MAESTRO-NAFLD1: A Phase 3 Study to Evaluate the Safety and Biomarkers of Resmetirom (MGL-3196) in Non Alcoholic Fatty Liver Disease (NAFLD) Patients

Sponsor

Madrigal Pharmaceuticals, Inc. (Industry)

Overall Status

Unknown status

CT.gov ID

NCT04197479

Collaborator

(none)

700

Enrollment

Locations

Arms

23.5

Anticipated Duration (Months)

10.4

Patients Per Site

0.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

A double-blind placebo controlled randomized Phase 3 study to evaluate the safety and tolerability of once-daily, oral administration of 80 or 100 mg resmetirom versus matching placebo. 100 patients will be enrolled in a 100 mg open-label arm.

Condition or Disease	Intervention/Treatment	Phase
Non-Alcoholic Fatty Liver Disease	Drug: Placebo Drug: Resmetirom	Phase 3

Study Design

Study Type:

Interventional

Anticipated Enrollment :

700 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

A 52-Week, Phase 3 Study to Evaluate Safety and Biomarkers of Resmetirom (MGL-3196) in Patients With Non-alcoholic Fatty Liver Disease (NAFLD) (MAESTRO-NAFLD-1)

Actual Study Start Date :

Dec 16, 2019

Anticipated Primary Completion Date :

Dec 1, 2021

Anticipated Study Completion Date :

Dec 1, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Open label: resmetirom 100 mg daily	Drug: Resmetirom Tablet Other Names: MGL-3196
Placebo Comparator: Double blinded: matching placebo Placebo daily	Drug: Placebo Matching tablets
Experimental: Double blinded: resmetirom 80 mg 80 mg daily	Drug: Resmetirom Tablet Other Names: MGL-3196
Experimental: Double blinded: resmetirom 100 mg 100 mg daily	Drug: Resmetirom Tablet Other Names: MGL-3196

Outcome Measures

Primary Outcome Measures

The effect of once daily, oral administration of 80 or 100 mg resmetirom versus placebo on the incidence of adverse events. [52 weeks]

Secondary Outcome Measures

The effect of once daily, oral administration of 80 or 100 mg resmetirom versus placebo on the percent change in low density lipoprotein C (LDL-C) from baseline to Week 24 [24 weeks]
The effect of once daily, oral administration of 80 or 100 mg resmetirom versus placebo on the percent change in apolipoprotein B (ApoB) from baseline to Week 24 [24 weeks]
The effect of once daily, oral administration of 80 or 100 mg resmetirom versus placebo on the percent change in hepatic fat fraction as determined by MRI-PDFF from baseline to Week 16. [16 weeks]
The effect of once daily, oral administration of 80 or 100 mg resmetirom versus placebo on the percent change in triglycerides (TGs) from baseline to Week 24 in patients with baseline TG > 150 mg/dL. [24 weeks]
The effect of once daily, oral administration of 80 or 100 mg resmetirom versus placebo after 52 weeks on N-terminal type III collagen propeptide (PRO-C3) in patients with baseline PRO-C3 ≥10 ng/mL. [52 weeks]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Must be willing to participate in the study and provide written informed consent.
Male and female adults ≥18 years of age.
Suspected or confirmed diagnosis of NASH or NAFLD (presumed NASH):
Fibroscan with kPa ≥5.5 and <8.5; CAP ≥280 dB.m-1 OR
MRE >2 and <4.0; MRI-PDFF ≥8% liver fat consistent with steatosis and fibrosis stage ≥1 and <4. OR
Recent liver biopsy (within past 2 years) documenting NASH/NAFLD with steatosis showing one of the following:
NAS ≥4, steatosis ≥1, fibrosis stage 0 or 1A/1C with PRO-C3 <14
NAS <4, steatosis ≥1, with fibrosis stage ≤3
NAS ≥4, steatosis ≥1, fibrosis stage ≤3 without ballooning
MRI-PDFF fat fraction ≥8% obtained during the Screening Period (baseline MRI-PDFF) or a historic MRI-PDFF ≤8 weeks old at the time of randomization.
Stable dyslipidemia therapy for ≥30 days prior to randomization.

Exclusion Criteria:

History of significant alcohol consumption for a period of more than 3 consecutive months within 1 year prior to Screening.
Regular use of drugs historically associated with NAFLD.
History of bariatric surgery or intestinal bypass surgery within the 5 years prior to randomization or planned during the conduct of the study.
Weight gain or loss ≥5% total body weight within 12 weeks prior to randomization.
HbA1c >9.0%.
Glucagon-like peptide 1 [GLP-1] agonist therapy or high dose vitamin E (>400 IU/day) unless stable for 24 weeks prior to biopsy.
Presence of cirrhosis on liver biopsy defined as stage 4 fibrosis.
Diagnosis of hepatocellular carcinoma (HCC).
Model for End-stage Liver Disease (MELD) score ≥12, as determined at Screening, unless due to therapeutic anti coagulation or Gilbert syndrome.
Hepatic decompensation.
Chronic liver diseases.
Has an active autoimmune disease.
Serum ALT >250 U/L.
History of biliary diversion.
Uncontrolled hypertension (either treated or untreated).
Active, serious medical disease with a likely life expectancy <2 years.
Participation in an investigational new drug trial in the 60 days or 5 half-lives, whichever is longer, prior to randomization.
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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Central Research Associates	Birmingham	Alabama	United States	35205
2	Arizona Liver Health - Chandler	Chandler	Arizona	United States	85224
3	East Valley Family Physicians	Chandler	Arizona	United States	85224
4	The Institute For Liver Health - Glendale	Glendale	Arizona	United States	85306
5	Arizona - Desert Clinical Research	Mesa	Arizona	United States	85213
6	The Institute For Liver Health - Tucson	Tucson	Arizona	United States	85711
7	Adobe Gastroenterology	Tucson	Arizona	United States	85712
8	Arkansas Gastroenterology	North Little Rock	Arkansas	United States	72117
9	Fresno Clinical Research Center	Fresno	California	United States	93720
10	National Research Institute - Huntington Park	Huntington Park	California	United States	90255
11	Ruane Clinical Research Group	Los Angeles	California	United States	90036
12	National Research Institute - Los Angeles	Los Angeles	California	United States	90057
13	Catalina Research Institute	Montclair	California	United States	91763
14	National Research Institute - Panorama City	Panorama City	California	United States	91402
15	Alliance Clinical Research	Poway	California	United States	92064
16	San Fernando Valley Health Institute	Van Nuys	California	United States	91405
17	South Denver Gastroenterology - Swedish Medical Center Office	Englewood	Colorado	United States	80113
18	Excel Medical Clinical Trials	Boca Raton	Florida	United States	33434
19	Medicinae Doctor Clinical	Hallandale Beach	Florida	United States	33009
20	Floridian Clinical Research	Hialeah	Florida	United States	33016
21	Nature Coast Clinical Research - Inverness	Inverness	Florida	United States	34452
22	Jacksonville Center for Clinical Research	Jacksonville	Florida	United States	32216
23	Florida Research Institute	Lakewood Ranch	Florida	United States	34211
24	Miami Dade Medical Research Institute	Miami	Florida	United States	33176
25	Orlando Research Center	Orlando	Florida	United States	32806
26	Progressive Medical Research	Port Orange	Florida	United States	32127
27	Covenant Research	Sarasota	Florida	United States	34240
28	The Villages Research Center	The Villages	Florida	United States	32162
29	Gastrointestinal Specialists of Georgia	Marietta	Georgia	United States	30060
30	East-West Medical Research Institute	Honolulu	Hawaii	United States	96814
31	Kansas Medical Clinic - Gastroenterology	Topeka	Kansas	United States	66606
32	L-MARC Research Center	Louisville	Kentucky	United States	40213
33	Digestive Health Center of Louisiana	Baton Rouge	Louisiana	United States	70809
34	Tandem Clinical Research - New Orleans Area Site	Marrero	Louisiana	United States	70072
35	Clinical Trials of America	West Monroe	Louisiana	United States	71291
36	Gastrointestinal Associates & Endoscopy Center - Flowood	Flowood	Mississippi	United States	39232
37	Southern Therapy and Advanced Research	Jackson	Mississippi	United States	39216
38	Kansas City Research Institute	Kansas City	Missouri	United States	64131
39	Henderson Research Center	Henderson	Nevada	United States	89052
40	Clarity Clinical Research	East Syracuse	New York	United States	13057
41	Cumberland Research Associates	Fayetteville	North Carolina	United States	28304
42	Diabetes and Endocrinology Consultants	Morehead City	North Carolina	United States	28557
43	TMA - Wilmington Gastroenterology Accociates	Wilmington	North Carolina	United States	28403
44	Platinum - Sterling Research Group - Springdale	Cincinnati	Ohio	United States	45246
45	Aventiv Research Columbus	Columbus	Ohio	United States	43213
46	Awasty Research Network	Marion	Ohio	United States	43302
47	Northeast Clinical Research Center	Bethlehem	Pennsylvania	United States	18017
48	Premier Medical Group - Clarksville - Dunlop Lane	Clarksville	Tennessee	United States	37040
49	Gastro One - Germantown Office - Wolf Park Drive	Germantown	Tennessee	United States	38138
50	Pinnacle Clinical Research - Austin	Austin	Texas	United States	78746
51	The Liver Institute At Methodist Dallas	Dallas	Texas	United States	75203
52	Dallas Research Center	Dallas	Texas	United States	75234
53	Liver Center of Texas	Dallas	Texas	United States	75234
54	Texas Digestive Disease Consultants - Dallas - Baylor University Medical Center Gaston Ave	Dallas	Texas	United States	75246
55	South Texas Research Institute	Edinburg	Texas	United States	78539
56	Liver Associates of Texas	Houston	Texas	United States	77030
57	Doctor's Hospital at Renaissance	McAllen	Texas	United States	78504
58	Plano Research Center	Plano	Texas	United States	75093
59	Texas Liver Institute/American Research Corporation	San Antonio	Texas	United States	78215
60	Pinnacle Clinical Research - San Antonio	San Antonio	Texas	United States	78229
61	San Antonio Research Center	San Antonio	Texas	United States	78229
62	Texas Digestive Disease Consultants - San Marcos	San Marcos	Texas	United States	78666
63	Texas Digestive Disease Consultants - Bay Area Houston Endoscopy Center	Webster	Texas	United States	77598
64	Wasatch Peak Family Practice	Layton	Utah	United States	84041
65	Salt Lake City Research Center	Murray	Utah	United States	84123
66	National Clinical Research - Richmond	Richmond	Virginia	United States	23294
67	Fundacion de Investigacion de Diego	San Juan		Puerto Rico