The ITCH study was a randomized, double-blind, placebo-controlled, parallel group, multi-center study in children with Alagille syndrome (ALGS). The study was designed to investigate the effects of LUM001 (Maralixibat), compared to placebo, on pruritus, serum bile acids, liver enzymes, and other biochemical markers associated with cholestatic liver disease, following daily dosing over a 13-week period.

The objectives of the ITCH study were:

• To evaluate the effect of LUM001 versus placebo on pruritus, as measured by the Itch Reported Outcome (ItchRO) instrument
• To evaluate the safety and tolerability of LUM001
• To evaluate the effect of LUM001 versus placebo on serum bile acids
• To explore the effect of LUM001 versus placebo on other biochemical markers of cholestasis and liver disease

The primary outcome measure of the study was the change from baseline to endpoint in pruritus. Pruritus was assessed using the ItchRO and was administered as an electronic diary (eDiary) two times a day (morning and evening). The ItchRO score ranged from 0 to 4, with the higher score indicating increasing itch severity. The highest score between the morning and evening ItchRO reports represented the daily score (i.e., a measure of the worst itching over the previous 24-hour period).

Secondary outcome measures:

• Change from baseline to endpoint in fasting serum bile acid levels
• Change from baseline to endpoint in liver enzyme levels
• Change from baseline to endpoint in total and direct bilirubin concentrations

Inclusion criteria:

• Diagnosis of ALGS
• Evidence of cholestasis
• Moderate to severe pruritus
• Ability to understand and willingness to sign informed consent/assent prior to initiation of any study procedures

Exclusion criteria:

• Surgical disruption of the enterohepatic circulation
• Liver transplant
• History or presence of other concomitant liver disease
• Females who are pregnant or lactating
• Known HIV infection

A 1-point reduction in pruritus was more common in LUM001-treated versus placebo-treated participants (caregiver ItchRO, 65% versus 25%, p = 0.06; clinician score, 76% versus 25%, p = 0.01). There were no significant changes in liver chemistries or bile acids relative to placebo. Adverse and serious adverse events were similar between LUM001 and placebo. Although the prespecified primary analyses of ItchRO were not all statistically significant, the data suggest that LUM001 is safe and may reduce pruritus in ALGS.