A study to determine the long term effect and safety of A4250 in treatment of children with Progressive Familial Intrahepatic Cholestasis Types 1 and 2.

Recruitment & Eligibility

Status: Authorised-recruitment may be ongoing or finished

Sex: All

Target Recruitment: 120

Inclusion Criteria

Cohort 1:
1. Completion of the 24-week Treatment Period of Study A4250-005 or withdrawn from Study A4250-005 due to patient/caregiver judgment of intolerable symptoms after completing at least 12 weeks of treatment. Patients who withdraw from A4250-005 due to a study drug related AE will not be eligible.
2. Signed informed consent and assent as appropriate. Patients who turn 18 years of age (or legal age per country) during the study will be required to re-consent to remain on the study
3. Patients expected to have a consistent caregiver for the duration of the study
4. Caregivers (and age appropriate patients) must be willing and able to use an eDiary device as required by the study

Cohort 2:
1. A male or female patient of any age, with a clinical diagnosis of PFIC and with a
body weight =5 kg at Visit S-1
2. Patient must have clinical genetic confirmation of PFIC.
3. Patient must have elevated s-BA concentration.
4. Patient must have history of significant pruritus and a caregiver-reported observed scratching or patient-reported itching.
5. Patient and/or legal guardian must sign informed consent (and assent) as appropriate.
6. Age appropriate patients are expected to have a consistent caregiver for the duration of the study
7. Caregivers and age-appropriate patients (=8 years of age, if able) must be willing and able to use an eDiary device as required by the study
Are the trial subjects under 18? yes
Number of subjects for this age range: 120
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 4
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

Patients meeting any of the following criteria at Visit 1 or Visit S-1 will not be eligible for study participation:

Cohort 1:
1. Decompensated liver disease: coagulopathy, history, or presence of clinically significant ascites, variceal hemorrhage, and/or encephalopathy
2. Sexually active males and females who are not using a reliable contraceptive method with =1% failure rate (such as hormonal contraception, intra-uterine device, or complete abstinence) throughout the duration of the study and 90 days thereafter (from signed informed consent through 90 days after last dose of study drug).
3. Patients not compliant with treatment in study A4250-005
4. Any other conditions or abnormalities which, in the opinion of the investigator or Medical Monitor, may compromise the safety of the patient, or interfere with the patient participating in or completing the study

Cohort 2:
1. Known pathologic variations of the ABCB11 gene that have been
demonstrated to result in complete absence of the BSEP protein
2. Patient with past medical history or ongoing presence of other types of liver disease.
3. Patient has had a liver transplant, or a liver transplant is planned within 6 months of the Screening/Inclusion Visit
4. Decompensated liver disease, coagulopathy, history, or presence of clinically significant ascites, variceal hemorrhage, and/or encephalopathy
5. INR >1.4 (the patient may be treated with Vitamin K intravenously, and if INR is =1.4 at resampling the patient may be randomized)
6. Serum ALT >10 × upper limit of normal (ULN) at Screening
7. Serum ALT >15 × ULN at any time point during the last 6 months unless an alternate etiology was confirmed for the elevation
8. Total bilirubin >5 × ULN at Screening
9. Patient suffers from uncontrolled, recalcitrant pruritic condition other than PFIC.
10. Administration of bile acid or lipid binding resins and medications
that slow GI motility
11. Any other conditions or abnormalities which, in the opinion of the investigator or Medical Monitor, may compromise the safety of the patient, or interfere with the patient participating in or completing the study
12. Patient with surgical history of disruption of the enterohepatic circulation (biliary diversion surgery) within 6 months prior to start of Screening Period.

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method

Secondary Outcome Measures

Name	Time	Method

Updated 7/26/2021

A study to determine the long term effect and safety of A4250 in treatment of children with Progressive Familial Intrahepatic Cholestasis Types 1 and 2.

Recruitment & Eligibility

Study & Design

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