NASH - Nonalcoholic Steatohepatitis
Conditions
Brief summary
This is a multi-center evaluation of efruxifermin (EFX) in a randomized, double-blind, placebo-controlled study in non-cirrhotic subjects with biopsy-proven F2 - F3 NASH.
Interventions
DRUGEfruxifermin
subcutaneous injection
DRUGPlacebo
subcutaneous injection
Sponsors
Akero Therapeutics, 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 75 Years
Healthy volunteers
No
Inclusion criteria
* Males and non-pregnant, non-lactating females between 18 - 75 years of age inclusive, based on the date of the screening visit. * Previous history or presence of 2 out of 4 components of metabolic syndrome (obesity, dyslipidemia, elevated blood pressure, elevated fasting glucose) or type 2 diabetes. * FibroScan measurement \> 8.5 kPa \[kilopascal\]. * Biopsy-proven NASH. Must have had a liver biopsy obtained ≤ 180 days prior to randomization with fibrosis stage 2 to 3 and a non-alcoholic fatty liver disease (NAFLD) activity score (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).
Exclusion criteria
* Weight loss \> 5% in the 3 months prior to screening until randomization or from the time of the diagnostic liver biopsy until randomization, whichever is longer. * Presence of cirrhosis on liver biopsy (stage 4 fibrosis). * Type 1 or uncontrolled Type 2 diabetes. Other inclusion and
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Effect of Efruxifermin (EFX) vs Placebo on Fibrosis Regression in Participants With Metabolic Dysfunction-associated Steatohepatitis (MASH)-Associated Stage 2 or 3 Fibrosis (F2 or F3) | 24 Weeks | Proportions of subjects in EFX vs placebo groups with improvement in liver fibrosis, defined as ≥ 1 stage NASH Clinical Research Network \[CRN\] fibrosis score (score ranges from 0 to 4, increasing with fibrosis severity), and no worsening of steatohepatitis (no increase in NASH Activity Score \[NAS\], which ranges from 0 to 8 and is the sum of scores of steatosis, lobular inflammation, and hepatocyte ballooning), at Week 24 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Subjects Who Achieve Improvement in Liver Fibrosis ≥ 1 Stage and no Worsening of Steatohepatitis at Week 96 | 96 Weeks | Proportions of subjects in EFX vs baseline groups who achieve improvement in liver fibrosis (decrease of ≥ 1 stage in NASH CRN fibrosis score) and no worsening of steatohepatitis (no increase in NAS for ballooning, inflammation, or steatosis) at Week 96 |
| Proportion of Subjects Who Achieve Resolution of Steatohepatitis and no Worsening of Liver Fibrosis at Week 24 and Week 96 | 24 and 96 weeks | Proportions of subjects in EFX vs placebo groups who achieve resolution of steatohepatitis (defined as a NAS of 0-1 for inflammation, 0 for ballooning, and any value for steatosis) and no worsening of liver fibrosis (determined by the NASH CRN criteria) |
| Proportion of Subjects Who Achieve Improvement in Liver Fibrosis ≥ 1 Stage at Week 24 and Week 96 | 24 and 96 Weeks | Proportion of subjects in EFX vs placebo groups who achieve improvement in liver fibrosis (decrease ≥ 1 stage in NASH CRN fibrosis score) |
| Change From Baseline in Hepatic Fat Fraction in EFX vs Placebo Groups | 24 and 96 Weeks | Change from baseline in hepatic fat fraction, measured by magnetic resonance imaging proton-density fat fraction (MRI-PDFF): Week 24 and Week 96 MRI-PDFF Analysis Set |
| Change From Baseline in Lipoproteins at Week 24 and Week 96 | 24 and 96 weeks | Change from baseline of lipoproteins (triglycerides, Non-HDL-C, HDL-C and LDL-C) in EFX vs placebo groups |
| Change From Baseline of Hemoglobin A1c (Glycated Hemoglobin, HbA1c) at Week 24 and Week 96 | 24 Weeks, 96 Weeks | Change from baseline in hemoglobin A1c (glycated hemoglobin, HbA1c) in EFX vs placebo groups |
| Change From Baseline in C-peptide at Week 24 and Week 96 | 24 Weeks, 96 Weeks | Change from baseline in C-peptide in EFX vs placebo groups |
| Change From Baseline in Adiponectin at Week 24 and Week 96 | 24 Weeks, 96 Weeks | Change from baseline in adiponectin in EFX vs placebo groups |
| Change From Baseline in Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) at Week 24 and Week 96 | 24 Weeks, 96 Weeks | Change from baseline in Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) in EFX vs placebo groups The Homeostatic Model Assessment of Insulin Resistance, HOMA-IR, is a calculated index that estimates insulin resistance based on fasting glucose and insulin levels. Higher values indicate greater insulin resistance. \< 1.0: Normal insulin sensitivity 1.0-1.9: Mild insulin resistance 2.0-2.9: Moderate insulin resistance \> 2.9: Severe insulin resistance |
| Change From Baseline in Enhanced Liver Fibrosis (ELF) Score at Week 24 and Week 96 | 24 and 96 Weeks | Change from Baseline in Enhanced Liver Fibrosis (ELF) Score in EFX vs placebo groups The Enhanced Liver Fibrosis (ELF) score is a non-invasive blood test that assesses the risk of liver fibrosis and its progression. Lower risk (\<9.8): Suggests a lower risk of advanced liver fibrosis. Mid risk (9.8-11.2): Indicates a moderate risk of disease progression. Higher risk (≥11.3): Suggests a higher risk of developing cirrhosis or liver-related events |
| Change From Baseline in N-terminal Type III Collagen Propeptide (Pro-C3) at Week 24 and Week 96 | 24 and 96 Weeks | Change from Baseline in N-terminal Type III Collagen Propeptide (Pro-C3) in EFX vs placebo groups |
| Change From Baseline in Collagen III Neo-Peptide (C3M) at Week 24 and Week 96 | 24 and 96 Weeks | Change from Baseline in Collagen III Neo-Peptide (C3M) in EFX vs placebo groups |
| Change From Baseline in NIS4 Score at Week 24 and Week 96 | 24 and 96 Weeks | Change from Baseline in NIS4 score in EFX vs placebo groups NIS4 scores range from 0 to 1 and are calculated by combining the results of four individual biomarker assays \[miR34a-5p, α2-macroglobulin (A2M), YKL-40 and HbA1c\] each of which contributes to the test's ability to detect liver inflammation and/or fibrosis. \>0.63: Higher risk of NASH or advanced fibrosis 0.37-0.63: Moderate risk, and additional testing may be considered \<0.36: Lower risk of of NASH or advanced fibrosis |
| Change in Body Weight at Week 24 and Week 96 | 24 and 96 weeks | Change from baseline in body weight (kg) in EFX vs placebo groups |
| Change From Baseline in Liver Stiffness (kPa) at Week 24 and Week 96 | 24 and 96 weeks | Change from Baseline in Liver Stiffness Evaluated by FibroScan in EFX vs placebo groups at Week 24 and Week 96: Full Analysis Set |
Countries
Puerto Rico, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Double-blind, once-weekly subcutaneous administration | 43 |
| Efruxifermin 28 mg Double-blind, once-weekly subcutaneous administration | 42 |
| Efruxifermin 50 mg Double-blind, once-weekly subcutaneous administration | 43 |
| Total | 128 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 4 | 3 |
| Overall Study | At the discretion of the Investigator or Sponsor for noncompliance | 1 | 0 | 3 |
| Overall Study | clinical outcomes endpoint (excluding death) | 1 | 3 | 3 |
| Overall Study | Lost to Follow-up | 0 | 2 | 3 |
| Overall Study | Required use of a prohibited medication | 0 | 1 | 0 |
| Overall Study | Withdrawal by Subject | 7 | 5 | 4 |
Baseline characteristics
| Characteristic | Efruxifermin 28 mg | Total | Placebo | Efruxifermin 50 mg |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 11 Participants | 26 Participants | 9 Participants | 6 Participants |
| Age, Categorical Between 18 and 65 years | 31 Participants | 102 Participants | 34 Participants | 37 Participants |
| Age, Continuous | 56.5 years STANDARD_DEVIATION 9.3 | 54.7 years STANDARD_DEVIATION 10.4 | 55.0 years STANDARD_DEVIATION 10.1 | 52.4 years STANDARD_DEVIATION 11.4 |
| Baseline Fibrosis Stage Fibrosis stage 2 | 15 Participants | 44 Participants | 13 Participants | 16 Participants |
| Baseline Fibrosis Stage Fibrosis stage 3 | 27 Participants | 84 Participants | 30 Participants | 27 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 17 Participants | 52 Participants | 15 Participants | 20 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 25 Participants | 76 Participants | 28 Participants | 23 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Race American Indian or Alaskan Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Race Asian | 3 Participants | 5 Participants | 2 Participants | 0 Participants |
| Race/Ethnicity, Customized Race Black or African American | 1 Participants | 4 Participants | 2 Participants | 1 Participants |
| Race/Ethnicity, Customized Race Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Race Other | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Race White | 38 Participants | 118 Participants | 39 Participants | 41 Participants |
| Region of Enrollment United States | 42 participants | 128 participants | 43 participants | 43 participants |
| Sex: Female, Male Female | 29 Participants | 79 Participants | 27 Participants | 23 Participants |
| Sex: Female, Male Male | 13 Participants | 49 Participants | 16 Participants | 20 Participants |
| Type 2 diabetes status T2D no | 10 Participants | 38 Participants | 15 Participants | 13 Participants |
| Type 2 diabetes status T2D yes | 32 Participants | 90 Participants | 28 Participants | 30 Participants |
| Weight | 103.9 kg STANDARD_DEVIATION 22.7 | 104.8 kg STANDARD_DEVIATION 23.2 | 107.6 kg STANDARD_DEVIATION 25.6 | 102.8 kg STANDARD_DEVIATION 21.1 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 43 | 0 / 40 | 0 / 43 |
| other Total, other adverse events | 42 / 43 | 38 / 40 | 43 / 43 |
| serious Total, serious adverse events | 4 / 43 | 4 / 40 | 7 / 43 |
Outcome results
Primary
Effect of Efruxifermin (EFX) vs Placebo on Fibrosis Regression in Participants With Metabolic Dysfunction-associated Steatohepatitis (MASH)-Associated Stage 2 or 3 Fibrosis (F2 or F3)
Proportions of subjects in EFX vs placebo groups with improvement in liver fibrosis, defined as ≥ 1 stage NASH Clinical Research Network \[CRN\] fibrosis score (score ranges from 0 to 4, increasing with fibrosis severity), and no worsening of steatohepatitis (no increase in NASH Activity Score \[NAS\], which ranges from 0 to 8 and is the sum of scores of steatosis, lobular inflammation, and hepatocyte ballooning), at Week 24
Time frame: 24 Weeks
Population: Week 24 Liver Biopsy Analysis Set
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Effect of Efruxifermin (EFX) vs Placebo on Fibrosis Regression in Participants With Metabolic Dysfunction-associated Steatohepatitis (MASH)-Associated Stage 2 or 3 Fibrosis (F2 or F3) | 8 Participants |
| Efruxifermin 28 mg | Effect of Efruxifermin (EFX) vs Placebo on Fibrosis Regression in Participants With Metabolic Dysfunction-associated Steatohepatitis (MASH)-Associated Stage 2 or 3 Fibrosis (F2 or F3) | 15 Participants |
| Efruxifermin 50 mg | Effect of Efruxifermin (EFX) vs Placebo on Fibrosis Regression in Participants With Metabolic Dysfunction-associated Steatohepatitis (MASH)-Associated Stage 2 or 3 Fibrosis (F2 or F3) | 14 Participants |
Comparison: Comparison between proportion of participants in efruxifermin 28 mg group who met the primary endpoint vs the placebo groupp-value: 0.02595% CI: [3.8, 41.4]Cochran-Mantel-Haenszel
Comparison: Comparison between proportion of participants in efruxifermin 50 mg group who met the primary endpoint vs the placebo groupp-value: 0.03695% CI: [1.6, 43.3]Cochran-Mantel-Haenszel
Secondary
Change From Baseline in Adiponectin at Week 24 and Week 96
Change from baseline in adiponectin in EFX vs placebo groups
Time frame: 24 Weeks, 96 Weeks
Population: Biomarker Analysis Set
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Adiponectin at Week 24 and Week 96 | Change from baseline in adiponectin at Week 24 | 296.4 ng/mL | Standard Error 312.56 |
| Placebo | Change From Baseline in Adiponectin at Week 24 and Week 96 | Change from baseline in adiponectin at Week 96 | 531.5 ng/mL | Standard Error 416.93 |
| Efruxifermin 28 mg | Change From Baseline in Adiponectin at Week 24 and Week 96 | Change from baseline in adiponectin at Week 24 | 1411.5 ng/mL | Standard Error 333.48 |
| Efruxifermin 28 mg | Change From Baseline in Adiponectin at Week 24 and Week 96 | Change from baseline in adiponectin at Week 96 | 975.3 ng/mL | Standard Error 459.4 |
| Efruxifermin 50 mg | Change From Baseline in Adiponectin at Week 24 and Week 96 | Change from baseline in adiponectin at Week 24 | 3088.8 ng/mL | Standard Error 333.82 |
| Efruxifermin 50 mg | Change From Baseline in Adiponectin at Week 24 and Week 96 | Change from baseline in adiponectin at Week 96 | 2018.3 ng/mL | Standard Error 458.91 |
Secondary
Change From Baseline in Collagen III Neo-Peptide (C3M) at Week 24 and Week 96
Change from Baseline in Collagen III Neo-Peptide (C3M) in EFX vs placebo groups
Time frame: 24 and 96 Weeks
Population: Biomarker Analysis Set
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Collagen III Neo-Peptide (C3M) at Week 24 and Week 96 | Change from baseline in Collagen III Neo-Peptide (C3M) (ng/mL) at Week 24 | 0.2 ng/mL | Standard Error 0.35 |
| Placebo | Change From Baseline in Collagen III Neo-Peptide (C3M) at Week 24 and Week 96 | Change from baseline in Collagen III Neo-Peptide (C3M) (ng/mL) at Week 96 | 3.1 ng/mL | Standard Error 0.71 |
| Efruxifermin 28 mg | Change From Baseline in Collagen III Neo-Peptide (C3M) at Week 24 and Week 96 | Change from baseline in Collagen III Neo-Peptide (C3M) (ng/mL) at Week 24 | -0.8 ng/mL | Standard Error 0.37 |
| Efruxifermin 28 mg | Change From Baseline in Collagen III Neo-Peptide (C3M) at Week 24 and Week 96 | Change from baseline in Collagen III Neo-Peptide (C3M) (ng/mL) at Week 96 | 3.3 ng/mL | Standard Error 0.8 |
| Efruxifermin 50 mg | Change From Baseline in Collagen III Neo-Peptide (C3M) at Week 24 and Week 96 | Change from baseline in Collagen III Neo-Peptide (C3M) (ng/mL) at Week 24 | -1.1 ng/mL | Standard Error 0.38 |
| Efruxifermin 50 mg | Change From Baseline in Collagen III Neo-Peptide (C3M) at Week 24 and Week 96 | Change from baseline in Collagen III Neo-Peptide (C3M) (ng/mL) at Week 96 | 4.4 ng/mL | Standard Error 0.8 |
Secondary
Change From Baseline in C-peptide at Week 24 and Week 96
Change from baseline in C-peptide in EFX vs placebo groups
Time frame: 24 Weeks, 96 Weeks
Population: Biomarker Analysis Set
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in C-peptide at Week 24 and Week 96 | Change from baseline in C-Peptide at Week 24 | 0.0 ng/mL | Standard Error 0.19 |
| Placebo | Change From Baseline in C-peptide at Week 24 and Week 96 | Change from baseline in C-Peptide at Week 96 | -0.2 ng/mL | Standard Error 0.22 |
| Efruxifermin 28 mg | Change From Baseline in C-peptide at Week 24 and Week 96 | Change from baseline in C-Peptide at Week 24 | -0.8 ng/mL | Standard Error 0.2 |
| Efruxifermin 28 mg | Change From Baseline in C-peptide at Week 24 and Week 96 | Change from baseline in C-Peptide at Week 96 | -0.4 ng/mL | Standard Error 0.25 |
| Efruxifermin 50 mg | Change From Baseline in C-peptide at Week 24 and Week 96 | Change from baseline in C-Peptide at Week 24 | -1.2 ng/mL | Standard Error 0.19 |
| Efruxifermin 50 mg | Change From Baseline in C-peptide at Week 24 and Week 96 | Change from baseline in C-Peptide at Week 96 | -1.0 ng/mL | Standard Error 0.25 |
Secondary
Change From Baseline in Enhanced Liver Fibrosis (ELF) Score at Week 24 and Week 96
Change from Baseline in Enhanced Liver Fibrosis (ELF) Score in EFX vs placebo groups The Enhanced Liver Fibrosis (ELF) score is a non-invasive blood test that assesses the risk of liver fibrosis and its progression. Lower risk (\<9.8): Suggests a lower risk of advanced liver fibrosis. Mid risk (9.8-11.2): Indicates a moderate risk of disease progression. Higher risk (≥11.3): Suggests a higher risk of developing cirrhosis or liver-related events
Time frame: 24 and 96 Weeks
Population: Biomarker Analysis Set
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Enhanced Liver Fibrosis (ELF) Score at Week 24 and Week 96 | Change from baseline in ELF Score at Week 24 | 0.1 score on a scale | Standard Error 0.1 |
| Placebo | Change From Baseline in Enhanced Liver Fibrosis (ELF) Score at Week 24 and Week 96 | Change from baseline in ELF Score at Week 96 | -0.1 score on a scale | Standard Error 0.14 |
| Efruxifermin 28 mg | Change From Baseline in Enhanced Liver Fibrosis (ELF) Score at Week 24 and Week 96 | Change from baseline in ELF Score at Week 24 | -0.6 score on a scale | Standard Error 0.1 |
| Efruxifermin 28 mg | Change From Baseline in Enhanced Liver Fibrosis (ELF) Score at Week 24 and Week 96 | Change from baseline in ELF Score at Week 96 | -0.7 score on a scale | Standard Error 0.16 |
| Efruxifermin 50 mg | Change From Baseline in Enhanced Liver Fibrosis (ELF) Score at Week 24 and Week 96 | Change from baseline in ELF Score at Week 24 | -0.7 score on a scale | Standard Error 0.1 |
| Efruxifermin 50 mg | Change From Baseline in Enhanced Liver Fibrosis (ELF) Score at Week 24 and Week 96 | Change from baseline in ELF Score at Week 96 | -0.8 score on a scale | Standard Error 0.16 |
Secondary
Change From Baseline in Hepatic Fat Fraction in EFX vs Placebo Groups
Change from baseline in hepatic fat fraction, measured by magnetic resonance imaging proton-density fat fraction (MRI-PDFF): Week 24 and Week 96 MRI-PDFF Analysis Set
Time frame: 24 and 96 Weeks
Population: Week 24 and 96 MRI-PDFF Analysis Set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Hepatic Fat Fraction in EFX vs Placebo Groups | Week 24 | -1.9 percentage hepatic fat | Standard Error 0.78 |
| Placebo | Change From Baseline in Hepatic Fat Fraction in EFX vs Placebo Groups | Week 96 | -2.5 percentage hepatic fat | Standard Error 0.89 |
| Efruxifermin 28 mg | Change From Baseline in Hepatic Fat Fraction in EFX vs Placebo Groups | Week 24 | -8.8 percentage hepatic fat | Standard Error 0.84 |
| Efruxifermin 28 mg | Change From Baseline in Hepatic Fat Fraction in EFX vs Placebo Groups | Week 96 | -6.3 percentage hepatic fat | Standard Error 1.01 |
| Efruxifermin 50 mg | Change From Baseline in Hepatic Fat Fraction in EFX vs Placebo Groups | Week 24 | -11.2 percentage hepatic fat | Standard Error 0.86 |
| Efruxifermin 50 mg | Change From Baseline in Hepatic Fat Fraction in EFX vs Placebo Groups | Week 96 | -8.3 percentage hepatic fat | Standard Error 1 |
Comparison: Percent change from baseline in hepatic fat fraction between the EFX 28 mg and placebo groupsp-value: <0.00195% CI: [-9.09, -4.71]Mixed Models Analysis
Comparison: Percent change from baseline in hepatic fat fraction between the EFX 50 mg and placebo groupsp-value: <0.00195% CI: [-11.47, -7.02]Mixed Models Analysis
Comparison: Percent change from baseline in hepatic fat fraction between the EFX 28 mg and placebo groupsp-value: 0.00595% CI: [-6.39, -1.18]Mixed Models Analysis
Comparison: Percent change from baseline in hepatic fat fraction between the EFX 50 mg and placebo groupsp-value: <0.00195% CI: [-8.38, -3.25]Mixed Models Analysis
Secondary
Change From Baseline in Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) at Week 24 and Week 96
Change from baseline in Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) in EFX vs placebo groups The Homeostatic Model Assessment of Insulin Resistance, HOMA-IR, is a calculated index that estimates insulin resistance based on fasting glucose and insulin levels. Higher values indicate greater insulin resistance. \< 1.0: Normal insulin sensitivity 1.0-1.9: Mild insulin resistance 2.0-2.9: Moderate insulin resistance \> 2.9: Severe insulin resistance
Time frame: 24 Weeks, 96 Weeks
Population: Biomarker Analysis Set
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) at Week 24 and Week 96 | Change from baseline in Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) at Week 24 | 0.7 units on a scale | Standard Error 1.09 |
| Placebo | Change From Baseline in Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) at Week 24 and Week 96 | Change from baseline in Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) at Week 96 | -1.3 units on a scale | Standard Error 0.87 |
| Efruxifermin 28 mg | Change From Baseline in Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) at Week 24 and Week 96 | Change from baseline in Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) at Week 24 | -4.7 units on a scale | Standard Error 1.19 |
| Efruxifermin 28 mg | Change From Baseline in Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) at Week 24 and Week 96 | Change from baseline in Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) at Week 96 | -4.1 units on a scale | Standard Error 1.01 |
| Efruxifermin 50 mg | Change From Baseline in Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) at Week 24 and Week 96 | Change from baseline in Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) at Week 24 | -5.6 units on a scale | Standard Error 1.14 |
| Efruxifermin 50 mg | Change From Baseline in Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) at Week 24 and Week 96 | Change from baseline in Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) at Week 96 | -5.5 units on a scale | Standard Error 0.99 |
Secondary
Change From Baseline in Lipoproteins at Week 24 and Week 96
Change from baseline of lipoproteins (triglycerides, Non-HDL-C, HDL-C and LDL-C) in EFX vs placebo groups
Time frame: 24 and 96 weeks
Population: Full Analysis Set
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Lipoproteins at Week 24 and Week 96 | Change from baseline in triglycerides (mg/dL) at Week 24 | 10.5 mg/dL | Standard Error 6.82 |
| Placebo | Change From Baseline in Lipoproteins at Week 24 and Week 96 | Change from baseline in triglycerides (mg/dL) at Week 96 | 16.1 mg/dL | Standard Error 7.69 |
| Placebo | Change From Baseline in Lipoproteins at Week 24 and Week 96 | Change from baseline in HDL cholesterol (mg/dL) at Week 24 | -0.9 mg/dL | Standard Error 1.09 |
| Placebo | Change From Baseline in Lipoproteins at Week 24 and Week 96 | Change from baseline in HDL cholesterol (mg/dL) at Week 96 | 1.3 mg/dL | Standard Error 1.43 |
| Placebo | Change From Baseline in Lipoproteins at Week 24 and Week 96 | Change from baseline in LDL cholesterol (mg/dL) at Week 24 | 4.0 mg/dL | Standard Error 3.47 |
| Placebo | Change From Baseline in Lipoproteins at Week 24 and Week 96 | Change from baseline in LDL cholesterol (mg/dL) at Week 96 | -1.3 mg/dL | Standard Error 4.74 |
| Placebo | Change From Baseline in Lipoproteins at Week 24 and Week 96 | Change from baseline in non-HDL cholesterol (mg/dL) at Week 24 | 6.1 mg/dL | Standard Error 3.83 |
| Placebo | Change From Baseline in Lipoproteins at Week 24 and Week 96 | Change from baseline in non-HDL cholesterol (mg/dL) at Week 96 | 1.5 mg/dL | Standard Error 5.31 |
| Efruxifermin 28 mg | Change From Baseline in Lipoproteins at Week 24 and Week 96 | Change from baseline in HDL cholesterol (mg/dL) at Week 24 | 10.1 mg/dL | Standard Error 1.16 |
| Efruxifermin 28 mg | Change From Baseline in Lipoproteins at Week 24 and Week 96 | Change from baseline in non-HDL cholesterol (mg/dL) at Week 24 | -16.6 mg/dL | Standard Error 4.08 |
| Efruxifermin 28 mg | Change From Baseline in Lipoproteins at Week 24 and Week 96 | Change from baseline in HDL cholesterol (mg/dL) at Week 96 | 7.3 mg/dL | Standard Error 1.59 |
| Efruxifermin 28 mg | Change From Baseline in Lipoproteins at Week 24 and Week 96 | Change from baseline in LDL cholesterol (mg/dL) at Week 24 | -10.4 mg/dL | Standard Error 3.7 |
| Efruxifermin 28 mg | Change From Baseline in Lipoproteins at Week 24 and Week 96 | Change from baseline in LDL cholesterol (mg/dL) at Week 96 | -1.2 mg/dL | Standard Error 5.29 |
| Efruxifermin 28 mg | Change From Baseline in Lipoproteins at Week 24 and Week 96 | Change from baseline in triglycerides (mg/dL) at Week 24 | -41.1 mg/dL | Standard Error 7.26 |
| Efruxifermin 28 mg | Change From Baseline in Lipoproteins at Week 24 and Week 96 | Change from baseline in triglycerides (mg/dL) at Week 96 | -26.9 mg/dL | Standard Error 8.63 |
| Efruxifermin 28 mg | Change From Baseline in Lipoproteins at Week 24 and Week 96 | Change from baseline in non-HDL cholesterol (mg/dL) at Week 96 | -4.5 mg/dL | Standard Error 5.92 |
| Efruxifermin 50 mg | Change From Baseline in Lipoproteins at Week 24 and Week 96 | Change from baseline in HDL cholesterol (mg/dL) at Week 24 | 11.5 mg/dL | Standard Error 1.15 |
| Efruxifermin 50 mg | Change From Baseline in Lipoproteins at Week 24 and Week 96 | Change from baseline in triglycerides (mg/dL) at Week 96 | -31.7 mg/dL | Standard Error 8.54 |
| Efruxifermin 50 mg | Change From Baseline in Lipoproteins at Week 24 and Week 96 | Change from baseline in triglycerides (mg/dL) at Week 24 | -44.7 mg/dL | Standard Error 7.2 |
| Efruxifermin 50 mg | Change From Baseline in Lipoproteins at Week 24 and Week 96 | Change from baseline in HDL cholesterol (mg/dL) at Week 96 | 10.7 mg/dL | Standard Error 1.57 |
| Efruxifermin 50 mg | Change From Baseline in Lipoproteins at Week 24 and Week 96 | Change from baseline in non-HDL cholesterol (mg/dL) at Week 24 | -16.6 mg/dL | Standard Error 4.05 |
| Efruxifermin 50 mg | Change From Baseline in Lipoproteins at Week 24 and Week 96 | Change from baseline in LDL cholesterol (mg/dL) at Week 96 | -1.4 mg/dL | Standard Error 5.23 |
| Efruxifermin 50 mg | Change From Baseline in Lipoproteins at Week 24 and Week 96 | Change from baseline in LDL cholesterol (mg/dL) at Week 24 | -9.6 mg/dL | Standard Error 3.69 |
| Efruxifermin 50 mg | Change From Baseline in Lipoproteins at Week 24 and Week 96 | Change from baseline in non-HDL cholesterol (mg/dL) at Week 96 | -6.7 mg/dL | Standard Error 5.86 |
Comparison: Treatment comparison of least squares (LS) mean change from baseline (EFX 28 mg - placebo) in triglycerides (mg/dL)p-value: <0.00195% CI: [-71.17, -32.11]Mixed Models Analysis
Comparison: Treatment comparison of least squares (LS) mean change from baseline (EFX 50 mg - placebo) in triglycerides (mg/dL)p-value: <0.00195% CI: [-74.63, -35.71]Mixed Models Analysis
Comparison: Treatment comparison of least squares (LS) mean change from baseline (EFX 28 mg - placebo) in triglycerides (mg/dL)p-value: <0.00195% CI: [-65.73, -20.27]Mixed Models Analysis
Comparison: Treatment comparison of LS mean change from baseline (EFX 50 mg - placebo) in triglycerides (mg/dL)p-value: <0.00195% CI: [-70.39, -25.24]Mixed Models Analysis
Comparison: Treatment comparison of LS mean change from baseline (EFX 28 mg - placebo) in HDL cholesterol (mg/dL)p-value: <0.00195% CI: [7.92, 14.17]Mixed Models Analysis
Comparison: Treatment comparison of LS mean change from baseline (EFX 50 mg - placebo) in HDL cholesterol (mg/dL)p-value: <0.00195% CI: [9.35, 15.57]Mixed Models Analysis
Comparison: Treatment comparison of LS mean change from baseline (EFX 28 mg - placebo) in HDL cholesterol (mg/dL)p-value: 0.00595% CI: [1.84, 10.23]Mixed Models Analysis
Comparison: Treatment comparison of LS mean change from baseline (EFX 50 mg - placebo) in HDL cholesterol (mg/dL)p-value: <0.00195% CI: [5.3, 13.65]Mixed Models Analysis
Comparison: Treatment comparison of change from baseline (EFX 28 mg - placebo) in LDL cholesterol (mg/dL)p-value: 0.00595% CI: [-24.28, -4.53]Mixed Models Analysis
Comparison: Treatment comparison of LS mean change from baseline (EFX 50 mg - placebo) in LDL cholesterol (mg/dL)p-value: 0.00795% CI: [-23.5, -3.76]Mixed Models Analysis
Comparison: Treatment comparison of change from baseline (EFX 28 mg - placebo) in LDL cholesterol (mg/dL)p-value: 0.9995% CI: [-13.86, 14.04]Mixed Models Analysis
Comparison: Treatment comparison of LS mean change from baseline (EFX 50 mg - placebo) in LDL cholesterol (mg/dL)p-value: 0.9895% CI: [-14.07, 13.71]Mixed Models Analysis
Comparison: Treatment comparison of LS mean change from baseline (EFX 28 mg - placebo) in non-HDL cholesterol (mg/dL)p-value: <0.00195% CI: [-33.58, -11.71]Mixed Models Analysis
Comparison: Treatment comparison of LS mean change from baseline (EFX 50mg - placebo) in non-HDL cholesterol (mg/dL)p-value: <0.00195% CI: [-33.56, -11.74]Mixed Models Analysis
Comparison: Treatment comparison of LS mean change from baseline (EFX 28 mg - placebo) in non-HDL cholesterol (mg/dL)p-value: 0.44395% CI: [-21.72, 9.56]Mixed Models Analysis
Comparison: Treatment comparison of LS mean change from baseline (EFX 50 mg - placebo) in non-HDL cholesterol (mg/dL)p-value: 0.29995% CI: [-23.77, 7.36]Mixed Models Analysis
Secondary
Change From Baseline in Liver Stiffness (kPa) at Week 24 and Week 96
Change from Baseline in Liver Stiffness Evaluated by FibroScan in EFX vs placebo groups at Week 24 and Week 96: Full Analysis Set
Time frame: 24 and 96 weeks
Population: Full Analysis Set
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Liver Stiffness (kPa) at Week 24 and Week 96 | Change from baseline in liver stiffness measurement (LSM, kPa) at Week 24 | -0.8 kPa | Standard Error 0.88 |
| Placebo | Change From Baseline in Liver Stiffness (kPa) at Week 24 and Week 96 | Change from baseline in liver stiffness measurement (LSM, kPa) at Week 96 | -0.6 kPa | Standard Error 0.98 |
| Efruxifermin 28 mg | Change From Baseline in Liver Stiffness (kPa) at Week 24 and Week 96 | Change from baseline in liver stiffness measurement (LSM, kPa) at Week 24 | -2.9 kPa | Standard Error 0.93 |
| Efruxifermin 28 mg | Change From Baseline in Liver Stiffness (kPa) at Week 24 and Week 96 | Change from baseline in liver stiffness measurement (LSM, kPa) at Week 96 | -4.0 kPa | Standard Error 1.09 |
| Efruxifermin 50 mg | Change From Baseline in Liver Stiffness (kPa) at Week 24 and Week 96 | Change from baseline in liver stiffness measurement (LSM, kPa) at Week 24 | -4.2 kPa | Standard Error 0.95 |
| Efruxifermin 50 mg | Change From Baseline in Liver Stiffness (kPa) at Week 24 and Week 96 | Change from baseline in liver stiffness measurement (LSM, kPa) at Week 96 | -7.2 kPa | Standard Error 1.08 |
Comparison: Treatment comparison of change from baseline (EFX 28 mg - placebo) in Liver Stiffness Measurement (kPa)p-value: 0.10295% CI: [-4.5, 0.4]Mixed Models Analysis
Comparison: Treatment comparison of change from baseline (EFX 50 mg - placebo) in Liver Stiffness Measurement (kPa)p-value: 0.00995% CI: [-5.8, -0.8]Mixed Models Analysis
Comparison: Treatment comparison of change from baseline (EFX 28 mg - placebo) in Liver Stiffness Measurement (kPa)p-value: 0.02195% CI: [-6.2, -0.5]Mixed Models Analysis
Comparison: Treatment comparison of change from baseline (EFX 50 mg - placebo) in Liver Stiffness Measurement (kPa)p-value: <0.00195% CI: [-9.4, -3.7]Mixed Models Analysis
Secondary
Change From Baseline in NIS4 Score at Week 24 and Week 96
Change from Baseline in NIS4 score in EFX vs placebo groups NIS4 scores range from 0 to 1 and are calculated by combining the results of four individual biomarker assays \[miR34a-5p, α2-macroglobulin (A2M), YKL-40 and HbA1c\] each of which contributes to the test's ability to detect liver inflammation and/or fibrosis. \>0.63: Higher risk of NASH or advanced fibrosis 0.37-0.63: Moderate risk, and additional testing may be considered \<0.36: Lower risk of of NASH or advanced fibrosis
Time frame: 24 and 96 Weeks
Population: Biomarker Analysis Set
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in NIS4 Score at Week 24 and Week 96 | Change from baseline in NIS-4 score at Week 24 | -0.0 score on a scale | Standard Error 0.03 |
| Placebo | Change From Baseline in NIS4 Score at Week 24 and Week 96 | Change from baseline in NIS-4 score at Week 96 | -0.1 score on a scale | Standard Error 0.05 |
| Efruxifermin 28 mg | Change From Baseline in NIS4 Score at Week 24 and Week 96 | Change from baseline in NIS-4 score at Week 24 | -0.3 score on a scale | Standard Error 0.04 |
| Efruxifermin 28 mg | Change From Baseline in NIS4 Score at Week 24 and Week 96 | Change from baseline in NIS-4 score at Week 96 | -0.2 score on a scale | Standard Error 0.05 |
| Efruxifermin 50 mg | Change From Baseline in NIS4 Score at Week 24 and Week 96 | Change from baseline in NIS-4 score at Week 24 | -0.3 score on a scale | Standard Error 0.04 |
| Efruxifermin 50 mg | Change From Baseline in NIS4 Score at Week 24 and Week 96 | Change from baseline in NIS-4 score at Week 96 | -0.3 score on a scale | Standard Error 0.05 |
Secondary
Change From Baseline in N-terminal Type III Collagen Propeptide (Pro-C3) at Week 24 and Week 96
Change from Baseline in N-terminal Type III Collagen Propeptide (Pro-C3) in EFX vs placebo groups
Time frame: 24 and 96 Weeks
Population: Biomarker Analysis Set
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in N-terminal Type III Collagen Propeptide (Pro-C3) at Week 24 and Week 96 | Change from baseline in N-terminal Type III Collagen Propeptide (Pro-C3) GEN2 at Week 96 | -17.2 ng/mL | Standard Error 7.87 |
| Placebo | Change From Baseline in N-terminal Type III Collagen Propeptide (Pro-C3) at Week 24 and Week 96 | Change from baseline in N-terminal Type III Collagen Propeptide (Pro-C3) GEN2 at Week 24 | -2.7 ng/mL | Standard Error 6.99 |
| Efruxifermin 28 mg | Change From Baseline in N-terminal Type III Collagen Propeptide (Pro-C3) at Week 24 and Week 96 | Change from baseline in N-terminal Type III Collagen Propeptide (Pro-C3) GEN2 at Week 24 | -51.1 ng/mL | Standard Error 7.37 |
| Efruxifermin 28 mg | Change From Baseline in N-terminal Type III Collagen Propeptide (Pro-C3) at Week 24 and Week 96 | Change from baseline in N-terminal Type III Collagen Propeptide (Pro-C3) GEN2 at Week 96 | -40.2 ng/mL | Standard Error 8.89 |
| Efruxifermin 50 mg | Change From Baseline in N-terminal Type III Collagen Propeptide (Pro-C3) at Week 24 and Week 96 | Change from baseline in N-terminal Type III Collagen Propeptide (Pro-C3) GEN2 at Week 24 | -53.9 ng/mL | Standard Error 7.37 |
| Efruxifermin 50 mg | Change From Baseline in N-terminal Type III Collagen Propeptide (Pro-C3) at Week 24 and Week 96 | Change from baseline in N-terminal Type III Collagen Propeptide (Pro-C3) GEN2 at Week 96 | -50.5 ng/mL | Standard Error 8.92 |
Secondary
Change From Baseline of Hemoglobin A1c (Glycated Hemoglobin, HbA1c) at Week 24 and Week 96
Change from baseline in hemoglobin A1c (glycated hemoglobin, HbA1c) in EFX vs placebo groups
Time frame: 24 Weeks, 96 Weeks
Population: Biomarker Analysis Set
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline of Hemoglobin A1c (Glycated Hemoglobin, HbA1c) at Week 24 and Week 96 | Change from baseline in hemoglobin A1C (HbA1c, %) at Week 24 | -0.0 % glycated hemoglobin | Standard Error 0.12 |
| Placebo | Change From Baseline of Hemoglobin A1c (Glycated Hemoglobin, HbA1c) at Week 24 and Week 96 | Change from baseline in hemoglobin A1C (HbA1c, %) at Week 96 | -0.0 % glycated hemoglobin | Standard Error 0.22 |
| Efruxifermin 28 mg | Change From Baseline of Hemoglobin A1c (Glycated Hemoglobin, HbA1c) at Week 24 and Week 96 | Change from baseline in hemoglobin A1C (HbA1c, %) at Week 24 | -0.3 % glycated hemoglobin | Standard Error 0.12 |
| Efruxifermin 28 mg | Change From Baseline of Hemoglobin A1c (Glycated Hemoglobin, HbA1c) at Week 24 and Week 96 | Change from baseline in hemoglobin A1C (HbA1c, %) at Week 96 | 0.0 % glycated hemoglobin | Standard Error 0.24 |
| Efruxifermin 50 mg | Change From Baseline of Hemoglobin A1c (Glycated Hemoglobin, HbA1c) at Week 24 and Week 96 | Change from baseline in hemoglobin A1C (HbA1c, %) at Week 96 | 0.2 % glycated hemoglobin | Standard Error 0.24 |
| Efruxifermin 50 mg | Change From Baseline of Hemoglobin A1c (Glycated Hemoglobin, HbA1c) at Week 24 and Week 96 | Change from baseline in hemoglobin A1C (HbA1c, %) at Week 24 | -0.4 % glycated hemoglobin | Standard Error 0.12 |
Secondary
Change in Body Weight at Week 24 and Week 96
Change from baseline in body weight (kg) in EFX vs placebo groups
Time frame: 24 and 96 weeks
Population: Full Analysis Set
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change in Body Weight at Week 24 and Week 96 | Change from Baseline in Body Weight (kg) at Week 24 | -0.6 kg | Standard Error 0.82 |
| Placebo | Change in Body Weight at Week 24 and Week 96 | Change from Baseline in Body Weight (kg) at Week 96 | -1.5 kg | Standard Error 1.4 |
| Efruxifermin 28 mg | Change in Body Weight at Week 24 and Week 96 | Change from Baseline in Body Weight (kg) at Week 24 | -0.2 kg | Standard Error 0.86 |
| Efruxifermin 28 mg | Change in Body Weight at Week 24 and Week 96 | Change from Baseline in Body Weight (kg) at Week 96 | -0.3 kg | Standard Error 1.53 |
| Efruxifermin 50 mg | Change in Body Weight at Week 24 and Week 96 | Change from Baseline in Body Weight (kg) at Week 24 | -3.0 kg | Standard Error 0.85 |
| Efruxifermin 50 mg | Change in Body Weight at Week 24 and Week 96 | Change from Baseline in Body Weight (kg) at Week 96 | -3.5 kg | Standard Error 1.52 |
Comparison: Treatment comparison of LS mean change from baseline (EFX 28 mg - placebo) in body weight (kg)p-value: 0.7595% CI: [-1.96, 2.72]Mixed Models Analysis
Comparison: Treatment comparison of LS mean change from baseline (EFX 50 mg - placebo) in body weight (kg)p-value: 0.04295% CI: [-4.75, -0.09]Mixed Models Analysis
Comparison: Treatment comparison of LS mean change from baseline (28 mg EFX - placebo) in body weight (kg)p-value: 0.56495% CI: [-2.9, 5.29]Mixed Models Analysis
Comparison: Treatment comparison of LS mean change from baseline (EFX 50 mg - placebo) in body weight (kg)p-value: 0.34895% CI: [-6.02, 2.14]Mixed Models Analysis
Secondary
Proportion of Subjects Who Achieve Improvement in Liver Fibrosis ≥ 1 Stage and no Worsening of Steatohepatitis at Week 96
Proportions of subjects in EFX vs baseline groups who achieve improvement in liver fibrosis (decrease of ≥ 1 stage in NASH CRN fibrosis score) and no worsening of steatohepatitis (no increase in NAS for ballooning, inflammation, or steatosis) at Week 96
Time frame: 96 Weeks
Population: Week 96 Liver Biopsy Analysis Set
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Proportion of Subjects Who Achieve Improvement in Liver Fibrosis ≥ 1 Stage and no Worsening of Steatohepatitis at Week 96 | 8 Participants |
| Efruxifermin 28 mg | Proportion of Subjects Who Achieve Improvement in Liver Fibrosis ≥ 1 Stage and no Worsening of Steatohepatitis at Week 96 | 12 Participants |
| Efruxifermin 50 mg | Proportion of Subjects Who Achieve Improvement in Liver Fibrosis ≥ 1 Stage and no Worsening of Steatohepatitis at Week 96 | 21 Participants |
p-value: 0.0795% CI: [-1.3, 45]Cochran-Mantel-Haenszel
Comparison: Week 96p-value: <0.00195% CI: [31.2, 72.7]Cochran-Mantel-Haenszel
Secondary
Proportion of Subjects Who Achieve Improvement in Liver Fibrosis ≥ 1 Stage at Week 24 and Week 96
Proportion of subjects in EFX vs placebo groups who achieve improvement in liver fibrosis (decrease ≥ 1 stage in NASH CRN fibrosis score)
Time frame: 24 and 96 Weeks
Population: Week 24 and Week 96 Liver Biopsy Analysis Sets
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Proportion of Subjects Who Achieve Improvement in Liver Fibrosis ≥ 1 Stage at Week 24 and Week 96 | Week 24 | 9 Participants |
| Placebo | Proportion of Subjects Who Achieve Improvement in Liver Fibrosis ≥ 1 Stage at Week 24 and Week 96 | Week 96 | 9 Participants |
| Efruxifermin 28 mg | Proportion of Subjects Who Achieve Improvement in Liver Fibrosis ≥ 1 Stage at Week 24 and Week 96 | Week 24 | 15 Participants |
| Efruxifermin 28 mg | Proportion of Subjects Who Achieve Improvement in Liver Fibrosis ≥ 1 Stage at Week 24 and Week 96 | Week 96 | 12 Participants |
| Efruxifermin 50 mg | Proportion of Subjects Who Achieve Improvement in Liver Fibrosis ≥ 1 Stage at Week 24 and Week 96 | Week 24 | 14 Participants |
| Efruxifermin 50 mg | Proportion of Subjects Who Achieve Improvement in Liver Fibrosis ≥ 1 Stage at Week 24 and Week 96 | Week 96 | 21 Participants |
Comparison: Week 24p-value: 0.05395% CI: [0.4, 39.5]Cochran-Mantel-Haenszel
Comparison: Week 24p-value: 0.06995% CI: [-1.5, 41.2]Cochran-Mantel-Haenszel
Comparison: Week 96p-value: 0.12395% CI: [-4.8, 42.8]Cochran-Mantel-Haenszel
Comparison: Week 96p-value: <0.00195% CI: [27.7, 70.2]Cochran-Mantel-Haenszel
Secondary
Proportion of Subjects Who Achieve Resolution of Steatohepatitis and no Worsening of Liver Fibrosis at Week 24 and Week 96
Proportions of subjects in EFX vs placebo groups who achieve resolution of steatohepatitis (defined as a NAS of 0-1 for inflammation, 0 for ballooning, and any value for steatosis) and no worsening of liver fibrosis (determined by the NASH CRN criteria)
Time frame: 24 and 96 weeks
Population: Liver Biopsy Analysis Set - Week 24 and Week 96
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Proportion of Subjects Who Achieve Resolution of Steatohepatitis and no Worsening of Liver Fibrosis at Week 24 and Week 96 | Week 24 | 6 Participants |
| Placebo | Proportion of Subjects Who Achieve Resolution of Steatohepatitis and no Worsening of Liver Fibrosis at Week 24 and Week 96 | Week 96 | 8 Participants |
| Efruxifermin 28 mg | Proportion of Subjects Who Achieve Resolution of Steatohepatitis and no Worsening of Liver Fibrosis at Week 24 and Week 96 | Week 24 | 18 Participants |
| Efruxifermin 28 mg | Proportion of Subjects Who Achieve Resolution of Steatohepatitis and no Worsening of Liver Fibrosis at Week 24 and Week 96 | Week 96 | 16 Participants |
| Efruxifermin 50 mg | Proportion of Subjects Who Achieve Resolution of Steatohepatitis and no Worsening of Liver Fibrosis at Week 24 and Week 96 | Week 24 | 26 Participants |
| Efruxifermin 50 mg | Proportion of Subjects Who Achieve Resolution of Steatohepatitis and no Worsening of Liver Fibrosis at Week 24 and Week 96 | Week 96 | 16 Participants |
Comparison: Week 24p-value: 0.00295% CI: [12.9, 50.9]Cochran-Mantel-Haenszel
Comparison: Week 24p-value: <0.00195% CI: [44.1, 79.4]Cochran-Mantel-Haenszel
Comparison: Week 96p-value: 0.00295% CI: [17.2, 60.7]Cochran-Mantel-Haenszel
Comparison: Week 96p-value: 0.00695% CI: [10.5, 55.8]Cochran-Mantel-Haenszel