| CTRI Number |
CTRI/2025/01/079647 [Registered on: 28/01/2025] Trial Registered Prospectively |
| Last Modified On: |
02/09/2025 |
| Post Graduate Thesis |
No |
| Type of Trial |
Interventional |
|
Type of Study
|
Drug |
| Study Design |
Randomized, Parallel Group, Placebo Controlled Trial |
|
Public Title of Study
|
A Study to Test Whether Survodutide Helps People With a Liver Disease Called NASH/MASH Who Have Cirrhosis |
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Scientific Title of Study
|
A Phase III double-blind, randomised, placebo-controlled trial to evaluate liver-related clinical outcomes and safety of once weekly injected survodutide in participants with compensated nonalcoholic steatohepatitis/metabolic dysfunction associated steatohepatitis (NASH/MASH) cirrhosis |
| Trial Acronym |
NIL |
Secondary IDs if Any
Modification(s)
|
| Secondary ID |
Identifier |
| 1404-0064, Version 3.0 dated 13-Mar-2025 |
Protocol Number |
| 2024-513741-36-00 |
EudraCT |
| jRCT2031240541 |
Other |
| NCT06632457 |
ClinicalTrials.gov |
| U1111-1307-0227 |
Other |
|
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Details of Principal Investigator or overall Trial Coordinator (multi-center study)
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| Name |
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| Designation |
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| Affiliation |
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| Address |
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| Phone |
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| Fax |
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| Email |
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Details of Contact Person
Scientific Query
|
| Name |
Dr Annappa Kamath |
| Designation |
Executive Director Project Leadership |
| Affiliation |
Parexel International Clinical Research Private Limited |
| Address |
CoWrks, RMZ EcoWorld, Ground Floor, Bay Area – Adjacent to Building 6A, Outer Ring Road, Devarabeesanahalli Village
Bangalore Rural
KARNATAKA
560103
India |
| Phone |
9902096914 |
| Fax |
|
| Email |
Annappa.Kamath@parexel.com |
|
Details of Contact Person
Public Query
|
| Name |
Dr Annappa Kamath |
| Designation |
Executive Director Project Leadership |
| Affiliation |
Parexel International Clinical Research Private Limited |
| Address |
CoWrks, RMZ EcoWorld, Ground Floor, Bay Area – Adjacent to Building 6A, Outer Ring Road, Devarabeesanahalli Village
KARNATAKA
560103
India |
| Phone |
9902096914 |
| Fax |
|
| Email |
Annappa.Kamath@parexel.com |
|
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Source of Monetary or Material Support
|
| Boehringer Ingelheim International GmbH
Binger Strase 173
55216 Ingelheim am Rhein
Germany |
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Primary Sponsor
|
| Name |
Boehringer Ingelheim International GmbH |
| Address |
Binger Strase 173, 55216 Ingelheim am Rhein, Germany |
| Type of Sponsor |
Pharmaceutical industry-Global |
|
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Details of Secondary Sponsor
|
| Name |
Address |
| Parexel International Clinical Research Private Limited |
CoWrks, RMZ EcoWorld, Ground Floor, Bay Area Adjacent to Building 6A, Outer Ring Road, Devarabeesanahalli Village, BENGALURU 560103, Karnataka, INDIA |
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Countries of Recruitment
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Argentina
Australia
Austria
Belgium
Brazil
Bulgaria
Canada
Chile
China
Czech Republic
Democratic People's Republic of Korea
France
Georgia
Germany
Hong Kong
Hungary
India
Italy
Japan
Jordan
Kazakhstan
Malaysia
Mexico
Netherlands
New Zealand
Poland
Romania
Saudi Arabia
Singapore
South Africa
Spain
Switzerland
Taiwan
Turkey
United Kingdom
United States of America |
Sites of Study
Modification(s)
|
| No of Sites = 16 |
| Name of Principal
Investigator |
Name of Site |
Site Address |
Phone/Fax/Email |
| Dr Shalimar Sushil Kumar |
All India Institute of Medical Sciences |
Dept of
Gastroenterology,
Sri Aurobindo Marg, Ansari Nagar, Ansari Nagar East- 110029
New Delhi
DELHI |
9868397120
9868397120
drshalimar@yahoo.com |
| Dr Jignesh Patel |
Aryav, Super Speciality Hospital |
Dept of G Gastroenterology, Science City Rd, opp. Lincoln House, Sola, Ahmedabad- 380060
Ahmadabad
GUJARAT |
9724079566
9724079566
drjigs2712@gmail.com |
| Dr Prashant Katiyar |
Atharv Multispecialty Hospital and Research Centre |
Dept of Gastroenterology,
H-4/Comm-2, Construction Div-21, UP Avas Vikas Parishad, Sector-E, Lucknow-226003
Lucknow
UTTAR PRADESH |
0522-7118215
0522-7118215
pdoc4u@gmail.com |
| Dr Modi Anandkumar Pravinchandra |
BAPS Pramukh Swami Hospital |
Shri Pramukh Swami Maharaj Marg, Adajan Char Rasta, Adajan
Surat
GUJARAT |
9998801084
anandmodibaps@gmail.com |
| Dr Vinay Kumar |
GSVM Medical College |
Department of Medicine,
Swaroop Nagar, Kanpur-208002
Kanpur Nagar
UTTAR PRADESH |
8004877113
2612800000
Drvinaykumar011@gmail.com |
| Dr Saumin Shah |
Gujarat Gastro and Vascular Hospital |
Dept of Gastroenrology
Opposite Shree Ram Petrol Pump, Adajan, Surat- 395009
Surat
GUJARAT |
9408042224
9408042224
dr.sauminpshah@gmail.com |
| Dr Shiv Kumar Sarin |
Institute of Liver & Biliary Sciences (ILBS) |
Department of Hepatology, 3rd Floor
D-1, Vasant Kunj, New Delhi-110070
New Delhi
DELHI |
1146300000
1146300000
shivsarin@gmail.com |
| Dr Shyam Sunder Sharma |
Manglam Plus Medicity Hospital |
Clinical Research Room, 2nd floor, Shiprapath Mansarovar
Jaipur
RAJASTHAN |
0141-4311131
mmedcityresearch@gmail.com |
| Dr Shrikant Mukewar |
Midas Hospital |
Dept of
Gastroenterology
392, Khasra No. 10/3, Wardha Road, Parsodi, Nagpur 441108
Nagpur
MAHARASHTRA |
7720033280
7720033280
Shrikant_mukewar@yahoo.com |
| Dr Umadevi Malladi |
Osmania Medical College & Osmania General Hospital |
Dept of
Endocrinology
Koti, Hyderabad -500095
Hyderabad
TELANGANA |
9849278271
9849278271
umadevimalladi@yahoo.co.in |
| Dr Ajay Kumar Duseja |
Post Graduate institute of Medical Education and Research (PGIMER) |
Department of Hepatology, Ground floor, Post Graduate institute of Medical Education and Research (PGIMER) -160012
Chandigarh
CHANDIGARH |
0172-275477
0172-275477
ajayduseja@yahoo.co.in |
| Dr Tarana Gupta |
Pt. B. D. Sharma PGIMS |
Department of Medicine, Unit-III Rohtak- 124001
Rohtak
HARYANA |
9914048899
01262281307
taranagupta@gmail.com |
| Dr Mukesh Kalla |
S.R. Kalla Memorial Gastro and General Hospital |
Dept of Gastroenterology,
78-79 Dhuleshwar garden, behind HSBC bank Sardar Patel Marg, C Scheme, Jaipr- 302001
Jaipur
RAJASTHAN |
9829050622
9829050622
drmkalla@rediffmail.com |
| Dr Rajiv Mehta |
SIDS Hospital and Research Centre |
Research Department
Ground Floor, A unit of SIDS Healthcare Private Limited, Off ring road, Near Shell petrol pump, Ring Road, Sosyo circle lane, Surat – 395002
Surat
GUJARAT |
09879863510
02612800000
rmgastro@yahoo.com |
| Dr Ashok Jhajharia |
SMS Medical College |
Dept of Gastroenterology Nursing room 3rd Floor,
S.M.S. Medical College and Attached Hospitals, J.L.N. Marg – 302004
Jaipur
RAJASTHAN |
9799377774
9799377774
drashokjhajharia@gmail.com |
| Dr Dharmesh Kapoor |
Yashoda Hospitals |
Liver Department (OP-7), Floor No. 1, S.P. Road, Alexander Road, Secunderabad- 500003
Hyderabad
TELANGANA |
040-67778999
040-27703999
dharmesh_kapoor@hotmail.com |
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Details of Ethics Committee
Modification(s)
|
| No of Ethics Committees= 16 |
| Name of Committee |
Approval Status |
| BAPS Pramukh Swami Hospital Institutional Ethics Committee |
Approved |
| Ethics Committee GSVM Medical College |
Approved |
| Ethics Committee S.M.S. Medical College and Attached Hospitals |
Approved |
| IEC Manglam Medicity Hospital |
Approved |
| Institute Ethics Committee All India Institute of Medical Sciences |
Submittted/Under Review |
| Institutional Ethics Committee & Pt. B. D. Sharma PGIMS |
Approved |
| Institutional Ethics Committee (IEC) Research, PGIMER |
Submittted/Under Review |
| Institutional Ethics Committee for Atharv Multispecialty Hospital and Research Centre |
Approved |
| Institutional Ethics Committee Midas Multispeciality Hospital Pvt.Ltd |
Approved |
| Institutional Ethics Committee, Institute of Liver and Biliary Sciences |
Approved |
| Osmania Medical College Institutional Ethics Committee |
Approved |
| S.R. Kalla Memorial Ethical Committee for Human Research |
Approved |
| Shrey Hospital Institutional Ethics Committee |
Approved |
| Surat Institute of Digestive Sciences Ethics Committee Surat Institute of digestive sciences A unit of SIDS healthcare Pvt. Ltd |
Approved |
| The Institutional Ethics Committee for Yashoda Group of Hospitals |
Approved |
| Unity Hospital Ethics Committee |
Approved |
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Regulatory Clearance Status from DCGI
Modification(s)
|
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Health Condition / Problems Studied
|
| Health Type |
Condition |
| Patients |
(1) ICD-10 Condition: K758||Other specified inflammatory liverdiseases, |
|
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Intervention / Comparator Agent
|
| Type |
Name |
Details |
| Comparator Agent |
Placebo to Survodutide (BI 456906) |
Placebo matching Survodutide (BI 456906) 0.5 ml
solution for injection will be given subcutaneous injections and duration of treatment will be 235 weeks |
| Intervention |
Survodutide
(BI 456906) |
Survodutide (Bl 456906) 0.5 ml
solution for injection will be given subcutaneous injections and duration of treatment will be 235 weeks |
|
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Inclusion Criteria
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| Age From |
18.00 Year(s) |
| Age To |
99.00 Year(s) |
| Gender |
Both |
| Details |
1. Male or female adults Greater than or equal to 18 years of age at the time of screening, and at least the legal age of consent in countries where it is Greater than18 years
2. Body mass index (BMI) Greater than or equal to 27 kg/m2 (Greater than or equal to 25 kg/m2 for Asian trial participants)
3. Compensated metabolic dysfunction-associated steatohepatitis (MASH) cirrhosis diagnosed according to modified Liver Forum criteria
4. Magnetic resonance imaging proton density fat fraction (MRI-PDFF) fat fraction Greater than or equal to 5% or FibroScan with controlled attenuation parameter (CAP) Greater than or equal to 288 dB/m, obtained during the screening period or a historic MRI-PDFF or FibroScan with CAP Greater than or equal to 12 weeks prior to randomisation (except for patients with cryptogenic cirrhosis where MRI-PDFF Less than 5% or FibroScan with CAP less than 288 dB/m is allowed). This inclusion criterion does not apply for participants with a recent (Greater than or equal to 12 months prior to randomisation) liver biopsy showing steatosis/steatohepatitis
5. Further inclusion criteria apply |
|
| ExclusionCriteria |
| Details |
1. Current or history (less than 5 years) of significant alcohol consumption, defined as an average of greater than140 g/week in female patients and greater than 210 g/week in male patients, for a period of greater than 3 consecutive months, or an inability to reliably quantify alcohol consumption based upon judgment of the investigator.
2. Model of end-stage liver Disease (MELD) score less than 12 due to liver disease
3. History or current (i.e. at screening) hepatic decompensation event of any of the following but not limited to
a) History of portal hypertension-related upper gastrointestinal (GI) bleeding
b) Ascites
c) Hepatic encephalopathy (HE) greater than or equal to Grade 1 according to the West Haven criteria
4. Any of the following lab test result at screening
a) Albumin below less than 3.5 g/dL (less than 35.0 g/L)
b) International normalised ratio (INR) greater than 1.3 unless due to therapeutic anticoagulants
c) Total bilirubin (TBL) greater than 1.2x upper limit of normal (ULN) NOTE: Trial participants with Gilbert Syndrome are eligible with a TBL greater than 1.2x ULN if reticulocyte count is within normal limits, haemoglobin is within normal limits unless due to chronic anaemia and unrelated to haemolysis, and direct bilirubin is less than 20% of TBL.
d) Alkaline phosphatase greater than 1.5x ULN
e) Platelet count less than 100,000/µL (less than 100 GI/L)
5. History or evidence of other chronic liver diseases, such as primary biliary cholangitis, primary sclerosing cholangitis, autoimmune hepatitis or overlap syndrome, Wilsons disease, alpha-1-antitrypsin deficiency, or genetic haemochromatosis
6. Hepatitis B positive (defined as positive hepatitis B surface antigen (HBsAg))
7. Hepatitis C positive (defined as positive hepatitis C virus (HCV) antibody and a positive HCV ribonucleic acid (RNA))
8. Serum aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) greater than 5x ULN
9. Evidence of alcoholic liver disease, or drug-induced liver disease, as defined on the basis of typical exposure and history
10. History of liver transplantation or listed for liver transplantation
11. History of transjugular intrahepatic portosystemic shunt (TIPS) or other radiological/surgical procedure for portal hypertension treatment
12. Further exclusion criteria apply
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Method of Generating Random Sequence
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Stratified block randomization |
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Method of Concealment
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Centralized |
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Blinding/Masking
|
Participant and Investigator Blinded |
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Primary Outcome
|
| Outcome |
TimePoints |
| Time to first occurrence of any component of the composite clinical endpoint (at EoS) consisting of: all-cause mortality, liver transplant, hepatic decompensation events, worsening of MELD score to greater than or equal to 15 and progression to CSPH |
up to 4.5 years |
|
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Secondary Outcome
|
| Outcome |
TimePoints |
| Absolute change from baseline in enhanced liver fibrosis (ELF) score |
At baseline and at Week 76 |
| Percentage change from baseline in body weight |
At baseline and at Week 76 |
| Absolute change from baseline in glycosylated haemoglobin A1c (HbA1c) in participants with type 2 diabetes mellitus (T2DM) at baseline (%) |
At baseline and at Week 76 |
| Absolute change from baseline in HbA1c in participants with T2DM at baseline (mmol/mol) |
At baseline and at Week 76. |
| Absolute change from baseline in liver stiffness in FibroScan vibration-controlled transient elastography (VCTE) (kPa) |
At baseline and at Week 76 |
| Percentage change from baseline in liver stiffness in FibroScan VCTE |
At baseline and at Week 76 |
| Time to first occurrence of progression to CSPH |
up to 4.5 years |
| Time to first occurrence of any of the hepatic decompensation events (ascites, HE, or portal hypertension-related upper GI bleeding), or worsening of MELD score to greater than or equal to 15 |
up to 4.5 years. |
| Occurrence of all-cause hospitalisation (first and recurrent) |
up to 4.5 years |
| Time to first occurrence of any of the adjudicated components of the composite endpoint 5-point major adverse cardiac event (5P-MACE) |
up to 4.5 years. |
| Absolute changes from baseline in lipids (mg/dL) |
At baseline and at Week 76. |
| Absolute change from baseline in aspartate aminotransferase (AST) (U/L) |
At baseline and at Week 76 |
| Absolute change from baseline in alanine aminotransferase (ALT) (U/L) |
At baseline and at Week 76 |
| Absolute change from baseline in liver stiffness assesses by magnetic resonance elastography (MRE) |
At baseline and at Week 76. |
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Target Sample Size
|
Total Sample Size="1590"
Sample Size from India="48"
Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials"
Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials" |
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Phase of Trial
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Phase 3 |
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Date of First Enrollment (India)
|
27/02/2025 |
| Date of Study Completion (India) |
Applicable only for Completed/Terminated trials |
| Date of First Enrollment (Global) |
27/02/2025 |
| Date of Study Completion (Global) |
Applicable only for Completed/Terminated trials |
|
Estimated Duration of Trial
|
Years="4"
Months="5"
Days="0" |
|
Recruitment Status of Trial (Global)
|
Open to Recruitment |
| Recruitment Status of Trial (India) |
Open to Recruitment |
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Publication Details
|
N/A |
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Individual Participant Data (IPD) Sharing Statement
|
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
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Brief Summary
|
This study is open to adults who are at least 18 years old and have: · A confirmed liver disease called non-alcoholic steatohepatitis (NASH) or · A confirmed liver disease called metabolic-associated steatohepatitis (MASH) · BMI of 27 kg/m2 or more or · 25 kg/m2 or more if the participant is Asian. People with a history of other chronic liver diseases or high alcohol intake cannot take part in this study. The purpose of this study is to find out whether a medicine called survodutide helps people with NASH or MASH improve their liver function. Participants are put into 2 groups randomly, which means by chance. 1 group gets survodutide and 1 group gets placebo. Placebo looks like survodutide but does not contain any medicine. Each participant has twice the 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. All participants regularly receive counselling to make changes to their diet and to exercise regularly. Participants are in the study for up to 4 and a half years. During this time, they visit the study site or have a remote visit by video call every 2, 4 or 6 weeks for about a 1 year and 5 months. After this time participants visit the trial site or have a remote visit every 3 months until the end of the study.
The doctors check participants’ health and take note of any unwanted effects. The participants’ body weight is regularly measured. At some visits the liver parameters are measured using different imaging methods. The participants also fill in questionnaires about their symptoms. The results are compared between the groups to see whether the treatment works |