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A Study to Test Safety and Efficacy of Survodutide (BI456906) in Adults With Non-alcoholic Steatohepatitis (NASH) and Fibrosis (F1-F3)
Multicenter, Double-blind, Parallel-group, Randomized, 48 Weeks, Dose-ranging, Placebo-controlled Phase II Trial to Evaluate Efficacy, Safety and Tolerability of Multiple Subcutaneous (s.c.) Doses of BI 456906 in Patients With Non-alcoholic Steatohepatitis (NASH) and Fibrosis.
Lead sponsor
Asset
Survodutide
Subcutaneous · GLP-1 / glucagon dual
Listed sites
154
Recruiting sites
—
Enrollment
295
actual
Study population
MASH / NAFLD / liver fibrosis
Key I/E criterion
—
Primary endpoints
•Improvement (Yes/ no) From Baseline in Liver Histological Findings•MASH resolution, no fibrosis worsening
Footprint
Where this trial recruits
Site locations as reported to ClinicalTrials.gov. Site count is not enrollment count; per-site enrollment is not available from source.
Identifiers
Registered as
Timeline
Milestones
Assets
Investigational agents
Study populations
Who this study enrolls
Eligibility
Who can enroll
Inclusion criteria
1. Male or female patients ≥ 18 years (or who are of legal age in countries where that is greater than 18 years) and ≤ 80 years of age at time of consent.
2. Diagnosis of non-alcoholic steatohepatitis (NASH) (Non-alcoholic Fatty Liver Disease (NAFLD) Activity Score (NAS) ≥ 4, with at least 1 point in inflammation and ballooning each) and fibrosis stage F1-F3 proven by a biopsy conducted during the screening period or by a historical biopsy conducted within the last 6 months prior to randomization and stable body weight defined as less than 5% self-reported change in body weight between the historical biopsy and randomization, if a historical biopsy is used.
3. Liver fat fraction ≥ 8% measured by Magnetic Resonance Imaging (MRI)-Proton Density Fat Fraction (PDFF) and liver stiffness > 6.0 kPa measured by FibroScan® at Visit 1 (if biopsy is scheduled during the screening period MRI-PDFF and FibroScan® assessments have to be performed prior to the biopsy). However, the diagnosis of NASH and fibrosis at liver biopsy (including historical biopsy) is the primary assessment to establish patient eligibility.
4. Patients willing and able to undergo liver biopsies per protocol as judged by the Investigator.
5. Signed and dated written informed consent in accordance with ICH-GCP and local legislation prior to admission to the trial.
6. Women of childbearing potential (WOCBP)1 must be willing and able to use two forms of effective contraception where at least one form is highly effective methods of birth control per International Council on Harmonisation (ICH) M3 (R2) that result in a low failure rate of less than 1% per year when used consistently and correctly. A list of contraception methods meeting these criteria is provided in the patient information.
Further inclusion criteria apply.
Exclusion criteria
1. Current or history of significant alcohol consumption (defined as intake of > 210 g/ week in males and > 140 g/ week in females on average over a consecutive period of more than 3 months) or inability to reliably quantify alcohol consumption based on Investigator judgement within the last 5 years.
2. Intake of medications historically associated with liver injury, hepatic steatosis or steatohepatitis within 12 weeks prior to Visit 1. Intake of restricted medications or any medications considered likely to interfere with the safe conduct of the trial.
3. History of other forms of chronic liver disease (e.g., viral hepatitis, autoimmune liver disease, primary biliary sclerosis, primary sclerosing cholangitis, Wilson's disease, hemochromatosis, Alpha-1 Antitrypsin (A1At) deficiency, history of liver transplantation). Hepatitis B and C testing will be done at Visit 1. Patients with positive Hepatitis B surface antigen (HBsAg) should be excluded. Patients treated for hepatitis C must have a negative RNA test at screening and also be Hepatitis C Virus (HCV) RNA negative for at least 3 years prior to screening in order to be eligible for the trial.
4. Suspicion, diagnosis, or history of hepatocellular carcinoma (HCC), or any documented active or suspected malignancy or history of malignancy within 5 years prior to screening, except appropriately treated basal cell carcinoma of the skin or in situ carcinoma of uterine cervix.
5. Personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia syndrome type 2, manifest hypo- or hyperthyroidism at Visit 1.
6. History of chronic or acute pancreatitis or elevation of serum lipase/amylase > 2x ULN or fasting serum triglyceride levels of > 500 mg/dL (> 5.65 mmol/L) at screening.
7. Known history of HIV (Human Immunodeficiency Virus) infection and/or tuberculosis and/or an acute COVID-19 infection at Visit 1 (confirmed by SARS CoV-2 RT-PCR test). Further exclusion criteria apply.
Endpoints (24)
What's being measured
Protocol endpoints and posted registry outcome measures, grouped into outcome categories. Composite endpoints show their component event types. Standard codes (LOINC, SNOMED CT) are shown where available.
MASH / liver
24 endpointsImprovement (Yes/ no) From Baseline in Liver Histological Findings Based on Liver Biopsy After 48 Weeks of Treatment in Patients With NASH (NAS ≥ 4, Fibrosis F1-F3) - Actual Maintenance Treatment
Time frame:At baseline and at 48 weeks.
categorical status, improvement
SNOMED 442685003
Posted result
| Group | Value (number), Percentage of participants | 95% CI |
|---|---|---|
| Survodutide 2.4 mg - Actual Maintenance Treatment | 38.7 | — |
| Survodutide 4.8 mg - Actual Maintenance Treatment | 63.8 | — |
| Survodutide 6.0 mg - Actual Maintenance Treatment | 55.8 | — |
| Placebo - Actual Maintenance Treatment | 15.2 | — |
The logistic regression model included actual treatment, presence of diabetes of any type and Baseline Fibrosis Score. Firth's penalized regression was used.
The logistic regression model included actual treatment, presence of diabetes of any type and Baseline Fibrosis Score. Firth's penalized regression was used.
The logistic regression model included actual treatment, presence of diabetes of any type and Baseline Fibrosis Score. Firth's penalized regression was used.
Improvement (Yes/ no) From Baseline in Liver Histological Findings Based on Liver Biopsy After 48 Weeks of Treatment in Patients With NASH (NAS ≥ 4, Fibrosis F1-F3) - Planned Maintenance Treatment
Time frame:At baseline and after 48 weeks of treatment.
MASH resolution, no fibrosis worsening
categorical status, improvement
SNOMED 442685003
Posted result
| Group | Value (number), percentage of participants | 95% CI |
|---|---|---|
| Survodutide 2.4 mg - Planned Maintenance Treatment | 46.6 | — |
| Survodutide 4.8 mg - Planned Maintenance Treatment | 62.5 | — |
| Survodutide 6.0 mg - Planned Maintenance Treatment | 43.2 | — |
| Placebo - Planned Maintenance Treatment | 13.5 | — |
The logistic regression model includes planned treatment, presence of diabetes of any type and Baseline Fibrosis Score. Firth's penalized regression was used.
The logistic regression model includes planned treatment, presence of diabetes of any type and Baseline Fibrosis Score. Firth's penalized regression was used.
The logistic regression model includes planned treatment, presence of diabetes of any type and Baseline Fibrosis Score. Firth's penalized regression was used.
Improvement (Yes/ no) From Baseline in Liver Histological Findings Based on Liver Biopsy After 48 Weeks of Treatment in Patients With NASH (NAS ≥ 4, Fibrosis F1-F3) - Actual Maintenance Treatment
Time frame:At baseline and at 48 weeks.
categorical status, improvement
SNOMED 442685003
Improvement (Yes/ no) From Baseline in Liver Histological Findings Based on Liver Biopsy After 48 Weeks of Treatment in Patients With NASH (NAS ≥ 4, Fibrosis F1-F3) - Planned Maintenance Treatment
Time frame:At baseline and after 48 weeks of treatment.
MASH resolution, no fibrosis worsening
categorical status, improvement
SNOMED 442685003
Improvement of Liver Fat Content (Yes/ no) Defined as at Least 30% Relative Reduction in Liver Fat Content After 48 Weeks of Treatment Compared to Baseline Assessed by MRI-PDFF - Actual Maintenance Treatment
Time frame:At baseline and after 48 weeks.
MRI-PDFF ≥30% responders
threshold achievement, improvement
Posted result
| Group | Value (number), Percentage of participants | 95% CI |
|---|---|---|
| Survodutide 2.4 mg - Actual Maintenance Treatment | 50.5 | — |
| Survodutide 4.8 mg - Actual Maintenance Treatment | 66.7 | — |
| Survodutide 6.0 mg - Actual Maintenance Treatment | 76.9 | — |
| Placebo - Actual Maintenance Treatment | 16.5 | — |
The logistic regression model included actual treatment, presence of diabetes of any type, baseline liver fat content and baseline fibrosis score. Firth's penalized regression was used.
The logistic regression model included actual treatment, presence of diabetes of any type, baseline liver fat content and baseline fibrosis score. Firth's penalized regression was used.
The logistic regression model included actual treatment, presence of diabetes of any type, baseline liver fat content and baseline fibrosis score. Firth's penalized regression was used.
Improvement of Liver Fat Content (Yes/ no) Defined as at Least 30% Relative Reduction in Liver Fat Content After 48 Weeks of Treatment Compared to Baseline Assessed by MRI-PDFF - Planned Maintenance Treatment
Time frame:At baseline and at 48 weeks.
MRI-PDFF ≥30% responders
threshold achievement, improvement
Posted result
| Group | Value (number), Percentage of participants | 95% CI |
|---|---|---|
| Survodutide 2.4 mg - Planned Maintenance Treatment | 63.0 | — |
| Survodutide 4.8 mg - Planned Maintenance Treatment | 66.7 | — |
| Survodutide 6.0 mg - Planned Maintenance Treatment | 56.8 | — |
| Placebo - Planned Maintenance Treatment | 13.5 | — |
The logistic regression model included planned treatment, presence of diabetes of any type, baseline liver fat content and baseline fibrosis score. Firth's penalized regression was used.
The logistic regression model included planned treatment, presence of diabetes of any type, baseline liver fat content and baseline fibrosis score. Firth's penalized regression was used.
The logistic regression model included planned treatment, presence of diabetes of any type, baseline liver fat content and baseline fibrosis score. Firth's penalized regression was used.
Absolute Change of Liver Fat Content From Baseline After 48 Weeks of Treatment Assessed by MRI-PDFF - Actual Maintenance Treatment
Time frame:MMRM included measurements from baseline and at Week 28 and at Week 48 after first drug administration. MMRM estimates of absolute change from baseline to Week 48 is reported.
Liver fat content, change
change from baseline, improvement
Posted result
| Group | Value (least_squares_mean), percentage of liver fat content | 95% CI |
|---|---|---|
| Survodutide 2.4 mg - Actual Maintenance Treatment | -10.48 | -11.92 – -9.04 |
| Survodutide 4.8 mg - Actual Maintenance Treatment | -12.80 | -14.32 – -11.28 |
| Survodutide 6.0 mg - Actual Maintenance Treatment | -12.96 | -14.62 – -11.30 |
| Placebo - Actual Maintenance Treatment | -1.89 | -3.26 – -0.51 |
Absolute Change of Liver Fat Content From Baseline After 48 Weeks of Treatment Assessed by MRI-PDFF - Planned Maintenance Treatment
Time frame:MMRM included measurements from baseline and at Week 28 and at Week 48 after first drug administration. MMRM estimates of absolute change from baseline to Week 48 is reported.
Liver fat content, change
change from baseline, improvement
Posted result
| Group | Value (least_squares_mean), percentage of liver fat content | 95% CI |
|---|---|---|
| Survodutide 2.4 mg - Planned Maintenance Treatment | -10.73 | -12.25 – -9.22 |
| Survodutide 4.8 mg - Planned Maintenance Treatment | -12.40 | -13.90 – -10.91 |
| Survodutide 6.0 mg - Planned Maintenance Treatment | -12.48 | -14.06 – -10.89 |
| Placebo - Planned Maintenance Treatment | -1.61 | -3.04 – -0.19 |
Percent Change of Liver Fat Content From Baseline After 48 Weeks of Treatment Assessed by MRI-PDFF - Actual Maintenance Treatment
Time frame:MMRM included measurements from baseline and at Week 28 and at Week 48 after first drug administration. MMRM estimates of percent change from baseline to Week 48 is reported.
MRI-PDFF, % change
percent change from baseline, improvement
Posted result
| Group | Value (least_squares_mean), percent change of liver fat content | 95% CI |
|---|---|---|
| Survodutide 2.4 mg - Actual Maintenance Treatment | -50.92 | -58.05 – -43.80 |
| Survodutide 4.8 mg - Actual Maintenance Treatment | -62.79 | -70.26 – -55.32 |
| Survodutide 6.0 mg - Actual Maintenance Treatment | -64.30 | -72.48 – -56.12 |
| Placebo - Actual Maintenance Treatment | -7.28 | -14.06 – -0.50 |
Percent Change of Liver Fat Content From Baseline After 48 Weeks of Treatment Assessed by MRI-PDFF - Planned Maintenance Treatment
Time frame:MMRM included measurements from baseline and at Week 28 and at Week 48 after first drug administration. MMRM estimates of percent change from baseline to Week 48 is reported.
MRI-PDFF, % change
percent change from baseline, improvement
Posted result
| Group | Value (least_squares_mean), percent change of liver fat content | 95% CI |
|---|---|---|
| Survodutide 2.4 mg - Planned Maintenance Treatment | -52.20 | -59.66 – -44.75 |
| Survodutide 4.8 mg - Planned Maintenance Treatment | -60.82 | -68.16 – -53.48 |
| Survodutide 6.0 mg - Planned Maintenance Treatment | -61.97 | -69.78 – -54.16 |
| Placebo - Planned Maintenance Treatment | -5.71 | -12.70 – 1.28 |
Improvement of Fibrosis (Yes/ no) Defined as at Least One Stage Decrease in Fibrosis Stage After 48 Weeks of Treatment Assessed by Liver Biopsy - Actual Maintenance Treatment
Time frame:At baseline and after 48 weeks of treatment.
Fibrosis ≥1-stage improvement, no MASH worsening
threshold achievement, improvement
Posted result
| Group | Value (number), Percentage of participants | 95% CI |
|---|---|---|
| Survodutide 2.4 mg - Actual Maintenance Treatment | 30.1 | — |
| Survodutide 4.8 mg - Actual Maintenance Treatment | 34.8 | — |
| Survodutide 6.0 mg - Actual Maintenance Treatment | 44.2 | — |
| Placebo - Actual Maintenance Treatment | 21.5 | — |
The logistic regression model included actual treatment, presence of diabetes of any type and baseline fibrosis score. Firth's penalized regression was used.
The logistic regression model included actual treatment, presence of diabetes of any type and baseline fibrosis score. Firth's penalized regression was used.
The logistic regression model included actual treatment, presence of diabetes of any type and baseline fibrosis score. Firth's penalized regression was used.
Improvement of Fibrosis (Yes/ no) Defined as at Least One Stage Decrease in Fibrosis Stage After 48 Weeks of Treatment Assessed by Liver Biopsy - Planned Maintenance Treatment
Time frame:At baseline and after 48 weeks of treatment.
Fibrosis ≥1-stage improvement, no MASH worsening
categorical status, improvement
Posted result
| Group | Value (number), Percentage of participants | 95% CI |
|---|---|---|
| Survodutide 2.4 mg - Planned Maintenance Treatment | 34.2 | — |
| Survodutide 4.8 mg - Planned Maintenance Treatment | 36.1 | — |
| Survodutide 6.0 mg - Planned Maintenance Treatment | 33.8 | — |
| Placebo - Planned Maintenance Treatment | 21.6 | — |
The logistic regression model included planned treatment, presence of diabetes of any type and baseline fibrosis score. Firth's penalized regression was used.
The logistic regression model included planned treatment, presence of diabetes of any type and baseline fibrosis score. Firth's penalized regression was used.
The logistic regression model included planned treatment, presence of diabetes of any type and baseline fibrosis score. Firth's penalized regression was used.
Absolute Change From Baseline in NAS After 48 Weeks of Treatment Assessed by Liver Biopsy - Actual Maintenance Treatment
Time frame:At baseline and 48 weeks of treatment.
change from baseline, improvement
Posted result
| Group | Value (mean), units on a scale | 95% CI |
|---|---|---|
| Survodutide 2.4 mg - Actual Maintenance Treatment | -2.8 | — |
| Survodutide 4.8 mg - Actual Maintenance Treatment | -3.2 | — |
| Survodutide 6.0 mg - Actual Maintenance Treatment | -3.3 | — |
| Placebo - Actual Maintenance Treatment | -0.4 | — |
Absolute Change From Baseline in NAS After 48 Weeks of Treatment Assessed by Liver Biopsy - Planned Maintenance Treatment
Time frame:At baseline and 48 weeks of treatment.
change from baseline, improvement
Posted result
| Group | Value (mean), units on a scale | 95% CI |
|---|---|---|
| Survodutide 2.4 mg - Planned Maintenance Treatment | -2.8 | — |
| Survodutide 4.8 mg - Planned Maintenance Treatment | -3.2 | — |
| Survodutide 6.0 mg - Planned Maintenance Treatment | -3.3 | — |
| Placebo - Planned Maintenance Treatment | -0.2 | — |
Improvement of Liver Fat Content (Yes/ no) Defined as at Least 30% Relative Reduction in Liver Fat Content After 48 Weeks of Treatment Compared to Baseline Assessed by MRI-PDFF - Actual Maintenance Treatment
Time frame:At baseline and after 48 weeks.
MRI-PDFF ≥30% responders
threshold achievement, improvement
Improvement of Liver Fat Content (Yes/ no) Defined as at Least 30% Relative Reduction in Liver Fat Content After 48 Weeks of Treatment Compared to Baseline Assessed by MRI-PDFF - Planned Maintenance Treatment
Time frame:At baseline and at 48 weeks.
MRI-PDFF ≥30% responders
threshold achievement, improvement
Absolute Change of Liver Fat Content From Baseline After 48 Weeks of Treatment Assessed by MRI-PDFF - Actual Maintenance Treatment
Time frame:MMRM included measurements from baseline and at Week 28 and at Week 48 after first drug administration. MMRM estimates of absolute change from baseline to Week 48 is reported.
Liver fat content, change
change from baseline, improvement
Absolute Change of Liver Fat Content From Baseline After 48 Weeks of Treatment Assessed by MRI-PDFF - Planned Maintenance Treatment
Time frame:MMRM included measurements from baseline and at Week 28 and at Week 48 after first drug administration. MMRM estimates of absolute change from baseline to Week 48 is reported.
Liver fat content, change
change from baseline, improvement
Percent Change of Liver Fat Content From Baseline After 48 Weeks of Treatment Assessed by MRI-PDFF - Actual Maintenance Treatment
Time frame:MMRM included measurements from baseline and at Week 28 and at Week 48 after first drug administration. MMRM estimates of percent change from baseline to Week 48 is reported.
MRI-PDFF, % change
percent change from baseline, improvement
Percent Change of Liver Fat Content From Baseline After 48 Weeks of Treatment Assessed by MRI-PDFF - Planned Maintenance Treatment
Time frame:MMRM included measurements from baseline and at Week 28 and at Week 48 after first drug administration. MMRM estimates of percent change from baseline to Week 48 is reported.
MRI-PDFF, % change
percent change from baseline, improvement
Improvement of Fibrosis (Yes/ no) Defined as at Least One Stage Decrease in Fibrosis Stage After 48 Weeks of Treatment Assessed by Liver Biopsy - Actual Maintenance Treatment
Time frame:At baseline and after 48 weeks of treatment.
Fibrosis ≥1-stage improvement, no MASH worsening
categorical status, improvement
Improvement of Fibrosis (Yes/ no) Defined as at Least One Stage Decrease in Fibrosis Stage After 48 Weeks of Treatment Assessed by Liver Biopsy - Planned Maintenance Treatment
Time frame:At baseline and after 48 weeks of treatment.
Fibrosis ≥1-stage improvement, no MASH worsening
categorical status, improvement
Absolute Change From Baseline in NAS After 48 Weeks of Treatment Assessed by Liver Biopsy - Actual Maintenance Treatment
Time frame:At baseline and 48 weeks of treatment.
change from baseline, improvement
Absolute Change From Baseline in NAS After 48 Weeks of Treatment Assessed by Liver Biopsy - Planned Maintenance Treatment
Time frame:At baseline and 48 weeks of treatment.
change from baseline, improvement
Publications (1)
Bibliography
Records linked to this trial through ClinicalTrials.gov references, PubMed NCT search, and curated study seeds. 'Canonical' marks design/result papers; others are registry references or candidates.
Registry references + supporting bibliography
- The New England journal of medicine2024 Jul 25PMID38847460doi:10.1056/NEJMoa2401755via clinicaltrials gov reference derived + pubmed nct search
Provenance
Sources
Trial facts come from public ClinicalTrials.gov records. Endpoint categories are Delfa's classification of those records, not a ClinicalTrials.gov field. All figures reflect the July 1, 2026 snapshot.