This Study Will Investigate the Efficacy and Safety of A4250 in Children With PFIC Types 1 or 2

A Double-Blind, Randomized, Placebo-Controlled, Phase 3 Study to Demonstrate Efficacy and Safety of A4250 in Children With Progressive Familial Intrahepatic Cholestasis Types 1 and 2 (PEDFIC 1)

Double blind, randomized, placebo controlled, Phase 3 study to investigate the efficacy and safety of low doses and high doses of A4250 compared to placebo in children with progressive familial intrahepatic cholestasis (PFIC) types 1 and 2.

Up to 50 sites in the following countries will take part in this study:

Australia, Belgium, Canada, France, Germany, Israel, Italy, Netherlands, Poland, Spain, Sweden, Turkey, United Kingdom, United States, and Saudi Arabia

Key Inclusion Criteria:

• A male or female participant with a clinical diagnosis of PFIC Type 1 or 2 and with a body weight above 5 kg
• Participant must have clinical genetic confirmation of PFIC-1 or PFIC-2
• Participant must have elevated serum bile acid (s-BA) concentration
• Participant must have history of significant pruritus and a caregiver reported observed scratching in the eDiary
• Participant and/or legal guardian must sign informed consent (and assent) as appropriate.
• Participants will be expected to have a consistent caregiver(s) for the duration of the study
• Caregivers and age-appropriate participants (≥8 years of age) must be willing and able to use an eDiary device as required by the study

Key Exclusion Criteria:

• Participant with pathologic variations of the ABCB11 gene that predict complete absence of the bile salt export pump (BSEP) protein

• Participant with past medical history or ongoing presence of other types of liver disease including, but not limited to, the following:

  1. Biliary atresia of any kind
  2. Benign recurrent intrahepatic cholestasis, indicated by any history of normal s BAs
  3. Suspected or proven liver cancer or metastasis to the liver on imaging studies
  4. Histopathology on liver biopsy that is suggestive of alternate non-PFIC related etiology of cholestasis

• Participant with past medical history or ongoing chronic diarrhea

• Any participant with suspected or confirmed cancers except for basal cell carcinoma

• Participant with a past medical history of chronic kidney disease with an impaired renal function and a glomerular filtration rate <70 mL/min/1.73 m^2

• Participant with surgical history of disruption of the enterohepatic circulation (biliary diversion surgery) within 6 months prior to start of Screening Period

• Participant has had a liver transplant or a liver transplant is planned within 6 months of randomization

• Decompensated liver disease

• Participant suffers from uncontrolled, recalcitrant pruritic condition other than PFIC

• Participant who has been previously treated with an IBAT inhibitor whose pruritus has not responded to treatment