Non-alcoholic Steatohepatitis
Conditions
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 participants with biopsy-proven Non-alcoholic Steatohepatitis (NASH).
Interventions
DRUGMGL-3196
DRUGPlacebo
Sponsors
Madrigal Pharmaceuticals, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
. Participants 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; * Female participants 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 (that is, condoms, diaphragm, nonhormonal intrauterine device \[IUD\], or sexual abstinence \[only if this is in line with the participant's current lifestyle\]) 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 (for example, condoms); or female participants of non-child bearing potential (that is, surgically \[bilateral oophorectomy, hysterectomy, or tubal ligation\] or naturally sterile \[\>12 consecutive months without menses\]); Male participants 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 participants 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 magnetic resonance imaging proton density fat fraction; * Biopsy-proven NASH. Must have had prior liver biopsy within 180 days of randomization with fibrosis stage 1 to 3 and a non-alcoholic fatty liver disease activity score (NAS) of ≥4 with a score of 1 or more 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) alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels consistent with the screening ALT and AST values.
Exclusion criteria
. Participants 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; * Hyperthyroidism; * Participants on thyroid replacement therapy (with exceptions); * Prior or planned (during the study period) bariatric surgery (for example, gastroplasty, roux-en-Y gastric bypass); * Type 1 diabetes; * Uncontrolled Type 2 diabetes defined as Hemoglobin A1c (HbA1c) ≥ 9.5% at screening (participants 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 participant, or interfere with the study outcomes.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline To Week 12 In Hepatic Fat Fraction Assessed By Magnetic Resonance Imaging Proton Density Fat Fraction (MRI-PDFF) | Week 12 | The primary endpoint was relative change in MRI-PDFF assessed hepatic fat fraction compared with placebo at Week 12 in participants who had both a baseline and Week 12 MRI-PDFF. Least squares (LS) mean was provided for the statistical comparison of MGL-3196 versus placebo. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline To Week 36 In Hepatic Fat Fraction Assessed By MRI-PDFF | Week 36 | The endpoint was relative change assessed hepatic fat fraction compared with placebo at Week 36. LS mean was provided for the statistical comparison of MGL-3196 versus placebo. |
| Change From Baseline To Week 12 In Absolute Hepatic Fat Fraction Assessed By MRI-PDFF | Week 12 | The endpoint was change in MRI-PDFF assessed absolute hepatic fat fraction compared with placebo at Week 12. LS mean was provided for the comparison of MGL-3196 versus placebo. |
| Change From Baseline To Week 36 In Absolute Hepatic Fat Fraction Assessed By MRI-PDFF | Week 36 | The endpoint was change in assessed absolute hepatic fat fraction compared with placebo at Week 36. LS mean was provided for the comparison of MGL-3196 versus placebo. |
| Percentage Of Participants With At Least 30% Relative Fat Reduction at Week 12 | Week 12 | The endpoint presented the percentage of participants achieving a relative fat reduction of ≥30% at Week 12. |
| Percentage Of Participants With At Least 30% Relative Fat Reduction At Week 36 | Week 36 | The endpoint presented the percentage of participants achieving a relative fat reduction of ≥30% at Week 36. |
| Percentage Of Participants Achieving A 1-Point Reduction In Non-alcoholic Fatty Liver Disease Activity Score (NAS) At Week 36 | Week 36 | The NAS is a histologic scale for non-alcoholic steatohepatitis (NASH) activity, which combines into a single score steatosis (Grade 0 to 3), ballooning (Grade 0 to 2), and lobular inflammation (Grade 0 to 3). The endpoint presented the percentage of participants with a 1-point or greater reduction in NAS. |
| Percentage Of Participants Achieving A 2-Point Reduction In NAS At Week 36 | Week 36 | The NAS is a histologic scale for NASH activity, which combines into a single score steatosis (Grade 0 to 3), ballooning (Grade 0 to 2), and lobular inflammation (Grade 0 to 3). The endpoint presented the percentage of participants with a 2-point or greater reduction in NAS. |
| Percentage Of Participants Achieving A 2-Point Reduction In NAS And Either A ≥1-Point Reduction In Lobular Inflammation Or Hepatocellular Ballooning At Week 36 | Week 36 | The NAS is a histologic scale for NASH activity, which combines into a single score steatosis (Grade 0 to 3), ballooning (Grade 0 to 2), and lobular inflammation (Grade 0 to 3). The endpoint presented the percentage of participants with a 2-point or greater reduction in NAS and a 1-point or greater reduction in lobular inflammation or hepatocellular ballooning. |
| Percentage Of Participants Achieving A 2-Point Reduction In NAS Without Fibrosis Worsening At Week 36 | Week 36 | The NAS is a histologic scale for NASH activity, which combines into a single score steatosis (Grade 0 to 3), ballooning (Grade 0 to 2), and lobular inflammation (Grade 0 to 3). Fibrosis stage (0 to 3) was also included in the assessment. The endpoint presented the percentage of participants with a 2-point or greater reduction in NAS without worsening fibrosis. |
| Percentage Of Participants With A Reduction In Hepatocellular Steatosis At Week 36 | Week 36 | The NAS is a histologic scale for NASH activity, which combines into a single score steatosis (Grade 0 to 3), ballooning (Grade 0 to 2), and lobular inflammation (Grade 0 to 3). The endpoint presented the percentage of participants with a reduction in hepatocellular steatosis. |
| Percentage Of Participants With A Reduction In Lobular Inflammation At Week 36 | Week 36 | The NAS is a histologic scale for NASH activity, which combines into a single score steatosis (Grade 0 to 3), ballooning (Grade 0 to 2), and lobular inflammation (Grade 0 to 3). The endpoint presented the percentage of participants with a reduction in lobular inflammation. |
| Percentage Of Participants With A Reduction In Hepatocellular Ballooning At Week 36 | Week 36 | The NAS is a histologic scale for NASH activity, which combines into a single score steatosis (Grade 0 to 3), ballooning (Grade 0 to 2), and lobular inflammation (Grade 0 to 3). The endpoint presented the percentage of participants with a reduction in hepatocellular ballooning. |
| Percentage Of Participants Achieving NASH Resolution With At Least 2-Point Reduction In NAS At Week 36 | Week 36 | The endpoint presented the percentage of participants achieving NASH resolution with a 2-point reduction at Week 36. |
| Percent Change From Baseline To Week 12 In High-sensitivity C-reactive Protein (hsCRP) | Week 12 | hsCRP was used as a non-invasive inflammation marker for this study. Blood samples were collected to determine the effect of MGL-3196 on hsCRP. |
| Percent Change From Baseline To Week 36 In hsCRP | Week 36 | hsCRP was used as a non-invasive inflammation marker for this study. Blood samples were collected to determine the effect of MGL-3196 on hsCRP. |
| Change From Baseline To Week 12 In Serum Alanine Aminotransferase (ALT) | Week 12 | Blood samples were collected to determine the effect of MGL-3196 on serum ALT. |
| Change From Baseline To Week 36 In ALT | Week 36 | Blood samples were collected to determine the effect of MGL-3196 on serum ALT. |
| Change From Baseline To Week 12 In Serum Aspartate Aminotransferase (AST) | Week 12 | Blood samples were collected to determine the effect of MGL-3196 on serum AST. |
| Change From Baseline To Week 36 In AST | Week 36 | Blood samples were collected to determine the effect of MGL-3196 on serum AST. |
| Percent Change From Baseline To Week 12 In Lipid Parameters | Week 12 | Blood samples were collected to determine the effect of MGL-3196 on lipid parameters including low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), non-HDL-C, total cholesterol (TC), triglycerides (TG), apolipoprotein B (ApoB), and Apolipoprotein CIII (ApoCIII). |
| Percent Change From Baseline To Week 36 In Lipid Parameters | Week 36 | Blood samples were collected to determine the effect of MGL-3196 on lipid parameters including LDL-C, HDL-C, non-HDL-C, TC, TG, ApoB, and ApoCIII. |
| Percent Change From Baseline To Week 12 In Lipid Parameter Lipoprotein(a) (Lp[a]) | Week 12 | Blood samples were collected to determine the effect of MGL-3196 on lipid parameter Lp(a). |
| Percent Change From Baseline To Week 36 In Lipid Parameter Lp[a] | Week 36 | Blood samples were collected to determine the effect of MGL-3196 on lipid parameter Lp(a). |
| Change From Baseline To Week 12 And Week 36 In Cytokeratin-18 (CK-18) | Week 12 and Week 36 | Serum CK-18 fragments, detected using the M30 antibody, is a non-invasive biomarker for NASH that may reflect hepatocyte apoptosis. |
| Change From Baseline To Week 12 And Week 36 In Enhanced Liver Fibrosis (ELF) Test | Week 12 and Week 36 | The ELF Test is a non-invasive blood test that provides a simple, unitless numeric score that is used as a marker of collagen formation and fibrogenic activity and can be used to assess the risk of progression to cirrhosis. Scores below 9.8 indicate low risk of disease progression, and scores above 11.29 indicate high risk. The ELF score is derived from values of three serum biomarkers: hyaluronic acid (HA), procollagen III N-terminal peptide (PIIINP), and tissue inhibitor of metalloproteinase-1 (TIMP-1). The formula is 2.278 + 0.851 × ln(HA) + 0.751 × ln(PIIINP) + 0.394 × ln(TIMP-1); there are no minimum or maximum values. |
| Change From Baseline To Week 12 And Week 36 In Fibrosis-4 (Fib-4) Score | Week 12 and Week 36 | The Fib-4 score is a scoring system used to estimate the amount of scarring in the liver. It is based on common clinical parameters (age, AST, ALT, and platelets) and has been shown to have the best diagnostic accuracy for advanced fibrosis when compared with other noninvasive clinical scores. Scores are categorized into low (\<1.30), indeterminate (1.30-2.67), or high (\>2.67) risk of fibrosis. The formula for Fib-4 is: (Age \[yr\] x AST \[U/L\]) / ((PLT \[109/L\]) x (ALT \[U/L\])½); there are no minimum or maximum values |
| Change From Baseline of Thyrotropin at Week 12 | Baseline up to Week 12 | Thyrotropin (TSH) was assessed at each study visit. |
| Change From Baseline of Total Thyroxine at Week 12 | Baseline up to Week 12 | Total thyroxine (FT4) was assessed at each study visit. |
| Change From Baseline of Free Thyroxine at Week 12 | Baseline up to Week 12 | Free thyroxine (FT4) was assessed at each study visit. |
| Change From Baseline of Total Triiodothyronine at Week 12 | Baseline up to Week 12 | Total Triiodothyronine (T3) was assessed at each study visit. |
| Change From Baseline of Free Triiodothyronine at Week 12 | Baseline up to Week 12 | Free triiodothyronine (T3) was assessed at each study visit. |
| Change From Baseline of Thyroxine Binding Globulin at Week 12 | Baseline up to Week 12 | Thyroxine Binding Globulin was assessed at each study visit. |
| Change From Baseline of Reverse Triiodothyronine Globulin at Week 12 | Baseline up to Week 12 | Reverse Triiodothyronine (T3) was assessed at each study visit. |
| Change From Baseline of Thyrotropin at Week 36 | Baseline up to Week 36 | Tyrotropin (TSH) was assessed at each study visit. |
| Change From Baseline of Total Thyroxine at Week 36 | Baseline up to Week 36 | Total thyroxine (FT4), thyrotropin (TSH) was assessed at each study visit. |
| Percentage Of Participants With Adverse Events (AEs) | Week 12 and Week 36 | An AE was defined as any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product, which does not necessarily have a causal relationship with the treatment. A summary of serious and all other non-serious AEs, regardless of causality, is located in the Reported Adverse Events module. |
| Change From Baseline of Total Triiodothyronine at Week 36 | Baseline up to Week 36 | Total triiodothyronine (T3) was assessed at each study visit. |
| Change From Baseline of Free Triiodothyronine at Week 36 | Baseline up to Week 36 | Free triiodothyronine (T3) was assessed at each study visit. |
| Change From Baseline of Thyroxine-Binding Globulin at Week 36 | Baseline up to Week 36 | Thyroxine-binding globulin (TBG) was assessed at each study visit. |
| Change From Baseline of Reverse Triiodothyronine at Week 36 | Baseline up to Week 36 | Reverse triiodothyronine (T3) was assessed at each study visit. |
| Change From Baseline of Free Thyroxine Week 36 | Baseline up to Week 36 | Total free thyroxine (FT4) was assessed at each study visit. |
Countries
United States
Participant flow
Recruitment details
Participants underwent screening procedures within 42 days of randomization. To participate in the study, participants were required to have had a qualifying liver biopsy within 180 days of randomization.
Participants by arm
| Arm | Count |
|---|---|
| MGL-3196 Randomized participants received MGL-3196 80 mg orally once daily in the morning for 36 weeks. | 84 |
| Placebo Randomized participants received matching placebo orally once daily in the morning for 36 weeks. | 41 |
| Total | 125 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Extension Study | Withdrawal by Subject | 1 | 1 |
| Main Study | Adverse Event | 3 | 0 |
| Main Study | Lost to Follow-up | 5 | 4 |
| Main Study | Physician Decision | 0 | 1 |
| Main Study | Withdrawal by Subject | 2 | 2 |
Baseline characteristics
| Characteristic | MGL-3196 | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 51.8 years STANDARD_DEVIATION 10.35 | 47.3 years STANDARD_DEVIATION 11.71 | 50.3 years STANDARD_DEVIATION 10.97 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 37 Participants | 22 Participants | 59 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 47 Participants | 19 Participants | 66 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Hepatic Fat Fraction by MRI-PDFF at Screening | 20.25 percentage STANDARD_DEVIATION 6.843 | 19.63 percentage STANDARD_DEVIATION 8.159 | 20.05 percentage STANDARD_DEVIATION 7.274 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 3 Participants | 5 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 80 Participants | 37 Participants | 117 Participants |
| Sex: Female, Male Female | 46 Participants | 17 Participants | 63 Participants |
| Sex: Female, Male Male | 38 Participants | 24 Participants | 62 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 84 | 0 / 41 | 0 / 31 |
| other Total, other adverse events | 73 / 84 | 28 / 41 | 6 / 31 |
| serious Total, serious adverse events | 5 / 84 | 2 / 41 | 0 / 31 |
Outcome results
Primary
Percent Change From Baseline To Week 12 In Hepatic Fat Fraction Assessed By Magnetic Resonance Imaging Proton Density Fat Fraction (MRI-PDFF)
The primary endpoint was relative change in MRI-PDFF assessed hepatic fat fraction compared with placebo at Week 12 in participants who had both a baseline and Week 12 MRI-PDFF. Least squares (LS) mean was provided for the statistical comparison of MGL-3196 versus placebo.
Time frame: Week 12
Population: MRI-PDFF evaluable population: all participants who were randomized in the study, received study drug, and finished Week 12 visit, with valid MRI-PDFF measurements at both baseline and Week 12 Visit.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| MGL-3196 | Percent Change From Baseline To Week 12 In Hepatic Fat Fraction Assessed By Magnetic Resonance Imaging Proton Density Fat Fraction (MRI-PDFF) | -32.9 percent change | Standard Error 3 |
| Placebo | Percent Change From Baseline To Week 12 In Hepatic Fat Fraction Assessed By Magnetic Resonance Imaging Proton Density Fat Fraction (MRI-PDFF) | -10.4 percent change | Standard Error 4.3 |
Comparison: LS mean difference in hepatic fat fraction between MGL-3196 and placebo at Week 12.p-value: <0.000195% CI: [-32.9, -12.2]ANCOVA
Secondary
Change From Baseline of Free Thyroxine at Week 12
Free thyroxine (FT4) was assessed at each study visit.
Time frame: Baseline up to Week 12
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MGL-3196 | Change From Baseline of Free Thyroxine at Week 12 | -0.147 ng/dL | Standard Deviation 0.1154 |
| Placebo | Change From Baseline of Free Thyroxine at Week 12 | 0.001 ng/dL | Standard Deviation 0.093 |
Secondary
Change From Baseline of Free Thyroxine Week 36
Total free thyroxine (FT4) was assessed at each study visit.
Time frame: Baseline up to Week 36
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MGL-3196 | Change From Baseline of Free Thyroxine Week 36 | -0.138 ng/dL | Standard Deviation 0.128 |
| Placebo | Change From Baseline of Free Thyroxine Week 36 | -0.007 ng/dL | Standard Deviation 0.1162 |
Secondary
Change From Baseline of Free Triiodothyronine at Week 12
Free triiodothyronine (T3) was assessed at each study visit.
Time frame: Baseline up to Week 12
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MGL-3196 | Change From Baseline of Free Triiodothyronine at Week 12 | 0.05 ng/L | Standard Deviation 0.363 |
| Placebo | Change From Baseline of Free Triiodothyronine at Week 12 | -0.02 ng/L | Standard Deviation 0.513 |
Secondary
Change From Baseline of Free Triiodothyronine at Week 36
Free triiodothyronine (T3) was assessed at each study visit.
Time frame: Baseline up to Week 36
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MGL-3196 | Change From Baseline of Free Triiodothyronine at Week 36 | 0.02 ng/L | Standard Deviation 0.404 |
| Placebo | Change From Baseline of Free Triiodothyronine at Week 36 | -0.02 ng/L | Standard Deviation 0.475 |
Secondary
Change From Baseline of Reverse Triiodothyronine at Week 36
Reverse triiodothyronine (T3) was assessed at each study visit.
Time frame: Baseline up to Week 36
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MGL-3196 | Change From Baseline of Reverse Triiodothyronine at Week 36 | -4.41 ng/dL | Standard Deviation 5.582 |
| Placebo | Change From Baseline of Reverse Triiodothyronine at Week 36 | -1.04 ng/dL | Standard Deviation 5.493 |
Secondary
Change From Baseline of Reverse Triiodothyronine Globulin at Week 12
Reverse Triiodothyronine (T3) was assessed at each study visit.
Time frame: Baseline up to Week 12
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MGL-3196 | Change From Baseline of Reverse Triiodothyronine Globulin at Week 12 | -5.22 ng/dL | Standard Deviation 5.255 |
| Placebo | Change From Baseline of Reverse Triiodothyronine Globulin at Week 12 | -0.96 ng/dL | Standard Deviation 5.757 |
Secondary
Change From Baseline of Thyrotropin at Week 12
Thyrotropin (TSH) was assessed at each study visit.
Time frame: Baseline up to Week 12
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MGL-3196 | Change From Baseline of Thyrotropin at Week 12 | 0.096 mIU/L | Standard Deviation 0.9136 |
| Placebo | Change From Baseline of Thyrotropin at Week 12 | -0.101 mIU/L | Standard Deviation 0.9742 |
Secondary
Change From Baseline of Thyrotropin at Week 36
Tyrotropin (TSH) was assessed at each study visit.
Time frame: Baseline up to Week 36
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MGL-3196 | Change From Baseline of Thyrotropin at Week 36 | 0.034 mIU/L | Standard Deviation 0.9705 |
| Placebo | Change From Baseline of Thyrotropin at Week 36 | 0.043 mIU/L | Standard Deviation 0.9481 |
Secondary
Change From Baseline of Thyroxine Binding Globulin at Week 12
Thyroxine Binding Globulin was assessed at each study visit.
Time frame: Baseline up to Week 12
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MGL-3196 | Change From Baseline of Thyroxine Binding Globulin at Week 12 | -1.42 mg/L | Standard Deviation 3.859 |
| Placebo | Change From Baseline of Thyroxine Binding Globulin at Week 12 | 0.39 mg/L | Standard Deviation 3.522 |
Secondary
Change From Baseline of Thyroxine-Binding Globulin at Week 36
Thyroxine-binding globulin (TBG) was assessed at each study visit.
Time frame: Baseline up to Week 36
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MGL-3196 | Change From Baseline of Thyroxine-Binding Globulin at Week 36 | -0.38 mg/L | Standard Deviation 4.411 |
| Placebo | Change From Baseline of Thyroxine-Binding Globulin at Week 36 | 1.35 mg/L | Standard Deviation 5.639 |
Secondary
Change From Baseline of Total Thyroxine at Week 12
Total thyroxine (FT4) was assessed at each study visit.
Time frame: Baseline up to Week 12
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MGL-3196 | Change From Baseline of Total Thyroxine at Week 12 | -1.18 μg/dL | Standard Deviation 0.958 |
| Placebo | Change From Baseline of Total Thyroxine at Week 12 | -0.07 μg/dL | Standard Deviation 0.726 |
Secondary
Change From Baseline of Total Thyroxine at Week 36
Total thyroxine (FT4), thyrotropin (TSH) was assessed at each study visit.
Time frame: Baseline up to Week 36
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MGL-3196 | Change From Baseline of Total Thyroxine at Week 36 | -1.10 μg/dL | Standard Deviation 1.013 |
| Placebo | Change From Baseline of Total Thyroxine at Week 36 | -0.17 μg/dL | Standard Deviation 0.846 |
Secondary
Change From Baseline of Total Triiodothyronine at Week 12
Total Triiodothyronine (T3) was assessed at each study visit.
Time frame: Baseline up to Week 12
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MGL-3196 | Change From Baseline of Total Triiodothyronine at Week 12 | 0.03 μg/L | Standard Deviation 0.189 |
| Placebo | Change From Baseline of Total Triiodothyronine at Week 12 | 0.02 μg/L | Standard Deviation 0.236 |
Secondary
Change From Baseline of Total Triiodothyronine at Week 36
Total triiodothyronine (T3) was assessed at each study visit.
Time frame: Baseline up to Week 36
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MGL-3196 | Change From Baseline of Total Triiodothyronine at Week 36 | 0.02 μg/L | Standard Deviation 0.212 |
| Placebo | Change From Baseline of Total Triiodothyronine at Week 36 | -0.2 μg/L | Standard Deviation 0.19 |
Secondary
Change From Baseline To Week 12 And Week 36 In Cytokeratin-18 (CK-18)
Serum CK-18 fragments, detected using the M30 antibody, is a non-invasive biomarker for NASH that may reflect hepatocyte apoptosis.
Time frame: Week 12 and Week 36
Population: mITT population: all participants who were randomized in the study, received at least 1 dose of study drug, and had lipid and other efficacy measurements at Week 4 or later visits.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| MGL-3196 | Change From Baseline To Week 12 And Week 36 In Cytokeratin-18 (CK-18) | Week 12 | -146.2 U/L | Standard Error 35 |
| MGL-3196 | Change From Baseline To Week 12 And Week 36 In Cytokeratin-18 (CK-18) | Week 36 | -272.0 U/L | Standard Error 33 |
| Placebo | Change From Baseline To Week 12 And Week 36 In Cytokeratin-18 (CK-18) | Week 12 | -87.5 U/L | Standard Error 51 |
| Placebo | Change From Baseline To Week 12 And Week 36 In Cytokeratin-18 (CK-18) | Week 36 | -101.0 U/L | Standard Error 47 |
Comparison: LS mean difference in CK-18 between MGL-3196 and placebo at Week 12.p-value: 0.341995% CI: [-180.7, 63.21]Linear model
Comparison: LS mean difference in CK-18 between MGL-3196 and placebo at Week 36.p-value: 0.003595% CI: [-285.06, -57.42]Linear model
Secondary
Change From Baseline To Week 12 And Week 36 In Enhanced Liver Fibrosis (ELF) Test
The ELF Test is a non-invasive blood test that provides a simple, unitless numeric score that is used as a marker of collagen formation and fibrogenic activity and can be used to assess the risk of progression to cirrhosis. Scores below 9.8 indicate low risk of disease progression, and scores above 11.29 indicate high risk. The ELF score is derived from values of three serum biomarkers: hyaluronic acid (HA), procollagen III N-terminal peptide (PIIINP), and tissue inhibitor of metalloproteinase-1 (TIMP-1). The formula is 2.278 + 0.851 × ln(HA) + 0.751 × ln(PIIINP) + 0.394 × ln(TIMP-1); there are no minimum or maximum values.
Time frame: Week 12 and Week 36
Population: mITT population: all participants who were randomized in the study, received at least 1 dose of study drug, and had lipid and other efficacy measurements at Week 4 or later visits.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| MGL-3196 | Change From Baseline To Week 12 And Week 36 In Enhanced Liver Fibrosis (ELF) Test | Week 12 | -0.38 score on a scale | Standard Error 0.09 |
| MGL-3196 | Change From Baseline To Week 12 And Week 36 In Enhanced Liver Fibrosis (ELF) Test | Week 36 | -0.66 score on a scale | Standard Error 0.12 |
| Placebo | Change From Baseline To Week 12 And Week 36 In Enhanced Liver Fibrosis (ELF) Test | Week 12 | -0.02 score on a scale | Standard Error 0.12 |
| Placebo | Change From Baseline To Week 12 And Week 36 In Enhanced Liver Fibrosis (ELF) Test | Week 36 | -0.18 score on a scale | Standard Error 0.16 |
Comparison: LS mean difference in ELF-test between MGL-3196 and placebo at Week 12.p-value: 0.008995% CI: [-0.686, -0.103]Linear model
Comparison: LS mean difference in ELF test between MGL-3196 and placebo at Week 36.p-value: 0.017495% CI: [-0.879, -0.088]Linear model
Secondary
Change From Baseline To Week 12 And Week 36 In Fibrosis-4 (Fib-4) Score
The Fib-4 score is a scoring system used to estimate the amount of scarring in the liver. It is based on common clinical parameters (age, AST, ALT, and platelets) and has been shown to have the best diagnostic accuracy for advanced fibrosis when compared with other noninvasive clinical scores. Scores are categorized into low (\<1.30), indeterminate (1.30-2.67), or high (\>2.67) risk of fibrosis. The formula for Fib-4 is: (Age \[yr\] x AST \[U/L\]) / ((PLT \[109/L\]) x (ALT \[U/L\])½); there are no minimum or maximum values
Time frame: Week 12 and Week 36
Population: mITT population: all participants who were randomized in the study, received at least 1 dose of study drug, and had lipid and other efficacy measurements at Week 4 or later visits.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| MGL-3196 | Change From Baseline To Week 12 And Week 36 In Fibrosis-4 (Fib-4) Score | Week 12 | -0.03 score on a scale | Standard Deviation 0.386 |
| MGL-3196 | Change From Baseline To Week 12 And Week 36 In Fibrosis-4 (Fib-4) Score | Week 36 | 0.02 score on a scale | Standard Deviation 0.356 |
| Placebo | Change From Baseline To Week 12 And Week 36 In Fibrosis-4 (Fib-4) Score | Week 12 | 0.05 score on a scale | Standard Deviation 0.374 |
| Placebo | Change From Baseline To Week 12 And Week 36 In Fibrosis-4 (Fib-4) Score | Week 36 | 0.07 score on a scale | Standard Deviation 0.436 |
Secondary
Change From Baseline To Week 12 In Absolute Hepatic Fat Fraction Assessed By MRI-PDFF
The endpoint was change in MRI-PDFF assessed absolute hepatic fat fraction compared with placebo at Week 12. LS mean was provided for the comparison of MGL-3196 versus placebo.
Time frame: Week 12
Population: MRI-PDFF evaluable population: all participants who were randomized in the study, received study drug, and finished Week 12 visit, with valid MRI-PDFF measurements at both baseline and Week 12 Visit.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| MGL-3196 | Change From Baseline To Week 12 In Absolute Hepatic Fat Fraction Assessed By MRI-PDFF | -7.0 percentage | Standard Error 0.6 |
| Placebo | Change From Baseline To Week 12 In Absolute Hepatic Fat Fraction Assessed By MRI-PDFF | -2.7 percentage | Standard Error 0.8 |
Comparison: LS mean difference in absolute hepatic fat fraction between MGL-3196 and placebo at Week 12.p-value: <0.000195% CI: [-6.3, -2.4]ANCOVA
Secondary
Change From Baseline To Week 12 In Serum Alanine Aminotransferase (ALT)
Blood samples were collected to determine the effect of MGL-3196 on serum ALT.
Time frame: Week 12
Population: MRI-PDFF evaluable population: all participants who were randomized in the study, received study drug, and finished Week 12 visit, with valid MRI-PDFF measurements at both baseline and Week 12 Visit.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| MGL-3196 | Change From Baseline To Week 12 In Serum Alanine Aminotransferase (ALT) | -8.2 IU/L | Standard Error 2.7 |
| Placebo | Change From Baseline To Week 12 In Serum Alanine Aminotransferase (ALT) | -5.2 IU/L | Standard Error 3.9 |
Comparison: LS mean difference in ALT between MGL-3196 and placebo at Week 12.p-value: 0.52695% CI: [-12.4, 6.4]Linear model
Secondary
Change From Baseline To Week 12 In Serum Aspartate Aminotransferase (AST)
Blood samples were collected to determine the effect of MGL-3196 on serum AST.
Time frame: Week 12
Population: MRI-PDFF evaluable population: all participants who were randomized in the study, received study drug, and finished Week 12 visit, with valid MRI-PDFF measurements at both baseline and Week 12 Visit.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| MGL-3196 | Change From Baseline To Week 12 In Serum Aspartate Aminotransferase (AST) | -5.8 IU/L | Standard Error 1.8 |
| Placebo | Change From Baseline To Week 12 In Serum Aspartate Aminotransferase (AST) | -1.1 IU/L | Standard Error 2.5 |
Comparison: LS mean difference in AST between MGL-3196 and placebo at Week 12.p-value: 0.127595% CI: [-10.9, 1.4]Linear model
Secondary
Change From Baseline To Week 36 In Absolute Hepatic Fat Fraction Assessed By MRI-PDFF
The endpoint was change in assessed absolute hepatic fat fraction compared with placebo at Week 36. LS mean was provided for the comparison of MGL-3196 versus placebo.
Time frame: Week 36
Population: mITT population: all participants who were randomized in the study, received at least 1 dose of study drug, and had lipid and other efficacy measurements at Week 4 or later visits.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| MGL-3196 | Change From Baseline To Week 36 In Absolute Hepatic Fat Fraction Assessed By MRI-PDFF | -8.2 percentage | Standard Error 0.7 |
| Placebo | Change From Baseline To Week 36 In Absolute Hepatic Fat Fraction Assessed By MRI-PDFF | -2.9 percentage | Standard Error 1 |
Comparison: LS mean difference in absolute hepatic fat fraction between MGL-3196 and placebo at Week 36.p-value: <0.000195% CI: [-7.8, -2.8]ANCOVA
Secondary
Change From Baseline To Week 36 In ALT
Blood samples were collected to determine the effect of MGL-3196 on serum ALT.
Time frame: Week 36
Population: mITT population: all participants who were randomized in the study, received at least 1 dose of study drug, and had lipid and other efficacy measurements at Week 4 or later visits
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| MGL-3196 | Change From Baseline To Week 36 In ALT | -15.4 IU/L | Standard Error 4.7 |
| Placebo | Change From Baseline To Week 36 In ALT | 11.0 IU/L | Standard Error 6.8 |
Comparison: LS mean difference in ALT between MGL-3196 and placebo at Week 36.p-value: 0.001995% CI: [-42.8, -9.9]Linear model
Secondary
Change From Baseline To Week 36 In AST
Blood samples were collected to determine the effect of MGL-3196 on serum AST.
Time frame: Week 36
Population: mITT population: all participants who were randomized in the study, received at least 1 dose of study drug, and had lipid and other efficacy measurements at Week 4 or later visits.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| MGL-3196 | Change From Baseline To Week 36 In AST | -7.4 IU/L | Standard Error 1.9 |
| Placebo | Change From Baseline To Week 36 In AST | 3.6 IU/L | Standard Error 2.8 |
Comparison: LS mean difference in ALT between MGL-3196 and placebo at Week 36.p-value: 0.001695% CI: [-17.8, -4.3]Linear model
Secondary
Percentage Of Participants Achieving A 1-Point Reduction In Non-alcoholic Fatty Liver Disease Activity Score (NAS) At Week 36
The NAS is a histologic scale for non-alcoholic steatohepatitis (NASH) activity, which combines into a single score steatosis (Grade 0 to 3), ballooning (Grade 0 to 2), and lobular inflammation (Grade 0 to 3). The endpoint presented the percentage of participants with a 1-point or greater reduction in NAS.
Time frame: Week 36
Population: mITT population: all participants who were randomized in the study, received at least 1 dose of study drug, and had lipid and other efficacy measurements at Week 4 or later visits.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MGL-3196 | Percentage Of Participants Achieving A 1-Point Reduction In Non-alcoholic Fatty Liver Disease Activity Score (NAS) At Week 36 | 76.7 percentage of participants |
| Placebo | Percentage Of Participants Achieving A 1-Point Reduction In Non-alcoholic Fatty Liver Disease Activity Score (NAS) At Week 36 | 64.7 percentage of participants |
Secondary
Percentage Of Participants Achieving A 2-Point Reduction In NAS And Either A ≥1-Point Reduction In Lobular Inflammation Or Hepatocellular Ballooning At Week 36
The NAS is a histologic scale for NASH activity, which combines into a single score steatosis (Grade 0 to 3), ballooning (Grade 0 to 2), and lobular inflammation (Grade 0 to 3). The endpoint presented the percentage of participants with a 2-point or greater reduction in NAS and a 1-point or greater reduction in lobular inflammation or hepatocellular ballooning.
Time frame: Week 36
Population: mITT population: all participants who were randomized in the study, received at least 1 dose of study drug, and had lipid and other efficacy measurements at Week 4 or later visits.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MGL-3196 | Percentage Of Participants Achieving A 2-Point Reduction In NAS And Either A ≥1-Point Reduction In Lobular Inflammation Or Hepatocellular Ballooning At Week 36 | 50.7 percentage of participants |
| Placebo | Percentage Of Participants Achieving A 2-Point Reduction In NAS And Either A ≥1-Point Reduction In Lobular Inflammation Or Hepatocellular Ballooning At Week 36 | 32.4 percentage of participants |
Secondary
Percentage Of Participants Achieving A 2-Point Reduction In NAS At Week 36
The NAS is a histologic scale for NASH activity, which combines into a single score steatosis (Grade 0 to 3), ballooning (Grade 0 to 2), and lobular inflammation (Grade 0 to 3). The endpoint presented the percentage of participants with a 2-point or greater reduction in NAS.
Time frame: Week 36
Population: mITT population: all participants who were randomized in the study, received at least 1 dose of study drug, and had lipid and other efficacy measurements at Week 4 or later visits.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MGL-3196 | Percentage Of Participants Achieving A 2-Point Reduction In NAS At Week 36 | 56.2 percentage of participants |
| Placebo | Percentage Of Participants Achieving A 2-Point Reduction In NAS At Week 36 | 32.4 percentage of participants |
Secondary
Percentage Of Participants Achieving A 2-Point Reduction In NAS Without Fibrosis Worsening At Week 36
The NAS is a histologic scale for NASH activity, which combines into a single score steatosis (Grade 0 to 3), ballooning (Grade 0 to 2), and lobular inflammation (Grade 0 to 3). Fibrosis stage (0 to 3) was also included in the assessment. The endpoint presented the percentage of participants with a 2-point or greater reduction in NAS without worsening fibrosis.
Time frame: Week 36
Population: mITT population: all participants who were randomized in the study, received at least 1 dose of study drug, and had lipid and other efficacy measurements at Week 4 or later visits.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MGL-3196 | Percentage Of Participants Achieving A 2-Point Reduction In NAS Without Fibrosis Worsening At Week 36 | 45.2 percentage of participants |
| Placebo | Percentage Of Participants Achieving A 2-Point Reduction In NAS Without Fibrosis Worsening At Week 36 | 32.4 percentage of participants |
Secondary
Percentage Of Participants Achieving NASH Resolution With At Least 2-Point Reduction In NAS At Week 36
The endpoint presented the percentage of participants achieving NASH resolution with a 2-point reduction at Week 36.
Time frame: Week 36
Population: mITT population: all participants who were randomized in the study, received at least 1 dose of study drug, and had lipid and other efficacy measurements at Week 4 or later visits.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MGL-3196 | Percentage Of Participants Achieving NASH Resolution With At Least 2-Point Reduction In NAS At Week 36 | 27.4 percentage of participants |
| Placebo | Percentage Of Participants Achieving NASH Resolution With At Least 2-Point Reduction In NAS At Week 36 | 14.7 percentage of participants |
Secondary
Percentage Of Participants With Adverse Events (AEs)
An AE was defined as any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product, which does not necessarily have a causal relationship with the treatment. A summary of serious and all other non-serious AEs, regardless of causality, is located in the Reported Adverse Events module.
Time frame: Week 12 and Week 36
Population: Safety population: all randomized participants who received at least 1 dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| MGL-3196 | Percentage Of Participants With Adverse Events (AEs) | Week 12 | 71.4 percentage of participants |
| MGL-3196 | Percentage Of Participants With Adverse Events (AEs) | Week 36 | 86.9 percentage of participants |
| Placebo | Percentage Of Participants With Adverse Events (AEs) | Week 12 | 46.3 percentage of participants |
| Placebo | Percentage Of Participants With Adverse Events (AEs) | Week 36 | 68.3 percentage of participants |
Secondary
Percentage Of Participants With A Reduction In Hepatocellular Ballooning At Week 36
The NAS is a histologic scale for NASH activity, which combines into a single score steatosis (Grade 0 to 3), ballooning (Grade 0 to 2), and lobular inflammation (Grade 0 to 3). The endpoint presented the percentage of participants with a reduction in hepatocellular ballooning.
Time frame: Week 36
Population: mITT population: all participants who were randomized in the study, received at least 1 dose of study drug, and had lipid and other efficacy measurements at Week 4 or later visits.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MGL-3196 | Percentage Of Participants With A Reduction In Hepatocellular Ballooning At Week 36 | 58.9 percentage of participants |
| Placebo | Percentage Of Participants With A Reduction In Hepatocellular Ballooning At Week 36 | 58.8 percentage of participants |
Secondary
Percentage Of Participants With A Reduction In Hepatocellular Steatosis At Week 36
The NAS is a histologic scale for NASH activity, which combines into a single score steatosis (Grade 0 to 3), ballooning (Grade 0 to 2), and lobular inflammation (Grade 0 to 3). The endpoint presented the percentage of participants with a reduction in hepatocellular steatosis.
Time frame: Week 36
Population: mITT population: all participants who were randomized in the study, received at least 1 dose of study drug, and had lipid and other efficacy measurements at Week 4 or later visits.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MGL-3196 | Percentage Of Participants With A Reduction In Hepatocellular Steatosis At Week 36 | 61.6 percentage of participants |
| Placebo | Percentage Of Participants With A Reduction In Hepatocellular Steatosis At Week 36 | 44.1 percentage of participants |
Secondary
Percentage Of Participants With A Reduction In Lobular Inflammation At Week 36
The NAS is a histologic scale for NASH activity, which combines into a single score steatosis (Grade 0 to 3), ballooning (Grade 0 to 2), and lobular inflammation (Grade 0 to 3). The endpoint presented the percentage of participants with a reduction in lobular inflammation.
Time frame: Week 36
Population: mITT population: all participants who were randomized in the study, received at least 1 dose of study drug, and had lipid and other efficacy measurements at Week 4 or later visits.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MGL-3196 | Percentage Of Participants With A Reduction In Lobular Inflammation At Week 36 | 21.9 percentage of participants |
| Placebo | Percentage Of Participants With A Reduction In Lobular Inflammation At Week 36 | 17.6 percentage of participants |
Secondary
Percentage Of Participants With At Least 30% Relative Fat Reduction at Week 12
The endpoint presented the percentage of participants achieving a relative fat reduction of ≥30% at Week 12.
Time frame: Week 12
Population: MRI-PDFF evaluable population: all participants who were randomized in the study, received study drug, and finished Week 12 visit, with valid MRI-PDFF measurements at both baseline and Week 12 Visit.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MGL-3196 | Percentage Of Participants With At Least 30% Relative Fat Reduction at Week 12 | 60.3 percentage of participants |
| Placebo | Percentage Of Participants With At Least 30% Relative Fat Reduction at Week 12 | 18.4 percentage of participants |
Secondary
Percentage Of Participants With At Least 30% Relative Fat Reduction At Week 36
The endpoint presented the percentage of participants achieving a relative fat reduction of ≥30% at Week 36.
Time frame: Week 36
Population: mITT population: all participants who were randomized in the study, received at least 1 dose of study drug, and had lipid and other efficacy measurements at Week 4 or later visits.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MGL-3196 | Percentage Of Participants With At Least 30% Relative Fat Reduction At Week 36 | 67.6 percentage of participants |
| Placebo | Percentage Of Participants With At Least 30% Relative Fat Reduction At Week 36 | 29.4 percentage of participants |
Secondary
Percent Change From Baseline To Week 12 In High-sensitivity C-reactive Protein (hsCRP)
hsCRP was used as a non-invasive inflammation marker for this study. Blood samples were collected to determine the effect of MGL-3196 on hsCRP.
Time frame: Week 12
Population: mITT population: all participants who were randomized in the study, received at least 1 dose of study drug, and had lipid and other efficacy measurements at Week 4 or later visits.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| MGL-3196 | Percent Change From Baseline To Week 12 In High-sensitivity C-reactive Protein (hsCRP) | 29.3 percent change | Standard Error 18.36 |
| Placebo | Percent Change From Baseline To Week 12 In High-sensitivity C-reactive Protein (hsCRP) | 13.2 percent change | Standard Error 25.97 |
Comparison: LS mean difference in hsCRP between MGL-3196 and placebo at Week 12.p-value: 0.615595% CI: [-47, 79]Linear model
Secondary
Percent Change From Baseline To Week 12 In Lipid Parameter Lipoprotein(a) (Lp[a])
Blood samples were collected to determine the effect of MGL-3196 on lipid parameter Lp(a).
Time frame: Week 12
Population: mITT population: all participants who were randomized in the study, received at least 1 dose of study drug, and had lipid and other efficacy measurements at Week 4 or later visits.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| MGL-3196 | Percent Change From Baseline To Week 12 In Lipid Parameter Lipoprotein(a) (Lp[a]) | -8.6 percent change | Standard Error 7.54 |
| Placebo | Percent Change From Baseline To Week 12 In Lipid Parameter Lipoprotein(a) (Lp[a]) | 12.3 percent change | Standard Error 10.67 |
Comparison: LS mean difference in Lp(a) between MGL-3196 and placebo at Week 12.p-value: 0.112395% CI: [-46.8, 5]Linear model
Secondary
Percent Change From Baseline To Week 12 In Lipid Parameters
Blood samples were collected to determine the effect of MGL-3196 on lipid parameters including low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), non-HDL-C, total cholesterol (TC), triglycerides (TG), apolipoprotein B (ApoB), and Apolipoprotein CIII (ApoCIII).
Time frame: Week 12
Population: mITT population: all participants who were randomized in the study, received at least 1 dose of study drug, and had lipid and other efficacy measurements at Week 4 or later visits.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| MGL-3196 | Percent Change From Baseline To Week 12 In Lipid Parameters | LDL-C | -10.6 percent change | Standard Error 1.96 |
| MGL-3196 | Percent Change From Baseline To Week 12 In Lipid Parameters | HDL-C | 5.0 percent change | Standard Error 1.91 |
| MGL-3196 | Percent Change From Baseline To Week 12 In Lipid Parameters | non-HDL-C | -12.1 percent change | Standard Error 1.74 |
| MGL-3196 | Percent Change From Baseline To Week 12 In Lipid Parameters | TC | -8.7 percent change | Standard Error 1.37 |
| MGL-3196 | Percent Change From Baseline To Week 12 In Lipid Parameters | TG | -6.8 percent change | Standard Error 4.23 |
| MGL-3196 | Percent Change From Baseline To Week 12 In Lipid Parameters | ApoB | -14.5 percent change | Standard Error 1.59 |
| MGL-3196 | Percent Change From Baseline To Week 12 In Lipid Parameters | ApoCIII | -9.1 percent change | Standard Error 3.23 |
| MGL-3196 | Percent Change From Baseline To Week 12 In Lipid Parameters | Lp(a) | -8.6 percent change | Standard Error 7.54 |
| Placebo | Percent Change From Baseline To Week 12 In Lipid Parameters | Lp(a) | 12.3 percent change | Standard Error 10.67 |
| Placebo | Percent Change From Baseline To Week 12 In Lipid Parameters | LDL-C | 2.2 percent change | Standard Error 2.79 |
| Placebo | Percent Change From Baseline To Week 12 In Lipid Parameters | TG | 9.8 percent change | Standard Error 6.01 |
| Placebo | Percent Change From Baseline To Week 12 In Lipid Parameters | HDL-C | 1.8 percent change | Standard Error 2.72 |
| Placebo | Percent Change From Baseline To Week 12 In Lipid Parameters | ApoCIII | 8.7 percent change | Standard Error 4.62 |
| Placebo | Percent Change From Baseline To Week 12 In Lipid Parameters | non-HDL-C | 1.2 percent change | Standard Error 2.47 |
| Placebo | Percent Change From Baseline To Week 12 In Lipid Parameters | ApoB | 0.8 percent change | Standard Error 2.25 |
| Placebo | Percent Change From Baseline To Week 12 In Lipid Parameters | TC | 0.9 percent change | Standard Error 1.95 |
Comparison: LS mean difference in LDL-C between MGL-3196 and placebo at Week 12.p-value: 0.000295% CI: [-19.6, -6.1]Linear model
Comparison: LS mean difference in HDL-C between MGL-3196 and placebo at Week 12.p-value: 0.338895% CI: [-3.4, 9.8]Linear model
Comparison: LS mean difference in non-HDL-C between MGL-3196 and placebo at Week 12.p-value: <0.000195% CI: [-19.3, -7.4]Linear model
Comparison: LS mean difference in TC between MGL-3196 and placebo at Week 12.p-value: 0.000195% CI: [-14.3, -4.9]Linear model
Comparison: LS mean difference in TG between MGL-3196 and placebo at Week 12.p-value: 0.025895% CI: [-31.2, -2]Linear model
Comparison: LS mean difference in ApoB between MGL-3196 and placebo at Week 12.p-value: <0.000195% CI: [-20.8, -9.9]Linear model
Comparison: LS mean difference in ApoCIII between MGL-3196 and placebo at Week 12.p-value: 0.002195% CI: [-28.9, -6.6]Linear model
Comparison: LS mean difference in Lp(a) between MGL-3196 and placebo at Week 12.p-value: 0.112395% CI: [-46.8, 5]ANOVA
Secondary
Percent Change From Baseline To Week 36 In Hepatic Fat Fraction Assessed By MRI-PDFF
The endpoint was relative change assessed hepatic fat fraction compared with placebo at Week 36. LS mean was provided for the statistical comparison of MGL-3196 versus placebo.
Time frame: Week 36
Population: Modified Intent-to-Treat (mITT) population: all participants who were randomized in the study, received at least 1 dose of study drug, and had lipid and other efficacy measurements at Week 4 or later visits.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| MGL-3196 | Percent Change From Baseline To Week 36 In Hepatic Fat Fraction Assessed By MRI-PDFF | -37.3 percent change | Standard Error 3.7 |
| Placebo | Percent Change From Baseline To Week 36 In Hepatic Fat Fraction Assessed By MRI-PDFF | -8.9 percent change | Standard Error 5.4 |
Comparison: LS mean difference in hepatic fat fraction between MGL-3196 and placebo at Week 36.p-value: <0.000195% CI: [-41.3, -15.4]ANCOVA
Secondary
Percent Change From Baseline To Week 36 In hsCRP
hsCRP was used as a non-invasive inflammation marker for this study. Blood samples were collected to determine the effect of MGL-3196 on hsCRP.
Time frame: Week 36
Population: mITT population: all participants who were randomized in the study, received at least 1 dose of study drug, and had lipid and other efficacy measurements at Week 4 or later visits.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| MGL-3196 | Percent Change From Baseline To Week 36 In hsCRP | 90.9 percent change | Standard Error 67.52 |
| Placebo | Percent Change From Baseline To Week 36 In hsCRP | 34.0 percent change | Standard Error 96.88 |
Comparison: LS mean difference in hsCRP between MGL-3196 and placebo at Week 36.p-value: 0.631195% CI: [-177.4, 291.1]Linear model
Secondary
Percent Change From Baseline To Week 36 In Lipid Parameter Lp[a]
Blood samples were collected to determine the effect of MGL-3196 on lipid parameter Lp(a).
Time frame: Week 36
Population: mITT population: all participants who were randomized in the study, received at least 1 dose of study drug, and had lipid and other efficacy measurements at Week 4 or later visits.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| MGL-3196 | Percent Change From Baseline To Week 36 In Lipid Parameter Lp[a] | 19.0 percent change | Standard Error 10.95 |
| Placebo | Percent Change From Baseline To Week 36 In Lipid Parameter Lp[a] | 39.0 percent change | Standard Error 15.82 |
Comparison: LS mean difference in Lp(a) between MGL-3196 and placebo at Week 36.p-value: 0.300895% CI: [-58.2, 18.2]Linear model
Secondary
Percent Change From Baseline To Week 36 In Lipid Parameters
Blood samples were collected to determine the effect of MGL-3196 on lipid parameters including LDL-C, HDL-C, non-HDL-C, TC, TG, ApoB, and ApoCIII.
Time frame: Week 36
Population: mITT population: all participants who were randomized in the study, received at least 1 dose of study drug, and had lipid and other efficacy measurements at Week 4 or later visits
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| MGL-3196 | Percent Change From Baseline To Week 36 In Lipid Parameters | LDL-C | -11.0 percent change | Standard Error 2.14 |
| MGL-3196 | Percent Change From Baseline To Week 36 In Lipid Parameters | HDL-C | 10.5 percent change | Standard Error 3.72 |
| MGL-3196 | Percent Change From Baseline To Week 36 In Lipid Parameters | non-HDL-C | -14.0 percent change | Standard Error 1.9 |
| MGL-3196 | Percent Change From Baseline To Week 36 In Lipid Parameters | TC | -8.9 percent change | Standard Error 1.61 |
| MGL-3196 | Percent Change From Baseline To Week 36 In Lipid Parameters | TG | -19.8 percent change | Standard Error 4.29 |
| MGL-3196 | Percent Change From Baseline To Week 36 In Lipid Parameters | ApoB | -16.5 percent change | Standard Error 1.79 |
| MGL-3196 | Percent Change From Baseline To Week 36 In Lipid Parameters | ApoCIII | -12.0 percent change | Standard Error 3.72 |
| MGL-3196 | Percent Change From Baseline To Week 36 In Lipid Parameters | Lp(a) | 19.0 percent change | Standard Error 10.95 |
| Placebo | Percent Change From Baseline To Week 36 In Lipid Parameters | Lp(a) | 39.0 percent change | Standard Error 15.82 |
| Placebo | Percent Change From Baseline To Week 36 In Lipid Parameters | LDL-C | 1.5 percent change | Standard Error 3.11 |
| Placebo | Percent Change From Baseline To Week 36 In Lipid Parameters | TG | 17.5 percent change | Standard Error 6.24 |
| Placebo | Percent Change From Baseline To Week 36 In Lipid Parameters | HDL-C | 12.0 percent change | Standard Error 5.41 |
| Placebo | Percent Change From Baseline To Week 36 In Lipid Parameters | ApoCIII | 24.5 percent change | Standard Error 5.42 |
| Placebo | Percent Change From Baseline To Week 36 In Lipid Parameters | non-HDL-C | 2.1 percent change | Standard Error 2.76 |
| Placebo | Percent Change From Baseline To Week 36 In Lipid Parameters | ApoB | 0.9 percent change | Standard Error 2.58 |
| Placebo | Percent Change From Baseline To Week 36 In Lipid Parameters | TC | 3.6 percent change | Standard Error 2.34 |
Comparison: LS mean difference in LDL-C between MGL-3196 and placebo at Week 36.p-value: 0.001395% CI: [-19.9, -5]Linear model
Comparison: LS mean difference in HDL-C between MGL-3196 and placebo at Week 36.p-value: 0.821395% CI: [-14.5, 11.5]Linear model
Comparison: LS mean difference in nonHDL-C between MGL-3196 and placebo at Week 36.p-value: <0.000195% CI: [-22.7, -9.4]Linear model
Comparison: LS mean difference in TC between MGL-3196 and placebo at Week 36.p-value: <0.000195% CI: [-18.1, -6.9]Linear model
Comparison: LS mean difference in TG between MGL-3196 and placebo at Week 36.p-value: <0.000195% CI: [-52.3, -22.3]Linear model
Comparison: LS mean difference in ApoB between MGL-3196 and placebo at Week 36.p-value: <0.000195% CI: [-23.6, -11.2]Linear model
Comparison: LS mean difference in ApoCIII between MGL-3196 and placebo at Week 36.p-value: <0.000195% CI: [-49.6, -23.5]Linear model
Comparison: LS mean difference in Lp(a) between MGL-3196 and placebo at Week 36.p-value: 0.300895% CI: [-58.2, 18.2]ANOVA