FXR Effect on Severe Alcohol-Associated Hepatitis (FRESH) Study

Launched by INTERCEPT PHARMACEUTICALS · Nov 28, 2022

Keywords

ClinConnect Summary

The FRESH Study is a clinical trial designed to explore the safety and effectiveness of a new medication called INT-787 for people suffering from severe alcohol-associated hepatitis (sAH). This condition occurs when the liver is damaged due to excessive alcohol consumption, leading to significant health issues. The trial is currently recruiting participants between the ages of 18 and 65 who have been diagnosed with sAH based on specific medical criteria, such as a history of heavy drinking and certain blood test results.

Participants in this study can expect to receive the investigational medication and will be closely monitored by healthcare professionals. They will also need to agree to take part in an alcohol use disorder program during the study. It’s important to note that individuals with certain health conditions or those who have recently taken specific medications may not qualify for the trial. If you or someone you know is interested in participating, it’s a good idea to discuss it with a healthcare provider to understand all the eligibility requirements and what the study entails.

Gender

ALL

Eligibility criteria

• Inclusion Criteria:
• • 1. Males or females aged 18 to 65 years (inclusive)
• 2. Clinical diagnosis of sAH based on all the following:
• • 1. 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
• • 2. Serum total bilirubin \>3.0 mg/dL
• • 3. Aspartate aminotransferase (AST) ≥50 U/L
• • 4. AST/Aspartate aminotransferase (ALT) ratio ≥1.5
• • 5. Onset of jaundice within prior 8 weeks
• • 6. Maddrey's Discriminant Factor (mDF) ≥32 and ≤70
• • 3. MELD score 18 to 25 (inclusive)
• 4. Female participants 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 hormone-releasing 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: 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
• • 5. Male participants 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.
• • 6. Male participants must refrain from sperm donation from the initiation of Screening and until at least 90 days after the last dose of investigational product
• • 7. Must provide written informed consent and agree to comply with the study protocol. In participants with hepatic encephalopathy which may impair decision-making, consent will be obtained per hospital procedures (e.g., by Legally Authorized Representative).
• • 8. Participants 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:
• • 1. Participants taking products containing obeticholic acid in the 30 days prior to randomization
• • 2. Participants taking \>2 doses of systemic corticosteroids within 30 days prior to randomization.
• • 3. Participants who have been inpatient at a referral hospital for \>7 days prior to transfer.
• • 4. Pregnancy, planned pregnancy, potential for pregnancy (e.g., unwillingness to use effective birth control during the study), or current or planned breast feeding.
• • 5. Abstinence from alcohol consumption for \>2 months before Day 1.
• • 6. AST or ALT \>400 U/L.
• • 7. mDF \<32 or \>70 at Screening
• • 8. MELD score \<18 or \>25 at Screening.
• • 9. Other causes of liver disease including chronic hepatitis B (hepatitis B surface antigen \[HBsAg\] positive), chronic hepatitis C virus (HCV) RNA positive, drug-induced liver injury (DILI), biliary obstruction, and autoimmune liver disease.
• • 10. Current or previous history of hepatocellular carcinoma (HCC)
• • 11. History of liver transplantation or currently listed for liver transplant
• • 12. Untreated infection (e.g., has not initiated appropriate medical treatment for infection)
• • 13. Known positivity for human immunodeficiency virus infection
• • 14. 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.
• • 15. Kidney injury defined as a serum creatinine \>133 μmol/L (\>1.5 mg/dL) or the requirement for renal replacement therapy.
• • 16. Portal vein thrombosis
• • 17. Acute pancreatitis or acute gallbladder disease (e.g., cholecystitis)
• • 18. Severe, on-going associated disease (e.g., cardiac failure, acute myocardial infarction, severe cardiac arrhythmias, severe pulmonary disease, neurologic disease)
• • 19. 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). Participants under evaluation for possible malignancy are not eligible.
• • 20. 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 in-patient management. Participants being treated for alcohol withdrawal may be exempt for this reason, verify with Medical Monitor.
• • 21. 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
• • 22. Participation in a study of another investigational medicine or device within 30 days before Screening
• • 23. 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