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

• Sponsor: Madrigal Pharmaceuticals, Inc. (Industry)
• Overall Status: Unknown status
• CT.gov ID: NCT02912260
• Collaborator: (none)
• Enrollment: 125
• Locations: 26
• Arms: 2
• Duration (Months): 19
• Patients Per Site: 4.8
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

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).

Condition or Disease	Intervention/Treatment	Phase
Non-alcoholic Steatohepatitis	Drug: MGL-3196; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 125 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase 2, Multi-Center, Double-Blind, Randomized, Placebo-controlled Study of MGL-3196 in Patients With Non-alcoholic Steatohepatitis
• Study Start Date: Sep 1, 2016
• Actual Primary Completion Date: Oct 1, 2017
• Anticipated Study Completion Date: Apr 1, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: MGL-3196 Study Drug	Drug: MGL-3196
Placebo Comparator: Placebo Matching Placebo	Drug: Placebo

Outcome Measures

Primary Outcome Measures

1. Change from baseline in hepatic fat fraction assessed by MRI-PDFF [12 weeks]

Secondary Outcome Measures

1. Two-point reduction in Non-alcoholic fatty liver disease NASH CRN (NAFLD) activity score (NAS) [36 weeks]

2. Resolution of Non-alcoholic steatohepatitis (NASH) (ballooning = 0; inflammation = 0 to 1) as determined by the NASH CRN NAS score [36 weeks]

3. Improvement in fibrosis by at least 1 stage with no worsening of steatohepatitis [36 weeks]

4. Change from baseline in hepatic fat fraction [36 weeks]

5. Safety and tolerability of MGL-3196 based on Adverse Events and Changes in Laboratory Values [12 and 36 weeks]

6. Effect on high-sensitivity C-reactive protein (hsCRP) [12 and 36 weeks]

7. Effect on serum alanine aminotransferase (ALT) [12 and 36 weeks]

8. Effect on aspartate aminotransferase (AST) [12 and 36 weeks]

9. Effect on lipid parameters [12 and 36 weeks]

   Determine the effect on lipid parameters including low-density lipoprotein cholesterol (LDL-C), non- LDL-C, high-density lipoprotein cholesterol (HDL-C), non-HDL-C, total cholesterol, triglycerides, apolipoprotein B (ApoB), and lipoprotein(a) (Lp[a]) particles.

10. Effect on NASH and fibrosis biomarkers [12 and 36 weeks]

    Determine the effect on NASH and fibrosis biomarkers including cytokeratin-18 (CK-18), fibrosis-4 (FIB-4), and enhanced liver function (ELF) test.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria. Patients who meet all of the following criteria will be eligible to participate in the study:

• 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. Patients who meet any of the following criteria will be excluded from participation in the study:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Madrigal Research Site	Dothan	Alabama	United States
2	Madrigal Research Site	Tucson	Arizona	United States
3	Madrigal Research Site	Coronado	California	United States
4	Madrigal Research Site	Los Angeles	California	United States	90057
5	Madrigal Research Site	Rialto	California	United States
6	Madrigal Research Site	San Diego	California	United States
7	Madrigal Research Site	Ventura	California	United States
8	Madrigal Research Site	Englewood	Colorado	United States
9	Madrigal Research Site	Boca Raton	Florida	United States
10	Madrigal Research Site	Lakewood Ranch	Florida	United States
11	Madrigal Research Site	Lauderdale Lakes	Florida	United States
12	Madrigal Research Site	Miami	Florida	United States
13	Madrigal Research Site	New Port Richey	Florida	United States
14	Madrigal Research Site	Kansas City	Kansas	United States
15	Madrigal Research Site	Monroe	Louisiana	United States
16	Madrigal Research Site	Baltimore	Maryland	United States
17	Madrigal Research Site	Jackson	Mississippi	United States	39202
18	Madrigal Research Site	Saint Louis	Missouri	United States
19	Madrigal Research Site	Albuquerque	New Mexico	United States
20	Madrigal Research Site	New York	New York	United States
21	Madrigal Research Site	Durham	North Carolina	United States
22	Madrigal Research Site	Rapid City	South Dakota	United States
23	Madrigal Research Site	Live Oak	Texas	United States	78233
24	Madrigal Research Site	San Antonio	Texas	United States
25	Madrigal Research Site	Charlottesville	Virginia	United States
26	Madrigal Research Site	Seattle	Washington	United States

Sponsors and Collaborators

• Madrigal Pharmaceuticals, Inc.

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Madrigal Pharmaceuticals, Inc.
• ClinicalTrials.gov Identifier: NCT02912260
• Other Study ID Numbers: MGL-3196-05
• First Posted: Sep 23, 2016
• Last Update Posted: Dec 19, 2017
• Last Verified: Dec 1, 2017

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Additional relevant MeSH terms: Fatty Liver; Non-alcoholic Fatty Liver Disease

Study Results

No Results Posted as of Dec 19, 2017