Phase 2 Study of MGL-3196 in Patients With Non-Alcoholic Steatohepatitis (NASH)

NCT ID: NCT02912260

Last Updated: 2017-12-19

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE2

Total Enrollment

125 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-09-30

Study Completion Date

2018-04-30

Brief Summary

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The primary objective of this study is to determine the effect of once-daily oral MGL-3196 on the percent change in hepatic fat fraction from baseline in patients with biopsy-proven Non-alcoholic Steatohepatitis (NASH).

Detailed Description

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Conditions

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Non-alcoholic Steatohepatitis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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MGL-3196

Study Drug

Group Type EXPERIMENTAL

MGL-3196

Intervention Type DRUG

Placebo

Matching Placebo

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Interventions

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MGL-3196

Intervention Type DRUG

Placebo

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* Must be willing to participate in the study and provide written informed consent;
* Male and female adults ≥18 years of age with a BMI \<45 kg/m\^2;
* Female patients of child bearing potential with negative serum pregnancy (beta human chorionic gonadotropin) tests who are not breastfeeding, do not plan to become pregnant during the study, and agree to use effective birth control (ie, condoms, diaphragm, non hormonal intrauterine device \[IUD\], or sexual abstinence \[only if this is in line with the patient's current lifestyle\]) throughout the study and for at least 1 month after study completion; hormonal contraception (estrogens stable ≥3 months) and hormonal IUDs are permitted if used with a secondary birth control measure (eg, condoms); OR female patients of non-child bearing potential (ie, surgically \[bilateral oophorectomy, hysterectomy, or tubal ligation\] or naturally sterile \[\>12 consecutive months without menses\]); Male patients who have sexual intercourse with a female partner of child bearing potential from the first dose of study drug until 1 month after study completion must be either surgically sterile (confirmed by documented azoospermia \>90 days after the procedure) OR agree to use a condom with spermicide. All male patients must agree not to donate sperm from the first dose of study drug until 1 month after study completion;
* Must have confirmation of ≥10% liver fat content on PDFF-MRI;
* Biopsy-proven NASH. Must have had prior liver biopsy within 180 days of randomization with fibrosis stage 1 to 3 and a NAS of ≥4 with at least a score of 1 in each of the following NAS components:

* Steatosis (scored 0 to 3),
* Ballooning degeneration (scored 0 to 2), and
* Lobular inflammation (scored 0 to 3);
* Must have documented historical (3 weeks to 6 months prior to the study entry) ALT and AST levels consistent with the screening ALT and AST values.

Exclusion Criteria

Note: Unless otherwise specified, repeat testing may be performed in consultation with the Medical Monitor.

* History of significant alcohol consumption for a period of more than 3 consecutive months within 1 year prior to screening;
* Weight gain or loss \>5% in the 6 months prior to randomization or \>10% in the 12 months prior to screening;
* Hyperthyroidism;
* Patients on thyroid replacement therapy;
* Prior or planned (during the study period) bariatric surgery (eg, gastroplasty, roux-en-Y gastric bypass);
* Type 1 diabetes;
* Uncontrolled Type 2 diabetes defined as Hemoglobin A1c ≥ 9.5% at screening (patients with HbA1c ≥ 9.5% may be rescreened);
* Use of obeticholic acid, ursodeoxycholic acid (Ursodiol® and Urso®), high dose vitamin E (\>400 IU/day) unless on stable dose of vitamin E \>400 IU/day for at least 6 months at the time of liver biopsy, or pioglitazone within 90 days prior to enrollment or since screening biopsy, whichever is longer;
* Presence of cirrhosis on liver biopsy (stage 4 fibrosis);
* Platelet count \< 140,000/mm\^3;
* Clinical evidence of hepatic decompensation;
* Evidence of other forms of chronic liver disease;
* Active, serious medical disease with likely life expectancy \<2 years;
* Participation in an investigational new drug trial in the 30 days prior to randomization; or
* 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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Madrigal Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Madrigal Research Site

Dothan, Alabama, United States

Site Status

Madrigal Research Site

Tucson, Arizona, United States

Site Status

Madrigal Research Site

Coronado, California, United States

Site Status

Madrigal Research Site

Los Angeles, California, United States

Site Status

Madrigal Research Site

Rialto, California, United States

Site Status

Madrigal Research Site

San Diego, California, United States

Site Status

Madrigal Research Site

Ventura, California, United States

Site Status

Madrigal Research Site

Englewood, Colorado, United States

Site Status

Madrigal Research Site

Boca Raton, Florida, United States

Site Status

Madrigal Research Site

Lakewood Rch, Florida, United States

Site Status

Madrigal Research Site

Lauderdale Lakes, Florida, United States

Site Status

Madrigal Research Site

Miami, Florida, United States

Site Status

Madrigal Research Site

New Port Richey, Florida, United States

Site Status

Madrigal Research Site

Kansas City, Kansas, United States

Site Status

Madrigal Research Site

Monroe, Louisiana, United States

Site Status

Madrigal Research Site

Baltimore, Maryland, United States

Site Status

Madrigal Research Site

Jackson, Mississippi, United States

Site Status

Madrigal Research Site

St Louis, Missouri, United States

Site Status

Madrigal Research Site

Albuquerque, New Mexico, United States

Site Status

Madrigal Research Site

New York, New York, United States

Site Status

Madrigal Research Site

Durham, North Carolina, United States

Site Status

Madrigal Research Site

Rapid City, South Dakota, United States

Site Status

Madrigal Research Site

Live Oak, Texas, United States

Site Status

Madrigal Research Site

San Antonio, Texas, United States

Site Status

Madrigal Research Site

Charlottesville, Virginia, United States

Site Status

Madrigal Research Site

Seattle, Washington, United States

Site Status

Countries

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United States

References

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Harrison SA, Ratziu V, Anstee QM, Noureddin M, Sanyal AJ, Schattenberg JM, Bedossa P, Bashir MR, Schneider D, Taub R, Bansal M, Kowdley KV, Younossi ZM, Loomba R. Design of the phase 3 MAESTRO clinical program to evaluate resmetirom for the treatment of nonalcoholic steatohepatitis. Aliment Pharmacol Ther. 2024 Jan;59(1):51-63. doi: 10.1111/apt.17734. Epub 2023 Oct 2.

Reference Type DERIVED
PMID: 37786277 (View on PubMed)

Younossi ZM, Stepanova M, Taub RA, Barbone JM, Harrison SA. Hepatic Fat Reduction Due to Resmetirom in Patients With Nonalcoholic Steatohepatitis Is Associated With Improvement of Quality of Life. Clin Gastroenterol Hepatol. 2022 Jun;20(6):1354-1361.e7. doi: 10.1016/j.cgh.2021.07.039. Epub 2021 Jul 27.

Reference Type DERIVED
PMID: 34329774 (View on PubMed)

Harrison SA, Bashir M, Moussa SE, McCarty K, Pablo Frias J, Taub R, Alkhouri N. Effects of Resmetirom on Noninvasive Endpoints in a 36-Week Phase 2 Active Treatment Extension Study in Patients With NASH. Hepatol Commun. 2021 Jan 4;5(4):573-588. doi: 10.1002/hep4.1657. eCollection 2021 Apr.

Reference Type DERIVED
PMID: 33860116 (View on PubMed)

Harrison SA, Bashir MR, Guy CD, Zhou R, Moylan CA, Frias JP, Alkhouri N, Bansal MB, Baum S, Neuschwander-Tetri BA, Taub R, Moussa SE. Resmetirom (MGL-3196) for the treatment of non-alcoholic steatohepatitis: a multicentre, randomised, double-blind, placebo-controlled, phase 2 trial. Lancet. 2019 Nov 30;394(10213):2012-2024. doi: 10.1016/S0140-6736(19)32517-6. Epub 2019 Nov 11.

Reference Type DERIVED
PMID: 31727409 (View on PubMed)

Other Identifiers

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MGL-3196-05

Identifier Type: -

Identifier Source: org_study_id