Phase 2
N=101
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
NASH
Bottom Line
View on ClinicalTrials.gov: NCT04048135 ↗Enrolled (actual)
101
Serious AEs
2.0%
Results posted
Apr 2024
Primary outcome: Primary: Part 1: Number of Participants With Treatment-emergent Adverse Event (TEAEs) — 6; 4; 7; 7 Participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Pegozafermin (Drug); Placebo (Other)
- Age
- Adult, Older Adult · 21+ yrs
- Sex
- All
- Sponsor
- 89bio, Inc.
- Primary completion
- Aug 2020
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Part 1: Number of Participants With Treatment-emergent Adverse Event (TEAEs) |
6; 4; 7; 7; 8; 8 | — |
| PRIMARY Part 2: Number of Participants With TEAEs |
18 | — |
| PRIMARY Part 1: Maximum Observed Serum Concentration (Cmax) of Pegozafermin |
103; 439; 901; 1166; 649; 1674 | — |
| PRIMARY Part 1: Area Under the Serum Concentration Versus Time Curve From Time Zero to the Last Measurable Concentration (AUClast) of Pegozafermin |
11879; 42576; 95765; 112632; 78761; 209436 | — |
| PRIMARY Part 1: Time to Peak Serum Concentration (Tmax) of Pegozafermin |
59.5; 48.0; 48.0; 48.1; 72.0; 48.0 | — |
| PRIMARY Part 1: Terminal Elimination Half-life (t1/2) of Pegozafermin |
57.1; 46.3; 68.1; 53.0; 54.4; 53.2 | — |
| PRIMARY 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 |
12 | — |
| SECONDARY Part 1: Number of Participants With a Positive Anti-Drug Antibodies (ADA) Response to Pegozafermin |
1; 9; 7; 7; 11; 6 | — |
| SECONDARY Parts 1 and 2: Percent Change From Baseline in Body Weight |
1.19; 2.59; 2.47; -0.80; 2.11; 2.64 | — |
| SECONDARY 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) |
-22.74; -23.95; -17.71; -27.63; -28.49; -20.71 | — |
| SECONDARY Part 1: Percent Change From Baseline in Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) at Day 92 |
10.37; 7.40; 37.07; -41.42; -4.57; -41.11 | — |
| SECONDARY Part 1: Percent Change From Baseline in Adiponectin at Day 92 |
37.65; 25.46; 29.09; 60.85; 23.11; 24.14 | — |
| SECONDARY Part 1: Percent Change From Baseline in Free Fatty Acid at Day 92 |
28.70; 50.20; 27.08; 51.58; 43.85; 56.12 | — |
| SECONDARY Part 1: Percent Change From Baseline in Adipose Tissue Insulin Resistance (Adipo-IR) at Day 50 |
-6.12; 82.00; 3.28; 78.40; -25.96; -10.36 | — |
| SECONDARY Parts 1 and 2: Percent Change From Baseline in Liver Fat as Assessed Via Magnetic Resonance Imaging - Proton Density Fat Fraction (MRI-PDFF) |
-36.94; -49.62; -36.11; -60.39; -43.19; -50.39 | — |
| SECONDARY Part 2: Number of Participants With at Least an Improvement of Fibrosis ≥1 Stage Without Worsening of NASH |
5 | — |
| SECONDARY Part 2: Number of Participants With NASH Resolution Without Worsening of Fibrosis |
6 | — |
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).
Eligibility Criteria
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
Data sourced from ClinicalTrials.gov (NCT04048135). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.