Pegozafermin for Fatty Liver Disease

Recruiting at 262 trial locations

Overseen By ENLIGHTEN clinical trial

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: 89bio, Inc.

Disqualifiers: Chronic liver diseases, Cirrhosis, 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

1350 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness and safety of a new treatment called pegozafermin for individuals with MASH (formerly NASH), a liver condition involving inflammation and damage from fat buildup. Researchers are exploring two different dosing schedules of pegozafermin compared to a placebo, an inactive substance used for comparison. The trial seeks adults with a liver biopsy confirming stage 2 or 3 fibrosis (liver scarring) from MASH. Participants should also have a body mass index (BMI) of at least 25, often indicating overweight status. 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.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are taking vitamin E at more than 400 IU per day, you must have been on a stable dose for at least 6 months before the screening.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that pegozafermin is generally well tolerated. In one study, it significantly reduced liver fat and improved liver function without major side effects. Another study found that pegozafermin was well tolerated, suggesting potential benefits for individuals with liver issues like MASH (previously called NASH). Although side effects can occur with any treatment, evidence so far indicates that pegozafermin is safe for humans. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for fatty liver disease?

Unlike the standard treatments for fatty liver disease, which often focus on lifestyle changes and medications like vitamin E or pioglitazone, Pegozafermin offers a new approach. Pegozafermin is designed to target and reduce liver fat through its novel mechanism as an FGF21 analog, which can improve liver health by enhancing lipid metabolism and reducing inflammation. Researchers are excited about Pegozafermin because it has the potential to address the root causes of fatty liver disease more effectively than current options, providing a promising alternative for patients struggling with this condition.

What evidence suggests that pegozafermin might be an effective treatment for MASH?

Research shows that pegozafermin holds promise for treating fatty liver disease. Studies have found it significantly reduces liver fat and improves liver function. Participants in this trial will receive either Pegozafermin Regimen 1, Pegozafermin Regimen 2, or a placebo. In individuals with nonalcoholic steatohepatitis (NASH), pegozafermin treatment improved liver fibrosis, which is the scarring of the liver. It also enhanced metabolic health, crucial for overall well-being. Pegozafermin has generally been well-tolerated, making it a hopeful option for those with this liver condition. ^{1 6 7 8 9}

Who Is on the Research Team?

Millie Gottwald, PharmD

Principal Investigator

89bio, Inc.

Are You a Good Fit for This Trial?

Adults aged 18-75 with a BMI of ≥25 (≥23 for Asians) and <50, diagnosed with MASH (formerly NASH) having moderate to severe liver fibrosis are eligible. They must have had a recent biopsy confirming the disease stage and severity. Pregnant individuals or those outside the BMI range are excluded.

Inclusion Criteria

My liver biopsy shows I have moderate to severe fatty liver with inflammation and damage.

Body mass index (BMI) at screening ≥25.0 (≥23 for Asian participants) and <50.0 kg/m^2

Exclusion Criteria

I have type 1 diabetes or my type 2 diabetes is not well-controlled.

Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥250 U/L

I have been taking the same dose of vitamin E (>400 IU/day) for at least 6 months.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive pegozafermin or placebo for the treatment of liver fibrosis stage 2 or 3 in adult participants with MASH

52 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Pegozafermin

Trial Overview The trial is testing two different doses of Pegozafermin against a placebo to see if they're effective and safe in treating stages 2 or 3 liver fibrosis in adults with MASH. Participants will be randomly assigned to receive either the drug or placebo.

How Is the Trial Designed?

Group I: Pegozafermin Regimen 2 Experimental Treatment 1 Intervention

Group II: Pegozafermin Regimen 1 Experimental Treatment 1 Intervention

Group III: Placebo Placebo Group 1 Intervention

Matched Placebo will be administered in Regimens 1 and 2.

Who Is Running the Clinical Trial?

89bio, Inc.

Lead Sponsor

Trials

7

Recruited

2,600+

Published Research Related to This Trial

In a phase 1b/2a study involving 81 participants with non-alcoholic steatohepatitis (NASH), pegozafermin was found to be generally well tolerated and led to significant reductions in liver fat and improvements in liver function markers compared to placebo.

Pegozafermin also showed beneficial effects on lipid profiles, with notable reductions in triglycerides and LDL cholesterol, indicating its potential as a therapeutic option for managing NASH.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety, pharmacokinetics, and pharmacodynamics of pegozafermin in patients with non-alcoholic steatohepatitis: a randomised, double-blind, placebo-controlled, phase 1b/2a multiple-ascending-dose study. Loomba, R., Lawitz, EJ., Frias, JP., et al.[2023]

Pegozafermin, a modified version of FGF21, shows significantly higher potency in engaging its receptor and has demonstrated rapid improvements in metabolic biomarkers like triglycerides and cholesterol in diabetic monkeys with weekly or bi-weekly dosing.

In healthy volunteers, pegozafermin led to significant reductions in triglycerides and improvements in cholesterol levels, with a long half-life of 55 to 100 hours, indicating its potential as a long-acting treatment for nonalcoholic steatohepatitis and severe hypertriglyceridemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Novel GlycoPEGylated FGF21 Analog Pegozafermin Activates Human FGF Receptors and Improves Metabolic and Liver Outcomes in Diabetic Monkeys and Healthy Human Volunteers. Rosenstock, M., Tseng, L., Pierce, A., et al.[2023]

In a phase 2 trial involving 67 patients with severe hypertriglyceridemia, pegozafermin significantly reduced triglyceride levels by 57.3% compared to 11.9% in the placebo group, meeting the primary endpoint of the study.

Pegozafermin also led to significant decreases in apolipoprotein B and non-high-density lipoprotein cholesterol, as well as a reduction in liver fat, with no serious adverse events related to the drug, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The FGF21 analog pegozafermin in severe hypertriglyceridemia: a randomized phase 2 trial. Bhatt, DL., Bays, HE., Miller, M., et al.[2023]

In a phase 2a study involving 75 patients with non-alcoholic steatohepatitis, pegbelfermin significantly reduced hepatic fat fraction after 16 weeks of treatment, with a decrease of -6.8% for the daily dose and -5.2% for the weekly dose compared to placebo.

The treatment was generally well tolerated, with most adverse events being mild, indicating a favorable safety profile for pegbelfermin in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pegbelfermin (BMS-986036), a PEGylated fibroblast growth factor 21 analogue, in patients with non-alcoholic steatohepatitis: a randomised, double-blind, placebo-controlled, phase 2a trial. Sanyal, A., Charles, ED., Neuschwander-Tetri, BA., et al.[2019]

In a 12-week study involving 120 patients with obesity and type 2 diabetes, pegbelfermin did not significantly lower HbA1c levels, indicating it may not directly affect blood sugar control.

However, the 20 mg daily dose of pegbelfermin improved cholesterol and triglyceride levels, and increased adiponectin, suggesting potential benefits for metabolic health and liver fibrosis in patients predisposed to fatty liver disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pegbelfermin (BMS-986036), PEGylated FGF21, in Patients with Obesity and Type 2 Diabetes: Results from a Randomized Phase 2 Study. Charles, ED., Neuschwander-Tetri, BA., Pablo Frias, J., et al.[2020]

In a phase 2b trial involving 222 patients with biopsy-proven noncirrhotic NASH, pegozafermin significantly improved fibrosis, with 26% of patients in the 30 mg group showing improvement compared to only 7% in the placebo group.

Pegozafermin also demonstrated a notable effect on NASH resolution, with 37% of patients in the 15 mg group achieving resolution compared to just 2% in the placebo group, indicating its potential as an effective treatment for NASH.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized, Controlled Trial of the FGF21 Analogue Pegozafermin in NASH. Loomba, R., Sanyal, AJ., Kowdley, KV., et al.[2023]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/36521501/

a randomised, double-blind, placebo-controlled, phase 1b/ ... Pegozafermin was generally well tolerated and associated with clinically meaningful reductions in liver fat, measures of liver function, and circulating lipids.

2. ir.89bio.com ir.89bio.com/news-releases/news-release-details/89bio-announces-publication-results-phase-1b2a-study

89bio Announces Publication of Results of Phase 1b/2a ... Data from cohorts 1-6 in the proof-of-concept study showed pegozafermin was generally well tolerated and had beneficial therapeutic effect ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37718721/

Clinical trial: Effects of pegozafermin on the liver and on ... Pegozafermin treatment for 20 weeks had beneficial effects on hepatic and metabolic parameters and was well tolerated in subjects with NASH.

4. clinicaltrials.gov clinicaltrials.gov/study/NCT04929483

NCT04929483 | Study Evaluating the Safety, Efficacy and ... This is a randomized, double-blind, placebo-controlled study that will evaluate the safety, efficacy, tolerability of BIO89-100 in patients with ...

5. 2minutemedicine.com 2minutemedicine.com/pegozafermin-associated-with-improved-outcomes-in-nonalcoholic-steatohepatitis/

Pegozafermin associated with improved outcomes in ... 1. In this randomized controlled trial, treatment with pegozafermin improved fibrosis in patients with nonalcoholic steatohepatitis (NASH).

6. clinicaltrials.gov clinicaltrials.gov/ct2/show/NCT04048135?term=NASH+or+NAFLD&draw=2&rank=1

A Multiple Ascending Dose Study of Pegozafermin in ... A Multiple Ascending Dose Study of Pegozafermin in Participants With Biopsy Confirmed Nonalcoholic Steatohepatitis (NASH) or Nonalcoholic Fatty Liver Disease ( ...

7. ir.89bio.com ir.89bio.com/node/9271/pdf

November 27, 2023 Extension Phase Data at Week 48: Liver NITs Results [marker of]. F2-F3 Patients. Placebo. Pegozafermin. 30mg QW. 44mg Q2W. (n=35)1, 2. (n=50)2.

8. clinicaltrials.gov clinicaltrials.gov/study/NCT04929483

NCT04929483 | Study Evaluating the Safety, Efficacy and ... This is a randomized, double-blind, placebo-controlled study that will evaluate the safety, efficacy, tolerability of BIO89-100 in patients with ...

9. synapse.patsnap.com synapse.patsnap.com/drug/fce8e68c6a5847479ec8f935d896b61d

Pegozafermin - Drug Targets, Indications, Patents Its mechanism of action includes promoting adiponectin levels, enhancing insulin sensitivity, increasing triglyceride uptake, and reducing de novo lipogenesis.