BSEP Function Rescue During Childhood Inhereditary Cholestatic Diseases

NCT04531878 | Withdrawn Phase 2 DMC

• 1 other identifier: BSEP_FudanEK_001
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

The purpose of the study is to improve the prognosis of inhereditary cholestasis caused by ABCB11 gene mutations by using BSEP function rescue drugs

Conditions

Hereditary Diseases; Cholestasis, Intrahepatic

Keywords

BSEP; ABCB11; biliary diversion; liver biopsy; gene

Outcome Measures

Primary Outcomes (1)

• Native liver survive time

  Time of patient survived with native liver will be accessed.

  During follow-up (about 3 years）

Secondary Outcomes (14)

• ALT(Alanine Aminotransferase)

  at day 0, 7, 14, 28, 56, 90, 120, 180, 240, 300, 360, 540, 720 and 1080

• DB(direct bilirubin) levels

  at day 0, 7, 14, 28, 56, 90, 120, 180, 240, 300, 360, 540, 720 and 1080

• TB(total bilirubin)

  at day 0, 7, 14, 28, 56, 90, 120, 180, 240, 300, 360, 540, 720 and 1080

• AST(Aspartate Aminotransferase)

  at day 0, 7, 14, 28, 56, 90, 120, 180, 240, 300, 360, 540, 720 and 1080

• Weight

  at day 0, 7, 14, 28, 56, 90, 120, 180, 240, 300, 360, 540, 720 and 1080

Study Arms (1)

BSEP trafficking abnormal group

EXPERIMENTAL

Patients with ABCB11 missense mutations that were speculated to affect the BSEP trafficking

Drug: 4-Phenylbutyrate

Interventions

4-Phenylbutyrate DRUG

4-phenylbutyrate therapy will be started at a daily dose of 200 mg kg/d divided in 2 oral doses of sodium phenylbutyrate (AMMONAPS, Swedish Orphan Inter AB). In order to get the best effect, the dose will be increased up to a maximum of 500 mg kg/d.

Also known as: UDCA or biliary diversion

BSEP trafficking abnormal group

Eligibility Criteria

• Age: 2 Months - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• with signed informed consent form from the guardian, and the patient if applicable.
• aged from 2 month to 18 years old.
• with cholestatic disease caused by ABCB11 biallelic mutation.
• Long-term residence in China.

You may not qualify if:

• Currently receiving or previously received experimental drugs.
• The child is already in the stage of liver failure, or in unstable state that are not suitable for drug treatment according to the researcher's judgment: serious complications such as bleeding tendency and skin rash.
• accompany with other chronic liver disease (viral hepatitis B and C, autoimmune hepatitis, wilson disease, cystic fibrosis, primary biliary cirrhosis, biliary atresia, sclerosing cholangitis, bile acid synthesis defects, and infections, cholestasis caused by space-occupying and other reasons).
• Suffered from congenital TORCHES infection, including toxoplasma gondii, rubella virus, cytomegalovirus, herpes simplex virus, EB virus, syphilis, HIV, etc.
• With any other major medical conditions that may affect drug absorption, metabolism, or excretion based on the researcher's judgment.
• Known or suspected hypersensitivity to any experimental drugs or their indigents.
• Patients with alcohol or drug dependence.
• In receiving any investigational drugs or within 60 days before enrollment.

Sponsors & Collaborators

• Children's Hospital of Fudan University: lead

Related Links

• Targeted pharmacotherapy in ABCB11 mutation by 4-phenylbutyrate
• Pharmacological premature termination codon readthrough of ABCB11
• Functional rescue of an ABCB11 mutant by ivacaftor

MeSH Terms

Conditions

Genetic Diseases, Inborn; Cholestasis, Intrahepatic; Cholestasis, progressive familial intrahepatic 2

Interventions

4-phenylbutyric acid; Ursodeoxycholic Acid

Condition Hierarchy (Ancestors)

Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Cholestasis; Bile Duct Diseases; Biliary Tract Diseases; Digestive System Diseases; Liver Diseases

Intervention Hierarchy (Ancestors)

Deoxycholic Acid; Cholic Acids; Bile Acids and Salts; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Cholanes

Study Officials

• Jian-She Wang, Ph.D

  Children's hospital of Fudan Unviersity

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 26, 2020
• First Posted: August 31, 2020
• Study Start: February 8, 2023
• Primary Completion: February 8, 2023
• Study Completion: February 8, 2023
• Last Updated: February 9, 2023

Record last verified: 2023-02

Data Sharing

• IPD Sharing: Will not share