Open-label, Phase 3 Study to Evaluate Efficacy and Safety of Odevixibat (A4250) in Patients with Alagille Syndrome

JRCT ID: jRCT2041240037

Registered date:29/05/2024

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: Alagille Syndrome
• Date of first enrollment: 11/06/2024
• Target sample size: 10
• Study type: Interventional
• Intervention(s): Subjects will receive A4250 120 micro g/kg(once daily)of study drug.The investigator can decrease to 40 micro g/kg or increase to 120 micro g/kg of study drug according to the subject's safety and tolerability of A4250.

Outcome(s)

Primary Outcome

- Change from baseline in scratching to Month 6 (Weeks 21 to 24) as measured by the ObsRO
- Change in serum bile acid levels from baseline to the average of Week 20 and Week 24
- Evaluation of adverse events (AEs) including severity and relatedness to study drug

Key inclusion & exclusion criteria

• Age minimum: Not applicable
• Age maximum: Not applicable
• Gender: Both

Include criteria

1.A male or female patient (of any age) with genetically confirmed diagnosis of ALGS.
2.Patient must have a history of significant pruritus and a caregiver reported observed scratching or a patient-reported pruritus score at an average of >=2 (on 0 to 4 scale), as measured by the ObsRO (for patients <18 years of age) or the PRO (for patients >18 years of age) in the 14 consecutive days prior to registration.
3.Each of the serum bile acid levels (measured at each study site) obtained at Screening Visit 1 and Screening Visit 2 must be greater than the upper limit of normal (>ULN).
4.Patient and/or legal guardian must sign informed consent.
5.Caregivers must be willing and able to use an Patient Diary as required by the study and patients>=8 years of age must be willing to use an Patient Diary.
6.Sexually active males and females must agree to use 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.
7.Patients will be expected to have a consistent caregiver for the duration of the study). But the setting of the caregiver is not mandatory when the subject is 18 years old or older at Visit 1 (at the time of informed consent).

Exclude criteria

1.Patient with past medical history or ongoing presence of other types of liver disease including,but not limited to,the following
a)Biliary atresia of any kind
b)PFIC
c)Benign recurrent intrahepatic cholestasis
d)Suspected or proven liver cancer or metastasis to the liver on imaging studies
2.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
3.Patient with past medical history or ongoing chronic (i.e. >3 months) diarrhea requiring intravenous fluid or nutritional intervention for treatment of the diarrhea
4.Patient has a confirmed past diagnosis of infection with human immunodeficiency virus or other present and active, clinically significant chronic infection
5.Recent infection requiring hospitalization or treatment with parenteral anti-infective within 4 weeks prior to first dose (Visit 3) or completion of oral anti-infective treatment within 2 weeks prior to informed consent
6.History or presence of liver cancer, or cancer within the last 5 years of informed consent except for basal cell carcinoma
7.Chronic kidney disease with an impaired renal function and a glomerular filtration rate <70 mL/min/1.73 m2 at Screening
8.Patient with surgical history of disruption of the enterohepatic circulation (biliary diversion surgery) within 6 months prior to informed consent
9.Patient has had a liver transplant or a liver transplant is planned within 6 months prior to first dose (Visit 3)
10.Decompensated liver disease, history or presence of clinically significant ascites, variceal hemorrhage, and/or encephalopathy
11.INR >1.4 at Screening (the patient may be treated with Vitamin K intravenously, and if INR is =<1.4 at resampling the patient may be randomized)
12.Serum ALT >10 X ULN at Screening
13.Serum ALT >15 X ULN at any time point within 6 months prior to informed consent unless an alternate etiology was confirmed for the elevation.
14.Total bilirubin >15 X ULN at Screening
15.Patient suffers from uncontrolled, recalcitrant pruritic condition other than ALGS.
16.Any patient who is pregnant or lactating or who is planning to become pregnant
17.Patient with a past medical history of alcohol or substance abuse. Patient must agree to refrain from illicit drug and alcohol use during the study.
18.Administration of bile acid or lipid binding resins and medications that slow gastrointestinal motility at informed consent
19.Patient has had investigational exposure to a drug, biologic agent, or medical device within 30 days prior to informed consent, or 5 half-lives of the other study agent, whichever is longer
20.Patient who has been previously treated with an IBAT inhibitor whose pruritus has not responded to treatment. Of note, if the patient is taking IBAT inhibitors at the time of informed consent, IBAT inhibitors must be discontinued from the date of informed consent.
21.Patient who have changed dosage within 6 months prior to informe consent if taking sodium phenylbutyrate (excluding patients who have changed dosage due to weitht change)
22.Any other conditions or abnormalities which, in the opinion of the investigator or sponsor may compromise the safety of the patient, or interfere with the patient participating in or completing the study
23.Personnel and family members of the study site or sponsor
24.Patients who are scheduled to undergo surgery during the study period

Related Information

• Primary Sponsor: Achiwa Hiroyuki