An Open-label Extension Study to Evaluate Long-term Efficacy and Safety of A4250 in Children with Progressive Familial Intrahepatic Cholestasis Types 1 and 2 (PEDFIC 2)
- Conditions
- 10019806Progressive Familial Intrahepatic Cholestasis (PFIC)10019654
- Registration Number
- NL-OMON54766
- Lead Sponsor
- Albireo AB
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- Not specified
- Target Recruitment
- 8
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 Completion of the 24-week Treatment Period of Study A4250-005 or withdrawn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 cholestatis
[BRIC]) and with a body weight greater or equal to 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 (greater or equal to 8 years of age
if able) must be willing and able to use an eDiary device as required by the
study.
Patients meeting any of the following criteria at Visit 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 barrier protection, 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). See Appendix 6 for further
details.
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 less than or equal to 1.4 at resampling the patient may be included)
6. Serum ALT>10 x upper limit of normal (ULN) at Screening
7. Serum ALT>15 x ULN at any time point during the last 6 months unless an
alternate etiology was confirmed for the elevation
8. Total bilirubin >5 x ULN at Screening
9. Patient suffers from uncontrolled, recalcitrant pruritic condition other
that 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
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Primary Efficacy Endpoints<br /><br>European Union (EU) and rest of world: Change from baseline in serum bile acids<br /><br>after 72 weeks of treatment.<br /><br>US: Change in pruritus, as indexed by caregiver-reported observed scratching,<br /><br>from baseline over the treatment period i.e. up to 72 weeks, as measured by an<br /><br>overall mean of weekly averages of the worst daily scratch score using the<br /><br>Albireo observer-reported outcome (ObsRO) instrument.</p><br>
- Secondary Outcome Measures
Name Time Method