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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Boehringer Ingelheim International GmbH

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nutritional and Metabolic Diseases [C18]

Trial duration

26 Jul 2024 → ongoing

Decision date (initial)

2024-06-19

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

External identifiers

EU CT number

2023-505303-23-00

WHO UTN

U1111-1299-9925

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Others, Safety

This trial aims to provide evidence of the efficacy, safety, and tolerability of survodutide administered once weekly as an adjunct to a reduced-calorie diet and increased physical activity, in comparison with placebo, in participants with presumed or onfirmed NASH and obesity (BMI ≥30 kg/m²) or overweight (BMI ≥27 kg/m2) with at least one of the following weight-related complications (treated or untreated): hypertension, dyslipidaemia, obstructive sleep apnoea, cardiovascular disease or T2DM.

The primary objective is to demonstrate superiority of survodutide in:
- Reduction in liver fat content assessed by MRI-PDFF, defined as ≥30% from baseline at Week 48 (odds ratio, survodutide vs. placebo), AND
- The difference in adjusted means of relative change (%) in body weight from baseline to Week 48 (survodutide vs. placebo)

Secondary objectives 1

1. The secondary (exploratory) objectives are to demonstrate the superiority of survodutide vs. placebo in terms of the difference in adjusted means of changes from baseline to Week 48 in liver fat content assessed by MRI-PDFF, cT1, ALT levels, waist circumference, HOMA-IR, liver stiffness assessed by MRE, and liver volume assessed by MRI

Conditions and MedDRA coding

Obesity

Regulatory references

Plan to share IPD

Yes

IPD plan description

Researchers can use the following link https://www.mystudywindow.com/msw/datasharing to request access to the clinical study documents regarding this study, and upon a signed “Document Sharing Agreement”. Furthermore, researchers can request access to the clinical study data, for this and other listed studies, after the submission of a research proposal and according to the terms outlined on the website. Time Frame: One year after the approval has been granted by major Regulatory Authorities and after the primary manuscript has been accepted for publication, or after termination of the development program. Access Criteria: For study documents – upon signing of a ‚Document Sharing Agreement‘. For study data – 1. after the submission and approval of the research proposal (checks will be performed by the sponsor and/or the independent review panel, including checking that the planned analysis does not compete with sponsor's publication plan); 2. and upon signing of a legal agreement.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

1. 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
2. BMI ≥30 kg/m², OR BMI ≥27 kg/m² and at least one weight-related comorbidity at screening: • Hypertension (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) • Dyslipidaemia (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 • 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) • 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)
3. 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.
4. History of at least one self-reported unsuccessful dietary effort to lose body weight

Exclusion criteria 11

1. 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.
2. Intake of medications associated with liver injury, hepatic steatosis or steatohepatitis
3. 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.
4. 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.
5. Current decompensated liver disease or previous hepatic decompensation (ascites, spontaneous bacterial peritonitis, portal hypertension bleeding, hepatic encephalopathy, hepatorenal syndrome).
6. Previous or current evidence of portal hypertension (e.g. splenomegaly, oesophageal varices, or other portosystemic collateral pathways).
7. Any of the following liver laboratory test abnormalities at screening: • Serum AST and/or ALT elevation ≥5x ULN • Total serum bilirubin concentration ≥1.2x ULN (except for cases of known Gilbert’s Syndrome) • Alkaline phosphatase >2x ULN • INR ≥1.3 (unless patient is on anticoagulants)
8. Body weight variation (self-reported) >5% within 3 months before screening
9. Medications for obesity within 3 months before screening
10. 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.
11. 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)

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Relative reduction in liver fat content of at least 30% from baseline to Week 48 (yes/no) assessed by MRI-PDFF [%]
2. Relative change (%) in body weight [kg] from baseline to Week 48

Secondary endpoints 8

1. Absolute change from baseline to Week 48 in liver fat content assessed by MRI-PDFF [%]
2. Reduction from baseline to Week 48 in cT1 [ms] levels of ≥80 ms (yes/no)
3. Absolute and relative change from baseline to Week 48 in ALT [U/L] levels
4. Absolute and relative change from baseline to Week 48 in HOMA-IR (FPI [mlU/L]·FPG [mmol/L]/22.5)
5. Absolute and relative change from baseline to Week 48 in liver stiffness [kPa] assessed by MRE
6. Absolute and relative change in liver volume [mL] from baseline to Week 48 measured using MRI
7. Absolute and relative change from baseline to Week 48 in waist circumference [cm]
8. Relative change (%) from baseline to Week 48 in liver fat content assessed by MRI-PDFF [%]

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 7

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Boehringer Ingelheim International GmbH

Sponsor organisation

Boehringer Ingelheim International GmbH

Address

Binger Strasse 173

City

Ingelheim Am Rhein

Postcode

55216

Country

Germany

Scientific contact point

Organisation

Boehringer Ingelheim International GmbH

Contact name

CT Disclosure & Data Transparency

Public contact point

Organisation

Boehringer Ingelheim International GmbH

Contact name

CT Disclosure & Data Transparency

Third parties 7

Locations

3 EU/EEA countries · 12 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 90 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

5 submissions — initial application plus substantial / non-substantial modifications