US-based Lumena Pharmaceuticals has started dosing the first patient in the INDIGO Phase II clinical trial of its lead drug candidate, LUM001, in children with progressive familial intrahepatic cholestasis (PFIC).
In addition, the CAMEO Phase II clinical trial of LUM001 in adults with primary sclerosing cholangitis (PSC) is open for enrolment, the company said.
The company is developing LUM001 as a therapy for cholestatic liver diseases including PFIC, PSC, Alagille syndrome and primary biliary cirrhosis, which result in impaired bile acid flow and retention of bile acids in the liver, leading to progressive liver damage that may ultimately result in liver failure.
The most debilitating symptom afflicting children and adults with these diseases is severe itching.
LUM001 is an inhibitor of the apical sodium-dependent bile acid transporter (ASBT), which recycles bile acids from the intestine to the liver.
The company said that blocking bile acid transport in the intestine with ASBT inhibitors, such as LUM001, has the potential to lower bile acid levels in the body, slow disease progression, enhance liver function and improve the quality of life for patients suffering from cholestatic liver diseases.
King’s College, London, senior lecturer and one of the investigators enrolling patients into the INDIGO trial Richard Thompson said LUM001 may reproduce the effects of more invasive surgical procedures for children suffering from PFIC.
"The potential to alleviate debilitating itching whilst improving overall liver function with a once-daily drug represents a much-needed pharmacological treatment option for this rare, but serious, disease," Thompson said.
The open-label, Phase II INDIGO trial is designed to assess the efficacy and safety of LUM001 for treatment of cholestatic liver disease in patients with PFIC.
Twelve patients under the age of 18 who have been diagnosed with PFIC will be enrolled in the trial and its primary endpoint is change from baseline in fasting serum bile acids, while secondary endpoints include changes from baseline in liver enzymes and pruritus (itching).
The 14 week open-label clinical CAMEO trial is designed to assess the safety, tolerability and efficacy of LUM001 in around 20 adult patients with PSC.
The trial’s primary endpoint is change from baseline in fasting serum bile acids and secondary endpoints include changes from baseline in pruritus and other biochemical markers of cholestasis and liver disease.
University of California, Davis, professor and principal investigator of the CAMEO trial Christopher Bowlus said currently, there are no effective medical therapies which prevent the progression of primary sclerosing cholangitis, which on average leads to liver failure and the need for liver transplantation within 15 years of diagnosis.
"There is a significant need for drug treatments for this serious condition, and this trial is an important step in that direction," Bowlus said.
Image: High-magnification micrograph showing liver cholestasis. Photo: courtesy of Nephron.