Trial Outcomes & Findings for Study to Assess Efficacy, Safety, Tolerability, Pharmacokinetics (PK), and Pharmacodynamics (PD) of Obeticholic Acid (OCA) Compared to Placebo in Pediatric Participants With Biliary Atresia, Post-hepatoportoenterostomy (NCT NCT06121375)

This was a global, multicenter, double-blind, placebo-controlled study that evaluated efficacy, safety, and tolerability as well as pharmacokinetic/pharmacodynamic of Obeticholic Acid (OCA) in pediatric participants with biliary atresia with successful Hepatoportoenterostomy (HPE).

A total of 28 participants were enrolled.

Study to Assess Efficacy, Safety, Tolerability, Pharmacokinetics (PK), and Pharmacodynamics (PD) of Obeticholic Acid (OCA) Compared to Placebo in Pediatric Participants With Biliary Atresia, Post-hepatoportoenterostomy

Number of participants experiencing any of the following: All-cause death; Liver transplantation; Hospitalization (≥24 hours) for variceal bleeding, hepatic encephalopathy, or spontaneous bacterial peritonitis; Clinically relevant ascites requiring therapeutic paracentesis have been presented. No clinical outcome events were reported at the time of the study termination; hence It was not possible to conduct the planned primary efficacy analysis.

The Pediatric End-stage Liver Disease (PELD) score is a scale used to assess the severity of chronic liver disease in pediatric participants younger than 12 years of age. The total PELD score ranges from negative values to positive values, with no absolute minimum or maximum, with higher scores indicating more severe liver disease and greater urgency for liver transplantation. The score is calculated using total bilirubin, international normalized ratio (INR), albumin, age at listing, and growth failure. Baseline was defined as the last assessment prior to first study drug administration. Change from baseline was calculated as the last post-baseline value minus the baseline value. A negative change from baseline indicates improvement, while a positive change indicates worsening.

The Model of End-stage Liver Disease with Sodium (MELD-Na) score is a scale used to assess the severity of chronic liver disease in participants 12 years of age and older, ranging from 6 (less ill) to 40 (gravely ill). Higher scores indicate more severe liver disease and greater urgency for liver transplantation. The score is derived from total bilirubin, serum creatinine, INR, and serum sodium. Baseline was defined as the last assessment prior to first study drug administration. Change from baseline was calculated as the last post-baseline value minus the baseline value. A negative change from baseline indicates improvement, while a positive change indicates worsening.

Participants were considered responders if both of the following criteria were met at EOS: ≥40% reduction from baseline in Gamma Glutamyl Transferase (GGT), and ≥25% reduction from baseline in direct (conjugated) bilirubin. Participants with missing values were considered non-responders.

Blood samples were collected to assess GGT levels. Baseline was defined as the last assessment prior to first study drug administration. Change from baseline was computed by subtracting the baseline value from the post-baseline value, with a positive change indicating improvement.

Blood samples were collected to assess direct bilirubin levels. Baseline was defined as the last assessment prior to first study drug administration. Change from baseline was computed by subtracting the baseline value from the post-baseline value, with a positive change indicating improvement.

Plasma samples were collected to assess endogenous bile acids. Baseline was defined as the last assessment prior to first study drug administration. Change from baseline was computed by subtracting the baseline value from the post-baseline value, with a positive change indicating improvement.

Liver stiffness was measured using ultrasound elastography. Baseline was defined as the last assessment prior to first study drug administration. Change from baseline was computed by subtracting the baseline value from the post-baseline value, with a positive change indicating improvement.

TEAEs were defined as adverse events that were reported or worsened on or after the first dose of study treatment. Serious adverse events are adverse events resulting in death, are immediately life threatening, requires in-patient hospitalization or prolongation of existing hospitalization, or results in persistent or significant disability/incapacity.

Plasma samples were collected to assess levels of fat-soluble vitamins D. Baseline was defined as the last assessment prior to first study drug administration. Change from baseline was computed by subtracting the baseline value from the post-baseline value, with a positive change indicating improvement.

Plasma samples were collected to assess levels of fat-soluble vitamin K. Baseline was defined as the last assessment prior to first study drug administration. Change from baseline was computed by subtracting the baseline value from the post-baseline value, with a positive change indicating improvement.