| CTRI Number |
CTRI/2025/02/080714 [Registered on: 17/02/2025] Trial Registered Prospectively |
| Last Modified On: |
08/04/2026 |
| 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 moderate or advanced
liver fibrosis |
|
Scientific Title of Study
|
A randomised, double-blind, placebo-controlled, multicentre, Phase III trial evaluating long-term efficacy and safety of survodutide weekly injections in adult participants with noncirrhotic non-alcoholic steatohepatitis/metabolic associated steatohepatitis (NASH/MASH) and (F2) - (F3) stage of liver fibrosis |
| Trial Acronym |
NIL |
|
Secondary IDs if Any
|
| Secondary ID |
Identifier |
| 1404-0044, Version 1.0, dated 27-May-2024 |
Protocol Number |
| 2024-513739-25-00 |
EudraCT |
| NCT06632444 |
ClinicalTrials.gov |
| U1111-1306-9071 |
Other |
|
|
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
|
| Name |
|
| Designation |
|
| Affiliation |
|
| Address |
|
| Phone |
|
| Fax |
|
| Email |
|
|
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 |
918067723001 |
| 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 |
918067723001 |
| Email |
Annappa.Kamath@parexel.com |
|
|
Source of Monetary or Material Support
|
| Boehringer Ingelheim International GmbH
Binger Strase 173
55216 Ingelheim am Rhein
Germany
|
|
|
Primary Sponsor
|
| Name |
Boehringer Ingelheim International GmbH |
| Address |
Binger Strase 173, 55216 Ingelheim am Rhein, Germany |
| Type of Sponsor |
Pharmaceutical industry-Global |
|
|
Details of Secondary Sponsor
|
| Name |
Address |
| Parexel International Clinical Research Private Limited |
CoWrks, 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
|
Argentina
Australia
Austria
Belgium
Brazil
Bulgaria
Canada
Chile
China
Czech Republic
France
Georgia
Germany
Hong Kong
Hungary
India
Italy
Japan
Jordan
Kazakhstan
Mexico
Netherlands
New Zealand
Poland
Republic of Korea
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, New Delhi 110029
New Delhi
DELHI |
9868397120
9868397120
drshalimar@yahoo.com |
| Dr Jignesh Patel |
Aryav, Super Speciality Hospital |
Dept of 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-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-395009
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 Gastroenterology,
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, Faculty Area, Phase II, ILBS,
D-1, Vasant Kunj-110070
New Delhi
DELHI |
1146300000
1146300000
shivsarin@gmail.com |
| Dr Shyam Sunder Sharma |
Manglam Plus Medicity Hospital |
Clinical Research Rom, 2nd floor, Shiprapath Mansarovar 302020
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 Rakesh Sahay |
Osmania Medical College & Osmania General Hospital |
Dept of
Endocrinology, Koti, Hyderabad -500095
Hyderabad
TELANGANA |
9849597507
9849597507
sahayrk@gmail.com |
| 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, Jaipur- 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 |
91-9799377774
91-9799377774
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 |
|
Details of Ethics Committee
Modification(s)
|
| No of Ethics Committees= 17 |
| 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 (IEC), PGIMER |
Submittted/Under Review |
| Institutional Ethics Committee and Pt. B. D. Sharma PGIMS |
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, Fortis Hospital |
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 |
Approved |
| The Institutional Ethics Committee for Yashoda Group of Hospitals Yashoda Hospitals |
Approved |
| Unity Hospital Ethics Committee |
Approved |
|
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Regulatory Clearance Status from DCGI
|
|
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Health Condition / Problems Studied
|
| Health Type |
Condition |
| Patients |
(1) ICD-10 Condition: K758||Other specified inflammatory liverdiseases, |
|
|
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 365 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 365 weeks |
|
|
Inclusion Criteria
|
| Age From |
18.00 Year(s) |
| Age To |
99.00 Year(s) |
| Gender |
Both |
| Details |
1. Male or female participants greater than or equal to 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 (non-alcoholic fatty liver disease (NAFLD) activity score [NAS] greater than or equal to 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 randomization
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
4. Be willing to maintain a stable diet and physical activity levels throughout the entire trial
5. Further inclusion criteria apply |
|
| ExclusionCriteria |
| Details |
1. Any of the following liver laboratory test abnormalities at screening:
- Serum AST and/or alanine aminotransferase (ALT) elevation greater than or equal to 5x upper limit of normal (ULN)
- Platelet count less than 140 000/mm 3 (less than140 GI/L)
- Alkaline phosphatase greater than 2x upper limit of normal (ULN)
- Abnormal synthetic liver function as defined by screening central laboratory evaluation:
a) Albumin below less than 3.5 g/dL (35.0 g/L)
b) OR International normalised ratio (INR) of prothrombin time greater than 1.3 (unless participant is on anticoagulants)
c) OR total serum bilirubin concentration greater than or equal to 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. Model for end-stage liver disease (MELD) score greater than or equal to 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 greater than 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
12. Further exclusion criteria apply
|
|
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Method of Generating Random Sequence
|
Stratified block randomization |
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Method of Concealment
|
Centralized |
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Blinding/Masking
|
Participant and Investigator Blinded |
|
Primary Outcome
|
| Outcome |
TimePoints |
Part 1: Resolution of MASH without worsening of liver fibrosis on MASH Clinical Research Network (CRN) fibrosis score
Part 1: At least a 1-point improvement in fibrosis stage with no worsening of MASH
Part 2: 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 greater than or equal to 15, progression to CSPH |
Part 1: Baseline and at Week 52
Part 2: Up to 7 years |
|
|
Secondary Outcome
|
| Outcome |
TimePoints |
| part 1: Percentage change from baseline in body weight |
Baseline and at Week 52 |
| part 1: Absolute change from baseline in glycosylated haemoglobin (HbA1c) |
Baseline and at Week 52 |
| part 1: Absolute change from baseline in enhanced liver fibrosis (ELF) score |
Baseline and at Week 52 |
| part 1: Absolute change from baseline in liver stiffness assessed by vibration-controlled transient elastography (VCTE) |
Baseline and at Week 52 |
| part 1: Achievement of no progression of fibrosis assessed by central pathology (yes/no) |
Baseline and at Week 52 |
| part 2: Percentage change from baseline in body weight |
At baseline and at Week 114 |
| part 2: Absolute change from baseline in HbA1c |
At baseline and at Week 114 |
| part 2: Absolute change from baseline in ELF score |
At baseline and at Week 114 |
| part 2: Absolute change from baseline in liver stiffness assessed by VCTE |
At baseline and at Week 114 |
| part 2: Achievement of no progression of fibrosis assessed by central pathology (yes/no) |
At baseline and at 7 years |
| part 2: Occurrence of all-cause hospitalisation (first and recurrent) |
Up to 7 years |
| part 2: Time to first occurrence of any of the adjudicated components of the composite endpoint 5-point major adverse cardiac event (5P-MACE)5-point major adverse cardiac event (5P-MACE) |
Up to 7 years |
| Part 1: Improvement of liver fat content (LFC) |
At baseline and at Week 52 |
| Part 2: Improvement of LFC |
At baseline and at Week 114 |
| Part 1: Absolute change from baseline in LFC in MRI-PDFF |
At baseline and at Week 52 |
| Part 2: Absolute change from baseline in LFC in MRI-PDFF |
At baseline and at Week 114 |
| Part 1: Absolute change from baseline in alanine aminotransferase (ALT) [U/L] |
At baseline and at Week 52 |
| Part 2: Absolute change from baseline in alanine aminotransferase (ALT) [U/L] |
At baseline and at Week 114 |
| Part 1: Absolute change from baseline in aspartate aminotransferase (AST) [U/L] |
At baseline and at Week 52 |
| Part 2: Absolute change from baseline in aspartate aminotransferase (AST) [U/L] |
At baseline and at Week 114 |
| Part 1: Absolute change from baseline in systolic blood pressure (SBP) [mmHg] |
At baseline and at Week 52 |
| Part 2: Absolute change from baseline in systolic blood pressure (SBP) [mmHg] |
At baseline and at Week 114. |
| Part 1: Absolute change from baseline in diastolic blood pressure (DBP) [mmHg] |
At baseline and at Week 52 |
| Part 2: Absolute change from baseline in diastolic blood pressure (DBP) [mmHg] |
At baseline and at Week 114 |
| Part 1: 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]) |
At baseline and at Week 52 |
| Part 2: 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]) |
At baseline and at Week 114 |
| Part 1: Absolute change from baseline in free fatty acids [mg/dL] |
At baseline and at Week 52 |
| Part 2: Absolute change from baseline in free fatty acids [mg/dL] |
At baseline and at Week 114. |
| Part 1: Progression to cirrhosis (defined as histological fibrosis score CRN F4) (yes/no) |
At baseline and at Week 52 |
|
|
Target Sample Size
|
Total Sample Size="1800"
Sample Size from India="55"
Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials"
Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials" |
|
Phase of Trial
|
Phase 3 |
|
Date of First Enrollment (India)
|
07/03/2025 |
| Date of Study Completion (India) |
Applicable only for Completed/Terminated trials |
| Date of First Enrollment (Global) |
16/12/2024 |
| Date of Study Completion (Global) |
Applicable only for Completed/Terminated trials |
|
Estimated Duration of Trial
|
Years="7"
Months="0"
Days="0" |
|
Recruitment Status of Trial (Global)
|
Open to Recruitment |
| Recruitment Status of Trial (India) |
Open to Recruitment |
|
Publication Details
|
N/A |
|
Individual Participant Data (IPD) Sharing Statement
|
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
|
|
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)/metabolic-associated steatohepatitis (MASH) and
·
moderate or advanced liver fibrosis
People with a history of acute or chronic liver
diseases other than MASH or chronic 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 MASH and moderate or advanced liver fibrosis
improve their liver function.
This study has 2 parts. The purpose of the first
part of this study is to find out the effect of survodutide on MASH and liver
fibrosis. The purpose of the second part is to find out how safe and effective
survodutide is in improving 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. The survodutide doses are slowly
increased until the target dose is reached. All participants receive
counselling to make changes to their diet and to exercise regularly.
Participants are in the study for up to 7 years.
During this time, they regularly visit the study site or have remote visits by
video call. For about the first year of the study, participants have these
visits every 2 weeks, increasing to every 4 weeks and then every 6 weeks. After
being in the study for a little over a year participants will then alternate
between visiting the study site or having 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 and effects on the
stomach and intestines are regularly measured. At some visits the liver is
measured using different imaging methods. At 2 or 3 visits doctors take a small
sample of liver tissue (biopsy). The participants also fill in questionnaires
about their symptoms and quality of life. The results are compared between the
groups to see whether the treatment works |