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Trial details imported from ClinicalTrials.gov

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




Registration number
NCT03900429
Ethics application status
Date submitted
26/03/2019
Date registered
3/04/2019
Date last updated
20/02/2024

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
Treatment: Surgery - Liver Biopsy

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

Treatment: Surgery: Liver Biopsy
A procedure in which a needle is inserted into the liver to collect a tissue sample
Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Treatment: Surgery
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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
Timepoint [1] 0 0
52 weeks
Primary outcome [2] 0 0
Month 54 Primary Objective: Time to experiencing an adjudicated Composite Clinical Outcome event (Final Primary Endpoint, at 54 months)
Timepoint [2] 0 0
up to 54 months
Secondary outcome [1] 0 0
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)
Timepoint [1] 0 0
24 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 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)
Minimum age
18 Years
Maximum age
No limit
Sex
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. 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.

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
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
28/03/2019
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/01/2028
Actual
Sample size
Target
Accrual to date
Final
1759
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC,WA
Recruitment hospital [1] 0 0
Royal Prince Alfred Hospital - Camperdown
Recruitment hospital [2] 0 0
Saint Vincent's Hospital Sydney - Darlinghurst
Recruitment hospital [3] 0 0
Nepean Hospital - Kingswood
Recruitment hospital [4] 0 0
John Hunter Hospital - New Lambton
Recruitment hospital [5] 0 0
Westmead Hospital - Westmead
Recruitment hospital [6] 0 0
Royal Brisbane and Women's Hospital - Herston
Recruitment hospital [7] 0 0
Mater Misericordiae - South Brisbane
Recruitment hospital [8] 0 0
Royal Adelaide Hospital - Adelaide
Recruitment hospital [9] 0 0
Monash Medical Centre - Clayton
Recruitment hospital [10] 0 0
Austin Health - Heidelberg
Recruitment hospital [11] 0 0
The Alfred Hospital - Melbourne
Recruitment hospital [12] 0 0
The Royal Melbourne Hospital - Parkville
Recruitment hospital [13] 0 0
Sir Charles Gairdner Hospital - Nedlands
Recruitment hospital [14] 0 0
Royal Perth Hospital - Perth
Recruitment postcode(s) [1] 0 0
2050 - Camperdown
Recruitment postcode(s) [2] 0 0
2010 - Darlinghurst
Recruitment postcode(s) [3] 0 0
2747 - Kingswood
Recruitment postcode(s) [4] 0 0
2305 - New Lambton
Recruitment postcode(s) [5] 0 0
2145 - Westmead
Recruitment postcode(s) [6] 0 0
4029 - Herston
Recruitment postcode(s) [7] 0 0
4101 - South Brisbane
Recruitment postcode(s) [8] 0 0
5000 - Adelaide
Recruitment postcode(s) [9] 0 0
3168 - Clayton
Recruitment postcode(s) [10] 0 0
3084 - Heidelberg
Recruitment postcode(s) [11] 0 0
3004 - Melbourne
Recruitment postcode(s) [12] 0 0
3050 - Parkville
Recruitment postcode(s) [13] 0 0
6009 - Nedlands
Recruitment postcode(s) [14] 0 0
6000 - Perth
Recruitment outside Australia
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United States of America
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Alabama
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Arizona
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Arkansas
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Louisiana
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Maryland
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Massachusetts
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Mississippi
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Missouri
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Nevada
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North Carolina
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Washington
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Austria
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Madrid
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Barcelona
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Pontevedra
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Bern
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Lugano
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Zürich
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Northumberland, England
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Liverpool
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London
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Plymouth
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United Kingdom
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Portsmouth

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

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
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
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.

Results not provided in https://clinicaltrials.gov/study/NCT03900429