international normalized ratio.

∗

Based on ≥2 measurements.

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