Extension Study to Evaluate the Long-Term Safety and Durability of Effect of LUM001 in the Treatment of Cholestatic Liver Disease in Pediatric Subjects with Alagille Syndrome (IMAGINE-II)

General Description

The IMAGINE-II study was a multicenter, extension study of LUM001 in children diagnosed with Alagille syndrome (ALGS) who had completed participation in a core LUM001 treatment protocol (ITCH study). Efficacy was assessed by evaluating the effect of LUM001 on the biochemical markers and pruritus associated with ALGS.

Note: If requesting access to IMAGINE-II data, it is recommended to also request access to the ITCH Study data (https://repository.niddk.nih.gov/studies/itch/) as IMAGINE-II is an extension study of ITCH.

Objectives

The primary objective of IMAGINE-II was to evaluate long-term safety and tolerability of LUM001.

Outcome Measure

The primary outcome measure of IMAGINE-II was the change from LUM001 Baseline to Week 48 in fasting serum bile acid (sBA). Secondary outcome measures were changes from LUM001 Baseline to Week 216 in biochemical markers of cholestasis and liver disease, pruritus, xanthomas, clinician scratch scale, and sBA.

Criteria

Inclusion criteria:

• Male or female, 12 months to 18 years of age
• Competent to provide informed consent and assent
• Completed participation in the LUM001-301 protocol
• Females of childbearing potential must have a negative urine pregnancy test at the Baseline Visit
• Sexually active females must be prepared to use an effective method of contraception during the trial
• Participants and caregivers must be able to read and understand English or Spanish
• Caregivers (and age appropriate participants) must be willing and able to complete a daily electronic diary (ItchRO) and have access to a phone for scheduled calls
• Participants must be able to adhere to local Ethics Committee or Institutional Review Board (IRB) blood volume limits for laboratory testing

Exclusion criteria:

• Experienced an adverse event or serious adverse event (SAE) related to the study drug during the LUM001-301 protocol that led to the discontinuation of the participant from the core study
• Any conditions or abnormalities (including laboratory abnormalities) which in the opinion of the Investigator, Medical Monitor or ChiLDReN Protocol Chair, may compromise the safety of the participant, or interfere with the participant participating in or completing the study
• History or known presence of gallstones or kidney stones
• History of non-adherence during the participant's participation in the LUM001-301 protocol
• Unlikely to comply with the study protocol, or unsuitable for any other reason, as judged by the investigator

Detailed inclusion and exclusion criteria can be found in the study protocol.

Outcome

The IMAGINE-II study was not analyzed and reported separately. It was anticipated the results would be integrated with the ITCH study. A pooled analysis of the US- and Canadian-based ITCH randomized placebo-controlled trial and its extension study IMAGINE-II of LUM001 and the UK-based IMAGO randomized placebo-controlled trial and its extension study IMAGINE was reported since the structure of the US/Canadian-based and UK-based studies were comparable.