A Study of Efruxifermin in Subjects With Histologically Confirmed Nonalcoholic Steatohepatitis (NASH)

Back to results

Primary Purpose

Status

Completed

Phase

Phase 2

Locations

International

Study Type

Interventional

Intervention

EFX

Placebo

About this trial

This is an interventional treatment trial for NASH - Nonalcoholic Steatohepatitis

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Key Inclusion Criteria:

Males and non-pregnant, non-lactating females between 18 - 80 years of age inclusive, based on the date of the screening visit.
Main Study only: Body mass index (BMI) > 25 kg/m^2 (unless the patient has biopsy-proven NASH documented within the last 2 years).
Main Study only: Must have confirmation of ≥ 10% liver fat content on magnetic resonance imaging- proton density fat fraction (MRI-PDFF) at screening.
Main Study only: Biopsy-proven NASH. Must have had a liver biopsy within 180 days of randomization with fibrosis stage 1 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)
Cohort C only: FibroScan® measurement > 13.1 kPa.
Cohort C only: Cirrhosis due to NASH. Liver biopsy consistent with F4 fibrosis according to the NAS system, confirmed by the central or local reader.

Exclusion Criteria:

Weight gain or loss > 5% in the 3 months prior to randomization or > 10% in the 6 months prior to screening.
Type 1 and insulin-dependent Type 2 diabetes.
Poorly controlled hypertension (blood pressure > 160/100).

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm Type

Experimental

Placebo Comparator

Experimental

Placebo Comparator

Arm Label

EFX Dose 1

EFX Dose 2

EFX Dose 3

Placebo

EFX Dose (Cohort C)

Placebo (Cohort C)

Arm Description

Main Study

Outcomes

Primary Outcome Measures

Main: Absolute Change From Baseline in Hepatic Fat Fraction Assessed by MRI-PDFF at Week 12.

Main study. ANCOVA multiple imputation with treatment group and F1 fibrosis score (F1 vs F2-3) as factors and baseline hepatic fat fraction measured by MRI-PDFF as a covariate.

Secondary Outcome Measures

Main: Absolute Change From Baseline in Hepatic Fat Fraction Assessed by MRI-PDFF at Week 22-24.

Main study. Included subjects with ≥30% relative fat reduction on MRI-PDFF at Week 12 that were required to return between Weeks 22 - 24. ANCOVA model with treatment group and F1 fibrosis score (F1 vs F2-3) as factors and baseline hepatic fat fraction as a covariate were performed.

Main: Percent Change From Baseline in Hepatic Fat Fraction Measured by MRI-PDFF at Week 12.

Main study. ANCOVA multiple imputation with treatment group and F1 fibrosis score (F1 vs F2-3) as factors and baseline hepatic fat fraction measured by MRI-PDFF as a covariate.

Main: Percent Change From Baseline in Hepatic Fat Fraction Measured by MRI-PDFF at Week 22-24.

Main study. ANCOVA multiple imputation with treatment group and F1 fibrosis score (F1 vs F2-3) as factors and baseline hepatic fat fraction measured by MRI-PDFF as a covariate.

Main: Responder: Subjects Who Achieved a Clinically Meaningful Relative Reduction of at Least 30% in Liver Fat Content as Measured by MRI-PDFF at Week 12.

Main Study. The analyses included the treatment group and F1 fibrosis score (F1 vs F2-3) as factors and baseline hepatic fat fraction measured by MRI-PDFF as a covariate.

Main: Responder Based on NAFLD Activity Score System (NAS): Subjects Who Had a Decrease of ≥2 Points in NAS With at Least a 1-point Reduction in Either Lobular Inflammation or Hepatocellular Ballooning and With no Concurrent Worsening of Fibrosis Stage.

Main study: Responders were defined for subjects with ≥ 30% relative fat reduction on MRI-PDFF at Week 12 and required to return between Weeks 22 - 24. Fisher's exact test was used for the analysis using the Full Analysis Set with missing values imputed as non-responders and repeated on Liver Biopsy Evaluable Analysis Set without imputation.

Main: Change From Baseline in ALT at Week 12, 16, and 20.

ANCOVA model with treatment group, baseline hepatic fat fraction (<15% vs ≥15%), and F1 fibrosis score (F1 vs F2-3) as factors and baseline value as a covariate.

Cohort C: Change From Baseline in Liver Stiffness as Evaluated by FibroScan at Week 16

Cohort C: ANCOVA model with treatment group as a factor and baseline liver stiffness as evaluated by FibroScan® as a covariate using the Full Analysis Set. Missing values at Week 16 were imputed using the last-observed-carried-forward (LOCF) method.

Cohort C: Change From Baseline in Non-invasive Biomarkers Including Pro-C3 at Week 12, 16, and 20.

Cohort C. ANCOVA model with treatment group as a factor and baseline liver stiffness as evaluated by FibroScan® as a covariate using the Full Analysis Set. Missing values were imputed using the last-observed-carried-forward (LOCF) method.

Cohort C: Change From Baseline in Non-invasive Biomarkers Including Liver Fibrosis by ELF Test Score at Week 12 and 16.

Cohort C. The enhanced liver fibrosis (ELF) score describes the severity of liver fibrosis where a score of <7.7 indicates no or mild fibrosis, a score of ≥7.7 to <9.8 indicates moderate fibrosis, and a score of ≥9.8 indicates severe fibrosis. A change from baseline with a negative value indicates a decrease in severity of liver fibrosis. An ANCOVA model with treatment group as a factor and baseline liver stiffness as evaluated by FibroScan® as a covariate using the Full Analysis Set was used. Missing values were imputed using the last-observed-carried-forward (LOCF) method.

Full Information

NCT ID

NCT03976401

First Posted

June 3, 2019

Last Updated

August 3, 2022

Sponsor

Akero Therapeutics, Inc

1. Study Identification

Unique Protocol Identification Number

NCT03976401

Brief Title

A Study of Efruxifermin in Subjects With Histologically Confirmed Nonalcoholic Steatohepatitis (NASH)

Official Title

A Phase 2a, Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Safety and Efficacy of Efruxifermin in Subjects With Nonalcoholic Steatohepatitis (NASH)

Study Type

Interventional

2. Study Status

Record Verification Date

August 2022

Overall Recruitment Status

Completed

Study Start Date

May 28, 2019 (Actual)

Primary Completion Date

February 10, 2021 (Actual)

Study Completion Date

January 10, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Akero Therapeutics, Inc

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

No

5. Study Description

Brief Summary

This is a multi-center evaluation of efruxifermin (EFX) in a randomized, double-blind, placebo-controlled study administered for 16 weeks in subjects with biopsy proven F1 - F4 NASH.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

NASH - Nonalcoholic Steatohepatitis

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

110 (Actual)

8. Arms, Groups, and Interventions

Arm Title

EFX Dose 1

Arm Type

Experimental

Arm Description

Main Study

Arm Title

EFX Dose 2

Arm Type

Experimental

Arm Description

Main Study

Arm Title

EFX Dose 3

Arm Type

Experimental

Arm Description

Main Study

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

Main Study

Arm Title

EFX Dose (Cohort C)

Arm Type

Experimental

Arm Title

Placebo (Cohort C)

Arm Type

Placebo Comparator

Intervention Type

Drug

Intervention Name(s)

EFX

Intervention Description

Administered by subcutaneous injection

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

Administered by subcutaneous injection

Primary Outcome Measure Information:

Title

Main: Absolute Change From Baseline in Hepatic Fat Fraction Assessed by MRI-PDFF at Week 12.

Description

Main study. ANCOVA multiple imputation with treatment group and F1 fibrosis score (F1 vs F2-3) as factors and baseline hepatic fat fraction measured by MRI-PDFF as a covariate.

Time Frame

12 weeks

Secondary Outcome Measure Information:

Title

Main: Absolute Change From Baseline in Hepatic Fat Fraction Assessed by MRI-PDFF at Week 22-24.

Description

Main study. Included subjects with ≥30% relative fat reduction on MRI-PDFF at Week 12 that were required to return between Weeks 22 - 24. ANCOVA model with treatment group and F1 fibrosis score (F1 vs F2-3) as factors and baseline hepatic fat fraction as a covariate were performed.

Time Frame

22-24 weeks

Title

Main: Percent Change From Baseline in Hepatic Fat Fraction Measured by MRI-PDFF at Week 12.

Description

Main study. ANCOVA multiple imputation with treatment group and F1 fibrosis score (F1 vs F2-3) as factors and baseline hepatic fat fraction measured by MRI-PDFF as a covariate.

Time Frame

12 weeks

Title

Main: Percent Change From Baseline in Hepatic Fat Fraction Measured by MRI-PDFF at Week 22-24.

Description

Main study. ANCOVA multiple imputation with treatment group and F1 fibrosis score (F1 vs F2-3) as factors and baseline hepatic fat fraction measured by MRI-PDFF as a covariate.

Time Frame

22-24 weeks

Title

Main: Responder: Subjects Who Achieved a Clinically Meaningful Relative Reduction of at Least 30% in Liver Fat Content as Measured by MRI-PDFF at Week 12.

Description

Main Study. The analyses included the treatment group and F1 fibrosis score (F1 vs F2-3) as factors and baseline hepatic fat fraction measured by MRI-PDFF as a covariate.

Time Frame

12 weeks

Title

Main: Responder Based on NAFLD Activity Score System (NAS): Subjects Who Had a Decrease of ≥2 Points in NAS With at Least a 1-point Reduction in Either Lobular Inflammation or Hepatocellular Ballooning and With no Concurrent Worsening of Fibrosis Stage.

Description

Main study: Responders were defined for subjects with ≥ 30% relative fat reduction on MRI-PDFF at Week 12 and required to return between Weeks 22 - 24. Fisher's exact test was used for the analysis using the Full Analysis Set with missing values imputed as non-responders and repeated on Liver Biopsy Evaluable Analysis Set without imputation.

Time Frame

22-24 weeks

Title

Main: Change From Baseline in ALT at Week 12, 16, and 20.

Description

ANCOVA model with treatment group, baseline hepatic fat fraction (<15% vs ≥15%), and F1 fibrosis score (F1 vs F2-3) as factors and baseline value as a covariate.

Time Frame

12, 16, and 20 weeks

Title

Cohort C: Change From Baseline in Liver Stiffness as Evaluated by FibroScan at Week 16

Description

Cohort C: ANCOVA model with treatment group as a factor and baseline liver stiffness as evaluated by FibroScan® as a covariate using the Full Analysis Set. Missing values at Week 16 were imputed using the last-observed-carried-forward (LOCF) method.

Time Frame

16 weeks

Title

Cohort C: Change From Baseline in Non-invasive Biomarkers Including Pro-C3 at Week 12, 16, and 20.

Description

Cohort C. ANCOVA model with treatment group as a factor and baseline liver stiffness as evaluated by FibroScan® as a covariate using the Full Analysis Set. Missing values were imputed using the last-observed-carried-forward (LOCF) method.

Time Frame

12, 16, and 20 weeks

Title

Cohort C: Change From Baseline in Non-invasive Biomarkers Including Liver Fibrosis by ELF Test Score at Week 12 and 16.

Description

Cohort C. The enhanced liver fibrosis (ELF) score describes the severity of liver fibrosis where a score of <7.7 indicates no or mild fibrosis, a score of ≥7.7 to <9.8 indicates moderate fibrosis, and a score of ≥9.8 indicates severe fibrosis. A change from baseline with a negative value indicates a decrease in severity of liver fibrosis. An ANCOVA model with treatment group as a factor and baseline liver stiffness as evaluated by FibroScan® as a covariate using the Full Analysis Set was used. Missing values were imputed using the last-observed-carried-forward (LOCF) method.

Time Frame

12 and 16 weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

80 Years

Accepts Healthy Volunteers

No

Eligibility Criteria

Key Inclusion Criteria: Males and non-pregnant, non-lactating females between 18 - 80 years of age inclusive, based on the date of the screening visit. Main Study only: Body mass index (BMI) > 25 kg/m^2 (unless the patient has biopsy-proven NASH documented within the last 2 years). Main Study only: Must have confirmation of ≥ 10% liver fat content on magnetic resonance imaging- proton density fat fraction (MRI-PDFF) at screening. Main Study only: Biopsy-proven NASH. Must have had a liver biopsy within 180 days of randomization with fibrosis stage 1 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) Cohort C only: FibroScan® measurement > 13.1 kPa. Cohort C only: Cirrhosis due to NASH. Liver biopsy consistent with F4 fibrosis according to the NAS system, confirmed by the central or local reader. Exclusion Criteria: Weight gain or loss > 5% in the 3 months prior to randomization or > 10% in the 6 months prior to screening. Type 1 and insulin-dependent Type 2 diabetes. Poorly controlled hypertension (blood pressure > 160/100).

Facility Information:

Facility Name

Akero Clinical Study Site

City

Tucson

State/Province

Arizona

ZIP/Postal Code

85711

Country

United States

Facility Name

Akero Clinical Study Site

City

Little Rock

State/Province

Arkansas

ZIP/Postal Code

72117

Country

United States

Facility Name

Akero Clinical Study Site

City

Huntington Park

State/Province

California

ZIP/Postal Code

90255

Country

United States

Facility Name

Akero Clinical Study Site

City

Los Angeles

State/Province

California

ZIP/Postal Code

90036

Country

United States

Facility Name

Akero Clinical Study Site

City

Los Angeles

State/Province

California

ZIP/Postal Code

90057

Country

United States

Facility Name

Akero Clinical Study Site

City

Panorama City

State/Province

California

ZIP/Postal Code

91402

Country

United States

Facility Name

Akero Clinical Study Site

City

Poway

State/Province

California

ZIP/Postal Code

92064

Country

United States

Facility Name

Akero Clinical Study Site

City

Boca Raton

State/Province

Florida

ZIP/Postal Code

33434

Country

United States

Facility Name

Akero Clinical Study Site

City

Lakewood Ranch

State/Province

Florida

ZIP/Postal Code

34211

Country

United States

Facility Name

Akero Clinical Study Site

City

Miami

State/Province

Florida

ZIP/Postal Code

33156

Country

United States

Facility Name

Akero Clinical Study Site

City

New Port Richey

State/Province

Florida

ZIP/Postal Code

34653

Country

United States

Facility Name

Akero Clinical Study Site

City

Ocoee

State/Province

Florida

ZIP/Postal Code

34761

Country

United States

Facility Name

Akero Clinical Study Site

City

Port Orange

State/Province

Florida

ZIP/Postal Code

32127

Country

United States

Facility Name

Akero Clinical Study Site

City

Sarasota

State/Province

Florida

ZIP/Postal Code

34240

Country

United States

Facility Name

Akero Clinical Study Site

City

Baton Rouge

State/Province

Louisiana

ZIP/Postal Code

70809

Country

United States

Facility Name

Akero Clinical Study Site

City

Marrero

State/Province

Louisiana

ZIP/Postal Code

70072

Country

United States

Facility Name

Akero Clinical Study Site

City

Kansas City

State/Province

Missouri

ZIP/Postal Code

64131

Country

United States

Facility Name

Akero Clinical Study Site

City

Berlin

State/Province

New Jersey

ZIP/Postal Code

08009

Country

United States

Facility Name

Akero Clinical Study Site

City

Chattanooga

State/Province

Tennessee

ZIP/Postal Code

37421

Country

United States

Facility Name

Akero Clinical Study Site

City

Cedar Park

State/Province

Texas

ZIP/Postal Code

78613

Country

United States

Facility Name

Akero Clinical Study Site

City

Dallas

State/Province

Texas

ZIP/Postal Code

75246

Country

United States

Facility Name

Akero Clinical Study Site

City

Edinburg

State/Province

Texas

ZIP/Postal Code

78539

Country

United States

Facility Name

Akero Clinical Study Site

City

Fort Worth

State/Province

Texas

ZIP/Postal Code

76104

Country

United States

Facility Name

Akero Clinical Study Site

City

San Antonio

State/Province

Texas

ZIP/Postal Code

78215

Country

United States

Facility Name

Akero Clinical Study Site

City

San Antonio

State/Province

Texas

ZIP/Postal Code

78229

Country

United States

Facility Name

Akero Clinical Study Site

City

Webster

State/Province

Texas

ZIP/Postal Code

77598

Country

United States

Facility Name

Akero Clinical Study Site

City

San Juan

ZIP/Postal Code

00927

Country

Puerto Rico

12. IPD Sharing Statement

Citations:

PubMed Identifier

34239138

Citation

Harrison SA, Ruane PJ, Freilich BL, Neff G, Patil R, Behling CA, Hu C, Fong E, de Temple B, Tillman EJ, Rolph TP, Cheng A, Yale K. Efruxifermin in non-alcoholic steatohepatitis: a randomized, double-blind, placebo-controlled, phase 2a trial. Nat Med. 2021 Jul;27(7):1262-1271. doi: 10.1038/s41591-021-01425-3. Epub 2021 Jul 8.

Results Reference

derived

NASH - Nonalcoholic Steatohepatitis

About this trial

Eligibility Criteria

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

1. Study Identification

2. Study Status

3. Sponsor/Collaborators

4. Oversight

5. Study Description

6. Conditions and Keywords

7. Study Design

8. Arms, Groups, and Interventions

10. Eligibility

12. IPD Sharing Statement

Learn more about this trial