Clinical trial NCT06309992: A Study to Test Whether Survodutide Helps People Living With Obesity or Overweight and With a Confirmed or Presumed Liver Disease Called Non-alcoholic Steatohepatitis (NASH) to Reduce Liver Fat and to Lose Weight
Official title: Multicentre, Randomised, Double-blind, Placebo-controlled, 48-week, Phase III Trial to Evaluate the Efficacy and Safety of Survodutide Administered Subcutaneously in Participants With Overweight or Obesity and Presumed or Confirmed Nonalcoholic Steatohepatitis (NASH)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Obesity
Non-Alcoholic SteatoHepatitis (NASH)
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2024-03-13
Enrollment: 218
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study is open to adults who are at least 18 years old and have

* presumed or confirmed NASH together with overweight or obesity and
* a body mass index (BMI) of 30 kg/m² or more, or
* a BMI of 27 kg/m² and at least one weight-related health problem.

People with a history of other chronic liver diseases cannot take part in this study.

The purpose of this study is to find out whether a medicine called survodutide helps people living with obesity or overweight and a confirmed or presumed liver disease called nonalcoholic steatohepatitis (NASH) to have less liver fat and to lose weight. Participants are put into 2 groups randomly, which means by chance. 1 group gets different doses of survodutide and 1 group gets placebo. Placebo looks like survodutide but does not contain any medicine. Every participant has a 2 in 3 chance of getting survodutide. Participants and doctors do not know who is in which group. Participants inject survodutide or placebo under their skin once a week for about 1 year. In addition to the study medicine, all participants receive counselling to make changes to their diet and to exercise regularly.

Participants are in the study for about 1 year and 3 months. During this time, it is planned that participants visit the study site up to 14 times and receive 3 phone calls by the site staff. The doctors check participants' health and take note of any unwanted effects. The participants' body weight is regularly measured. At 3 of the visits, the participants' liver is measured using different imaging methods. The results are compared between the groups to see whether the treatment works.


Eligibility criteria: Key inclusion criteria:

* Age ≥18 years at the time of signing informed consent, and at least the legal age of consent in countries where it is \>18 years
* BMI ≥30 kg/m², OR BMI ≥27 kg/m² and at least one of the following weight-related comorbidities at screening:

  * Hypertension (defined as repeated, i.e. at least 3 measurements in resting condition, Systolic Blood Pressure (SBP) values of ≥140 mmHg and/or Diastolic Blood Pressure (DBP) values of ≥90 mmHg in the absence of anti-hypertensive treatment, or intake of at least 1 antihypertensive drug to maintain a normotensive blood pressure)
  * Dyslipidaemia (defined as at least 1 lipid-lowering treatment required to maintain normal blood lipid levels, or lowdensity lipoprotein (LDL) cholesterol ≥160 mg/dL (≥4.1 mmol/L) or triglycerides ≥150 mg/dL (≥1.7 mmol/L), or high-density lipoprotein (HDL) cholesterol \<40 mg/dL (\<1.0 mmol/L) for men or HDL cholesterol \<50 mg/dL (\<1.3 mmol/L) for women
  * Obstructive sleep apnoea
  * Cardiovascular disease (e.g. heart failure with New York Heart Association (NYHA) functional class II-III, history of ischaemic or haemorrhagic stroke or cerebrovascular revascularisation procedure \[e.g. carotid endarterectomy and/or stent\], MI, coronary artery disease, or peripheral vascular disease)
  * Type 2 diabetes mellitus (T2DM) (diagnosed at least 180 days prior to screening, with glycated haemoglobin \[HbA1c\] ≥6.5% (48 mmol/mol) and \<10% (86 mmol/mol) as measured by the central laboratory at screening)
* History of at least one self-reported unsuccessful dietary effort to lose body weight Further inclusion criteria apply.

Key exclusion criteria:

* Current or history of significant alcohol consumption (defined as intake of \>210 g/week in men and \>140 g/week in women on average over a consecutive period of more than 3 months) or inability to reliably quantify alcohol consumption based on the investigator's judgement within the last 5 years.
* Intake of medications associated with liver injury, hepatic steatosis or steatohepatitis.
* History of other chronic liver diseases (e.g. viral hepatitis, autoimmune liver disease, primary biliary cholangitis , 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. Participants with positive hepatitis B surface antigen (HBsAg) should be excluded. Participants treated for hepatitis C must have a negative ribonucleic acid (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. Trial participants with positive HCV antibody and no history of HCV treatment require a negative HCV RNA test at screening to be eligible for the trial.
* Cirrhosis based on clinical assessment, abdominal imaging, liver histology or non-invasive tests assessed at screening (enhanced liver fibrosis (ELF) ≥11.3 or Fibrosis (FIB)-4 ≥3.48 or FibroScan® VCTE™ ≥20 kPa or MRE ≥4.68 kPa) or a history of cirrhosis.
* Current decompensated liver disease or previous hepatic decompensation (ascites, spontaneous bacterial peritonitis, portal hypertension bleeding, hepatic encephalopathy, hepatorenal syndrome).
* Evidence of portal hypertension (e.g. splenomegaly, oesophageal varices, or other portosystemic collateral pathways).

Further exclusion criteria apply.

Primary outcomes:
measure: Relative reduction in liver fat content of at least 30% from baseline to Week 48 (yes/no) assessed by magnetic resonance imaging proton density fat fraction (MRI-PDFF) [%]
timeFrame: at baseline, at week 48
measure: Relative change (%) in body weight [kg] from baseline to Week 48
timeFrame: at baseline, at week 48
Secondary outcomes:
measure: Absolute change from baseline to Week 48 in liver fat content assessed by MRI-PDFF [%]
timeFrame: at baseline, at week 48
measure: Relative change (%) from baseline to Week 48 in liver fat content assessed by MRI-PDFF [%]
timeFrame: at baseline, at week 48
measure: Reduction from baseline to Week 48 in Iron corrected T1 (cT1) [ms] levels of ≥80 ms (yes/no)
timeFrame: at baseline, at week 48
measure: Absolute change from baseline to Week 48 in alanine amino transferase (ALT) [U/L] levels
timeFrame: at baseline, at week 48
measure: Relative change from baseline to Week 48 in alanine amino transferase (ALT) [U/L] levels
timeFrame: at baseline, at week 48
measure: Absolute change from baseline to Week 48 in waist circumference [cm]
timeFrame: at baseline, at week 48
measure: Relative change from baseline to Week 48 in waist circumference [cm]
timeFrame: at baseline, at week 48
measure: Absolute change from baseline to Week 48 in Homeostasis Model Assessment -Insulin Resistance (HOMA-IR) (Fasting Plasma Insulin (FPI) [mlU/L] · Fasting Plasma Glucose (FPG) [mmol/L]/22.5)
timeFrame: at baseline, at week 48
measure: Absolute change from baseline to Week 48 in liver stiffness [kPa] assessed by magnetic resonance elastography (MRE)
timeFrame: at baseline, at week 48
measure: Relative change from baseline to Week 48 in liver stiffness [kPa] assessed by magnetic resonance elastography (MRE)
timeFrame: at baseline, at week 48
measure: Absolute change in liver volume [mL] from baseline to Week 48 measured using MRI
timeFrame: at baseline, at week 48
measure: Relative change in liver volume [mL] from baseline to Week 48 measured using MRI
timeFrame: at baseline, at week 48
Other outcomes:
Locations:
city: Fountain Valley
country: United States
facility: ARK Clinical Research
state: California
city: Gardena
country: United States
facility: Velocity Clinical Research-Gardena-69773
state: California
city: Long Beach
country: United States
facility: ARK Clinical Research
state: California
city: Montclair
country: United States
facility: Catalina Research Institute, LLC-Montclair-69754
state: California
city: North Hollywood
country: United States
facility: Velocity Clinical Research-North Hollywood-69852
state: California
city: Panorama City
country: United States
facility: Velocity Clinical Research-Panorama City-68861
state: California
city: Santa Ana
country: United States
facility: Velocity Clinical Research-Santa Ana-68902
state: California
city: Boca Raton
country: United States
facility: Excel Medical Clinical Trials
state: Florida
city: Delray Beach
country: United States
facility: Bruce A. Segal, MD, PA
state: Florida
city: Fleming Island
country: United States
facility: Fleming Island Center for Clinical Research
state: Florida
city: Fort Myers
country: United States
facility: Covenant Metabolic Specialists, LLC-Fort Myers-69019
state: Florida
city: Hallandale Beach
country: United States
facility: Velocity Clinical Research-Hallandale Beach-67888
state: Florida
city: Inverness
country: United States
facility: Nature Coast Clinical Research-Inverness-48221
state: Florida
city: Jupiter
country: United States
facility: Health Awareness, Inc.
state: Florida
city: Miami Lakes
country: United States
facility: Panax Clinical Research
state: Florida
city: Miami
country: United States
facility: Verus Clinical Research Corporation
state: Florida
city: Sarasota
country: United States
facility: Covenant Research and Clinics, LLC
state: Florida
city: Springfield
country: United States
facility: Springfield Clinic, LLP
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University
state: Indiana
city: Iowa City
country: United States
facility: University of Iowa Hospitals and Clinics
state: Iowa
city: Topeka
country: United States
facility: Kansas Medical Center
state: Kansas
city: Shreveport
country: United States
facility: Louisiana Research Center, LLC
state: Louisiana
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Dayton
country: United States
facility: DSI Research Northridge LLC
state: Ohio
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Austin
country: United States
facility: Velocity Clinical Research, Austin
state: Texas
city: Georgetown
country: United States
facility: Amel Med LLC
state: Texas
city: Houston
country: United States
facility: Gastroenterology and Liver Research LLC
state: Texas
city: Houston
country: United States
facility: Biopharma Informatic, Inc. Research Center
state: Texas
city: Humble
country: United States
facility: Accurate Clinical Research, Inc.
state: Texas
city: San Antonio
country: United States
facility: Clinical Trials of Texas, LLC
state: Texas
city: Waco
country: United States
facility: Impact Research Institute
state: Texas
city: Richmond
country: United States
facility: GI Select Health Research LLC
state: Virginia
city: Amsterdam
country: Netherlands
facility: Amsterdam UMC, location VUMC
city: Rotterdam
country: Netherlands
facility: Erasmus Medisch Centrum-ROTTERDAM-50697
city: Barcelona
country: Spain
facility: Hospital Vall d'Hebron
city: Barcelona
country: Spain
facility: Hospital Clínic de Barcelona
city: Madrid
country: Spain
facility: Hospital Ramón y Cajal
city: Madrid
country: Spain
facility: Hospital La Paz
Study officials:
References: