Phase 2
Completed N=320
Investigation of Efficacy and Safety of Three Dose Levels of Subcutaneous Semaglutide Once Daily Versus Placebo in Subjects With Non-alcoholic Steatohepatitis.
Hepatobiliary Disorders · Metabolic Dysfunction-Associated Steatohepatitis
Source: ClinicalTrials.gov NCT02970942 ↗
Enrolled (actual)
320
Serious AEs
14.7%
Results posted
Apr 2021
Primary outcomePrimary: Percentage of Participants With Non- Alcoholic Steatohepatitis (NASH) Resolution Without Worsening of Fibrosis After 72 Weeks (Yes/No) — 40.4; 35.6; 58.9; 17.2 Percentage of participants
Summary
Investigation of efficacy and safety of three dose levels of subcutaneous semaglutide once daily versus placebo in subjects with non-alcoholic steatohepatitis
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Percentage of Participants With Non- Alcoholic Steatohepatitis (NASH) Resolution Without Worsening of Fibrosis After 72 Weeks (Yes/No) |
40.4; 35.6; 58.9; 17.2; 54.4; 47.5 | — |
| SECONDARY Percentage of Participants With at Least One Stage of Liver Fibrosis Improvement With no Worsening of NASH After 72 Weeks (Yes/No) |
49.1; 32.2; 42.9; 32.8; 45.6; 50.8 | — |
| SECONDARY Percentage of Participants With Change in Total NAFLD (Non- Alcoholic Fatty Liver Disease) Activity Score (NAS) |
71.3; 79.5; 82.9; 43.8; 7.5; 2.6 | — |
| SECONDARY Percentage of Participants With Change in Steatosis |
52.5; 60.3; 63.4; 26.3; 6.3; 2.6 | — |
| SECONDARY Percentage of Participants With Change in Lobular Inflammation |
41.3; 47.4; 37.8; 26.3; 7.5; 7.7 | — |
| SECONDARY Percentage of Participants With Change in Hepatocyte Ballooning |
61.3; 70.5; 74.4; 38.8; 2.5; 2.6 | — |
| SECONDARY Percentage of Participants With Change in Fibrosis Stage According to the Kleiner Fibrosis Classification |
46.3; 32.1; 42.7; 31.3; 10.0; 7.7 | — |
| SECONDARY Percentage of Participants With Change in Activity Component of Steatosis-activity-fibrosis (SAF) Score |
62.5; 71.8; 72.0; 42.5; 7.5; 3.8 | — |
| SECONDARY Change in Fibrosis-4 Score |
0.81; 0.77; 0.77; 0.95 | — |
| SECONDARY Change in NAFLD Fibrosis Score (NFS) |
-0.322; -0.617; -0.475; -0.040 | — |
| SECONDARY Change in Alanine Aminotransferase (ALT) |
0.62; 0.57; 0.40; 0.80 | — |
| SECONDARY Change in Aspartate Aminotransferase (AST) |
0.66; 0.63; 0.50; 0.84 | — |
| SECONDARY Change in Gamma Glutamyl Transferase (GGT) |
0.76; 0.64; 0.48; 0.92 | — |
| SECONDARY Change in Albumin |
1.02; 1.01; 1.01; 1.02 | — |
| SECONDARY Change in International Normalized Ratio (INR) |
0.97; 0.96; 0.93; 0.99 | — |
| SECONDARY Change in Enhanced Liver Fibrosis (ELF) |
-0.4; -0.4; -0.6; 0.1 | — |
| SECONDARY Change in Cytokeratin 18 (CK-18) Fragments |
0.52; 0.50; 0.40; 0.78; 0.51; 0.52 | — |
| SECONDARY Change in microRNA 122 (miR-122) |
0.86; 0.74; 0.58; 1.28 | — |
| SECONDARY Change in Interleukin-1 Receptor (IL-1R) Antagonist |
0.87; 0.85; 0.73; 0.94 | — |
| SECONDARY Change in Monocyte Chemoattractant Protein 1 (MCP-1) |
1.07; 1.08; 0.99; 1.04 | — |
| SECONDARY Change in Fibroblast Growth Factor 21 (FGF-21) |
0.72; 0.61; 0.55; 0.76 | — |
| SECONDARY Change in Liver Stiffness Assessed by FibroScan® |
0.72; 0.64; 0.66; 1.18 | — |
| SECONDARY Change in Liver Steatosis Assessed by FibroScan® |
-5.8; -50.9; -42.1; -18.7 | — |
| SECONDARY Percentage of Participants With Weight Loss of ≥ 5% of Baseline Body Weight at 72 Weeks (Yes/No) |
43.8; 62.8; 76.8; 16.3; 51.3; 28.2 | — |
| SECONDARY Percentage of Participants With Weight Loss of ≥ 10% of Baseline Body Weight at 72 Weeks (Yes/No) |
17.5; 38.5; 59.8; 2.5; 77.5; 52.6 | — |
| SECONDARY Change in Body Weight |
-4.8; -9.4; -12.3; -1.0 | — |
| SECONDARY Change in Waist Circumference |
-3.9; -7.1; -11.4; -1.7 | — |
| SECONDARY Change in Body Mass Index (BMI) |
-1.8; -3.5; -4.6; -0.3 | — |
| SECONDARY Change in Glycosylated Haemoglobin (HbA1c) (%-Point) |
-0.7; -1.2; -1.2; -0.0 | — |
| SECONDARY Change in HbA1c (Millimoles Per Mole) |
-7.9; -12.8; -12.8; -0.3 | — |
| SECONDARY Change in Fasting Plasma Glucose (FPG) |
-1.39; -2.17; -2.09; -0.34 | — |
| SECONDARY Change in Fasting Glucagon |
0.78; 0.65; 0.63; 1.04 | — |
| SECONDARY Change in Homeostatic Model Assessment - Insulin Resistance (HOMA-IR) |
0.77; 0.60; 0.58; 0.81 | — |
| SECONDARY Change in Diastolic Blood Pressure (DBP) |
0; -2; -2; -1 | — |
| SECONDARY Change in Systolic Blood Pressure (SBP) |
-2; -7; -6; -2 | — |
| SECONDARY Change in Total Cholesterol |
0.98; 1.00; 0.93; 0.93 | — |
| SECONDARY Change in Low Density Lipoprotein (LDL) Cholesterol |
0.96; 1.01; 0.92; 0.90 | — |
| SECONDARY Change in High Density Lipoprotein (HDL) Cholesterol |
1.04; 1.05; 1.09; 1.01 | — |
| SECONDARY Change in Very Low Density Lipoprotein (VLDL) Cholesterol |
0.89; 0.90; 0.74; 0.93 | — |
| SECONDARY Change in Triglycerides |
0.88; 0.89; 0.73; 0.95 | — |
| SECONDARY Change in Free Fatty Acids |
0.83; 0.92; 0.72; 1.05 | — |
| SECONDARY Change in High Sensitivity C-reactive Protein (hsCRP) |
0.78; 0.50; 0.41; 0.91 | — |
| SECONDARY Change in Short Form 36 (SF-36) Score |
2.2; 0.6; 1.2; -0.4; 2.1; 1.1 | — |
| SECONDARY Number of Treatment-emergent Adverse Events (TEAEs) |
525; 577; 511; 445 | — |
| SECONDARY Number of Treatment-emergent Hypoglycaemic Episodes |
54; 30; 66; 18 | — |
| SECONDARY Number of Treatment-emergent Severe or Blood Glucose (BG)-Confirmed Symptomatic Hypoglycaemic Episodes |
3; 5; 17; 2 | — |
| SECONDARY Number of Treatment-emergent Severe Hypoglycaemic Episodes |
2; 2; 0; 0 | — |
| SECONDARY Number of Participants Discontinuing Treatment Due to Gastrointestinal Adverse Events |
1; 6; 2; 0 | — |
| SECONDARY Number of Participants With Occurrence of Anti-semaglutide Antibodies During and After 72 Weeks Treatment (Yes/No) |
4; 1; 2; 76; 77; 79 | — |
| SECONDARY Number of Participants With Anti-semaglutide Antibodies With in Vitro Neutralising Effect During and After 72 Weeks Treatment (Yes/No) |
0; 0; 0; 80; 78; 81 | — |
| SECONDARY Number of Participants With Anti-semaglutide Binding Antibodies Cross Reacting With Native GLP-1 During and After 72 Weeks Treatment (Yes/No) |
4; 0; 2; 76; 78; 79 | — |
| SECONDARY Number of Participants With Cross-reacting Anti-semaglutide Binding Antibodies With in Vitro Neutralising Effect to Native GLP-1 During and After 72 Weeks Treatment (Yes/No) |
0; 0; 0; 80; 78; 81 | — |
| SECONDARY Change in Pulse From Baseline to Week 72 |
2.2; 2.1; 0.9; -0.3 | — |
| SECONDARY Percentage of Participants With Change in Electrocardiogram (ECG) |
58.8; 60.3; 66.7; 63.8; 41.3; 39.7 | — |
| SECONDARY Percentage of Participants With Change in Physical Examination: Cardiovascular System |
87.5; 93.6; 92.6; 92.5; 11.3; 5.1 | — |
| SECONDARY Percentage of Participants With Change in Physical Examination: Central and Peripheral Nervous System |
92.5; 94.8; 98.7; 95.0; 5.0; 5.2 | — |
| SECONDARY Percentage of Participants With Change in Physical Examination: Gastrointestinal System Including Mouth |
82.5; 83.1; 84.0; 86.3; 13.8; 15.6 | — |
| SECONDARY Percentage of Participants With Change in Physical Examination: General Appearance |
83.8; 85.9; 79.0; 80.0; 16.3; 12.8 | — |
| SECONDARY Percentage of Participants With Change in Physical Examination: Head, Ears, Eyes, Nose, Throat, Neck |
97.5; 94.8; 98.8; 97.5; 2.5; 5.2 | — |
| SECONDARY Percentage of Participants With Change in Physical Examination: Lymph Node Palpation |
100.0; 98.7; 100.0; 100.0; 0.0; 1.3 | — |
| SECONDARY Percentage of Participants With Change in Physical Examination: Musculoskeletal System |
95.0; 96.1; 94.9; 95.0; 3.8; 3.9 | — |
| SECONDARY Percentage of Participants With Change in Physical Examination: Respiratory System |
100.0; 100.0; 100.0; 97.5; 0.0; 0.0 | — |
| SECONDARY Percentage of Participants With Change in Physical Examination: Skin |
96.3; 92.3; 85.2; 90.0; 2.5; 6.4 | — |
| SECONDARY Percentage of Participants With Change in Physical Examination: Thyroid Gland |
88.8; 97.4; 97.5; 98.8; 10.0; 2.6 | — |
| SECONDARY Change in Haematocrit |
-0.79; -0.71; -1.43; -0.41 | — |
| SECONDARY Change in Haemoglobin (g/dL) |
0.18; 0.08; -0.07; 0.21 | — |
| SECONDARY Change in Haemoglobin (mmol/L) |
0.11; 0.05; -0.05; 0.13 | — |
| SECONDARY Change in Leukocytes |
0.489; 0.260; -0.047; 0.075 | — |
| SECONDARY Change in Thrombocytes |
8.8; 14.6; 9.0; 0.3 | — |
| SECONDARY Change in Erythrocytes |
0.038; 0.004; -0.034; 0.054 | — |
| SECONDARY Change in Creatinine (mg/dL) |
1.018; 1.069; 1.026; 1.021 | — |
| SECONDARY Change in Creatinine (Umol/L) |
1.018; 1.069; 1.026; 1.021 | — |
| SECONDARY Change in Estimated Glomerular Filtration Rate (eGFR) |
0.976; 0.940; 0.973; 0.969 | — |
| SECONDARY Change in Creatine Kinase |
0.975; 0.798; 0.825; 0.904 | — |
| SECONDARY Change in Urea |
1.018; 0.973; 1.042; 1.043 | — |
| SECONDARY Change in Total Bilirubin (mg/dL) |
0.978; 1.011; 0.949; 1.040 | — |
| SECONDARY Change in Total Bilirubin (Umol/L) |
0.978; 1.011; 0.949; 1.040 | — |
| SECONDARY Change in Alkaline Phosphatase |
0.980; 0.931; 0.884; 0.992 | — |
| SECONDARY Change in Ferritin |
0.660; 0.617; 0.603; 0.713 | — |
| SECONDARY Change in Sodium (mEq/L) |
0.999; 1.000; 1.002; 1.002 | — |
| SECONDARY Change in Sodium (mmol/L) |
0.999; 1.000; 1.002; 1.002 | — |
| SECONDARY Change in Potassium (mEq/L) |
1.004; 0.979; 0.998; 0.998 | — |
| SECONDARY Change in Potassium (mmol/L) |
1.004; 0.979; 0.998; 0.998 | — |
| SECONDARY Change in Calcium (mg/dL) |
1.017; 1.018; 1.008; 1.010 | — |
| SECONDARY Change in Calcium (mmol/L) |
1.017; 1.018; 1.008; 1.010 | — |
| SECONDARY Change in Amylase |
1.155; 1.120; 1.170; 1.051 | — |
| SECONDARY Change in Lipase |
1.305; 1.245; 1.375; 1.003 | — |
| SECONDARY Change in Calcitonin |
1.040; 0.937; 1.000; 0.950 | — |
Eligibility Criteria
Inclusion Criteria: - Informed consent obtained before any trial-related activities. Trial-related activities are any procedures that are carried out as part of the trial, including activities to determine suitability for the trial except for protocol described pre-screening activities which require a separate informed consent. - Male or female, aged 18-75 years (both inclusive) (for Japan: male or female aged 20-75 years (both inclusive)) at the time of signing informed consent - Local histological diagnosis of NASH followed by histological confirmation of NASH based on central pathologist evaluation of a liver biopsy obtained up to 21 weeks before screening - Histologic evidence of NASH based on central pathologist evaluation of a liver biopsy obtained up to 21 weeks before screening. - NASH fibrosis stage 1, 2 or 3 according to the NASH CRN fibrosis staging system based on central pathologist evaluation Exclusion Criteria: - Known or suspected abuse of alcohol (above 20 g/day for women or above 30 g/day for men), alcohol dependence* or narcotics. (* = assessed by the Alcohol Use Disorders Identification Test (AUDIT questionnaire)) - Diagnosis of type 1 diabetes according to medical records - HbA1c above 10% at screening - History or presence of pancreatitis (acute or chronic) - Calcitonin equal or above 50 ng/L at screening - Family or personal history of multiple endocrine neoplasia type 2 or medullary thyroid carcinoma. Family is defined as a first degree relative - Body Mass Index (BMI) ≤ 25.0 kg/sqm at the screening visit (visit 1) - Female who is pregnant, breast-feeding or intends to become pregnant or is of childbearing potential and not using an adequate contraceptive method (adequate contraceptive measures as required by local regulation or practice)
Data sourced from ClinicalTrials.gov (NCT02970942). 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.