A study on the efficacy and safety of a new drug (OCA) in patients with non-alcoholic fatty liver hepatitis (NASH).
Summary description of the study
The study examines a new treatment option for non-alcoholic steatohepatitis (NASH). There are currently no therapies approved for the treatment of NASH. The sponsor of this study, Intercept Pharmaceuticals, Inc., is investigating the investigational drug Obeticholic acid (also referred to as OCA) and its impact on your condition, NASH. If you are eligible to participate in this study, your treatment phase will begin, during which you will be randomly assigned to the study medication OCA (10 mg or 25 mg) or a placebo. Throughout the duration of the study, which is expected to last up to 7 years, you will take approximately 1 tablet every day at about the same time. Before your appointments, you must not eat or drink for at least 8 hours. At the appointment in month 0 (day 1), you will be randomly assigned by a computer program (i.e., like flipping a coin) to 1 of 3 study treatment groups (10 mg OCA, 25 mg OCA, or placebo). This appointment will be followed 4 weeks later (month 1) by another appointment. After that, you will need to visit the study center every 3 months (month 3, 6, 9, 12, 12, 15) until the appointment in month 18. After you complete the appointment in month 18, you will be asked to appear at the clinic every 6 months until the study is completed.
(BASEC)
Intervention under investigation
The study examines a new treatment option for non-alcoholic steatohepatitis (NASH).
NASH means that the liver is swollen and damaged due to an accumulation of fat and that a certain degree of liver fibrosis (damaged and scarred liver tissue) is present.
The investigational drug Obeticholic acid (OCA) is a synthetic version of a naturally occurring compound produced in the liver, namely a bile acid. Bile acids are used by the body to aid digestion and also have other effects on liver function.
This study aims to determine how safe and effective OCA can be in stopping certain medical conditions or health-related complications that may occur in patients with NASH and evidence of liver fibrosis.
(BASEC)
Disease under investigation
non-alcoholic fatty liver hepatitis (NASH)
(BASEC)
1. Evidence of non-alcoholic fatty liver hepatitis (NASH) based on microscopic tissue sections after liver biopsy. 2. Evidence of liver fibrosis based on microscopic tissue sections at stage 2 or 3 according to the NASH-CRN fibrosis classification. Or evidence of fibrosis based on microscopic tissue sections at stage 1a or 1b accompanied by at least one of the following risk factors: - Obesity (body mass index greater than 30 kg/m2) - Type 2 diabetes (sugar disease) - Elevated levels of the enzyme alanine aminotransferase 3. Stable body weight (i.e., no weight fluctuations of more than 10% in the last 3 months). (BASEC)
Exclusion criteria
1. Current or past significant alcohol consumption in the 3 consecutive months within 1 year prior to screening. 2. Previous or planned surgery (during the study period) that is intended to result in weight reduction (e.g., gastric banding). 3. Evidence of other forms of chronic liver disease, such as: - Hepatitis B or C - Alcoholic liver disease - Known or suspected liver cancer - Liver cirrhosis (BASEC)
Trial sites
Bern, Lugano, St. Gallen, Zurich
(BASEC)
Sponsor
not available
Contact
Contact Person Switzerland
Prof. Dr. Annalisa Berzigotti
+41 31 632 21 11
Annalisa.Berzigotti@clutterinsel.ch(BASEC)
General Information
Intercept Pharmaceuticals
(ICTRP)
Scientific Information
Intercept Pharmaceuticals
(ICTRP)
Name of the authorising ethics committee (for multicentre studies, only the lead committee)
Ethics Committee Bern
(BASEC)
Date of authorisation
01.06.2016
(BASEC)
ICTRP Trial ID
NCT02548351 (ICTRP)
Official title (approved by ethics committee)
not available
Academic title
A Phase 3, Double-Blind, Randomized, Long-Term, Placebo-Controlled, Multicenter Study Evaluating the Safety and Efficacy of Obeticholic Acid in Subjects With Nonalcoholic Steatohepatitis (ICTRP)
Public title
Randomized Global Phase 3 Study to Evaluate the Impact on NASH With Fibrosis of Obeticholic Acid Treatment (ICTRP)
Disease under investigation
Non Alcoholic Steatohepatitis (NASH) (ICTRP)
Intervention under investigation
Drug: Obeticholic Acid;Drug: Placebo (ICTRP)
Type of trial
Interventional (ICTRP)
Trial design
Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor). (ICTRP)
Inclusion/Exclusion criteria
Gender: All
Maximum age: 85 Years
Minimum age: 18 Years
Inclusion Criteria:
1. Histologic evidence of NASH upon central read of a liver biopsy obtained no more than
6 months before Day 1 defined by presence of all 3 key histological features of NASH
according to NASH CRN criteria.
2. Histologic evidence of fibrosis stage 2 or stage 3 as defined by the NASH CRN scoring
of fibrosis, or
Histologic evidence of fibrosis stage 1a or stage 1b if accompanied by =1 of the
following risk factors:
- Obesity (BMI =30 kg/m2)
- Type 2 diabetes diagnosed per 2013 American Diabetes Association criteria
- ALT >1.5? upper limit of normal (ULN).
3. For subjects with a historical biopsy, is either not taking or is on stable doses of
TZDs/glitazones or vitamin E for 6 months before Day 1.
4. Stable body weight.
Exclusion Criteria:
1. Model for End-stage Liver Disease (MELD) score >12
2. ALT =10? ULN
3. HbA1c >9.5%
4. Total bilirubin >1.5 mg/dL
5. Evidence of other known forms of known chronic liver disease such as alcoholic liver
disease, hepatitis B, hepatitis C, PBC, PSC, autoimmune hepatitis, Wilson disease,
iron overload, alpha-1-antitrypsin deficiency, drug-induced liver injury, known or
suspected hepatocellular carcinoma (HCC)
6. History of liver transplant, or current placement on a liver transplant list
7. Current or history of significant alcohol consumption
8. Prior or planned ileal resection, or prior or planned bariatric surgery
9. Histological presence of cirrhosis
10. History of biliary diversion
11. Known positivity for human immunodeficiency virus infection.
12. Acute cholecystitis or acute biliary obstruction.
13. BMI >45 kg/m2
(ICTRP)
not available
Primary and secondary end points
To evaluate the effect of Obeticholic Acid compared to placebo on liver histology in non-cirrhotic nonalcoholic steatohepatitis (NASH) subjects with stage 2 or 3 fibrosis by assessing the following primary endpoints;To evaluate the effect of Obeticholic Acid compared to placebo on all-cause mortality and liver-related clinical outcomes as measured by the time to first occurrence of any of the listed adjudicated events (clinical outcomes composite endpoint) (ICTRP)
To evaluate the effect of Obeticholic Acid compared to placebo on liver histology in NASH;To evaluate the effect of Obeticholic Acid compared to placebo on liver histology in NASH;To evaluate the effect of Obeticholic Acid compared to placebo on liver biochemistry and markers of liver function (ICTRP)
Registration date
not available
Incorporation of the first participant
not available
Secondary sponsors
not available
Additional contacts
Sangeeta Sawhney, MD, Intercept Pharmaceuticals (ICTRP)
Secondary trial IDs
747-303 (ICTRP)
Results-Individual Participant Data (IPD)
not available
Further information on the trial
https://clinicaltrials.gov/ct2/show/NCT02548351 (ICTRP)
Results of the trial
Results summary
not available
Link to the results in the primary register
not available