Clinical trial NCT06121375: 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
Official title: A Randomized, Double-blind, Placebo-controlled, Phase 2/3 Study to Assess the Efficacy, Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Obeticholic Acid Compared to Placebo in Pediatric Subjects With Biliary Atresia, Post-hepatoportoenterostomy
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
PHASE3
Conditions: Biliary Atresia
Keywords: Biliary Atresia
Placebo-controlled
Pharmacokinetics
Pharmacodynamics
Obeticholic Acid
Efficacy
Post-hepatoportoenterostomy
Lead sponsor: Intercept Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2023-11-07
Enrollment: 144
Sex: ALL
Minimum age (years): 1
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study will evaluate the efficacy, safety and tolerability, as well as PK/PD of OCA in eligible pediatric participants with biliary atresia with successful hepatoportoenterostomy (HPE, also known as a Kasai portoenterostomy). The double-blind period comprises of 2 phases: dose titration phase and age expansion treatment phase.


Eligibility criteria: Inclusion criteria:

* Male or female pediatric participants from birth to \<18 years old. Note: Participants aged \<2 years old will not be enrolled until after review of safety data during the planned interim analysis and agreement from the Data Safety Monitoring Board (DSMB) that there is sufficient safety data to enroll this age group.
* Diagnosis of non-syndromic biliary atresia.
* Demonstrated successful HPE as defined by total bilirubin \<2 milligrams per deciliter (mg/dL) (34.2 micromoles per liter \[μmol/L\]) at least 3 months post-HPE procedure.

Exclusion criteria:

* Prior liver transplant or active status on transplant list.
* Participants diagnosed with biliary atresia splenic malformation (BASM).
* Conjugated (direct) bilirubin ≥ upper limit of normal (ULN) of site-specific reference range. If conjugated bilirubin is not available: total bilirubin ≥2 mg/dL (34.2 mol/L).
* Platelets \<120,000/μL
* International normalized ratio (INR) ≥1.5.
* Current or history of complications of decompensated chronic liver disease including:

  1. Gastroesophageal varices and/or variceal bleeding
  2. Clinically evident ascites related to portal hypertension
  3. Hepatic encephalopathy
  4. Prior placement of portosystemic shunt
  5. Hepatopulmonary syndrome or portopulmonary hypertension
  6. Hepatorenal syndrome
  7. Any evidence of portal hypertension based on imaging (e.g., cavernous transformation of portal vein, abdominal varices, etc.)
  8. Hepatocellular carcinoma
  9. Childs-Pugh B or C
* Height and weight Z-score \<-2 per site-specific reference ranges.
* Acholic (pale) stools.
* Aspartate aminotransferase (AST) \>4x ULN.
* Alanine aminotransferase \>4x ULN
* GGT \>500 Units per Liter (U/L)
* On anticoagulation therapy
* Albumin \<3.5 grams per deciliter (g/dL).
* Inability to swallow tablets (i.e., tablet or mini-tablet formulations).

Primary outcomes:
measure: Time to the First Occurrence of Composite Endpoint
timeFrame: Up to Week 64
Secondary outcomes:
measure: Plasma concentration of unconjugated OCA (parent), glyco-OCA, tauro-OCA, and total OCA (molar sum of OCA and its active conjugates)
timeFrame: Up to Week 64
measure: Change from Baseline in Gamma Glutamyl Transferase (GGT)
timeFrame: Baseline and up to Week 64
measure: Change from Baseline in total and direct (conjugated) bilirubin
timeFrame: Baseline and up to Week 64
measure: Change from Baseline in Fibroblast Growth Factor-19 (FGF-19)
timeFrame: Baseline and up to Week 64
measure: Change from Baseline in 7-hydroxyl-4-cholesten-3-one (C4)
timeFrame: Baseline and up to Week 64
measure: Change from Baseline in endogenous bile acids
timeFrame: Baseline and up to Week 64
measure: Change from Baseline in liver stiffness as assessed by transient elastography
timeFrame: Baseline and up to Week 64
measure: Change from Baseline in plasma levels of fat-soluble vitamins (D and K)
timeFrame: Baseline and up to Week 64
measure: Safety and tolerability as assessed by the incidence of treatment-emergent adverse events (TEAEs) including serious adverse events (SAEs)
timeFrame: Up to Week 64
Other outcomes:
Locations:
city: South Brisbane
country: Australia
facility: Queensland Childrens Hospital
state: Queensland
city: North Adelaide
country: Australia
facility: Women's and Children's Hospital
state: South Australia
city: Parkville
country: Australia
facility: Royal Childrens Hospital
state: Victoria
city: Calgary
country: Canada
facility: Alberta Childrens Hospital
state: Alberta
city: Edmonton
country: Canada
facility: Stollery Children's Hospital
state: Alberta
city: Hangzhou
country: China
facility: Children's Hospital, Zhejiang University School of Medicine
state: Zhejiang
city: Hong Kong
country: Hong Kong
facility: Queen Mary Hospital
city: Jerusalem
country: Israel
facility: Hadassah Medical Center
city: Jerusalem
country: Israel
facility: Shaare-Zedek Medical Center
city: Kota Bharu
country: Malaysia
facility: Hospital Raja Perempuan Azinab II
state: Kelantan
city: Kuala Lumpur
country: Malaysia
facility: University Malaya Medical Center
city: Auckland
country: New Zealand
facility: Starship Child Health
city: Singapore
country: Singapore
facility: KK Women's and Children's Hospital
city: Taichung
country: Taiwan
facility: Taichung Veterans General Hospital
city: Tainan
country: Taiwan
facility: National Chen Kung University Hospital
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Taoyuan
country: Taiwan
facility: Linkou Chang Gung Memorial Hospital
city: Konyaaltı
country: Turkey
facility: Akdeniz Üniversitesi Tıp Fakültesi Hastanesi Pediatrik Gastroenteroloji
state: Antalya
city: Bornova
country: Turkey
facility: Ege Üniversitesi Hastanesi Pediatrik Gastroenteroloji Bölümü
state: İzmir
city: Ankara
country: Turkey
facility: Hacettepe Universitesi ihsan Dogramaci Cocuk Hastansesi
Study officials:
affiliation: Intercept Pharmaceuticals
name: Lynda Szczech, MD
role: STUDY_DIRECTOR
References: