Open label study of LUM001 in patients with ALGS or PFIC
Research type
Research Study
Full title
An Open-label, Multicenter Extension Study to Evaluate the Long-term Safety of LUM001, an Apical Sodium-dependent Bile Acid Transporter Inhibitor (ABSTi), in Patients with Alagille syndrome (ALGS) or Progressive Familial Intrahepatic Cholestasis (PFIC).
IRAS ID
178364
Contact name
Ciara Kennedy
Contact email
Sponsor organisation
Shire Human Genetic Therapies Inc
Eudract number
2015-000906-20
Duration of Study in the UK
3 years, 6 months, 19 days
Research summary
Alagille syndrome is an inherited disorder in which a person has fewer than the normal number of small bile ducts
inside the liver. Bile ducts, also called hepatic ducts, are tubes that carry bile from the liver cells to the gallbladder and
eventually drain into the small intestine. Bile is a liquid produced in the liver that serves two main functions: carrying
toxins and waste products out of the body and helping the digestion of fats and the fatsoluble vitamins A, D, E, and K. The decreased number of hepatic ducts causes bile to build up in the liver, leading to liver damage. Eventually the liver may stop working and a liver transplant is necessary. Progressive Familial Intrahepatic Cholestasis (PFIC) is the name given to a group of inherited conditions causing cholestasis (reduced bile flow) in children and young people.
The bile flow is reduced either because the liver cannot make bile properly or because it cannot get it out of the liver cells into the bile ducts, or both. The bile ducts themselves may also be abnormal reducing the flow of bile through them. In patients with PFIC, impairment of the egress of bile acids from the liver leads to cholestasis, hepatocellular injury and damage, and progressive liver disease that may ultimately lead to the need for liver transplantation. Itch is a common symptom associated with cholestasis, it can occur at all stages of cholestatic liver disease, with or without jaundice.
LUM001 is an inhibitor of the ileal bile acid transporter/apical sodiumdependent bile acid transporter/soluble carrier family 10 member 2 (IBAT/ASBT/SLC10A2), initially developed as a lipid lowering agent (SD5613).
At this time, further development for this indication is not planned. By virtue of its ability to inhibit bile acid absorption, LUM001 is being
developed as a therapeutic agent for signs and symptoms of cholestatic liver disease. Evaluation of the safety, tolerability and efficacy of LUM001 is being assessed in children with cholestatic liver
disease associated with ALGS, 12 months to 18 years in 5 clinical studies. Two 13week studies were initiated (LUM001301,
LUM001302), each with a 48week extension study (LUM001305,
LUM001303). A separate 48week randomized withdrawal study, LUM001304, is also ongoing. In addition a 72week study in children
with cholestatic liver disease associated with PFIC, 12 months to 18 years is ongoing, LUM001501.
This study, LUM001601, is an openlabel, multicenter study in patients with ALGS or PFIC who have completed participation in one of the following LUM001 protocols; LUM001303, LUM001304,
LUM001305, or LUM001501.
The study is designed to primarily evaluate the longterm
safety of daily dosing with LUM001, subjects will be dosed for 104 weeks in this study.REC name
South West - Central Bristol Research Ethics Committee
REC reference
15/SW/0115
Date of REC Opinion
8 May 2015
REC opinion
Favourable Opinion