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OpenTrials
Completed

NCT Number: NCT04048135

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

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).

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Key information

Conditions

NASH Digestive System Diseases Fatty Liver Liver Diseases Metabolic Diseases Non-alcoholic Fatty Liver Disease Nutritional and Metabolic Diseases

Age range

21 year–75 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1 / Phase 2

Primary location

89bio Clinical Study Site, San Juan, Puerto Rico

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Key Inclusion Criteria:

  • 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.

Key Exclusion Criteria:

  • 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

Treatment and study plan

Pegozafermin

Drug

Subcutaneous injection

Other names: BIO89-100

Placebo

Other

Subcutaneous injection

Primary outcomes

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

    Time frame: Up to 113 days

    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.

  2. Part 2: Number of Participants With TEAEs

    Time frame: Up to 162 days

    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.

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

    Time frame: Predose and up to 168 hours postdose on Day 29

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

    Time frame: Predose and up to 168 hours postdose on Day 29

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

    Time frame: Predose and up to 168 hours postdose on Day 29

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

    Time frame: Predose and up to 168 hours postdose on Day 29

  7. 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

    Time frame: Day 141

    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).

Secondary outcomes

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

    Time frame: Up to 113 days

    Number of participants with anti-pegozafermin antibodies (ADA) with status as ADA positive has been reported.

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

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

    Least Squares (LS) Mean was calculated using mixed-model repeated measures (MMRM).

  3. 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)

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

    LS Mean was calculated using MMRM.

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

    Time frame: Baseline, Day 92

    LS Mean was calculated using MMRM. HOMA-IR value was calculated by multiplying fasting Glucose (mg/dL) with fasting Insulin (uIU/ml) and then dividing by 405.

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

    Time frame: Baseline, Day 92

    LS Mean was calculated using MMRM.

  6. Part 1: Percent Change From Baseline in Free Fatty Acid at Day 92

    Time frame: Baseline, Day 92

    LS Mean was calculated using MMRM.

  7. Part 1: Percent Change From Baseline in Adipose Tissue Insulin Resistance (Adipo-IR) at Day 50

    Time frame: Baseline, Day 50

    LS Mean was calculated using MMRM. Adipo-IR was derived from fasting insulin and free fatty acid.

  8. Parts 1 and 2: Percent Change From Baseline in Liver Fat as Assessed Via Magnetic Resonance Imaging - Proton Density Fat Fraction (MRI-PDFF)

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

    LS Mean was calculated using MMRM.

  9. Part 2: Number of Participants With at Least an Improvement of Fibrosis ≥1 Stage Without Worsening of NASH

    Time frame: Day 141

    Fibrosis improvement was defined as ≥1-stage decrease in NASH CRN fibrosis score.

    Worsening of NASH was defined as increase ≥1 point in NAS for ballooning or inflammation.

    NASH CRN Fibrosis was staged on a 0-4 scale: 0 (none); 1 (perisinusoidal or periportal fibrosis); 2 (perisinusoidal and portal/periportal fibrosis); 3 (bridging fibrosis); 4 (cirrhosis).

  10. Part 2: Number of Participants With NASH Resolution Without Worsening of Fibrosis

    Time frame: Day 141

    Resolution of NASH included the total absence of ballooning (score=0) and absent or mild inflammation (score 0 to 1).

    Worsening of fibrosis was defined as progression of fibrosis ≥1 stage in NASH CRN fibrosis score.

    NASH CRN Fibrosis was staged on a 0-4 scale: 0 (none); 1 (perisinusoidal or periportal fibrosis); 2 (perisinusoidal and portal/periportal fibrosis); 3 (bridging fibrosis); 4 (cirrhosis).

Sponsors and collaborators

Lead sponsor

89bio, Inc.

Industry

Collaborators

  • ProSciento, Inc.

Registry information

Official study title

A Randomized, Double-Blind, Placebo-Controlled, Multiple Ascending Dose Study to Evaluate the Safety, Tolerability and Pharmacokinetic Properties of BIO89-100 Administered Subcutaneously in Subjects With Nonalcoholic Steatohepatitis (NASH) or With Nonalcoholic Fatty Liver Disease (NAFLD) and at High Risk of NASH

Important dates

Study start
2019
Primary completion
2020
Study completion
2022
First posted
Aug 7, 2019
Registry last updated
Apr 2, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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