A Phase 3 Study to Evaluate Safety and Biomarkers of Resmetirom (MGL-3196) in Patients With Non-alcoholic Fatty Liver Disease (NAFLD), MAESTRO-NAFLD-Open-Label-Extension (MAESTRO-NAFLD-OLE)

Madrigal Pharmaceuticals

Status and phase

Enrolling

Phase 3

Conditions

Non-Alcoholic Fatty Liver Disease

Treatments

Drug: Resmetirom

Study type

Interventional

Funder types

Industry

Identifiers

NCT04951219

MGL-3196-18

Details and patient eligibility

About

A 52-Week, Multi-center, Open-label, Active Treatment Extension Study to Evaluate Safety and Tolerability of Once Daily, Oral Administration of Resmetirom (MGL-3196)

Enrollment

1,000 estimated patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

For patients who completed MAESTRO-NAFLD-1, completed the Week 52 visit, and completed the Week 56 visit within 90 days of the Extension Day 1 visit, and are willing to participate in MAESTRO-NAFLD-OLE and provide written informed consent.
For patients who screen failed MAESTRO-NASH, must provide written informed consent for MAESTRO-NAFLD-OLE and must have screened and met all eligibility requirements for MAESTRO-NASH within 90 days of the Extension Day 1 visit for MAESTRO-NAFLD-OLE and have a liver biopsy that is ineligible for MAESTRO-NASH within 6 months of the Extension Day 1 visit. Eligible liver biopsy for MAESTRO-NAFLD-OLE must have one of the following results:
- NAS = 3, steatosis 1, ballooning 1, inflammation 1, OR NAS = 3, ballooning 0, with F1B, F2 or F3
- NAS ≥ 4, at least 1 in all NAS components, F1A or F1C, PRO-C3 ≤ 14 (NASH, but ineligible for MAESTRO-NASH)
- Compensated NASH cirrhosis based on biopsy at screening of MAESTRO-NASH and baseline of MAESTRO-NAFLD-OLE, including Child Pugh-A (score 5-6), MELD <12, albumin ≥3.2, and bilirubin <2
For patients who screen failed from MAESTRO-NASH OUTCOMES and de novo patients, must have documented CP-A/B (score <8) NASH cirrhosis (including minimal decompensation) and MELD <15 unless MELD >=15 based on non-cirrhotic parameters. MAESTRO-NASH OUTCOMES screen failures must have screened and met all eligibility requirements for MAESTRO-NASH OUTCOMES within 90 days of the Extension Day 1 visit for MAESTRO-NAFLD-OLE .

Exclusion criteria

A history of significant alcohol consumption for a period of more than 3 consecutive months within 1 year prior to Extension Day 1.
Diagnosis of hepatocellular carcinoma or other carcinomas that may prevent participation in the Extension study.
Chronic liver diseases
Has an active autoimmune disease
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.

Trial design

Primary purpose

Treatment

Allocation

Randomized

Interventional model

Parallel Assignment

Masking

Triple Blind

1,000 participants in 6 patient groups

Double-blind 80 mg Daily

Experimental group

Description:

For patients assigned to double-blind treatment and who completed Week 52 and 56 of MAESTRO-NAFLD-1, double-blind resmetirom 80 mg for first 12 weeks followed by open-label resmetirom 100 mg for weeks 12-52

Treatment:

Drug: Resmetirom

Double-blind 100 mg Daily

Experimental group

Description:

For patients assigned to double-blind treatment and who completed Week 52 and 56 of MAESTRO-NAFLD-1, double-blind resmetirom 100 mg for first 12 weeks followed by open-label resmetirom 100 mg for weeks 12-52

Treatment:

Drug: Resmetirom

Open-label

Experimental group

Description:

For patients assigned to open-label treatment and who completed Week 52 and 56 of MAESTRO-NAFLD-1, open-label resmetirom at same dose as MGL-3196-14 for an additional 52 weeks. NASH cirrhosis patients may receive open-label resmetirom for an additional 52 weeks (ie, 52 weeks in MGL-3196-14 and 104 weeks in MGL-3196-18).

Treatment:

Drug: Resmetirom

Open-Label 80 mg

Experimental group

Description:

For patients with NASH cirrhosis who were screen failures from MGL-3196-11, open-label resmetirom 80 mg for 104 weeks

Treatment:

Drug: Resmetirom

Open Label 100 mg

Experimental group

Description:

For patients without NASH cirrhosis who were screen failures from MGL-3196-11, open-label resmetirom 100 mg for 52 weeks