Evaluation of INT-787 in Severe Alcohol-Associated Hepatitis: A Phase 2a Randomized, Double-Blind, Placebo-Controlled, Dose-Escalation Study
- Trial ID
- 2024-512913-42-00
- Protocol
- 787-201
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to evaluate the **efficacy** of INT-787 in subjects with severe alcohol-associated hepatitis (sAH) by assessing disease progression. This is clinically relevant as sAH is a serious condition with limited treatment options, and understanding the efficacy of INT-787 could potentially lead to improved therapeutic strategies.
Participants
The clinical trial involves a total of **38 participants** diagnosed with **severe alcohol-associated hepatitis**. The study population includes both male and female subjects, aged between **18 to 65 years**. Participants were selected based on specific inclusion criteria, including a clinical diagnosis of severe alcohol-associated hepatitis characterized by ongoing excessive alcohol consumption, specific liver function test results, and recent onset of jaundice. The trial population is required to adhere to certain lifestyle considerations, such as participation in an alcohol use disorder program during the study period. Both male and female participants must comply with contraceptive measures to prevent pregnancy during and after the trial. The study includes a vulnerable population, as it involves individuals with a serious health condition. Participants must provide written informed consent, and in cases of impaired decision-making due to hepatic encephalopathy, consent is obtained through legally authorized representatives.
Plans and Procedures
The clinical trial is a **Phase 2a**, randomized, double-blind, placebo-controlled, multicenter, dose-escalation study designed to evaluate the safety, tolerability, efficacy, and pharmacokinetics of **INT-787** in subjects with severe alcohol-associated hepatitis. The trial aims to assess the efficacy of INT-787 by monitoring disease progression. The study is expected to run from July 3, 2023, to December 23, 2024, with an estimated maximum treatment period of 28 days for each participant.
Participants will be randomly assigned to receive either INT-787 or a placebo, administered orally in capsule form. The trial will include several key visits: an initial screening visit to confirm eligibility based on specific inclusion criteria, including age, clinical diagnosis, and alcohol use history. Following the screening, participants will undergo a series of follow-up visits to monitor their response to the treatment, with a primary endpoint assessment using the Lille score on Day 7. The study will conclude with an end-of-study visit to evaluate the overall outcomes and any adverse effects.
The expected length of participant involvement is approximately 28 days, with conditions for early termination including non-compliance with the study protocol, withdrawal of consent, or any adverse events that may compromise participant safety. Participants must agree to comply with the study protocol, including participation in an alcohol use disorder program as recommended by addiction medicine specialists. The trial is not classified as low intervention and is conducted under the sponsorship of Intercept Pharmaceuticals Inc.
Treatment
The clinical trial involves the administration of **INT-787**, an investigational medication developed by Intercept Pharmaceuticals Inc. **INT-787** is provided in a **capsule** form and is intended for **oral use**. The active substance, also named **INT-787**, is of chemical origin. The maximum daily dose is 120 mg, with a total maximum dose of 3360 mg over a treatment period of 28 days. The dosing schedule is designed to ensure participant safety and adherence, with compliance monitored throughout the study duration.
A **placebo** is utilized as a comparator treatment in this study. The placebo is designed to match the investigational product in appearance but contains no active pharmaceutical ingredient. The use of a placebo allows for a double-blind study design, ensuring that neither the participants nor the investigators are aware of the treatment assignments, thus minimizing bias in the assessment of the investigational drug's efficacy and safety.
Efficacy
The efficacy of INT-787 in the treatment of severe **alcohol-associated hepatitis** (sAH) will be assessed using the primary endpoint of the Lille score, which measures response at Day 7. This score is a validated tool used to evaluate the early response to treatment in patients with sAH. The trial is designed as a Phase 2a, randomized, double-blind, placebo-controlled, multicenter, dose-escalation study. The primary objective is to evaluate the efficacy of INT-787 by assessing disease progression in subjects with sAH. The study will involve the administration of INT-787 in capsule form, with a maximum daily dose of 120 mg and a total treatment period of 28 days. Efficacy assessments will be conducted at specified timepoints, with the primary measurement occurring on Day 7. The trial will ensure that data collection and analysis are conducted in a manner consistent with clinical trial protocols, utilizing appropriate statistical methods to evaluate the efficacy outcomes.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Males or females aged 18 to 65 years (inclusive)
- Clinical diagnosis of sAH based on all the following: a. History of ongoing excess alcohol (>60 g/day [male] or >40 g/day [female]) use for ≥6 months, with <60 days of abstinence prior to the onset of jaundice b. Serum total bilirubin >3.0 mg/dL c. AST ≥50 U/L d. AST/ALT ratio ≥1.5 e. Onset of jaundice within prior 8 weeks f. Cohort 1 through Cohort 4: mDF ≥32 and ≤70 g. Cohort 5 and Cohort 6: mDF ≥32 h. Cohort 1 through Cohort 4: MELD score ≥18 to ≤25 i. Cohort 5 and Cohort 6: MELD score ≥21 to ≤30
- Female patients must be postmenopausal, surgically sterile, or, if premenopausal (and not surgically sterile), be prepared to use ≥1 highly effective method of contraception from the initiation of Screening and for 90 days after the last dose of investigational product as follows: • Surgical sterilization (bilateral tubal occlusion, etc.) • Placement of an intrauterine device (IUD) or intrauterine system (e.g., intrauterine hormonereleasing system [IUS]) • Combined (estrogen and progesterone containing) hormonal contraceptive associated with inhibition of ovulation: − Oral − Intravaginal − Transdermal • Progesterone-only hormonal contraception associated with inhibition of ovulation: − Oral − Injectable − Implantable • Sexual Abstinence: When in line with the preferred and usual lifestyle of the participant, is defined as avoiding all types of activity that could result in conception (pregnancy) from the initiation of Screening and until at least 90 days after the last dose of investigational product.
- Male patients who are sexually active with female partners of childbearing potential must agree to use a condom with spermicide and to use 1 other approved method of highly effective contraception from the initiation of Screening and until at least 90 days after the dose of investigational product as listed in Inclusion Criteria #3
- Male patients must refrain from sperm donation from the initiation of Screening and until at least 90 days after the last dose of investigational product.
- Must provide written informed consent and agree to comply with the study protocol. In patients with hepatic encephalopathy which may impair decision-making, consent will be obtained per hospital procedures (e.g., by Legally Authorized Representative).
- Patients must agree to participate in an alcohol use disorder program during the study period, as recommended by the local institution’s addiction medicine specialists, including post-hospitalization.
Exclusion Criteria
- Patients taking products containing obeticholic acid in the 30 days prior to randomization
- Current or previous history of hepatocellular carcinoma (HCC)
- History of liver transplantation or currently listed for liver transplantation
- Uncontrolled infection (e.g., has not initiated appropriate medical treatment for infection)
- Known positivity for human immunodeficiency virus infection
- Uncontrolled gastrointestinal (GI) bleeding or controlled GI bleeding that was associated with shock or required transfusion of more than 3 units of blood within 7 days of Screening
- Kidney injury defined as a serum creatinine >133 μmol/L (>1.5 mg/dL) or the requirement for renal replacement therapy
- Portal vein thrombosis
- Acute pancreatitis or acute gallbladder disease (e.g., cholecystitis)
- Severe, ongoing associated disease (e.g., cardiac failure, acute myocardial infarction, severe cardiac arrhythmias, severe pulmonary disease, neurologic disease)
- Malignancy within the 2 years prior to Screening, with the exception of specific cancers that have been cured by surgical resection (e.g., basal cell skin cancer). Patients under evaluation for possible malignancy are not eligible
- Patients taking >2 doses of systemic corticosteroids within 30 days prior to randomization
- Positive urine drug screen (amphetamines, barbiturates, benzodiazepines, cocaine, and opiates) except tetrahydrocannabinol or in the setting of documented prescription medications (e.g., opiates, benzodiazepines, amphetamines, barbiturates), which also include medications prescribed as part of inpatient management. Patients being treated for alcohol withdrawal may be exempt for this reason, verify with Medical Monitor.
- Participated in a clinical research study and received any active investigational product being evaluated for the treatment of sAH within 3 months before Day 1
- Participation in a study of another investigational medicine or device within 30 days before Screening
- Any other condition or clinical laboratory result that, in the opinion of the Investigator, might confound the results, or would impede compliance or hinder completion of the study
- Patients who have been inpatient at a referral hospital for >7 days prior to transfer
- Pregnancy, planned pregnancy, potential for pregnancy (e.g., unwillingness to use effective birth control during the study), or current or planned breastfeeding
- Abstinence from alcohol consumption for >2 months before Day 1
- AST or ALT >400 U/L
- Cohort 1 through Cohort 4: mDF <32 or >70
- Cohort 1 through Cohort 4: MELD score <18 or >25
- Other causes of liver disease including chronic hepatitis B (hepatitis B surface antigen [HbsAg] positive), chronic hepatitis C virus (HCV) RNA positive, DILI, biliary obstruction, and autoimmune liver disease
- Cohort 5 and Cohort 6: mDF <32
- Cohort 5 and Cohort 6: MELD <21 or >30
- Participants treated in the Dose Escalation Phase (Cohort 1 through Cohort 4) are not eligible for enrollment into an Extension Cohort (Cohort 5 and Cohort 6), and participants treated in Cohort 5 are not eligible for enrollment into Cohort 6
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 France | Not Recruiting | 03 Jul 2023 | 12 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
Placebo | Placebo | N/A | — | — | — | N/A |