Progressive Familial Intrahepatic Cholestasis(PFIC)
Conditions
Interventions
Subjects who met the eligibility criteria at the screening test will receive A4250 40 micro g/kg (once daily) of study drug from the next day of Visit 3 (Day 1) for 12 weeks. If no safety problems are
Sponsors
Achiwa Hiroyuki
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Patients will be enrolled in the study if they meet all of the following criteria: 1. (Cohort 1) A Japense male or female patient, with diagnosis of PFIC Type 1 or 2 through identification of biallelic pathogenic variants in either the ATP8B1 or ABCB11 genes, between the ages of >=6 months and =100 micro mol/L, taken as the average of 2 samples at least 7 days apart (Visits 1 and 2) prior to randomization 4. Patient must have history of significant pruritus and a patient or guardian-reported observed scratching in the Patient Diary average of >=2 (on 0 to 4 scale) in the 2 weeks prior to Visit 3. However, if the patient in Cohort 2 is 18 years or older, the patient must have a history of significant pruritus and a patient -reported observed scratching in the Patient Diary with average itching score of >=2 (on 0 to 4 scale) in the 2 weeks prior to Visit 3. 5. Patient and/or legal guardian who can sign informed consent (or assent if the patient is below 15 years old) as appropriate. Patients who turn 18 years of age (or legal age per country) during the study will be required to re-consent in order to remain in the study 6. Patients who are judged by the investigator or subinvestigator to be able to continue treatment with the study drug for at least 24 weeks. 7. Patients will be expected to have a consistent guardian for the duration of the study (Parents and grandparents are preferred as guardians. It is preferable that the same guardian will answer the patient diary and other questionnaires, but parents and grandparents can be changed if it is unavoidable). For Cohort 2, if the patient is 18 years of age or older at the time of Visit 1 (when informed consent is obtained), setting of the guardian in this study is not mandatory. 8. Guardians and age-appropriate patients (>=8 years of age) and patients who achieve 8 years of age during the study must be willing and able to use an Patient Diary as required by the study
Exclusion criteria
Exclusion criteria: Patients who meet any of the following criteria will be excluded from the study: 1. Patient with pathologic variations of the ABCB11 gene that predict complete absence of the BSEP protein 2. Patient with past medical history or ongoing complication of liver disaese other than underlying disease, but not limited to, the following: a) Biliary atresia of any kind b) Benign recurrent intrahepatic cholestasis, indicated by any test results of normal s-Bas c) Suspected or proven liver cancer or metastasis to the liver on imaging studies d) Histopathology on liver biopsy is suggestive of alternate non-PFIC related etiology of cholestasis 3. Patient with a past medical history or ongoing presence of any other disease or condition known to interfere with the absorption, distribution, metabolism (specifically bile acid metabolism), or excretion of drugs in the intestine, including but not limited to, inflammatory bowel disease 4. Patient with past medical history or ongoing chronic (i.e., >3 months) diarrhea requiring intravenous fluid or nutritional intervention for treatment of the diarrhea and/or its sequelae 5. Patient who has the followings: a) A confirmed past diagnosis of infection with human immunodeficiency virus b) Present and active, clinically significant, acute, or chronic infection c) Past medical history of any major episode of infection requiring hospitalization within 4 weeks of treatment start (study Day 1) d) Treatment with parenteral anti-infective treatment within 4 weeks of treatment start (study Day 1) e) Completion of oral anti-infective treatment within 2 weeks prior to start of Screening Period 6. Patient who have diagnosis and treatment history of malignancy within 5 years prior to obtaining concent. 7. Patient with a past medical history of chronic kidney disease with an impaired renal function and a glomerular filtration rate 1.4 at Screening (the patient who is treated with Vitamin K intravenously, and the INR is =10^ upper limit of normal (ULN) at Screening 13. Serum ALT >15^ ULN at any time point during the last 6 months and the alternate etiology for the elevation is not confirmed 14. Total bilirubin >10^ ULN at Screening 15. Patient suffers from uncontrolled, recalcitrant pruritic condition other than PFIC. Examples include, but not limited to, refractory atopic dermatitis or other primary pruritic skin diseases 16. Any patient who is pregnant or lactating or who is planning to become pregnan 17. Sexually active males and females who are not using a reliable contraceptive method with =<1% failure rate (such as hormonal contraception, intrauterine 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). 18. Patient with a past medical history of alcohol or substance abuse will be excluded. Patient must agree to refrain from illicit drug and alcohol use during the study 19. Administr
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| - The proportion of patients experiencing at least a 70% reduction in fasting s-BA concentration from baseline to Week 24 or reaching a level - Change from baseline in s-BA after 72 weeks of treatment (the dose maintenance period) - The proportion of positive pruritus assessment at the subject level over the 72-week treatment period (the dose maintenance period) using the ObsRO instrument | — |
Contacts
Public ContactHiroyuki Achiwa
Jadeite Medicines Inc.
Outcome results
None listed