This Study Will Investigate the Efficacy and Safety of A4250 in Children With PFIC Types 1 or 2
Condition: PFIC1; PFIC2
MeSH terms: Cholestasis
Intervention: A4250 (odevixibat); Placebo
Intervention description: A4250 is a small molecule and selective inhibitor of ileal bile acid transporter (IBAT).; Placebo identical in appearance to active drug (A4250).
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Double-Blind, Randomized, Placebo-Controlled
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 62.0
Sex: All
Minimum age: 6 Months
Maximum age: 18 Years
Healthy volunteers: No
Keywords: Pediatric; Cholestasis

Summary:

      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.
    

Eligibility criteria:

        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