Liver Biopsy: A procedure in which a needle is inserted into the liver to collect a tissue sample
Study summary
A double-blind placebo controlled randomized Phase 3 study to determine if 80 or 100 mg of MGL-3196 as compared with placebo resolves NASH and/or reduces fibrosis on liver biopsy and prevents progression to cirrhosis and/or advanced liver disease
Eligibility
Sex
ALL
Min age
18 Years
Max age
—
Healthy volunteers
No
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.
Primary outcome measure(s)
Week 52 Dual Primary Objectives: To determine the effect of 80 or 100 mg MGL-3196 vs matching placebo on liver biopsy (NASH CRN score) at Week 52 compared with Baseline — 52 weeks 1. Proportion with resolution of NASH (ballooning 0, inflammation 0,1) associated with at least 2-point reduction in NAFLD Activity Score (NAS) without worsening of fibrosis stage OR
2. Proportion with at least a 1-point improvement in fibrosis stage with no worsening of NAS
Month 54 Primary Objective: Time to experiencing an adjudicated Composite Clinical Outcome event (Final Primary Endpoint, at 54 months) — up to 54 months The Composite Clinical Outcome is composed of all-cause mortality, liver transplant, and significant hepatic events (including hepatic decompensation events \[ascites, encephalopathy, or gastroesophageal variceal hemorrhage\], histological progression to cirrhosis, and a confirmed increase of MELD score from \<12 to ≥15).
Trial sites (247)
Facility
City
Region
Status
University of Alabama at Birmingham
Birmingham
Alabama
East Valley Family Physicians
Chandler
Arizona
The Institute for Liver Health - Chandler
Chandler
Arizona
The Institute for Liver Health - Glendale
Glendale
Arizona
Desert Clinical Research
Mesa
Arizona
Adobe Gastroenterology
Tucson
Arizona
The Institute for Liver Health - Tucson
Tucson
Arizona
Arkansas Gastroenterology
North Little Rock
Arkansas
Fresno Clinical Research Center
Fresno
California
National Research Institute - Huntington Park
Huntington Park
California
University of California San Diego
La Jolla
California
Cedars-Sinai Medical Center
Los Angeles
California
National Research Institute - Los Angeles
Los Angeles
California
Ruane Clinical Research
Los Angeles
California
Stanford University School of Medicine
Palo Alto
California
National Research Institute - Panorama City
Panorama City
California
Alliance Clinical Research
Poway
California
San Fernando Valley Health Institute
Van Nuys
California
Colorado Springs Family Practice
Colorado Springs
Colorado
South Denver Gastroenterology - Swedish Medical Center Office
Englewood
Colorado
Excel Medical Clinical Trials
Boca Raton
Florida
Covenant Metabolic Specialists - Fort Myers
Fort Myers
Florida
University of Florida Hepatology Research at CTRB
Gainesville
Florida
Nature Coast Clinical Research
Inverness
Florida
Florida Research Institute
Lakewood Rch
Florida
University of Miami
Miami
Florida
Miami Dade Medical Research Institute
Miami
Florida
Bioclinica Research - Orlando
Orlando
Florida
Progressive Medical Research
Port Orange
Florida
Covenant Research
Sarasota
Florida
Bioclinica Research - The Villages
The Villages
Florida
GI Specialists of Georgia
Marietta
Georgia
Clinical Research - Chicago
Chicago
Illinois
Northwestern Medical Faculty Foundation
Chicago
Illinois
The University of Chicago Medicine
Chicago
Illinois
University of Kansas Medical Center Research Institute
+ 207 more sites — see the full list on the official registry below.
Official registry record
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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