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Trial · Interventional

CompletedPhase 2Results postedRegistry data

A Study to Test Safety and Efficacy of Survodutide (BI456906) in Adults With Non-alcoholic Steatohepatitis (NASH) and Fibrosis (F1-F3)

NCTNCT04771273 (opens ClinicalTrials.gov in a new tab)Other id1404-0043Other id2020-002723-11
Open at ClinicalTrials.govAsk about this trial

Overview

Status
Completed
Phase
Phase 2
Enrollment
295 participants (actual)
Sponsor
Boehringer Ingelheim · Industry
Design
Randomized · Quadruple masking
Countries
25 countries

United States, Australia, Austria, Belgium, Canada, China, Czechia, France, Germany, Greece, Hong Kong, Hungary, Israel, Italy, Japan, Malaysia, Netherlands, New Zealand, Poland, Portugal, Singapore, South Korea, Spain, Taiwan, United Kingdom

Start
27 Apr 2021
Primary completion
9 Nov 2023
Completion
21 Dec 2023
First posted
25 Feb 2021
Last update posted
3 Dec 2024
Conditions
Non-alcoholic Steatohepatitis (NASH)

Timeline

1 trial · 1 completed · 1 with posted results

  • Completed
  • Ongoing
  • Not yet recruiting
  • Stopped
  • Estimated dates (est.)
  • Results posted
2021202220232024
  1. Ph 2

    A Study to Test Safety and Efficacy of Survodutide (BI456906) in Adults With Non-alcoholic Steatohepatitis (NASH) and Fibrosis (F1-F3)

    NCT04771273

    27 Apr 2021 to 21 Dec 2023

Registry summary

Text and fields below are the sponsor's entries at ClinicalTrials.gov, shown as posted.

This study is open for men and women with a liver disease called nonalcoholic steatohepatitis (NASH) and liver fibrosis. The purpose of the study is to find out whether a medicine called BI 456906 helps patients with NASH and liver fibrosis. The study tests 3 different doses of BI 456906 to find the dose that helps best. Participants are put into 4 groups randomly, which means by chance. There are 3 groups that each receive a different dose of BI 456906 and there is 1 group that receives placebo. BI 456906 and placebo are given as an injection under the skin once per week. The placebo injection looks like the BI 456906 injection but does not contain any medicine. Participants are in the study for a little over 1 year (60 weeks). During this time, they visit the study site several times and have some video calls in addition. At the visits, the study doctors take different measurements. To see whether the treatment works, the doctors take a very small sample of liver tissue (biopsy) from each participant at the start and at the end of the study. They also examine the liver by ultrasound and MRI. The doctors also regularly check the general health of the participants.

Interventions

  • SurvodutideDrug
  • PlaceboDrug

Arms4

  • Experimental

    Survodutide 2.4 mg - planned maintenance treatment

  • Experimental

    Survodutide 4.8 mg - planned maintenance treatment

  • Experimental

    Survodutide 6.0 mg - planned maintenance treatment

  • Placebo comparator

    Placebo - planned maintenance treatment

Primary outcomes2

Outcomes the sponsor listed as primary.

  1. 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.

    Registry description

    Percentage of patients who had an improvement from baseline in liver histological findings based on liver biopsy after 48 weeks of treatment is reported. Percentages were rounded to one decimal place. Improvement in histological findings was defined as a composite of improvement in NASH and no worsening of fibrosis. Improvement in non-alcoholic steatohepatitis (NASH) was defined as decrease of at least 2 points in non-alcoholic fatty liver disease (NAFLD) activity score (NAS) with at least 1 point decrease in NAS subscore of either lobular inflammation or ballooning. The NAS represents the sum of subscores for steatosis (scored from 0-3), lobular inflammation (scored from 0-3) and ballooning (scored from 0-2), and the total score ranges from 0 to 8 with higher scores representing worsening of the disease. The total score for the fibrosis stage ranges from 0 to 4 with higher score indication worsening of the disease. Patients without post-baseline data were considered non-responders.

  2. 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.

    Registry description

    Percentage of patients who had an improvement from baseline in liver histological findings based on liver biopsy after 48 weeks of treatment is reported. Percentages were rounded to one decimal place. Improvement in histological findings was defined as a composite of improvement in non-alcoholic steatohepatitis (NASH) and no worsening of fibrosis. Improvement in NASH was defined as decrease of at least 2 points in non-alcoholic fatty liver disease (NAFLD) activity score (NAS) with at least 1 point decrease in NAS subscore of either lobular inflammation or ballooning. The NAS represents the sum of subscores for steatosis (scored from 0-3), lobular inflammation (scored from 0-3) and ballooning (scored from 0-2), and the total score ranges from 0 to 8 with higher scores representing worsening of the disease. The total score for the fibrosis stage ranges from 0 to 4 with higher score indication worsening of the disease. Patients without post-baseline data were considered non-responders.

Secondary outcomes(10)

  1. 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.

    Registry description

    Percentage of participants with improvement in liver fat content is reported. Improvement in liver fat content was defined as percentage reduction from baseline of ≥30% in liver fat content after 48 weeks of treatment compared to baseline. Percentages were rounded to one decimal place. Liver fat content was assessed by Magnetic Resonance Imaging - Proton Density Fat Fraction (MRI-PDFF). Patients without post-baseline values were imputed as non-responders.

  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 - Planned Maintenance Treatment

    Time frame · At baseline and at 48 weeks.

    Registry description

    Percentage of participants with improvement in liver fat content is reported. Improvement in liver fat content was defined as percentage reduction from baseline of ≥30% in liver fat content after 48 weeks of treatment compared to baseline. Liver fat content was assessed by Magnetic Resonance Imaging - Proton Density Fat Fraction (MRI-PDFF). Patients without post-baseline values were imputed as non-responders.

  3. 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.

    Registry description

    Absolute change of liver fat content (percentage \[%\]) from baseline after 48 weeks of treatment is reported. Liver fat content was assessed by Magnetic Resonance Imaging - Proton Density Fat Fraction (MRI-PDFF). Least Squares Mean (Standard error) were calculated from mixed-effect model for repeated measures (MMRM) including fixed effects for baseline liver fat content (%) as a continuous linear covariate, and treatment, presence of diabetes of any type \[yes, no\], baseline fibrosis score \[F1, F2, F3\], visit, treatment by visit interaction and baseline by visit interaction as factors.

  4. 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.

    Registry description

    Absolute change of liver fat content from baseline after 48 weeks of treatment is reported. Liver fat content was assessed by Magnetic Resonance Imaging - Proton Density Fat Fraction (MRI-PDFF). Least Squares Mean (Standard error) were calculated from mixed-effect model for repeated measures (MMRM) including fixed effects for baseline liver fat content (%) as a continuous linear covariate, and treatment, presence of diabetes of any type \[yes, no\], baseline fibrosis score \[F1, F2, F3\], visit, treatment by visit interaction and baseline by visit interaction as factors.

  5. 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.

    Registry description

    Percent change of liver fat content (percentage \[%\]) from baseline after 48 weeks of treatment is reported. Liver fat content was assessed by Magnetic Resonance Imaging - Proton Density Fat Fraction (MRI-PDFF). Least Squares Mean (Standard error) were calculated from mixed-effect model for repeated measures (MMRM) including fixed effects for baseline liver fat content (%) as a continuous linear covariate, and treatment, presence of diabetes of any type \[yes, no\], baseline fibrosis score \[F1, F2, F3\], visit, treatment by visit interaction and baseline by visit interaction as factors.

  6. 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.

    Registry description

    Percent change of liver fat content (percentage \[%\]) from baseline after 48 weeks of treatment is reported. Liver fat content was assessed by Magnetic Resonance Imaging - Proton Density Fat Fraction (MRI-PDFF). Least Squares Mean (Standard error) were calculated from mixed-effect model for repeated measures (MMRM) including fixed effects for baseline liver fat content (%) as a continuous linear covariate, and treatment, presence of diabetes of any type \[yes, no\], baseline fibrosis score \[F1, F2, F3\], visit, treatment by visit interaction and baseline by visit interaction as factors.

  7. 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.

    Registry description

    Percentage of participants with improvement of liver fibrosis is reported. Improvement of fibrosis was defined as at least one stage decrease in fibrosis stage after 48 weeks of treatment assessed by liver biopsy. The total score for the fibrosis stage ranges from 0 to 4 with higher score indication worsening of the disease and the stages of fibrosis based on their location are the following: * 1A Zone 3, perisinusoidal, delicate; * 1B Zone 3, perisinusoidal, dense; * 1C Portal, periportal only; * 2 Zone 3, perisinusoidal + portal, periportal only; * 3 Bridging fibrosis; * 4 Cirrhosis. For analysis purposes no distinction was made between stages 1A, 1B and 1C.

  8. 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.

    Registry description

    Percentage of participants with improvement of liver fibrosis is reported. Improvement of fibrosis was defined as at least one stage decrease in fibrosis stage after 48 weeks of treatment assessed by liver biopsy. The total score for the fibrosis stage ranges from 0 to 4 with higher score indication worsening of the disease and the stages of fibrosis based on their location are the following: * 1A Zone 3, perisinusoidal, delicate; * 1B Zone 3, perisinusoidal, dense; * 1C Portal, periportal only; * 2 Zone 3, perisinusoidal + portal, periportal only; * 3 Bridging fibrosis; * 4 Cirrhosis. For analysis purposes no distinction was made between stages 1A, 1B and 1C.

  9. 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.

    Registry description

    Absolute change from baseline in NAS after 48 weeks of treatment assessed by liver biopsy is reported. The non-alcoholic fatty liver disease (NAFLD) activity score (NAS) represents the sum of subscores for steatosis (scored from 0-3), lobular inflammation (scored from 0-3) and ballooning (scored from 0-2), and the total score ranges from 0 to 8 with higher scores representing worsening of the disease.

  10. 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.

    Registry description

    Absolute change from baseline in NAS after 48 weeks of treatment assessed by liver biopsy is reported. The non-alcoholic fatty liver disease (NAFLD) activity score (NAS) represents the sum of subscores for steatosis (scored from 0-3), lobular inflammation (scored from 0-3) and ballooning (scored from 0-2), and the total score ranges from 0 to 8 with higher scores representing worsening of the disease.

Posted results

Values are shown as posted at ClinicalTrials.gov, with their units. PepBank has not converted, pooled or compared them.

Primary outcome results

Primary outcomeNumber· At baseline and at 48 weeks.

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

GroupValue (Percentage of participants)
Survodutide 2.4 mg - Actual Maintenance Treatment38.7
Survodutide 4.8 mg - Actual Maintenance Treatment63.8
Survodutide 6.0 mg - Actual Maintenance Treatment55.8
Placebo - Actual Maintenance Treatment15.2
Primary outcomeNumber· At baseline and after 48 weeks of treatment.

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

GroupValue (percentage of participants)
Survodutide 2.4 mg - Planned Maintenance Treatment46.6
Survodutide 4.8 mg - Planned Maintenance Treatment62.5
Survodutide 6.0 mg - Planned Maintenance Treatment43.2
Placebo - Planned Maintenance Treatment13.5
Secondary and other outcome results(6)
Secondary outcomeNumber· At baseline and after 48 weeks.

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

GroupValue (Percentage of participants)
Survodutide 2.4 mg - Actual Maintenance Treatment50.5
Survodutide 4.8 mg - Actual Maintenance Treatment66.7
Survodutide 6.0 mg - Actual Maintenance Treatment76.9
Placebo - Actual Maintenance Treatment16.5
Secondary outcomeNumber· At baseline and at 48 weeks.

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

GroupValue (Percentage of participants)
Survodutide 2.4 mg - Planned Maintenance Treatment63.0
Survodutide 4.8 mg - Planned Maintenance Treatment66.7
Survodutide 6.0 mg - Planned Maintenance Treatment56.8
Placebo - Planned Maintenance Treatment13.5
Secondary outcomeLeast squares mean· 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.

Absolute Change of Liver Fat Content From Baseline After 48 Weeks of Treatment Assessed by MRI-PDFF - Actual Maintenance Treatment

GroupValue (percentage of liver fat content)
Survodutide 2.4 mg - Actual Maintenance Treatment-10.48
Survodutide 4.8 mg - Actual Maintenance Treatment-12.80
Survodutide 6.0 mg - Actual Maintenance Treatment-12.96
Placebo - Actual Maintenance Treatment-1.89
Secondary outcomeLeast squares mean· 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.

Absolute Change of Liver Fat Content From Baseline After 48 Weeks of Treatment Assessed by MRI-PDFF - Planned Maintenance Treatment

GroupValue (percentage of liver fat content)
Survodutide 2.4 mg - Planned Maintenance Treatment-10.73
Survodutide 4.8 mg - Planned Maintenance Treatment-12.40
Survodutide 6.0 mg - Planned Maintenance Treatment-12.48
Placebo - Planned Maintenance Treatment-1.61
Secondary outcomeLeast squares mean· 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.

Percent Change of Liver Fat Content From Baseline After 48 Weeks of Treatment Assessed by MRI-PDFF - Actual Maintenance Treatment

GroupValue (percent change of liver fat content)
Survodutide 2.4 mg - Actual Maintenance Treatment-50.92
Survodutide 4.8 mg - Actual Maintenance Treatment-62.79
Survodutide 6.0 mg - Actual Maintenance Treatment-64.30
Placebo - Actual Maintenance Treatment-7.28
Secondary outcomeLeast squares mean· 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.

Percent Change of Liver Fat Content From Baseline After 48 Weeks of Treatment Assessed by MRI-PDFF - Planned Maintenance Treatment

GroupValue (percent change of liver fat content)
Survodutide 2.4 mg - Planned Maintenance Treatment-52.20
Survodutide 4.8 mg - Planned Maintenance Treatment-60.82
Survodutide 6.0 mg - Planned Maintenance Treatment-61.97
Placebo - Planned Maintenance Treatment-5.71

Adverse events, as posted

Adverse events as posted: participants affected out of participants at risk, by group
GroupDeathsSerious eventsOther events
Survodutide 2.4 mg - Actual Maintenance TreatmentThis arm includes patients who were treated with 2.4 mg of survodutide administered weekly at the start of the maintenance period, for patients who reached the maintenance period, regardless of whether this was the randomised (planned) dose or not, and regardless of whether the patient stayed on that dose throughout the maintenance period. This arm includes also those patients for whom the next maintenance dose up from the dose at treatment discontinuation was 2.4 mg of survodutide administered weekly, for patients who discontinued treatment prior to the maintenance period, regardless of the reason for the treatment discontinuation.0 / 935 / 9385 / 93
Survodutide 4.8 mg - Actual Maintenance TreatmentThis arm includes patients who were treated with 4.8 mg of survodutide administered weekly at the start of the maintenance period, for patients who reached the maintenance period, regardless of whether this was the randomised (planned) dose or not, and regardless of whether the patient stayed on that dose throughout the maintenance period. This arm includes also those patients for whom the next maintenance dose up from the dose at treatment discontinuation was 4.8 mg of survodutide administered weekly, for patients who discontinued treatment prior to the maintenance period, regardless of the reason for the treatment discontinuation.0 / 697 / 6960 / 69
Survodutide 6.0 mg - Actual Maintenance TreatmentThis arm includes patients who were treated with 6.0 mg of survodutide administered weekly at the start of the maintenance period, for patients who reached the maintenance period, regardless of whether this was the randomised (planned) dose or not, and regardless of whether the patient stayed on that dose throughout the maintenance period. This arm includes also those patients for whom the next maintenance dose up from the dose at treatment discontinuation was 6.0 mg of survodutide administered weekly, for patients who discontinued treatment prior to the maintenance period, regardless of the reason for the treatment discontinuation.0 / 525 / 5249 / 52
Placebo - Actual Maintenance TreatmentThis arm includes patients who were treated with placebo matching survodutide administered weekly at the start of the maintenance period, for patients who reached the maintenance period, regardless of whether this was the randomised (planned) dose or not, and regardless of whether the patient stayed on that dose throughout the maintenance period. This arm includes also those patients who were receiving Placebo matching survodutide administered weekly and who discontinued treatment prior to the maintenance period, regardless of the reason for the treatment discontinuation.0 / 795 / 7968 / 79

Each cell reads participants affected / participants at risk, as the registry posted them.

Registry data comes from ClinicalTrials.gov. Study results come from studies, not from the registry. How PepBank works

Studies1

Studies that cite this trial.

Studies with results

1 study on this page

Indexing hint: Randomized controlled trial · 2024

13 results

A Phase 2 Randomized Trial of Survodutide in MASH and Fibrosis.

Sanyal et al. 2024The New England journal of medicinecited by 426

PMID 38847460DOI 10.1056/nejmoa2401755PUB-38847460

Full text at the publisher13 results
Publisher pageSee results (13)

Eligibility

Who could join, as posted.

Sex
All
Age
from 18 Years up to 80 Years
Healthy volunteers
Not accepted
Inclusion and exclusion criteria, as posted
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.

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