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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Intercept Pharmaceuticals Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nutritional and Metabolic Diseases [C18]

Trial duration

21 Aug 2023 → 31 Mar 2026

Decision date (initial)

2024-05-22

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

External identifiers

EU CT number

2024-512913-42-00

EudraCT number

2022-001639-10

ClinicalTrials.gov

NCT05639543

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Pharmacodynamic, Pharmacogenomic, Safety, Dose response, Pharmacokinetic, Others

To evaluate the efficacy of INT-787 as assessed by disease progression in severe alcohol-associated hepatitis (sAH)

Conditions and MedDRA coding

Severe Alcohol-Associated Hepatitis

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. Males or females aged 18 to 65 years (inclusive)
2. 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
3. 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.
4. 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
5. 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.
6. 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).
7. 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 26

1. 1. Patients taking products containing obeticholic acid in the 30 days prior to randomization
2. 12. Current or previous history of hepatocellular carcinoma (HCC)
3. 13. History of liver transplantation or currently listed for liver transplantation
4. 14. Uncontrolled infection (e.g., has not initiated appropriate medical treatment for infection)
5. 15. Known positivity for human immunodeficiency virus infection
6. 16. 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
7. 17. Kidney injury defined as a serum creatinine >133 μmol/L (>1.5 mg/dL) or the requirement for renal replacement therapy
8. 18. Portal vein thrombosis
9. 19. Acute pancreatitis or acute gallbladder disease (e.g., cholecystitis)
10. 20. Severe, ongoing associated disease (e.g., cardiac failure, acute myocardial infarction, severe cardiac arrhythmias, severe pulmonary disease, neurologic disease)
11. 21. 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
12. 2. Patients taking >2 doses of systemic corticosteroids within 30 days prior to randomization
13. 22. 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.
14. 23. 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
15. 24. Participation in a study of another investigational medicine or device within 30 days before Screening
16. 25. 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
17. 3. Patients who have been inpatient at a referral hospital for >7 days prior to transfer
18. 4. Pregnancy, planned pregnancy, potential for pregnancy (e.g., unwillingness to use effective birth control during the study), or current or planned breastfeeding
19. 5. Abstinence from alcohol consumption for >2 months before Day 1
20. 6. AST or ALT >400 U/L
21. 7. Cohort 1 through Cohort 4: mDF <32 or >70
22. 9. Cohort 1 through Cohort 4: MELD score <18 or >25
23. 11. 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
24. 8. Cohort 5 and Cohort 6: mDF <32
25. 10. Cohort 5 and Cohort 6: MELD <21 or >30
26. 26. 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

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Marker of Efficacy - Lille score (response) at Day 7

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Intercept Pharmaceuticals Inc.

Sponsor organisation

Intercept Pharmaceuticals Inc.

Address

305 Madison Avenue

City

Morristown

Postcode

07960-6117

Country

United States

Scientific contact point

Organisation

Intercept Pharmaceuticals Inc.

Contact name

General Information

Public contact point

Organisation

Intercept Pharmaceuticals Inc.

Contact name

General Information

Third parties 3

Locations

1 EU/EEA country · 5 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 16 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

5 submissions — initial application plus substantial / non-substantial modifications