The purpose of this trial is to assess dose related safety, efficacy, and pharmacokinetics (PK) of INT-787 in participants with severe alcohol-associated hepatitis (sAH).
This is a Phase 2a, randomized, double-blind, placebo-controlled, dose-escalation, proof-of-concept study to evaluate the safety, tolerability, efficacy, and PK of INT-787 in participants, initially admitted to the hospital, with severe alcohol-associated hepatitis (sAH). The study aims to demonstrate and provide rationale for the selection of optimal dose(s) of INT-787 in the target population of participants with sAH. INT-787 will be evaluated for safety and tolerability prior to dose escalation. Overall efficacy, compared to placebo, will be assessed for each dose cohort. Additionally, PK measurements at various study timepoints will allow the Sponsor to better understand the systemic exposure of INT-787 and the relationship between exposure and efficacy and safety. Such insights in participants with more advanced liver disease will provide valuable information for future clinical trials of INT-787. The placebo-treated participants will provide important natural history information on outcomes in this participant population with sAH treated with supportive care. The placebo-treated participants within cohorts are meant to blind the study drug administration while the data across dose cohorts will be used in the overall analysis.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
80
Lille model response based on Lille score by treatment group
The Lille score response rate will be analyzed as a categorical variable. Participants with Lille score \<0.45 will be counted as responders and those with Lille score ≥0.45 will be counted as non-responders.
Time frame: Day 7
Change from baseline in the Model for End-Stage Liver Disease (MELD) score at 28-days by treatment group
The MELD scoring system is used to assess the severity of liver disease in participants in the setting of alcohol-associated hepatitis. The MELD score is derived from the participant's serum total bilirubin, serum creatinine, and international normalized ratio (INR). The MELD score ranges from 6 to 40 with higher scores indicating more severe liver disease and a worse outcome.
Time frame: Baseline and at Day 28
Change from Baseline in total bilirubin
Time frame: Baseline and at Day 7, 14, 21, 28, 56 and 84
Difference in 28-day, 56-day, and 84-day all-cause mortality or liver transplantation (TFS) between INT-787 and placebo
Time frame: Day 28, 56, 84
Number of participants with treatment emergent adverse events (TEAEs), serious adverse events (SAEs) and treatment emergent adverse event of special interest (AESIs)
Time frame: During the study period, up to 12 weeks
Number of participants reporting infectious adverse events by System organ class (SOC)/ preferred term by treatment group
Time frame: During the study period, up to 12 weeks
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Stanford Healthcare
Palo Alto, California, United States
RECRUITINGClinical Translational Research Site
Miami, Florida, United States
RECRUITINGTampa General Medical Group
Tampa, Florida, United States
RECRUITINGRush University Medical Center
Chicago, Illinois, United States
RECRUITINGMercy Medical Center
Baltimore, Maryland, United States
RECRUITINGBeth Israel Deaconess Medical Center
Boston, Massachusetts, United States
RECRUITINGUMass Memorial Medical Center
Worcester, Massachusetts, United States
RECRUITINGHenry Ford Health System
Detroit, Michigan, United States
RECRUITINGMayo Clinic
Rochester, Minnesota, United States
RECRUITINGRutgers-New Jersey Medical School
Newark, New Jersey, United States
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