Progressive Familial Intrahepatic Cholestasis Types 1 and 2 MedDRA version: 20.0 Level: PT Classification code 10076033 Term: Progressive familial intrahepatic cholestasis System Organ Class: 10010331 - Congenital, familial and genetic disorders
Conditions
Sponsors
Albireo AB
Eligibility
Sex/Gender
All
Inclusion criteria
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 Completion of the 24-week Treatment Period of Study A4250-005 or withdrawn from Study A4250-005 due to patient/caregiver judgment of intolerable symptoms after completing at least 12 weeks of treatment.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, including episodic forms (i.e., benign recurrent intrahepatic cholestasis [BRIC]), and with a body weight =5 kg at Visit S-1 2. Patient must have clinical genetic confirmation of PFIC. 3. Patients with PFIC, excluding BRIC, must have elevated serum bile acid concentration 4. Patients with PFIC, excluding BRIC, must have history of significant pruritus 5. Patients with episodic forms of PFIC (i.e., BRIC) must have an emerging flare characterized by clinically significant pruritus and elevated serum bile acid levels/cholestasis as judged by the investigator 6. Patient and/or legal guardian must sign informed consent (and assent) as appropriate. 7. Age appropriate patients are expected to have a consistent caregiver for the duration of the study 8. 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
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. Note: Patients with clinically significant portal hypertension are allowed. 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Primary Objective (Cohort 1) To demonstrate a sustained effect of A4250 on serum bile acids and pruritus in children with PFIC Types 1 and 2 Primary Objective (Cohort 2) To evaluate the effect of A4250 on serum bile acids and pruritus in patients with PFIC who either (1) do not meet eligibility criteria for Study A4250-005 (PEDFIC 1) or (2) who do meet the eligibility criteria for Study A4250-005 after recruitment of Study A4250-005 has been completed. ;Secondary Objective: Cohorts 1 and 2: • To evaluate the long-term safety and tolerability of repeated daily doses of A4250 • To evaluate the effect of A4250 on growth • To evaluate the effect of A4250 on biliary diversion and/or liver transplantation • To evaluate the effect of A4250 on biochemical markers of cholestasis and liver disease;Primary end point(s): The primary efficacy endpoint is: Change from baseline in serum bile acids after 72 weeks of treatment. ;Timepoint(s) of evaluation of this end point: Screening/ Inclusion Visit and week 72 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary efficacy endpoints include: • Proportion of positive pruritus assessments at the patient level over • Change from baseline in serum bile acids to Week76 • Proportion of individual assessments meeting the definition of a positive pruritus assessment at the patient level using the Albireo ObsRO instrument to Week 70 • Proportion of individual AM assessments meeting the definition of a positive pruritus assessment at the patient level using the Albireo ObsRO instrument to Week 72 • Proportion of individual PM assessments meeting the definition of a positive pruritus assessment at the patient level using the Albireo ObsRO instrument to Week 72 • All-cause mortality, number of patients undergoing biliary diversion surgery or liver transplantation. • Change in growth after initiation of A4250 treatment • Change in AST to platelet ratio index (APRI) score and Fib-4 score from baseline to Week 72 • Change in pediatric end-stage liver disease (PELD)/model for endstage liver disease (MELD) score from baseline to Week 72 • Change in use of antipruritic medication;Timepoint(s) of evaluation of this end point: • Weeks 24, 48, 72 and 76 | — |
Countries
Australia, Belgium, Canada, France, Germany, Israel, Italy, Netherlands, Poland, Saudi Arabia, Spain, Sweden, Turkey, United Kingdom, United States
Contacts
Public ContactClinical Operations Department
Albireo AB
Outcome results
None listed