Phase 2 Study of MGL-3196 in Patients With Non-Alcoholic Steatohepatitis (NASH)

Non-alcoholic Steatohepatitis Clinical Trial

Official title:

A Phase 2, Multi-Center, Double-Blind, Randomized, Placebo-controlled Study of MGL-3196 in Patients With Non-alcoholic Steatohepatitis

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02912260
• Other study ID #: MGL-3196-05
• Status: Active, not recruiting
• Phase: Phase 2
• First received: September 19, 2016
• Last updated: December 15, 2017
• Start date: September 2016
• Est. completion date: April 2018

Study information

• Verified date: December 2017
• Source: Madrigal Pharmaceuticals, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The primary objective of this study is to determine the effect of once-daily oral MGL-3196 on the percent change in hepatic fat fraction from baseline in patients with biopsy-proven Non-alcoholic Steatohepatitis (NASH).

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 125
• Est. completion date: April 2018
• Est. primary completion date: October 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria. Patients who meet all of the following criteria will be eligible to participate in the study:

• Must be willing to participate in the study and provide written informed consent;

• Male and female adults =18 years of age with a BMI <45 kg/m^2;

• Female patients of child bearing potential with negative serum pregnancy (beta human chorionic gonadotropin) tests who are not breastfeeding, do not plan to become pregnant during the study, and agree to use effective birth control (ie, condoms, diaphragm, non hormonal intrauterine device [IUD], or sexual abstinence [only if this is in line with the patient's current lifestyle]) throughout the study and for at least 1 month after study completion; hormonal contraception (estrogens stable =3 months) and hormonal IUDs are permitted if used with a secondary birth control measure (eg, condoms); OR female patients of non-child bearing potential (ie, surgically [bilateral oophorectomy, hysterectomy, or tubal ligation] or naturally sterile [>12 consecutive months without menses]); Male patients who have sexual intercourse with a female partner of child bearing potential from the first dose of study drug until 1 month after study completion must be either surgically sterile (confirmed by documented azoospermia >90 days after the procedure) OR agree to use a condom with spermicide. All male patients must agree not to donate sperm from the first dose of study drug until 1 month after study completion;

• Must have confirmation of =10% liver fat content on PDFF-MRI;

• Biopsy-proven NASH. Must have had prior liver biopsy within 180 days of randomization with fibrosis stage 1 to 3 and a NAS of =4 with at least a score of 1 in each of the following NAS components:

• Steatosis (scored 0 to 3),

• Ballooning degeneration (scored 0 to 2), and

• Lobular inflammation (scored 0 to 3);

• Must have documented historical (3 weeks to 6 months prior to the study entry) ALT and AST levels consistent with the screening ALT and AST values.

Exclusion Criteria. Patients who meet any of the following criteria will be excluded from participation in the study:

Note: Unless otherwise specified, repeat testing may be performed in consultation with the Medical Monitor.

• History of significant alcohol consumption for a period of more than 3 consecutive months within 1 year prior to screening;

• Weight gain or loss >5% in the 6 months prior to randomization or >10% in the 12 months prior to screening;

• Hyperthyroidism;

• Patients on thyroid replacement therapy;

• Prior or planned (during the study period) bariatric surgery (eg, gastroplasty, roux-en-Y gastric bypass);

• Type 1 diabetes;

• Uncontrolled Type 2 diabetes defined as Hemoglobin A1c = 9.5% at screening (patients with HbA1c = 9.5% may be rescreened);

• Use of obeticholic acid, ursodeoxycholic acid (Ursodiol® and Urso®), high dose vitamin E (>400 IU/day) unless on stable dose of vitamin E >400 IU/day for at least 6 months at the time of liver biopsy, or pioglitazone within 90 days prior to enrollment or since screening biopsy, whichever is longer;

• Presence of cirrhosis on liver biopsy (stage 4 fibrosis);

• Platelet count < 140,000/mm^3;

• Clinical evidence of hepatic decompensation;

• Evidence of other forms of chronic liver disease;

• Active, serious medical disease with likely life expectancy <2 years;

• Participation in an investigational new drug trial in the 30 days prior to randomization; or

• 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.

Related Conditions & MeSH terms

• Fatty Liver
• Non-alcoholic Fatty Liver Disease
• Non-alcoholic Steatohepatitis

Intervention

Drug:
• MGL-3196

• Placebo

Locations

Country	Name	City	State
United States	Madrigal Research Site	Albuquerque	New Mexico
United States	Madrigal Research Site	Baltimore	Maryland
United States	Madrigal Research Site	Boca Raton	Florida
United States	Madrigal Research Site	Charlottesville	Virginia
United States	Madrigal Research Site	Coronado	California
United States	Madrigal Research Site	Dothan	Alabama
United States	Madrigal Research Site	Durham	North Carolina
United States	Madrigal Research Site	Englewood	Colorado
United States	Madrigal Research Site	Jackson	Mississippi
United States	Madrigal Research Site	Kansas City	Kansas
United States	Madrigal Research Site	Lakewood Ranch	Florida
United States	Madrigal Research Site	Lauderdale Lakes	Florida
United States	Madrigal Research Site	Live Oak	Texas
United States	Madrigal Research Site	Los Angeles	California
United States	Madrigal Research Site	Miami	Florida
United States	Madrigal Research Site	Monroe	Louisiana
United States	Madrigal Research Site	New Port Richey	Florida
United States	Madrigal Research Site	New York	New York
United States	Madrigal Research Site	Rapid City	South Dakota
United States	Madrigal Research Site	Rialto	California
United States	Madrigal Research Site	Saint Louis	Missouri
United States	Madrigal Research Site	San Antonio	Texas
United States	Madrigal Research Site	San Diego	California
United States	Madrigal Research Site	Seattle	Washington
United States	Madrigal Research Site	Tucson	Arizona
United States	Madrigal Research Site	Ventura	California

Sponsors (1)

Lead Sponsor	Collaborator
Madrigal Pharmaceuticals, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change from baseline in hepatic fat fraction assessed by MRI-PDFF		12 weeks
Secondary	Two-point reduction in Non-alcoholic fatty liver disease NASH CRN (NAFLD) activity score (NAS)		36 weeks
Secondary	Resolution of Non-alcoholic steatohepatitis (NASH) (ballooning = 0; inflammation = 0 to 1) as determined by the NASH CRN NAS score		36 weeks
Secondary	Improvement in fibrosis by at least 1 stage with no worsening of steatohepatitis		36 weeks
Secondary	Change from baseline in hepatic fat fraction		36 weeks
Secondary	Safety and tolerability of MGL-3196 based on Adverse Events and Changes in Laboratory Values		12 and 36 weeks
Secondary	Effect on high-sensitivity C-reactive protein (hsCRP)		12 and 36 weeks
Secondary	Effect on serum alanine aminotransferase (ALT)		12 and 36 weeks
Secondary	Effect on aspartate aminotransferase (AST)		12 and 36 weeks
Secondary	Effect on lipid parameters	Determine the effect on lipid parameters including low-density lipoprotein cholesterol (LDL-C), non- LDL-C, high-density lipoprotein cholesterol (HDL-C), non-HDL-C, total cholesterol, triglycerides, apolipoprotein B (ApoB), and lipoprotein(a) (Lp[a]) particles.	12 and 36 weeks
Secondary	Effect on NASH and fibrosis biomarkers	Determine the effect on NASH and fibrosis biomarkers including cytokeratin-18 (CK-18), fibrosis-4 (FIB-4), and enhanced liver function (ELF) test.	12 and 36 weeks