Pegozafermin for High Triglycerides

(ENTRUST Trial)

Recruiting at 155 trial locations

Overseen By ENTRUST clinical trial

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: 89bio, Inc.

Must be taking: Lipid modifying therapy

Disqualifiers: Hepatitis B, Hepatitis C, HIV, 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: 26 weeks

360 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a treatment called Pegozafermin to evaluate its effectiveness in lowering high triglyceride levels in individuals with Severe Hypertriglyceridemia, a condition characterized by very high levels of fat in the blood. Participants will receive either Pegozafermin or a placebo (a harmless pill with no active ingredients) once a week for 26 weeks to compare the effects. Suitable candidates have triglyceride levels between 500 and 2000 mg/dL, are on stable medication for heart conditions, and can maintain consistent diet and exercise habits. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants the opportunity to contribute to a potentially groundbreaking treatment.

Will I have to stop taking my current medications?

The trial requires that you keep your current medications stable, especially those for managing cholesterol and blood sugar, for at least 4 weeks before starting and throughout the study.

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

Previous studies have shown that pegozafermin is safe for people with high triglycerides. Research indicates that pegozafermin is generally well-tolerated, with most experiencing only mild side effects. For example, some patients in earlier studies reported mild stomach discomfort or skin reactions at the injection site. These side effects were usually temporary and not serious. Overall, the evidence suggests that pegozafermin is generally safe for people with high triglycerides, making it a promising option for those considering joining a clinical trial. ^{1 2 3 4 5}

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

Unlike the standard treatments for high triglycerides, which often include lifestyle changes and medications like fibrates, niacin, and omega-3 fatty acids, Pegozafermin offers a fresh approach. Researchers are excited because Pegozafermin works by mimicking a natural hormone in the body called FGF21, which plays a key role in regulating lipid metabolism. This unique mechanism might improve how the body processes fats more effectively. Moreover, it is administered just once a week, potentially making it more convenient for patients compared to daily medications.

What evidence suggests that Pegozafermin might be an effective treatment for high triglycerides?

Research has shown that pegozafermin, which participants in this trial may receive, may help lower high triglyceride levels. In earlier studies, pegozafermin consistently and significantly reduced triglycerides, fats in the blood linked to heart disease. It also improved liver fat and blood sugar levels. Pegozafermin is a long-acting form of a natural protein that helps control these body functions. Importantly, it was safe and successfully lowered triglycerides in people with severe cases. These findings suggest that pegozafermin could effectively manage high triglycerides. ^{1 2 4 5 6}

Who Is on the Research Team?

Teresa Parli, MD

Principal Investigator

89bio, Inc.

Are You a Good Fit for This Trial?

This trial is for adults over 22 with severe hypertriglyceridemia, who are willing to follow a specific diet and exercise plan. They must be on stable lipid-modifying therapy but not have recent pancreatitis, uncontrolled diabetes, or infections like HBV, HCV, or HIV.

Inclusion Criteria

I am 22 years old or older.

I am on a consistent treatment plan for managing my cholesterol levels.

Willing to enter a lifestyle optimization period during the screening period and willing to maintain those eating and exercise habits for the duration of the study

Exclusion Criteria

I have Type 1 diabetes.

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 once a week for 26 weeks to evaluate the effect on fasting serum triglyceride levels

26 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Pegozafermin
• Placebo

Trial Overview The study tests Pegozafermin's ability to lower fasting serum triglyceride levels in patients with high triglycerides after 26 weeks. Participants will either receive Pegozafermin or a placebo.

How Is the Trial Designed?

Group I: Pegozafermin - 30mg once a week Experimental Treatment 1 Intervention

Group II: Pegozafermin - 20mg once a week Experimental Treatment 1 Intervention

Group III: Placebo once a week Placebo Group 1 Intervention

Who Is Running the Clinical Trial?

89bio, Inc.

Lead Sponsor

Trials

7

Recruited

2,600+

Published Research Related to This Trial

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]

A 5-year-old boy developed acute severe hypertriglyceridemia after an accidental rapid administration of pegylated asparaginase during treatment for relapsed acute lymphoblastic leukemia, highlighting a potential risk associated with the drug's administration rate.

The case suggests that the speed of pegylated asparaginase infusion may influence triglyceride levels, as no hypertriglyceridemia was observed with proper administration rates before and after the incident.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of severe hypertriglyceridemia associated with accidental pegylated asparaginase push in a child with relapsed acute lymphoblastic leukemia. Malbora, B., Avci, Z., Ozbek, N.[2019]

Pegozafermin (PGZ) has a significantly extended half-life of 55 to 100 hours compared to the natural FGF21, allowing for improved metabolic effects such as increased insulin sensitivity and reduced triglyceride levels.

In the ENTRIGUE phase 2 clinical trial, PGZ demonstrated a 57% reduction in triglyceride levels and a 45% reduction in liver fat, indicating its potential effectiveness in treating metabolic disorders like nonalcoholic fatty liver disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pegozafermin Is a Potential Master Therapeutic Regulator in Metabolic Disorders: A Review. Bailey, NN., Peterson, SJ., Parikh, MA., et al.[2023]

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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04541186

Study to Explore the Efficacy and Safety of BIO89-100 ... Study to Explore the Efficacy and Safety of BIO89-100 (Pegozafermin) in Participants With Severe Hypertriglyceridemia. ClinicalTrials.gov ID NCT04541186.

2. ir.89bio.com ir.89bio.com/news-releases/news-release-details/89bio-presents-positive-results-entrigue-phase-2-trial

89bio Presents Positive Results from ENTRIGUE Phase 2 ... Treatment with pegozafermin demonstrated consistent and significant benefit in triglyceride (TG) reduction as well as improvements in liver fat and glycemic ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10353930/

The FGF21 analog pegozafermin in severe ... Pegozafermin, a long-acting analog of human fibroblast growth factor 21, was safe and met the primary endpoint of the trial for reducing serum triglyceride ...

4. trial.medpath.com trial.medpath.com/clinical-trial/9ca8a54dbfffaf98/efficacy-safety-bio89-100-hypertriglyceridemia

Study to Explore the Efficacy and Safety of BIO89 ... - MedPath This study is designed to assess the efficacy, safety, and tolerability of different doses and dose regimens (once weekly \[QW\] or every 2 weeks...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT05852431

Study Details | NCT05852431 | To Evaluate the Efficacy ... To determine the effect of Pegozafermin on fasting serum triglyceride levels in subjects with Severe Hypertriglyceridemia (TG ≥500 to ≤2000 mg/dL) after 26 ...

6. ir.89bio.com ir.89bio.com/news-releases/news-release-details/89bio-presents-new-analysis-data-phase-2-entrigue-trial

89bio Presents New Analysis of Data from Phase 2 ... Post hoc analysis data demonstrated pegozafermin treatment significantly reduced triglycerides and other atherogenic lipids in patients with ...