SURVODUTIDE for Obesity | Non-alcoholic steatohepatitis (NASH)

Inclusion criteria

• {"criterion_text":"-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"}
• {"criterion_text":"-BMI ≥30 kg/m², OR BMI ≥27 kg/m² and at least one weight-related comorbidity at screening: •\tHypertension (defined as repeated, i.e. at least 3 measurements in resting condition, SBP values of ≥140 mmHg and/or DBP values of ≥90 mmHg in the absence of antihypertensive treatment, or intake of at least 1 anti-hypertensive drug to maintain a normotensive blood pressure) •\tDyslipidaemia (defined as at least 1 lipid-lowering treatment required to maintain normal blood lipid levels, or low-density lipoprotein [LDL] ≥160 mg/dL [≥4.1 mmol/L] or triglycerides ≥150 mg/dL [≥1.7 mmol/L], or high-density lipoprotein (HDL] <40 mg/dL (<1.0 mmol/L] for men or HDL<50 mg/dL (<1.3 mmol/L) for women •\tObstructive sleep apnoea •\tCardiovascular 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) •\t 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)"}
• {"criterion_text":"-Presumed/confirmed NASH: Evidence of hepatic steatosis (defined by an MRIPDFF ≥8% at screening) with the exclusion of secondary causes of hepatic fat accumulation such as significant alcohol consumption, other chronic liver diseases and/or steatogenic medications, AND at least one of the following: • MRE ≥2.61 and <4.68 kPa at screening, OR • MAST score ≥0.242 at screening, when MAST score = exp(MAST)/(1+exp[MAST]), where MAST = -12.17 + 7.07 logMRE + 0.037 PDFF + 3.55 log AST OR • FAST score ≥0.5 at screening, OR • FibroScan® VCTE™ ≥8 kPa and <20 kPa at screening, OR • FIB-4 score ≥2.67 and <3.48 at screening, OR • ELF score >7.7 and <11.3 at screening, OR • cT1 ≥875 ms at screening, OR • Recent liver biopsy (within 3 years of screening) consistent with NASH (defined as the presence of steatosis, inflammation, and ballooning) with stage ≤3 fibrosis according to the NASH Clinical Research Network classification."}
• {"criterion_text":"-History of at least one self-reported unsuccessful dietary effort to lose body weight"}

Exclusion criteria

• {"criterion_text":"-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."}
• {"criterion_text":"-Previous or planned (during the trial period) treatment for obesity with surgery or a weight loss device, or prior surgery of the GI tract that could interfere with body weight. The following are allowed: (1) liposuction and/or abdominoplasty, if performed >1 year before screening, (2) lap banding, if the band has been removed >1 year before screening, (3) intragastric balloon, if the balloon has been removed >1 year before screening, (4) duodenal-jejunal bypass sleeve, if the sleeve has been removed >1 year before screening (5) appendectomy, (6) simple hernia repair, or (7) cholecystectomy."}
• {"criterion_text":"-Obesity induced by other endocrinologic disorders (i.e. Cushing Syndrome) or diagnosed monogenetic or syndromic forms of obesity (i.e. melanocortin 4 receptor deficiency, leptin deficiency, or Prader Willi Syndrome)"}
• {"criterion_text":"-Intake of medications associated with liver injury, hepatic steatosis or steatohepatitis"}
• {"criterion_text":"-History of other chronic liver diseases (e.g. viral hepatitis, autoimmune liver disease, primary biliary cholangitis , primary sclerosing cholangitis, Wilson’s disease, hemochromatosis, A1At deficiency, history of liver transplantation). Hepatitis B and C testing will be done at Visit 1. Participants with positive HBsAg should be excluded. Participants treated for hepatitis C must have a negative RNA test at screening and also be HCV RNA negative for at least 3 years prior to screening in order to be eligible for the trial. Trial patients with positive HCV antibody and no history of HCV treatment require a negative HCV RNA test at screening to be eligible for the trial."}
• {"criterion_text":"-Cirrhosis based on clinical assessment, abdominal imaging, liver histology or noninvasive tests assessed at screening (ELF ≥11.3, FIB4 ≥3.48, FibroScan® VCTE™ ≥20 kPa, or MRE ≥4.68 kPa), or history of cirrhosis."}
• {"criterion_text":"-Current decompensated liver disease or previous hepatic decompensation (ascites, spontaneous bacterial peritonitis, portal hypertension bleeding, hepatic encephalopathy, hepatorenal syndrome)."}
• {"criterion_text":"-Previous or current evidence of portal hypertension (e.g. splenomegaly, oesophageal varices, or other portosystemic collateral pathways)."}
• {"criterion_text":"-Any of the following liver laboratory test abnormalities at screening: •\tSerum AST and/or ALT elevation ≥5x ULN •\tTotal serum bilirubin concentration ≥1.2x ULN (except for cases of known Gilbert’s Syndrome) •\tAlkaline phosphatase >2x ULN •\tINR ≥1.3 (unless patient is on anticoagulants)"}
• {"criterion_text":"-Body weight variation (self-reported) >5% within 3 months before screening"}
• {"criterion_text":"-Medications for obesity within 3 months before screening"}

Primary endpoints

• {"endpoint_text":"-Relative reduction in liver fat content of at least 30% from baseline to Week 48 (yes/no) assessed by MRI-PDFF [%]","definition_or_measurement_approach":"Assessed by MRI-PDFF; defined as ≥30% relative reduction from baseline to Week 48 (odds ratio, survodutide vs. placebo)."}
• {"endpoint_text":"-Relative change (%) in body weight [kg] from baseline to Week 48","definition_or_measurement_approach":"Relative change (%) in body weight from baseline to Week 48; primary objective compares difference in adjusted means of relative change (%) in body weight (survodutide vs. placebo)."}

Secondary endpoints

• {"endpoint_text":"-Absolute change from baseline to Week 48 in liver fat content assessed by MRI-PDFF [%]","definition_or_measurement_approach":"Absolute change in MRI-PDFF from baseline to Week 48."}
• {"endpoint_text":"-Reduction from baseline to Week 48 in cT1 [ms] levels of ≥80 ms (yes/no)","definition_or_measurement_approach":"Proportion with reduction in cT1 of ≥80 ms from baseline to Week 48 (yes/no)."}
• {"endpoint_text":"-Absolute and relative change from baseline to Week 48 in ALT [U/L] levels","definition_or_measurement_approach":"Absolute and relative change in ALT levels from baseline to Week 48."}
• {"endpoint_text":"-Absolute and relative change from baseline to Week 48 in HOMA-IR (FPI [mlU/L]·FPG [mmol/L]/22.5)","definition_or_measurement_approach":"Absolute and relative change in HOMA-IR from baseline to Week 48 (calculated as FPI·FPG/22.5)."}
• {"endpoint_text":"-Absolute and relative change from baseline to Week 48 in liver stiffness [kPa] assessed by MRE","definition_or_measurement_approach":"Absolute and relative change in liver stiffness by MRE from baseline to Week 48."}
• {"endpoint_text":"-Absolute and relative change in liver volume [mL] from baseline to Week 48 measured using MRI","definition_or_measurement_approach":"Absolute and relative change in liver volume measured by MRI from baseline to Week 48."}
• {"endpoint_text":"-Absolute and relative change from baseline to Week 48 in waist circumference [cm]","definition_or_measurement_approach":"Absolute and relative change in waist circumference from baseline to Week 48."}
• {"endpoint_text":"-Relative change (%) from baseline to Week 48 in liver fat content assessed by MRI-PDFF [%]","definition_or_measurement_approach":"Relative change (%) in MRI-PDFF from baseline to Week 48."}

Methods

• Patient poster (document: K2_Recruitment material_Patient Poster_san)
• Patient flyer (document: K2_Recruitment material_Patient Flyer_san)
• Patient brochure (document: K2_Recruitment material_Patient Brochure_san)
• Doctor-to-patient letter (document: K2_Recruitment material_Dr to Patient Letter_san)
• Recruitment arrangement document (document: K1_Recruitment Arrangement_san)
• eConsent materials and electronic recruitment support (eConsent landing page, eConsent participant-facing screenshots, eConsent video storyboard, eConsent Security and Privacy Quick Reference Guide)

Germany

Earliest CTIS Part Ii Submission Date

27-05-2024

Latest Decision Or Authorization Date

19-06-2024

Processing Time Days

23

Number Of Sites

4

Number Of Participants

4

Netherlands

Earliest CTIS Part Ii Submission Date

11-06-2024

Latest Decision Or Authorization Date

20-06-2024

Processing Time Days

9

Number Of Sites

4

Number Of Participants

4

Spain

Earliest CTIS Part Ii Submission Date

10-06-2024

Latest Decision Or Authorization Date

20-06-2024

Processing Time Days

10

Number Of Sites

4

Number Of Participants

8

Primary sponsor

Full Name

Boehringer Ingelheim International GmbH

Organisation Type

Pharmaceutical company

Country Of Registered Address

Germany

Contract research organisations

Name

Almac Clinical Technologies LLC

Responsibilities

code 3

Name

Cytel Inc.

Responsibilities

Data Monitoring Committee activites

Third parties

• {"country":"United States","full_name":"Actigraph LLC","duties_or_roles":"Actigraphy data","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Almac Clinical Technologies LLC","duties_or_roles":"code 3","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Cytel Inc.","duties_or_roles":"Data Monitoring Committee activites","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Medidata Solutions Inc.","duties_or_roles":"code 7","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"Perspectum Limited","duties_or_roles":"Medical Imaging services","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Labcorp Central Laboratory Services LP","duties_or_roles":"code 4","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Greenphire LLC","duties_or_roles":"Patient solutions","organisation_type":"Non-Pharmaceutical company"}