A Multiple Ascending Dose Study of Pegozafermin in Participants With Biopsy Confirmed Nonalcoholic Steatohepatitis (NASH) or Nonalcoholic Fatty Liver Disease (NAFLD) and at High Risk of NASH

NCT04048135 | Completed Phase 1 Results DMC FDA Drug

• 1 other identifier: BIO89-100-002
• Study Type: interventional
• Target: 101
• Locations: 2 countries
• Sites: 26

Brief Summary

Part 1: This is a multi-center evaluation of pegozafermin (administered weekly or every other week) in a randomized, double-blind, placebo-controlled study administered for 12 weeks in participants with NASH and NAFLD at high risk of NASH, including a pre-defined number of participants with biopsy confirmed NASH and fibrosis stages F1-F3 to be enrolled. Part 2: This is a multi-center, open label evaluation of pegozafermin at 27 mg administered weekly for 20 weeks in participants with biopsy-proven NASH (NAS ≥4, fibrosis stage F2 or F3).

Conditions

NASH

Keywords

NASH, NAFLD; Liver diseases; Fatty Liver; Metabolic diseases

Outcome Measures

Primary Outcomes (7)

• Part 1: Number of Participants With Treatment-emergent Adverse Event (TEAEs)

  An adverse event (AE) was any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. TEAEs were defined as AEs occurring at or after the first dose date and time, through study termination, or existing prior to the time of and worsening after the time of the first dose of investigational product. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.

  Up to 113 days

• Part 2: Number of Participants With TEAEs

  An AE was any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. TEAEs were defined as AEs occurring at or after the first dose date and time, through study termination, or existing prior to the time of and worsening after the time of the first dose of investigational product. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.

  Up to 162 days

• Part 1: Maximum Observed Serum Concentration (Cmax) of Pegozafermin

  Predose and up to 168 hours postdose on Day 29

• Part 1: Area Under the Serum Concentration Versus Time Curve From Time Zero to the Last Measurable Concentration (AUClast) of Pegozafermin

  Predose and up to 168 hours postdose on Day 29

• Part 1: Time to Peak Serum Concentration (Tmax) of Pegozafermin

  Predose and up to 168 hours postdose on Day 29

• Part 1: Terminal Elimination Half-life (t1/2) of Pegozafermin

  Predose and up to 168 hours postdose on Day 29

• Part 2: Number of Participants With at Least a 2-point Improvement in NAFLD Activity Score (NAS) With at Least a 1-point Improvement in Ballooning or Lobular Inflammation, and no Worsening of Fibrosis

  NAS was the sum of the scores of steatosis, inflammation, and ballooning. NAS score ranges from of 0 to 8, with higher scores indicating worse disease severity. Worsening of fibrosis was defined as progression of fibrosis ≥1 stage in NASH Clinical Research Network (CRN) fibrosis score. NASH CRN Fibrosis is staged on a 0-4 scale: 0 (none); 1 (perisinusoidal or periportal fibrosis); 2 (perisinusoidal and portal/periportal fibrosis); 3 (bridging fibrosis); 4 (cirrhosis).

  Day 141

Secondary Outcomes (10)

• Part 1: Number of Participants With a Positive Anti-Drug Antibodies (ADA) Response to Pegozafermin

  Up to 113 days

• Parts 1 and 2: Percent Change From Baseline in Body Weight

  Part 1: Baseline, Day 85; Part 2: Baseline, Day 141

• Parts 1 and 2: Percent Change From Baseline in Triglycerides, High Density Lipoprotein (HDL) Cholesterol (c), Non-HDLc, LDLc, Hemoglobin (HbA1C), Alanine Transaminase, Aspartate Aminotransferase, N-terminal Propeptide of Type III Collagen (Pro-C3)

  Part 1: Baseline, Day 92; Part 2: Baseline, Day 141

• Part 1: Percent Change From Baseline in Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) at Day 92

  Baseline, Day 92

• Part 1: Percent Change From Baseline in Adiponectin at Day 92

  Baseline, Day 92

Study Arms (8)

Part 1: Pegozafermin 3 milligrams (mg) weekly (QW)

EXPERIMENTAL

Participants were administered 3 mg of pegozafermin QW, via subcutaneous (SC) injection, starting on Day 1 through Day 85.

Drug: Pegozafermin

Part 1: Pegozafermin 9 mg QW

EXPERIMENTAL

Participants were administered 9 mg of pegozafermin QW, via SC injection, starting on Day 1 through Day 85.

Drug: Pegozafermin

Part 1: Pegozafermin 18 mg QW

EXPERIMENTAL

Participants were administered 18 mg of pegozafermin QW, via SC injection, starting on Day 1 through Day 85.

Drug: Pegozafermin

Part 1: Pegozafermin 27 mg QW

EXPERIMENTAL

Participants were administered 27 mg of pegozafermin QW, via SC injection, starting on Day 1 through Day 85.

Drug: Pegozafermin

Part 1: Pegozafermin 18 mg Every 2 Weeks (Q2W)

EXPERIMENTAL

Participants were administered 18 mg of pegozafermin Q2W, via SC injection, starting on Day 1 through Day 85.

Drug: Pegozafermin

Part 1: Pegozafermin 36 mg Q2W

EXPERIMENTAL

Participants were administered 36 mg of pegozafermin Q2W, via SC injection, starting on Day 1 through Day 85.

Drug: Pegozafermin

Part 1: Placebo QW or Q2W

PLACEBO COMPARATOR

Participants were administered placebo matching to pegozafermin QW or Q2W, via SC injection, starting on Day 1 through Day 85.

Other: Placebo

Part 2: Pegozafermin 27 mg QW

EXPERIMENTAL

Participants were administered 27 mg of pegozafermin QW, via SC injection, starting on Day 1 through Day 134.

Drug: Pegozafermin

Interventions

Pegozafermin DRUG

Subcutaneous injection

Also known as: BIO89-100

Part 1: Pegozafermin 18 mg Every 2 Weeks (Q2W); Part 1: Pegozafermin 18 mg QW; Part 1: Pegozafermin 27 mg QW; Part 1: Pegozafermin 3 milligrams (mg) weekly (QW); Part 1: Pegozafermin 36 mg Q2W; Part 1: Pegozafermin 9 mg QW; Part 2: Pegozafermin 27 mg QW

Placebo OTHER

Subcutaneous injection

Part 1: Placebo QW or Q2W

Eligibility Criteria

• Age: 21 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants must be 21 to 75 years of age inclusive, at the time of signing the informed consent form (ICF).
• Evidence of steatosis by Fibroscan and magnetic resonance imaging based proton density fat fraction (MRI-PDFF)
• NASH or NAFLD at high risk for NASH as reflected by AT LEAST ONE of the following:
• Diagnosis of NASH with fibrosis (stages F1, F2 or F3), without cirrhosis, by percutaneous liver biopsy within 24 months prior to screening
• Central obesity WITH type 2 diabetes mellitus (T2DM)
• Central obesity WITH either increased alanine transaminase (ALT) and/or Fibroscan vibration-controlled transient elastography (VCTE) score ≥7 KPa.
• Part 2 only: Biopsy-proven NASH in a liver biopsy obtained within 24 weeks of baseline with fibrosis stage F2 or F3 and NAS ≥4, with a score of at least 1 in each of steatosis, ballooning degeneration, and lobular inflammation. A small number of high risk F1 allowed.

You may not qualify if:

• Clinically significant disorder or a history of any illness that, in the opinion of the Investigator, might confound the results of the study, or pose additional risk to the participant by participation in the study.
• History of type 1 diabetes.
• Weight loss of more than 5% within 3 months prior to Day -1 or more than 10% within 6 months prior to Day -1 or planning to try to lose weight during conduct of study.
• History of a liver disorder other than NASH or clinical suspicion of a liver disorder other than NASH
• History of cirrhosis or evidence of cirrhosis

Sponsors & Collaborators

• 89bio, Inc.: lead
• ProSciento, Inc.: collaborator

Study Sites (26)

89bio Clinical Study Site

Madison, Alabama, 35758, United States

Location

89bio Clinical Study Site

Chandler, Arizona, 85224, United States

Location

89bio Clinical Study Site

Tucson, Arizona, 85712, United States

Location

89bio Clinical Study Site

Chula Vista, California, 91911, United States

Location

89bio Clinical Study Site

Huntington Beach, California, 92647, United States

Location

89bio Clinical Study Site

Montclair, California, 91763, United States

Location

89bio Clinical Study Site

Miami, Florida, 33014-3616, United States

Location

89bio Clinical Study Site

Miami Lakes, Florida, 33014, United States

Location

89bio Clinical Study Site

Ocala, Florida, 34471, United States

Location

89bio Clinical Study Site

Sarasota, Florida, 34240, United States

Location

89bio Clinical Study Site

Lake Charles, Louisiana, 70601, United States

Location

89bio Clinical Study Site

Berlin, New Jersey, 08009, United States

Location

89bio Clinical Study Site

Florham Park, New Jersey, 07932, United States

Location

89bio Clinical Study Site

East Syracuse, New York, 13057, United States

Location

89bio Clinical Study Site

Concord, North Carolina, 28027, United States

Location

89bio Clinical Study Site

Raleigh, North Carolina, 27612, United States

Location

89bio Clinical Study Site

Greenwood, South Carolina, 29646, United States

Location

89bio Clinical Study Site

Summerville, South Carolina, 29485, United States

Location

89bio Clinical Study Site

Hermitage, Tennessee, 37076, United States

Location

89bio Clinical Study Site

Austin, Texas, 78757, United States

Location

89bio Clinical Study Site

Edinburg, Texas, 78539, United States

Location

89bio Clinical Study Site

Houston, Texas, 77058, United States

Location

89bio Clinical Study Site

San Antonio, Texas, 78215, United States

Location

89bio Clinical Study Site

San Antonio, Texas, 78229, United States

Location

89bio Clinical Study Site

Wichita Falls, Texas, 76301, United States

Location

89bio Clinical Study Site

San Juan, 00927, Puerto Rico

Location

Related Publications (3)

• Alkhouri N, Lazas D, Loomba R, Frias JP, Feng S, Tseng L, Balic K, Agollah GD, Kwan T, Iyer JS, Morrow L, Mansbach H, Margalit M, Harrison SA. Clinical trial: Effects of pegozafermin on the liver and on metabolic comorbidities in subjects with biopsy-confirmed nonalcoholic steatohepatitis. Aliment Pharmacol Ther. 2023 Nov;58(10):1005-1015. doi: 10.1111/apt.17709. Epub 2023 Sep 18.

  PMID: 37718721 DERIVED

• Tseng CL, Balic K, Charlton RW, Margalit M, Mansbach H, Savic RM. Population Pharmacokinetics and Pharmacodynamics of Pegozafermin in Patients with Nonalcoholic Steatohepatitis. Clin Pharmacol Ther. 2023 Dec;114(6):1323-1331. doi: 10.1002/cpt.3046. Epub 2023 Oct 2.

  PMID: 37696614 DERIVED

• Loomba R, Lawitz EJ, Frias JP, Ortiz-Lasanta G, Johansson L, Franey BB, Morrow L, Rosenstock M, Hartsfield CL, Chen CY, Tseng L, Charlton RW, Mansbach H, Margalit M. 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. Lancet Gastroenterol Hepatol. 2023 Feb;8(2):120-132. doi: 10.1016/S2468-1253(22)00347-8. Epub 2022 Dec 12.

  PMID: 36521501 DERIVED

Related Links

• Related Info

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease; Liver Diseases; Fatty Liver; Metabolic Diseases

Condition Hierarchy (Ancestors)

Digestive System Diseases; Nutritional and Metabolic Diseases

Results Point of Contact

• Title: Clinical Director
• Organization: 89bio, Inc.

bio89-100-002@89bio.com

1-858-261-8838

Study Officials

• Charlton, MD

  89bio, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Part 1 was blinded, Part 2 was open label
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 4, 2019
• First Posted: August 7, 2019
• Study Start: July 29, 2019
• Primary Completion: August 28, 2020
• Study Completion: January 19, 2022
• Last Updated: April 2, 2024
• Results First Posted: April 2, 2024

Record last verified: 2024-02

Locations

PR (1); US (25)