A randomised, double-blind, placebo-controlled, multicentre, Phase III trial evaluating long-term efficacy and safety of survodutide weekly injections in adult participants with non-cirrhotic non-alcoholic steatohepatitis/metabolic associated steatohepatitis (NASH/MASH) and (F2) - (F3) stage of liver fibrosis
A study to test whether survodutide helps people with a liver disease called NASH/MASH who have moderate or advanced liver fibrosis
Gomez Lourdes
Boehringer Ingelheim Espana, S.A.
C/ Prat de la Riba, 50 Sant Cugat 08174, Spain
34-93-404-5100
lourdes.gomez.ext@boehringer-ingelheim.com
Rosario Chikako
Parexel International Inc.
Kayabacho Tower, 1-21-2, Shinkawa, Chuo-ku, Tokyo
+81-80-8929-3137
Clinicaltrial-registration@parexel.com
Recruiting
Dec. 16, 2024
126
Interventional
randomized controlled trial
double blind
placebo control
parallel assignment
treatment purpose
1. Male or female participants >=18 years (or who are of legal age in countries where that is greater than 18 years) of age at time of consent.
2. Diagnosis of MASH (NAS >=4, with at least 1 point in inflammation and ballooning each) and fibrosis stage F2-F3 proven by a biopsy conducted during the screening period or by a historical biopsy conducted within the last 6 months prior to randomisation.
3. Stable body weight defined as less than 5% self-reported change in body weight 3 months prior to the screening or during the period between the historical biopsy and randomisation, if a historical biopsy is used.
Further criteria apply
Liver related:
1. Any of the following liver laboratory test abnormalities at screening:
- Serum AST and/or ALT elevation >=5x ULN
- Platelet count <140 000/mm3 (<140 GI/L)
- Alkaline phosphatase >2x ULN
- Abnormal synthetic liver function as defined by screening central laboratory evaluation:
o Albumin below <3.5 g/dL (35.0 g/L)
o OR International normalised ratio (INR) of prothrombin time >1.3 (unless participant is on anticoagulants)
o OR total serum bilirubin concentration >=1.5x ULN (participants with a documented history of Gilberts syndrome can be enrolled if the direct bilirubin is within normal reference range)
2. Any history or evidence of acute or chronic liver disease other than MASH
3. Histologically documented liver cirrhosis (fibrosis stage F4), either at screening or in a historical biopsy
4. History of or current diagnosis of hepatocellular carcinoma
5. History of or planned liver transplant
6. Inability or unwillingness to undergo a liver biopsy at screening (if a suitable historical biopsy is unavailable for central review), or during trial conduct.
7. History of portal hypertension or presence of decompensated liver disease (including hepatic encephalopathy, variceal bleeding, ascites, and spontaneous bacterial peritonitis)
8. MELD score >=12 due to liver disease
9. Treatment with any medication for the indication obesity within 3 months before screening biopsy or historical biopsy time point
10 History of either chronic or acute pancreatitis or elevation of serum lipase or amylase >2x ULN as measured by the central laboratory at screening
11 Major surgery (in the opinion of the investigator) performed within 3 months prior to screening or planned during the trial
Further exclusion criteria apply
18age old over
No limit
Both
Non-cirrhotic non-alcoholic steatohepatitis/metabolic associated steatohepatitis (NASH/MASH) and F2-
Subcutaneous maintenance doses once weekly
Part 1: Primary efficacy endpoint (at Week 52)
1. Resolution of MASH without worsening of liver fibrosis on MASH Clinical Research Network (CRN) fibrosis score
2. At least a 1-point improvement in fibrosis stage with no worsening of MASH
Part 2: Primary efficacy endpoints (at EoS)
Time to first occurrence of any of components of the composite endpoint consisting of progression to cirrhosis, all-cause mortality, liver transplant, hepatic decompensation event(s), worsening of MELD score to >=15, progression to CSPH.
Progression to cirrhosis is defined as histological fibrosis score CRN F4. MELD = Model for End-stage Liver Disease CSPH =clinically significant portal hypertension
Key secondary efficacy endpoints are:
Part 1: (at Week 52)
- Percentage change from baseline in body weight
- Absolute change from baseline in HbA1c (in participants with T2DM)
- Absolute change from baseline in ELF score
- Absolute change from baseline in liver stiffness assessed by VCTE
- Achievement of no progression of fibrosis assessed by central pathology (yes/no)
Part 2: (at Week 114/EoT/EoS)
- Percentage change from baseline in body weight (Week 114)
- Absolute change from baseline in HbA1c (in participants with T2DM) (Week 114)
- Absolute change from baseline in ELF score (Week 114)
- Absolute change from baseline in liver stiffness assessed by VCTE (Week 114)
- Achievement of no progression of fibrosis assessed by central pathology (yes/no; at EoT)
- Occurrence of all-cause hospitalisation (first and recurrent)(EoS)
- Time to first occurrence of any of the adjudicated components of the composite endpoint consisting of: CV death, non-fatal stroke, non-fatal MI, ischaemia related coronary revascularisation, or HFE (this includes HHF, emergency room visit, urgent care visit, or urgent outpatient HF visit) (5P-MACE) (EoS)
Additional secondary objectives are related to following secondary endpoints:
In Part 1 (at Week 52) and
In Part 2 (at Week 114):
- Improvement of liver fat content (LFC) defined as at least 30% relative reduction in LFC compared with baseline assessed by MRI-PDFF (subset of participants with MRI)
- Absolute change from baseline in LFC in MRI-PDFF (subset of participants with MRI)
- Absolute change from baseline in Alanine aminotransferase (ALT) [U/L]
- Absolute change from baseline in Aspartate aminotransferase (AST) [U/L]
- Absolute change from baseline in systolic blood pressure (SBP) [mmHg]
- Absolute change from baseline in diastolic blood pressure (DBP) [mmHg]
- Absolute changes from baseline in lipids [mg/dL] (including but not limited to: total cholesterol, low-density lipoprotein [LDL] cholesterol, very low density lipoprotein [VLDL], high-density lipoprotein [HDL] cholesterol, triglycerides [TG])
- Absolute change from baseline in free fatty acids [mg/dL]
- Progression to cirrhosis (defined as histological fibrosis score CRN F4) (yes/no), only at Week 52
Boehringer Ingelheim Pharma GmbH & Co. KG
Adachikyousai Hospital Institutional Review Board
1-36-8, Yanagihara, Adachi-ku, Tokyo, 120-0022, Japan, Tokyo
+81-3-3881-6116
c-irb_ug@neues.co.jp
Approval
Yes
Once the criteria in section 'time frame' are fulfilled, 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 in the website.
