A clinical study to evaluate the safety and efficacy of MGL-3196 (Resmetirom) in patients with Non-Alcoholic Steatohepatitis (NASH), to delay the progression of liver damage and to treat NASH

Australia, Austria, Belgium, Canada, France, Germany, Hungary, Israel, Italy, Mexico, Poland, Puerto Rico, Spain, Switzerland, United Kingdom, United States (ICTRP)

ICTRP Trial ID
NCT03900429 (ICTRP)

Official title (approved by ethics committee)
A Phase 3, Multinational, Double-Blind, Randomized, Placebo-Controlled Study of MGL-3196 (resmetirom) in Patients With Non-Alcoholic Steatohepatitis (NASH) and Fibrosis to Resolve NASH and Reduce Progression to Cirrhosis and/or Hepatic Decompensation (BASEC)

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

Public title
A Phase 3 Study to Evaluate the Efficacy and Safety of MGL-3196 (Resmetirom) in Patients With NASH and Fibrosis (ICTRP)

Disease under investigation
NASH - Nonalcoholic Steatohepatitis (ICTRP)

Intervention under investigation
Drug: MGL-3196;Drug: Placebo;Procedure: Liver Biopsy (ICTRP)

Type of trial
Interventional (ICTRP)

Trial design
Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor). (ICTRP)

Inclusion/Exclusion criteria
Gender: All
Maximum age: N/A
Minimum age: 18 Years

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
?g 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.
(ICTRP)

not available

Primary and secondary end points
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;Month 54 Primary Objective: Time to experiencing an adjudicated Composite Clinical Outcome event (Final Primary Endpoint, at 54 months) (ICTRP)

Week 52 Key Secondary Objective: To determine the effect of once-daily, oral administration of MGL-3196 80 or 100 mg versus matching placebo on the percent change from Baseline at 24 weeks in directly measured low-density lipoprotein cholesterol (LDL-C) (ICTRP)

Registration date
not available

Incorporation of the first participant
not available

Secondary sponsors
not available

Additional contacts
Rebecca Taub, MD, Madrigal Pharmaceuticals, Inc. (ICTRP)

Secondary trial IDs
MGL-3196-11 (ICTRP)

Results-Individual Participant Data (IPD)
not available

Further information on the trial
https://clinicaltrials.gov/ct2/show/NCT03900429 (ICTRP)