MGL-3196 in Non-Alcoholic Steatohepatitis and Fibrosis

What is the Purpose of this Study?

The purpose of this study is to evaluate the effects of an investigational drug called MGL-3196 on individuals with nonalcoholic steatohepatitis (NASH). Researchers aim to determine the safety, effectiveness and optimal dosage of MGL-3196, as well as whether treatment with MGL-3196 for several years will benefit participants. MGL-3196 works together with a form of thyroid hormone receptor in the liver to decrease the amount of fat (in the liver) and possibly reduce the inflammation associated with NASH. Participants will be randomly assigned to 1 of 3 groups. The first group will receive 80mg MGL-3196; the second group will receive 100mg MGL-3196; and the third group will receive placebo (inactive substance).

Eligibility

1. Must be willing to participate in the study and provide written informed consent.
2. Male and female adults ≥ 18 years of age.
3. Suspected or confirmed diagnosis of NASH fibrosis suggested by the historical data. Meet one of the following criteria that is consistent with NASH liver fibrosis:

Inclusion Criteria:

1. Must be willing to participate in the study and provide written informed consent.
2. Male and female adults ≥ 18 years of age.
3. Suspected or confirmed diagnosis of NASH fibrosis suggested by the historical data. Meet one of the following criteria that is consistent with NASH liver fibrosis:
1. Historical biochemical test for fibrosis: PRO-C3 \>14 ng/mL or ELF ≥9
2. FibroScan with transient elastography ≥8.5 kPa and controlled attenuation parameter ≥280 dB.m-1
3. Historical liver biopsy obtained \<2 years before expected randomization showing Stage 1B, 2 or 3 fibrosis with NASH based on existing pathology review, with no significant change in body weight \>5% or medication that might affect NAS or fibrosis stage.
4. MRI-PDFF fat fraction ≥8% obtained during the screening period
5. Biopsy-proven NASH (baseline liver biopsy) based on a liver biopsy obtained ≤6 months before anticipated date of randomization (if the biopsy is deemed acceptable for interpretation by the central reader) with fibrosis stage 1A/1C, 1B, 2, or 3 on liver biopsy and NAS of ≥4 with a score of at least 1 in each of the following NAS components:
1. Steatosis (scored 0 to 3)
2. Ballooning degeneration (scored 0 to 2)
3. Lobular inflammation (scored 0 to 3)

Exclusion Criteria:

1. History of significant alcohol consumption for a period of more than 3 consecutive months within 1 year prior to Screening.
2. Regular use of drugs historically associated with NAFLD
3. Thyroid diseases:
1. Active hyperthyroidism.
2. Untreated clinical hypothyroidism defined by thyroid stimulating hormone (TSH) \>7 IU/L with symptoms of hypothyroidism or \>10 IU/L without symptoms.
3. Patients who have had a thyroidectomy and are on replacement thyroxine doses \>75 µg per day are allowed.
4. History of bariatric surgery or intestinal bypass surgery within the 5 years prior to randomization or planned during the conduct of the study.
5. Recent significant weight gain or loss
6. HbA1c ≥ 9.0%.
7. Glucagon-like peptide 1 \[GLP-1\] agonist, high dose Vitamin E (\> 400 IU/day), or pioglitazone therapy unless stable dose for 24 weeks prior to biopsy.
8. Presence of cirrhosis on liver biopsy defined as stage 4 fibrosis.
9. Diagnosis of hepatocellular carcinoma (HCC).
10. MELD score ≥12, as determined at Screening, unless due to therapeutic anti coagulation.
11. Hepatic decompensation
12. Chronic liver diseases other than NASH
13. Active autoimmune disease
14. Serum ALT \> 250 U/L.
15. Active, serious medical disease with a likely life expectancy \< 2 years.
16. Participation in an investigational new drug trial in the 60 days or 5 half-lives, whichever is longer.
17. Any other condition which, in the opinion of the Investigator, would impede compliance, hinder completion of the study, compromise the well-being of the patient, or interfere with the study outcomes.

Show less

Where can I participate?

Beverly

More about this Clinical Trial

What is the full name of this clinical trial?

A Phase 3, Multinational, Double-Blind, Randomized, Placebo-Controlled Study of MGL-3196 in Patients With Non-Alcoholic Steatohepatitis and Fibrosis to Resolve NASH and Reduce Progression to Cirrhosis and/or Hepatic Decompensation

Study Details

Disease Type/Condition

Other

Principal Investigator

Ayoub, Walid

Age Group

Adult

Phase

III

IRB Number

STUDY00000287

ClinicalTrials.gov ID

NCT03900429

Key Eligibility

ClinicalTrials.gov

How do I learn more about this study?

clinicaltrials@cshs.org