Pegozafermin for High Triglycerides

(ENTRUST Trial)

Recruiting in Palo Alto (17 mi)

+155 other locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

Sponsor: 89bio, Inc.

Must be taking: Lipid modifying therapy

Disqualifiers: Hepatitis B, Hepatitis C, HIV, others

Pivotal Trial (Near Approval)

Prior Safety Data

Trial Summary

What is the purpose of this trial?

This trial is testing a medication called Pegozafermin to see if it can lower high levels of fats in the blood in people with severe hypertriglyceridemia. These patients have very high triglyceride levels, which can lead to serious health issues. The medication aims to reduce these fat levels to improve their health.

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 Pegozafermin safe for humans?

Pegozafermin has been tested in humans and no serious side effects related to the drug were observed in a study for high triglycerides. It has also shown positive effects on metabolism in healthy volunteers and diabetic monkeys, suggesting it is generally safe. ^{1 2 3 4 5}

Research Team

Teresa Parli, MD

Principal Investigator

89bio, Inc.

Eligibility Criteria

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.

Trial Timeline

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

Treatment Details

Interventions

• Pegozafermin (Other)
• Placebo (Other)

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.

Participant Groups

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+

Findings from Research

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]

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 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 (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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

The FGF21 analog pegozafermin in severe hypertriglyceridemia: a randomized phase 2 trial. [2023]

2. United States 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. [2023]

3. United States pubmed.ncbi.nlm.nih.gov

Randomized, Controlled Trial of the FGF21 Analogue Pegozafermin in NASH. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

Pegozafermin Is a Potential Master Therapeutic Regulator in Metabolic Disorders: A Review. [2023]

5. United States pubmed.ncbi.nlm.nih.gov

Treatment of severe hypertriglyceridemia associated with accidental pegylated asparaginase push in a child with relapsed acute lymphoblastic leukemia. [2019]