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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT03900429




Registration number
NCT03900429
Ethics application status
Date submitted
26/03/2019
Date registered
3/04/2019
Date last updated
11/12/2019

Titles & IDs
Public title
A Phase 3 Study to Evaluate the Efficacy and Safety of MGL-3196 (Resmetirom) in Patients With NASH and Fibrosis
Scientific 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
Secondary ID [1] 0 0
MGL-3196-11
Universal Trial Number (UTN)
Trial acronym
MAESTRO-NASH
Linked study record

Health condition
Health condition(s) or problem(s) studied:
NASH - Nonalcoholic Steatohepatitis 0 0
Condition category
Condition code
Oral and Gastrointestinal 0 0 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon
Metabolic and Endocrine 0 0 0 0
Metabolic disorders
Diet and Nutrition 0 0 0 0
Obesity

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - MGL-3196
Treatment: Drugs - Placebo

Placebo Comparator: Matching Placebo - Placebo Daily

Active Comparator: 80 mg MGL-3196 - 80 mg daily

Active Comparator: 100 mg MGL-3196 - 100 mg daily


Treatment: Drugs: MGL-3196
Tablet

Treatment: Drugs: Placebo
Matching Tablets

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
To evaluate the effect of MGL-3196 80 mg or 100 mg compared to placebo to achieve NASH resolution on liver histology in non-cirrhotic NASH patients with stage 2 or 3 fibrosis - Assessment will be in the first 900 patients, at least 450 F3, and be based on the proportion of MGL-3196 80 mg or 100 mg treated patients relative to placebo achieving NASH resolution (NASH Activity Score (NAS), ballooning =0; lobular inflammation =0,1) with at least a 2 point reduction in NAS and no worsening of fibrosis.
Timepoint [1] 0 0
Measurements at Baseline and 52 weeks
Primary outcome [2] 0 0
Composite long-term outcome events composed of all-cause mortality, cirrhosis, and other significant liver-related events - To evaluate the effect of MGL-3196 80 mg or 100 mg compared to placebo on composite long-term outcome measured by the number of patients with the onset of any of the adjudicated events, composed of cirrhosis, all-cause mortality and liver-related clinical outcomes.
Timepoint [2] 0 0
Time frame to accrue a prespecified number of adjudicated events; up to 54 months
Secondary outcome [1] 0 0
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 low-density lipoprotein cholesterol (LDL-C) - Assess the effect of MGL-3196 80 mg or 100 mg compared to placebo on LDL-C measured by percent change from Baseline at 24 weeks.
Timepoint [1] 0 0
Measurements at Baseline and 24 weeks
Secondary outcome [2] 0 0
To evaluate the effect of MGL-3196 80 mg or 100 mg compared to placebo to achieve improvement in fibrosis on liver histology in non-cirrhotic NASH patients with stage 2 or 3 fibrosis - Assessment will be in the first 900 patients, at least 450 F3, and be based on the proportion of MGL-3196 80 mg or 100 mg treated patients relative to placebo achieving at least a 1-point improvement in fibrosis (NASH Clinical Research Network system) by liver biopsy with no worsening of NAS.
Timepoint [2] 0 0
Measurements at Baseline and 52 weeks

Eligibility
Key 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

1. Metabolic risk factors and AST > 20 U/L

2. Criteria consistent with liver fibrosis as defined as one of the following:

- Biochemical test for fibrosis OR

- Fibroscan test OR

- Historical liver biopsy with diagnosis of NASH with fibrosis Stage 2 or 3

4. MRI-PDFF with increased fat fraction

5. Biopsy-proven NASH (Baseline liver biopsy) based on a liver biopsy obtained within 24
weeks before anticipated date of randomization (if the biopsy is deemed acceptable for
interpretation by the central reader) with fibrosis stage 1A, 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)
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key 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. History of bariatric surgery or intestinal bypass surgery within the 5 years prior to
randomization or planned during the conduct of the study.

4. Recent significant weight gain or loss

5. HbA1c = 9.0%.

6. 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.

7. Presence of cirrhosis on liver biopsy defined as stage 4 fibrosis.

8. Diagnosis of hepatocellular carcinoma (HCC).

9. MELD score =12, as determined at Screening, unless due to therapeutic anti
coagulation.

10. Hepatic decompensation

11. Chronic liver diseases other than NASH

12. Active autoimmune disease

13. Serum ALT > 250 U/L.

14. Active, serious medical disease with a likely life expectancy < 2 years.

15. Participation in an investigational new drug trial in the 60 days or 5 half-lives,
whichever is longer.

16. 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Royal Adelaide Hospital - Adelaide
Recruitment hospital [2] 0 0
Monash Medical Centre - Clayton
Recruitment hospital [3] 0 0
Austin Health - Heidelberg
Recruitment hospital [4] 0 0
Royal Brisbane and Women's Hospital - Herston
Recruitment hospital [5] 0 0
John Hunter Hospital - New Lambton
Recruitment hospital [6] 0 0
The Royal Melbourne Hospital - Parkville
Recruitment hospital [7] 0 0
Royal Perth Hospital - Perth
Recruitment hospital [8] 0 0
Mater Misericordiae - South Brisbane
Recruitment hospital [9] 0 0
Westmead Hospital - Westmead
Recruitment postcode(s) [1] 0 0
- Adelaide
Recruitment postcode(s) [2] 0 0
- Clayton
Recruitment postcode(s) [3] 0 0
- Heidelberg
Recruitment postcode(s) [4] 0 0
- Herston
Recruitment postcode(s) [5] 0 0
- New Lambton
Recruitment postcode(s) [6] 0 0
- Parkville
Recruitment postcode(s) [7] 0 0
- Perth
Recruitment postcode(s) [8] 0 0
- South Brisbane
Recruitment postcode(s) [9] 0 0
- Westmead
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
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United States of America
State/province [2] 0 0
Arkansas
Country [3] 0 0
United States of America
State/province [3] 0 0
California
Country [4] 0 0
United States of America
State/province [4] 0 0
Colorado
Country [5] 0 0
United States of America
State/province [5] 0 0
Florida
Country [6] 0 0
United States of America
State/province [6] 0 0
Georgia
Country [7] 0 0
United States of America
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Kansas
Country [8] 0 0
United States of America
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Louisiana
Country [9] 0 0
United States of America
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Mississippi
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United States of America
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Missouri
Country [11] 0 0
United States of America
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Nevada
Country [12] 0 0
United States of America
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New Mexico
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United States of America
State/province [13] 0 0
New York
Country [14] 0 0
United States of America
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North Carolina
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United States of America
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Ohio
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United States of America
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Tennessee
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United States of America
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Texas
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United States of America
State/province [18] 0 0
Utah
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United States of America
State/province [19] 0 0
Virginia
Country [20] 0 0
Belgium
State/province [20] 0 0
Laeken
Country [21] 0 0
Belgium
State/province [21] 0 0
Leuven
Country [22] 0 0
Canada
State/province [22] 0 0
Alberta
Country [23] 0 0
Canada
State/province [23] 0 0
British Columbia
Country [24] 0 0
Canada
State/province [24] 0 0
Ontario
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France
State/province [25] 0 0
Clichy
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France
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Paris Cedex 13
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France
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VandÅ“uvre-lès-Nancy
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Hungary
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Budapest
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Israel
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Afula
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Israel
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Be'er Sheva
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Israel
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Petah Tikva
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Israel
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Tel Aviv
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Italy
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San Giovanni Rotondo
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United Kingdom
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Liverpool
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United Kingdom
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London
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United Kingdom
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Plymouth
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United Kingdom
State/province [37] 0 0
Portsmouth

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Madrigal Pharmaceuticals, Inc.
Address
Country

Ethics approval
Ethics application status

Summary
Brief 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 on liver biopsy and prevents progression to
cirrhosis and/or advanced liver disease
Trial website
https://clinicaltrials.gov/show/NCT03900429
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Rebecca Taub, MD
Address 0 0
Madrigal Pharmaceuticals, Inc.
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Kimberly Dorney, RN, MSN
Address 0 0
Country 0 0
Phone 0 0
267-520-0252
Fax 0 0
Email 0 0
info@madrigalpharma.com
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT03900429