Recruiting NCT06215716

A Study Evaluating Efruxifermin in Subjects With Non-Cirrhotic Nonalcoholic Steatohepatitis (NASH)/Metabolic Dysfunction-Associated Steatohepatitis (MASH) and Fibrosis

Phase III Interventional NASH With Fibrosis MASH With Fibrosis

For patients and families

In plain language

An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.

What is being studied: The protocol lists: Efruxifermin, Placebo.
Who it may be relevant to: Registry conditions: NASH With Fibrosis, MASH With Fibrosis. Basic parameters: 18 years — 80 years · All.
What needs checking: Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
Where it takes place: United States, Argentina, Australia, Canada, France +13
Next step: Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →

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Official title

A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Safety and Efficacy of Efruxifermin in Subjects With Non-Cirrhotic Nonalcoholic Steatohepatitis (NASH)/Metabolic Dysfunction-Associated Steatohepatitis (MASH) and Fibrosis

Overview

This is a multi-center evaluation of efruxifermin (EFX) in a randomized, double-blind, placebo-controlled study in subjects with non-cirrhotic NASH/MASH and fibrosis stage 2 or 3 (F2 or F3). The study will enroll subjects in two cohorts for a total samples size of 1650 subjects.

Detailed description

This is a Phase 3, multi-center, randomized, double-blind, placebo-controlled study evaluating the safety and efficacy of efruxifermin (EFX) in subjects with non-cirrhotic nonalcoholic steatohepatitis (NASH)/metabolic dysfunction-associated steatohepatitis (MASH) and fibrosis stage 2 or 3 (F2 or F3).

Approximately 1,650 subjects will be enrolled into 2 cohorts.

Cohort 1 will enroll approximately 750 subjects with biopsy-confirmed NASH/MASH and fibrosis stage F2 or F3. Subjects in Cohort 1 will undergo evaluation of histologic efficacy endpoints at Week 52.

Cohort 2 will enroll approximately 900 subjects with biopsy-confirmed fibrosis stage F3. Subjects in Cohort 2 may enroll regardless of NAFLD Activity Score (NAS). Subjects in Cohort 2 will undergo liver biopsy assessment at Week 96.

Eligible subjects will be randomized in a 1:1:1 ratio to receive:

* EFX 28 mg administered subcutaneously once weekly * EFX 50 mg administered subcutaneously once weekly * Placebo administered subcutaneously once weekly

Subjects will participate in:

* a screening period of up to 12 weeks, * a 52-week primary histology endpoint treatment period (Cohort 1), * a 96-week secondary histology endpoint period (Cohort 2), * long-term treatment and clinical outcomes follow-up for up to approximately -240 weeks total treatment duration, and * a follow-up visit approximately 30 days after the last dose of study drug.

The study will evaluate the effects of EFX compared with placebo on histologic improvement in NASH/MASH, fibrosis regression, noninvasive markers of liver fibrosis, biochemistry markers of lipidic and glycemic metabolism, liver-related clinical outcomes, and long-term safety.

Clinical outcomes assessments include evaluation of liver-related events and all-cause mortality. Key secondary and long-term outcome assessments include evaluation of fibrosis progression, liver stiffness by FibroScan, and Enhanced Liver Fibrosis (ELF) score at prespecified time points including Weeks 96 and 240.

Subjects who discontinue study drug may continue study assessments according to the protocol schedule to support long-term efficacy and safety evaluations.

Interventions

Drug Efruxifermin
Administered by subcutaneous injection
Drug Placebo
Administered by subcutaneous injection

Primary outcome measures

Cohort 1 Only: Resolution of NASH/MASH and a ≥ 1 stage improvement in fibrosis [Time frame: 52 Weeks]
Event-free survival [Time frame: 240 Weeks]

Secondary outcome measures (12)

Cohort 1 Only: Resolution of NASH/MASH and no worsening of fibrosis [Time frame: 52 Weeks]
Cohort 1 Only: ≥ 1 stage improvement in fibrosis and no worsening of steatohepatitis [Time frame: 52 Weeks]
Change from baseline of non-invasive markers of liver fibrosis: ELF score [Time frame: 52 Weeks]
Change from baseline of non-invasive markers of liver fibrosis: ELF score components (TIMP-1, HA, PIIINP, Pro-C3) [Time frame: 52 Weeks]
Change from baseline in non-invasive markers of liver fibrosis: ELF score [Time frame: 96 Weeks, 240 Weeks]
Change from baseline in non-invasive markers of liver fibrosis: ELF score components: TIMP-1, HA, PIIINP, Pro-C3 [Time frame: Week 240]
Change from baseline of non-invasive markers of liver fibrosis: Fibroscan [Time frame: 52 Weeks]
Change from baseline of non-invasive markers of liver fibrosis: Fibroscan [Time frame: 96 Weeks, 240 Weeks]
Change from baseline of markers of liver injury: ALT, AST, GGT [Time frame: 52 Weeks, 240 Weeks]
Change from baseline of markers of liver injury: Uric Acid [Time frame: 52 Weeks, 240 Weeks]
Change from baseline of lipoproteins: Total cholesterol, TG, Non-HDL-C, HDL-C, and LDL-C [Time frame: 52 Weeks, 240 Weeks]
Change from baseline of markers of insulin sensitivity and glycemic control: HbA1c [Time frame: 52 Weeks, 240 Weeks]

Eligibility criteria

Inclusion criteria

Males and non-pregnant, non-lactating females between 18 - 80 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.
Cohort 1: Biopsy-proven NASH/MASH. Must have had a liver biopsy obtained ≤ 180 days prior to screening with fibrosis stage 2 or 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 2: Biopsy-proven fibrosis stage 3. Must have had a liver biopsy obtained ≤ 180 days prior to screening. Subjects with NAS <4 may be enrolled and are not required to meet 1 point in each of the components of NAS.

Exclusion criteria

Other causes of liver disease based on medical history and/or liver histology and/or central laboratory results.
Presence of cirrhosis on liver biopsy (fibrosis stage 4).
Type 1 or uncontrolled Type 2 diabetes.

Other inclusion and exclusion criteria may apply.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation: Randomized
Model: Parallel assignment
Masking: Quadruple blind
Primary purpose: Treatment