A Study of the Experimental Medicine Obeticholic Acid For Nonalcoholic Steatohepatitis (NASH) (accumulation of liver fat)

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Age: 18 to 75 years old
Gender:
Any
Healthy Volunteers: No
Keywords: NASH, Nonalcoholic Steatohepatitis, liver damage, fatty liver
Type: Drug study, Phase 2
Target:
6 Participants
Investigator:
Description
The study team hopes to find out how safe and effective the experimental drug obeticholic acid (also known as OCA) is. It will be studied in patients with compensated cirrhosis caused by NASH. NASH (nonalcoholic steatohepatitis) is the accumulation of liver fat in people who drink little to no alcohol.

There are no therapies approved for the treatment of NASH. OCA (the brand name is Ocaliva) has been approved by the FDA for other liver conditions.

In this study, OCA is an experimetnal drug because it has not been approved to treat cirrhosis as the result of NASH. OCA is a manmade version of a natural compound made in the liver called bile acid. Bile acids are used by the body to help with digestion and also have additional effects on liver function
This study requires

The study team will make sure you qualify to take part in the study. Qualified participants will receive detailed information about the study. This may include a list of study-related tests and procedures.

Who can participate

Inclusion criteria:

  1. Must have given written informed consent (signed and dated) and any authorizations required by local law
  2. 18 to 75 years old (inclusive)
  3. Histological evidence of definite NASH on a liver biopsy (obtained during the screening period or historical liver biopsy obtained no more than 90 days prior to the initial screening visit)
  4. NAS of 4 or greater with a score of at least 1 in each component (steatosis, lobular inflammation, and ballooning)
  5. Fibrosis stage 1, 2, or 3 on liver biopsy
  6. MRI-PDFF ≥ 10%
  7. Females of reproductive potential must use at least one barrier contraceptive and a second effective birth control method during the study and for at least 90 days after the last dose of study drug. Male subjects who are sexually active with female partners of reproductive potential must use barrier contraception and their female partners must use a second effective birth control method during the study and for at least 90 days after the last dose of study drug.

Exclusion criteria:

  1. Significant alcohol consumption, defined as more than 2 drink units per day (equivalent to 20 g) in women and 3 drink units per day (equivalent to 30 g) in men, or inability to reliably quantify alcohol intake
  2. Treatment with drugs associated with nonalcoholic fatty liver disease (NAFLD) (amiodarone, methotrexate, oral glucocorticoids at doses greater than 5 mg/day, tamoxifen, estrogens at doses greater than those used for hormone replacement or contraception, anabolic steroids, valproic acid) for more than 4 weeks within the last 2 months prior to the initial screening
  3. Treatment with pioglitazone or high-dose vitamin E (>400 IU/day) within the last 2 months prior to the initial screening
  4. Initiation of treatment with a glucagon-like peptide-1 (GLP-1) agonist or a dose change within the last 2 months prior to the initial screening
  5. Prior or planned bariatric surgery (a prior reversed sleeve gastrectomy is permitted)
  6. Poorly controlled type 2 diabetes mellitus (hemoglobin A1c [HbA1c] 9.5% or higher) or type 1 diabetes mellitus
  7. Diabetic patients who are taking sodium/glucose cotransporter (SGLT) 2 inhibitors must be on a stable dose within 2 months prior to the initial screening and throughout the study
  8. Significant weight loss within the last 6 months (e.g., > 10%)
  9. Body mass index (BMI) < 18.5 kg/m2
  10. Hepatic decompensation defined as the presence of any of the following:
  11. Serum albumin less than 3.5 g/dL
  12. International normalized ratio (INR) greater than 1.4 (unless due to therapeutic anticoagulants)
  13. Total bilirubin greater than 2 mg/dL with the exception of Gilbert syndrome
  14. History of esophageal varices, ascites, or hepatic encephalopathy
  15. Other chronic liver diseases
  16. Hepatitis B as defined by presence of hepatitis B surface antigen (HBsAg)
  17. Hepatitis C as defined by presence of hepatitis C virus antibody (HCV AB) or positive HCV RNA (tested for known cured HCV infection, or positive HCV AB at screening)
  18. History or evidence of current active autoimmune hepatitis
  19. History or evidence of primary biliary cholangitis (PBC)
  20. History or evidence of primary sclerosing cholangitis
  21. History or evidence of Wilson's disease
  22. History or evidence of alpha-1-antitrypsin deficiency
  23. History or evidence of hemochromatosis
  24. History or evidence of drug-induced liver disease, as defined on the basis of typical exposure and history
  25. Known bile duct obstruction
  26. Suspected or proven liver cancer
  27. ALT greater than 200 U/L
  28. AST less than 20 U/L
  29. Creatine kinase (CK) above 1.0 × upper limit of normal (ULN)
  30. Serum creatinine above 1.0 × ULN
  31. Platelet below 1.0 × lower limit of normal (LLN)
  32. Inability to obtain a liver biopsy
  33. History of biliary diversion
  34. Known history of human immunodeficiency virus (HIV) infection
  35. Active, serious medical disease with likely life expectancy < 5 years
  36. Active substance abuse, based on Investigator judgment, including inhaled or injected drugs, within 1 year prior to the initial screening
  37. Females who are pregnant or breastfeeding
  38. Patients unable to undergo MRI-PDFF due to:
  39. Contraindication to MRI examination
  40. Severe claustrophobia impacting ability to perform MRI during the study, despite mild sedation/treatment with an anxiolytic
  41. Weight or girth exceeds the scanner capacities
  42. Treatment with any other investigational therapy or device within 30 days or within five half-lives, whichever is longer, prior to the initial screening
  43. Any other condition(s) that would compromise the safety of the subject or compromise study quality as judged by the Investigator
Benefits and risks of participating
BENEFITS:

We cannot promise any benefits to you as a result of taking part in this research study.


RISKS:

The study doctor will discuss the risks associated with taking part in this research study.
Compensation
If you agree to take part in this research study, we will compensate you the following amounts for your time and effort:
- Patient Stipend (includes mileage, parking, meals): $75.00 / visit
- AUDIT, Smoking Habits & Caffeine Consumption: $25.00 / completed questionnaire
- Questionnaire completion: $40.00/set of completed questionnaires
- TE and/or MRE: $35.00 /scan
- Liver biopsy: $150.00 / procedure
- For esophagogastroduodenoscopy (EGD) procedure performed during the study, you will be paid up to a total of $150.00
Resources
Schedule
Study duration and period
Your participation in both Part 1 and Part 2 of the study is expected to last for approximately 2 years, but could be shorter.
Recruitment period
From June 5, 2018
Location
UC Davis Medical Center
2315 Stockton Boulevard
Sacramento, CA 95817
Contact
Sandeep Dhaliwal
Research Topic
Conditions:
  • NASH - Nonalcoholic Steatohepatitis