Efruxifermin for NASH

Recruiting at 181 trial locations

Overseen By Akero Study Director

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Akero Therapeutics, Inc

Disqualifiers: Alcoholic liver disease, Autoimmune disorders, Type 1 diabetes, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 52 weeks

700 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a treatment called Efruxifermin, a new potential drug, to determine its safety and effectiveness for a liver condition known as NASH/MASH or NAFLD/MASLD, types of fatty liver diseases. Researchers compare Efruxifermin to a placebo, a substance with no active drug, to better understand its effects. Suitable participants include those with a history of two or more issues such as obesity, high cholesterol, high blood pressure, or high blood sugar, or those with a suspected or confirmed diagnosis of these liver conditions. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to a potentially groundbreaking treatment.

Do I need to stop my current medications for the Efruxifermin for NASH trial?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that Efruxifermin is likely to be safe for humans?

Research has shown that efruxifermin, a treatment being tested for liver conditions like NASH (a type of liver disease), has promising safety results. In one study, efruxifermin was safe and well-tolerated, with patients showing improvements in liver health markers, indicating improved signs of liver damage. Another study confirmed that efruxifermin had an acceptable safety profile, with most participants not experiencing serious side effects.

As this trial is in an advanced stage, strong evidence suggests that efruxifermin is generally well-tolerated in humans. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for NASH?

Most treatments for NASH (non-alcoholic steatohepatitis) focus on lifestyle changes or medications targeting insulin resistance and inflammation. But Efruxifermin is different because it mimics a hormone called FGF21, which plays a key role in regulating liver fat and inflammation. This novel mechanism may improve liver health more effectively by reducing fat buildup and scarring in the liver, which are central issues in NASH. Researchers are excited because Efruxifermin could offer a more direct and potentially more effective approach to tackling the root causes of NASH compared to existing treatments.

What evidence suggests that Efruxifermin might be an effective treatment for NASH?

Research has shown that efruxifermin (EFX) holds promise for treating NASH, a liver condition. In earlier studies, efruxifermin significantly reduced liver fat in patients with NASH, particularly those in the early to middle stages of liver damage. Reducing liver fat is crucial because it can slow the disease's progression. The treatment has been well-tolerated, with most people not experiencing serious side effects. With these early results, efruxifermin offers hope for those dealing with NASH. Participants in this trial may receive EFX at a dosage of 50 mg or a placebo, with some having the opportunity for an open-label rollover to continue receiving EFX. ^{3 4 6 7 8}

Are You a Good Fit for This Trial?

This trial is for adults aged 18-80 with a suspected or confirmed diagnosis of NASH/MASH or NAFLD/MASLD, and who have at least two components of metabolic syndrome or type 2 diabetes. It's not open to those with other liver diseases, type 1 diabetes, or unstable type 2 diabetes.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Efruxifermin or placebo for the assessment of safety and tolerability

52 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Efruxifermin

Trial Overview The study tests Efruxifermin (EFX) against a placebo in a controlled setting where neither the participants nor the researchers know who receives the actual drug. The goal is to see if EFX can help people with certain types of fatty liver disease.

How Is the Trial Designed?

Group I: EFX 50 mg (Open-Label Rollover) Experimental Treatment 1 Intervention

Group II: EFX 50 mg Experimental Treatment 1 Intervention

Group III: Placebo Placebo Group 1 Intervention

Who Is Running the Clinical Trial?

Akero Therapeutics, Inc

Lead Sponsor

Trials

6

Recruited

3,900+

Published Research Related to This Trial

Efgartigimod, an FcRn inhibitor, effectively reduced total IgG and autoreactive IgG levels in patients with pemphigus vulgaris and pemphigus foliaceus, showing early signs of improved disease activity and good tolerability during a phase 2 clinical trial.

Interestingly, while total IgG levels returned to baseline after treatment, autoreactive antibody levels remained low in some participants, suggesting a potential long-lasting immunomodulatory effect of efgartigimod beyond just blocking IgG recycling.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FcRn Antagonism Leads to a Decrease of Desmoglein-Specific B Cells: Secondary Analysis of a Phase 2 Study of Efgartigimod in Pemphigus Vulgaris and Pemphigus Foliaceus. Maho-Vaillant, M., Sips, M., Golinski, ML., et al.[2023]

Efruxifermin (EFX) is a promising treatment for liver fibrosis due to nonalcoholic steatohepatitis (NASH), showing a dose-proportional pharmacokinetic profile in a phase 2a study involving patients with moderate-to-advanced fibrosis or compensated cirrhosis.

A validated electrochemiluminescent immunoassay (ECLIA) was developed to accurately measure biologically active EFX in human serum, ensuring reliable pharmacokinetic assessments and demonstrating the importance of the intact C-terminus for EFX's pharmacological activity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Noncompetitive immunoassay optimized for pharmacokinetic assessments of biologically active efruxifermin. Kinne, AS., Tillman, EJ., Abdeen, SJ., et al.[2023]

Efruxifermin was found to be safe and well-tolerated in a study of 30 patients with compensated NASH cirrhosis, with most adverse events being mild to moderate gastrointestinal issues.

After 16 weeks of treatment, efruxifermin showed significant improvements in liver injury markers and fibrosis, with 33% of patients experiencing fibrosis improvement and 25% achieving resolution of NASH, compared to none in the placebo group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized, double-blind, placebo-controlled phase IIa trial of efruxifermin for patients with compensated NASH cirrhosis. Harrison, SA., Ruane, PJ., Freilich, B., et al.[2023]

The novel TNFR2 agonist NewSTAR2 shows improved serum retention and in vivo activity compared to the previously established STAR2, enhancing regulatory T cell (Treg) numbers by over 300% and maintaining elevated levels for up to 10 days after a single injection.

NewSTAR2 effectively protects against acute graft-versus-host disease (GvHD) when administered before allogeneic hematopoietic cell transplantation, demonstrating its potential as a powerful immunotherapy for autoinflammatory diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A TNFR2-Specific TNF Fusion Protein With Improved In Vivo Activity. Vargas, JG., Wagner, J., Shaikh, H., et al.[2022]

A scaled-up pharmacokinetic model accurately predicted the effects of anti-FcRn monoclonal antibodies, like rozanolixizumab, on the levels of endogenous IgG in healthy human subjects, showing a maximum prediction error of only -8.50%.

The model suggests that anti-FcRn therapies may be more effective at lower doses in healthy individuals compared to patients with autoimmune diseases, indicating its potential for optimizing dosing strategies in future treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development and Evaluation of a Physiologically Based Pharmacokinetic Model for Predicting the Effects of Anti-FcRn Therapy on the Disposition of Endogenous IgG in Humans. Li, T., Balthasar, JP.[2020]

Efruxifermin, a long-acting Fc-FGF21 fusion protein, significantly reduced hepatic fat fraction (HFF) in patients with non-alcoholic steatohepatitis (NASH) after 12 weeks of treatment, with reductions of -12.3%, -13.4%, and -14.1% for the 28 mg, 50 mg, and 70 mg doses, respectively, compared to a negligible change of 0.3% in the placebo group.

The treatment was generally well-tolerated, with 89% of patients experiencing at least one treatment-emergent adverse event, mostly mild to moderate gastrointestinal issues, indicating an acceptable safety profile for efruxifermin.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efruxifermin in non-alcoholic steatohepatitis: a randomized, double-blind, placebo-controlled, phase 2a trial. Harrison, SA., Ruane, PJ., Freilich, BL., et al.[2023]

In a phase 2b trial involving 128 patients with non-alcoholic steatohepatitis (NASH) and moderate to severe fibrosis, efruxifermin significantly improved liver fibrosis and resolved NASH in 39% of patients receiving 28 mg and 41% of those receiving 50 mg, compared to 20% in the placebo group.

Efruxifermin was generally well-tolerated, with most adverse events being mild to moderate, such as diarrhea and nausea, indicating its potential for further evaluation in larger phase 3 trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of once-weekly efruxifermin versus placebo in non-alcoholic steatohepatitis (HARMONY): a multicentre, randomised, double-blind, placebo-controlled, phase 2b trial. Harrison, SA., Frias, JP., Neff, G., et al.[2023]

Efruxifermin, an Fc-FGF21 fusion protein, was found to significantly reduce body weight gain in rats over both 4 and 26 weeks, even with increased food intake, indicating its potential efficacy in managing weight-related issues.

Unlike some other FGF21 analogues, efruxifermin decreased urine volume without affecting electrolyte balance, and it did not increase sympathetic activation, suggesting a favorable safety profile in terms of hormonal and blood pressure responses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efruxifermin, a long-acting Fc-fusion FGF21 analogue, reduces body weight gain but does not increase sympathetic tone or urine volume in Sprague Dawley rats. Tillman, EJ., Brock, WJ., Rolph, T.[2022]

A new panel of highly specific monoclonal antibodies (mAbs) against human FcRn has been developed, which can help researchers study the expression and function of this important receptor in the body.

These mAbs can selectively block the binding of IgG antibodies and serum albumin to FcRn, providing a valuable tool for exploring therapeutic strategies that target FcRn to enhance drug delivery and efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Monoclonal antibodies directed against human FcRn and their applications. Christianson, GJ., Sun, VZ., Akilesh, S., et al.[2022]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/34239138/

Efruxifermin in non-alcoholic steatohepatitis: a randomized, ... Treatment with efruxifermin significantly reduced HFF in patients with F1-F3 stage NASH, with an acceptable safety profile.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9832280/

A randomized, double-blind, placebo-controlled phase IIa trial ... Efruxifermin has shown clinical efficacy in patients with non-alcoholic steatohepatitis (NASH) and F1–F3 fibrosis. The primary objective of the BALANCED Cohort ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT06161571

NCT06161571 | A Study Evaluating Efruxifermin in ... The aim of this study is to assess the safety and tolerability of EFX compared to placebo in subjects with non-invasively diagnosed NASH/MASH and NAFLD/MASLD.

4. clinicaltrials.gov clinicaltrials.gov/study/NCT04767529

NCT04767529 | A Study of Efruxifermin in Non-Cirrhotic ... This is a multi-center evaluation of efruxifermin (EFX) in a randomized, double-blind, placebo-controlled study in non-cirrhotic subjects with biopsy-proven ...

5. jcto.weill.cornell.edu jcto.weill.cornell.edu/open_clinical_trials/a-phase-3-randomized-double-blind-placebo-controlled-study-evaluating-the-safety-and-efficacy-of-efruxifermin-in-subjects-with-compensated-cirrhosis-due-to-nonalcoholic-steatohepatitis-nashmetabolic-dysfunction-associated

A Phase 3, Randomized, Double-Blind, Placebo ... The purpose of this research study is to evaluate the effect of the investigational study drug Efruxifermin (EFX) in treating compensated liver cirrhosis ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/36644237/

A randomized, double-blind, placebo-controlled phase IIa ... Conclusions: Efruxifermin appeared safe and well-tolerated with encouraging improvements in markers of liver injury, fibrosis, and glucose and ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT06161571

NCT06161571 | A Study Evaluating Efruxifermin in ... The aim of this study is to assess the safety and tolerability of EFX compared to placebo in subjects with non-invasively diagnosed NASH/MASH and NAFLD/MASLD.

8. clinicaltrials.gov clinicaltrials.gov/study/NCT03976401

NCT03976401 | A Study of Efruxifermin in Subjects With ... This is a multi-center evaluation of efruxifermin (EFX) in a randomized, double-blind, placebo-controlled study administered for 16 weeks in subjects with ...