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

This is an interventional treatment trial for Non-alcoholic Steatohepatitis Read More

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.