Phase 2
Completed 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
Source: ClinicalTrials.gov NCT04048135 ↗Enrolled (actual)
101
Serious AEs
2.0%
Results posted
Apr 2024
Primary outcomePrimary: Part 1: Number of Participants With Treatment-emergent Adverse Event (TEAEs) — 6; 4; 7; 7 Participants
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).
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 | — |
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. Informational only — not medical advice.