Trial Review

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/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
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
Arizona
Country [3] 0 0
United States of America
State/province [3] 0 0
Arkansas
Country [4] 0 0
United States of America
State/province [4] 0 0
California
Country [5] 0 0
United States of America
State/province [5] 0 0
Colorado
Country [6] 0 0
United States of America
State/province [6] 0 0
Florida
Country [7] 0 0
United States of America
State/province [7] 0 0
Georgia
Country [8] 0 0
United States of America
State/province [8] 0 0
Illinois
Country [9] 0 0
United States of America
State/province [9] 0 0
Kansas
Country [10] 0 0
United States of America
State/province [10] 0 0
Louisiana
Country [11] 0 0
United States of America
State/province [11] 0 0
Maryland
Country [12] 0 0
United States of America
State/province [12] 0 0
Massachusetts
Country [13] 0 0
United States of America
State/province [13] 0 0
Mississippi
Country [14] 0 0
United States of America
State/province [14] 0 0
Missouri
Country [15] 0 0
United States of America
State/province [15] 0 0
Nevada
Country [16] 0 0
United States of America
State/province [16] 0 0
New York
Country [17] 0 0
United States of America
State/province [17] 0 0
North Carolina
Country [18] 0 0
United States of America
State/province [18] 0 0
Ohio
Country [19] 0 0
United States of America
State/province [19] 0 0
Tennessee
Country [20] 0 0
United States of America
State/province [20] 0 0
Texas
Country [21] 0 0
United States of America
State/province [21] 0 0
Utah
Country [22] 0 0
United States of America
State/province [22] 0 0
Virginia
Country [23] 0 0
United States of America
State/province [23] 0 0
Washington
Country [24] 0 0
Austria
State/province [24] 0 0
Carinthia
Country [25] 0 0
Austria
State/province [25] 0 0
Upper Austria
Country [26] 0 0
Austria
State/province [26] 0 0
Vienna
Country [27] 0 0
Austria
State/province [27] 0 0
Salzburg
Country [28] 0 0
Austria
State/province [28] 0 0
St. Pölten
Country [29] 0 0
Austria
State/province [29] 0 0
Wels
Country [30] 0 0
Belgium
State/province [30] 0 0
Antwerpen
Country [31] 0 0
Belgium
State/province [31] 0 0
Brussels
Country [32] 0 0
Belgium
State/province [32] 0 0
Flemish Brabant
Country [33] 0 0
Belgium
State/province [33] 0 0
Limburg
Country [34] 0 0
Belgium
State/province [34] 0 0
Oost-Vlaanderen
Country [35] 0 0
Belgium
State/province [35] 0 0
West-Vlaanderen
Country [36] 0 0
Belgium
State/province [36] 0 0
Brussel
Country [37] 0 0
Belgium
State/province [37] 0 0
Laeken
Country [38] 0 0
Belgium
State/province [38] 0 0
Leuven
Country [39] 0 0
Canada
State/province [39] 0 0
Alberta
Country [40] 0 0
Canada
State/province [40] 0 0
Nova Scotia
Country [41] 0 0
Canada
State/province [41] 0 0
Ontario
Country [42] 0 0
Canada
State/province [42] 0 0
Vancouver
Country [43] 0 0
France
State/province [43] 0 0
Alsace
Country [44] 0 0
France
State/province [44] 0 0
Auvergne
Country [45] 0 0
France
State/province [45] 0 0
Bretagne
Country [46] 0 0
France
State/province [46] 0 0
Franche-Comte
Country [47] 0 0
France
State/province [47] 0 0
Ile-de-France
Country [48] 0 0
France
State/province [48] 0 0
Languedoc-Roussillon
Country [49] 0 0
France
State/province [49] 0 0
Limousin
Country [50] 0 0
France
State/province [50] 0 0
Midi-Pyrenees
Country [51] 0 0
France
State/province [51] 0 0
Nord Pas-de-Calais
Country [52] 0 0
France
State/province [52] 0 0
Pays De La Loire
Country [53] 0 0
France
State/province [53] 0 0
Provence Alpes Cote D'Azur
Country [54] 0 0
France
State/province [54] 0 0
Rhone-Alpes
Country [55] 0 0
France
State/province [55] 0 0
Amiens
Country [56] 0 0
France
State/province [56] 0 0
Clichy
Country [57] 0 0
France
State/province [57] 0 0
Paris Cedex 13
Country [58] 0 0
France
State/province [58] 0 0
Vandœuvre-lès-Nancy
Country [59] 0 0
Germany
State/province [59] 0 0
Berlin
Country [60] 0 0
Germany
State/province [60] 0 0
Frankfurt am main
Country [61] 0 0
Germany
State/province [61] 0 0
Homburg
Country [62] 0 0
Germany
State/province [62] 0 0
Leipzig
Country [63] 0 0
Germany
State/province [63] 0 0
Mainz
Country [64] 0 0
Germany
State/province [64] 0 0
Würzburg
Country [65] 0 0
Hungary
State/province [65] 0 0
Bekes
Country [66] 0 0
Hungary
State/province [66] 0 0
Hajdu-Bihar
Country [67] 0 0
Hungary
State/province [67] 0 0
Szabolcs-Szatmar-Bereg
Country [68] 0 0
Hungary
State/province [68] 0 0
Budapest
Country [69] 0 0
Israel
State/province [69] 0 0
Tel Aviv
Country [70] 0 0
Israel
State/province [70] 0 0
Afula
Country [71] 0 0
Israel
State/province [71] 0 0
Be'er Sheva
Country [72] 0 0
Israel
State/province [72] 0 0
Haifa
Country [73] 0 0
Israel
State/province [73] 0 0
Jerusalem
Country [74] 0 0
Israel
State/province [74] 0 0
Nahariya
Country [75] 0 0
Israel
State/province [75] 0 0
Nazareth
Country [76] 0 0
Israel
State/province [76] 0 0
Petah Tikva
Country [77] 0 0
Italy
State/province [77] 0 0
Bergamo
Country [78] 0 0
Italy
State/province [78] 0 0
Firenze
Country [79] 0 0
Italy
State/province [79] 0 0
Messina
Country [80] 0 0
Italy
State/province [80] 0 0
Milano
Country [81] 0 0
Italy
State/province [81] 0 0
Novara
Country [82] 0 0
Italy
State/province [82] 0 0
Palermo
Country [83] 0 0
Italy
State/province [83] 0 0
Pisa
Country [84] 0 0
Italy
State/province [84] 0 0
Roma
Country [85] 0 0
Italy
State/province [85] 0 0
San Giovanni Rotondo
Country [86] 0 0
Mexico
State/province [86] 0 0
Distrito Federal
Country [87] 0 0
Mexico
State/province [87] 0 0
Jalisco
Country [88] 0 0
Mexico
State/province [88] 0 0
Morelos
Country [89] 0 0
Mexico
State/province [89] 0 0
Nuevo Leon
Country [90] 0 0
Poland
State/province [90] 0 0
Czestochowa
Country [91] 0 0
Poland
State/province [91] 0 0
Gdansk
Country [92] 0 0
Poland
State/province [92] 0 0
Gdynia
Country [93] 0 0
Poland
State/province [93] 0 0
Katowice
Country [94] 0 0
Poland
State/province [94] 0 0
Poznan
Country [95] 0 0
Poland
State/province [95] 0 0
Skórzewo
Country [96] 0 0
Poland
State/province [96] 0 0
Warszawa
Country [97] 0 0
Poland
State/province [97] 0 0
Wroclaw
Country [98] 0 0
Poland
State/province [98] 0 0
Lódz
Country [99] 0 0
Puerto Rico
State/province [99] 0 0
San Juan
Country [100] 0 0
Spain
State/province [100] 0 0
Madrid
Country [101] 0 0
Spain
State/province [101] 0 0
Almeria
Country [102] 0 0
Spain
State/province [102] 0 0
Barcelona
Country [103] 0 0
Spain
State/province [103] 0 0
Pontevedra
Country [104] 0 0
Spain
State/province [104] 0 0
Santander
Country [105] 0 0
Spain
State/province [105] 0 0
Sevilla
Country [106] 0 0
Spain
State/province [106] 0 0
Valencia
Country [107] 0 0
Switzerland
State/province [107] 0 0
Bern
Country [108] 0 0
Switzerland
State/province [108] 0 0
Lugano
Country [109] 0 0
Switzerland
State/province [109] 0 0
Zürich
Country [110] 0 0
United Kingdom
State/province [110] 0 0
England
Country [111] 0 0
United Kingdom
State/province [111] 0 0
Northern Ireland
Country [112] 0 0
United Kingdom
State/province [112] 0 0
Northumberland, England
Country [113] 0 0
United Kingdom
State/province [113] 0 0
Wales
Country [114] 0 0
United Kingdom
State/province [114] 0 0
Liverpool
Country [115] 0 0
United Kingdom
State/province [115] 0 0
London
Country [116] 0 0
United Kingdom
State/province [116] 0 0
Plymouth
Country [117] 0 0
United Kingdom
State/province [117] 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 and/or reduces fibrosis on liver biopsy and
prevents progression to cirrhosis and/or advanced liver disease
Trial website
https://clinicaltrials.gov/ct2/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
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT03900429