A Study to Evaluate Seladelpar in Subjects With Nonalcoholic Steatohepatitis (NASH)

• Status: Completed
• Trial end date: 2020-08-10
• Target enrollment: 0
• Participant gender: All

Summary

A Phase 2, Double-Blind, Randomized, Placebo-Controlled Study to Evaluate the Activity of Seladelpar in Subjects with Nonalcoholic Steatohepatitis (NASH)

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: CymaBay Therapeutics, Inc.
• Treatments: Seladelpar

Criteria

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:

• Serum albumin less than 3.5 g/dL

• International normalized ratio (INR) greater than 1.4 (unless due to therapeutic anticoagulants)

• Total bilirubin greater than 2 mg/dL with the exception of Gilbert syndrome

• History of esophageal varices, ascites, or hepatic encephalopathy

11. Other chronic liver diseases

• Hepatitis B as defined by presence of hepatitis B surface antigen (HBsAg)

• 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)

• History or evidence of current active autoimmune hepatitis

• History or evidence of primary biliary cholangitis (PBC)

• History or evidence of primary sclerosing cholangitis

• History or evidence of Wilson's disease

• History or evidence of alpha-1-antitrypsin deficiency

• History or evidence of hemochromatosis

• History or evidence of drug-induced liver disease, as defined on the basis of typical exposure and history

• Known bile duct obstruction

• Suspected or proven liver cancer

12. ALT greater than 200 U/L

13. AST less than 20 U/L

14. Creatine kinase (CK) above 1.0 × upper limit of normal (ULN)

15. Serum creatinine above 1.0 × ULN

16. Platelet below 1.0 × lower limit of normal (LLN)

17. Inability to obtain a liver biopsy

18. History of biliary diversion

19. Known history of human immunodeficiency virus (HIV) infection

20. Active, serious medical disease with likely life expectancy < 5 years

21. Active substance abuse, based on Investigator judgment, including inhaled or injected drugs, within 1 year prior to the initial screening

22. Females who are pregnant or breastfeeding

23. Patients unable to undergo MRI-PDFF due to:

• Contraindication to MRI examination

• Severe claustrophobia impacting ability to perform MRI during the study, despite mild sedation/treatment with an anxiolytic

• Weight or girth exceeds the scanner capacities

24. Treatment with any other investigational therapy or device within 30 days or within five half-lives, whichever is longer, prior to the initial screening

25. Any other condition(s) that would compromise the safety of the subject or compromise study quality as judged by the Investigator